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Exam 2 W 79 in class
Today Development and Genome Organization
Development differentiating cells to become an organism
Cells function differently because they express differentgenes
The proper control of gene expression is critical for proper development
So development in animals is one way
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Development differentiating cells to become an organism
Cells function differently because they express differentgenes
The proper control of gene expression is critical for proper development
So development in animals is one way
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Cells function differently because they express differentgenes
The proper control of gene expression is critical for proper development
So development in animals is one way
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
The proper control of gene expression is critical for proper development
So development in animals is one way
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
So development in animals is one way
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Inverse relationship between smoking and weight more smoking less weight
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Effect of smoking on fetal development and how that can affect adults
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Adults exposed to smoke as fetuses have higher risk of obesity and heart disease
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What is the connection
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Obesity Diabetes Heart Disease High Blood Pressure Some Cancers all may have some origins during fetal development
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Adults metabolism may react to poor nutrition as fetuseshellip
Adaptation of Thriftiness
or
Catch Up Growth
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Adults metabolism may react to poor nutrition as fetuseshellipAdaptation of Thriftiness or Catch Up Growth
Study of babies born during Dutch famine of 1944-45hellip
20 years later found that these babies had higher rates of obesity
Precise mechanism is not known
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
For Momrsquos who abstained during pregnancy no effect on fetus or as adult
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
17000 births studied and checked at age 16 and 33
Fetuses exposed to smoking had increased rate of obesity and more smoking meant more obesity
Smoking during first trimester had same effect as during whole pregnancy
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
For diabetes more than 10 cigarettes per day gave a 4 times greater risk of diabetes
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What about smoking
Risk of high blood pressure also increases with increased exposure to fetus of smoking during pregnancy
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
Nicotine can inhibit hunger and increase energy expenditure
This can lead to poor fetal nutrition
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
AAL 388
Mammalian circulation
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Nicotine causes blood vessels to constrict
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
CO in blood decreases delivery of O2 to fetus
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
These are all indirect affects leading to ldquoadaptation to thriftinessrdquohellip
Nicotine can inhibit hunger and increase energy expenditure
Nicotine causes constriction of blood vessels and may limit blood flow to the fetus
CO in blood decreases delivery of O2 to fetus
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Hormones are molecules produced in one cell and signal another
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why
Nicotine and other toxins in smoke may directly affect hormones that direct fetal development
Including hormones that direct brain development
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
So
Smoking during pregnancy may have indirect andor direct affects on fetal development and these affects may manifest themselves in adults
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Correlation of weight (BMI)
Identical twins reared together 80
Identical twins reared apart 72
Fraternal twins reared together 43
Biological siblings 34
Parents and children living together 26
Adopted children and parents 4
Unrelated children living together 1
Correlation of weight and relatedness
The nature of environmental influences on weight and obesity A behavior genetic analysis Grilo Carlos M Pogue-Geile Michael F Psychological Bulletin Vol 110(3) Nov 1991 pp 520-537 And two books by Matt Ridley Nature via Nurture (2003) and Genome the Autobiography of a Species in 23 Chapters (1999)
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Nature and Nurture
Are traits coded for by genes fixed while traits coded for by the environment are under our control
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
So development in animals is one way
Why
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Fig 233
Developmental mutants of Drosophila melanogaster
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Vertebrate Development
from zygote to adult
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Early embryo developmentFig 1913
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Totipotent ability to differentiate into any cell-type
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Totipotency is limited to early stages of animal development
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why do cells lose totipotency
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why do cells lose totipotency
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Mature differentiated plant cells are totipotent
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why do cells lose totipotency
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
bullGene expression can be controlled at many points between DNA and making the final proteins
bullChanges in the various steps of gene expression control when and how much of a product are produced
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
DNA packaging fluctuateshellipgenes being expressed are unpackaged genes not needed are tightly packaged
Fig 1021
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Normally DNA is loosely packaged
During mitosis DNA is tightly packaged as chromosomes and
individually visible
Fig 38
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
DNA packaging fluctuateshellipSome of the tight packaging of DNA is irreversible
Fig 1021
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Irreversible packaging of DNA partially explains the loss of totipotency
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Stem cells still have totipotencyFig 1913
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Embryonic Stem Cells are totipotent
Adult Stem Cells are pluripotent (only form some cell types)
Fig 1914
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
What genetic mechanisms regulateallow development
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Increases in cell number play a
rolehellip
Fig 231
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
hellipso does cell death
Fig 231
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
CB 2119
Development of a mouse paw yellow areas show dying cells
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
All humans are female for the first nine weeks of development
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Fig 2327
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
All humans are female for
the first nine weeks of
development
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Each whorl expresses a specific combination of three genes
Fig 2324
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Fig 2323
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Changing expression of A B or C genes
changes organ identity
Fig 2324
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Flower partsComplexity from a few simple genes
4 whorls of a flowerFig 2323
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
How does a cell know where it is
Fig 232
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Drosophila Development
Fig 234
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Polarity development by mRNA localization
Fig 235
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Hox genes regulate the identity of body parts Fig 2311
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Expression of hox genes in the embryo give rise to different adult body parts
embryo
adult
Fig 2311
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Drosophila and vertebrate Hox protein show striking similarities (500 million years since common ancestor)
Fig 2316
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Many hox proteins have common sequences(these are from Drosophila)
Fig 2313
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
helix-turn-helix a common DNA-binding motif
Fig 2313
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Many developmental genes are transcription factors
these are from Drosophila
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Reporter gene
protein
coding region
promoter reporter gene (luciferase etc)
easily visualized protein
promoter
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1219
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Interaction of genes can set gradients in cellsorganisms that signal how different regions should develop
ldquoIntroduction to Genetic Analysisrdquo 9th ed copy2008 by Griffiths et al Fig 1218
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Why change gene expressionbullDifferent cells need different componentsbullResponding to the environmentbullReplacement of damagedworn-out parts
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
The order of Hox genes parallels the order of body parts in which they are expressed
Fig 2317
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
25000 12
How are genomes organized Tbl 202
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
httpwwwncbinlmnihgovmapviewmapscgiORG=humanampCHR=XampMAPS=ideogr[XpterXqter]genes[10015369239100]
Map of human chromosome 20
How does the organization of a genome affect its function
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Figure 7-113 Molecular Biology of the Cell 4th ed by Alberts et al(Adapted from S Baxendale et al Nat Genet 1067ndash76 1995)
Comparison of Fugu and human huntingtin gene
75 X bigger
both have 67 exons connected by lines
(green indicates transposons prevalent in human version)
(puffer fish)
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Some genes have several similar sequences within the genome known as a gene family
Fig 87
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Hemoglobin (carries O2 in the blood) is comprised of a gene family in humans
Fig 87
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Different members of the hemoglobin gene family are expressed at different developmental stages
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Fetal Hb binds O2 more strongly than maternal Hb
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Pseudogenes have the structure of a gene but are not expressed
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Most cells in an organism have the same DNAWhich cells have different DNA
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
DNA is rearranged in B-cells during antibody production
Fig 179
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Each B-cell produces a unique antibody
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
DNA rearrangements in B-cells allow each B-cell to produce a unique antibody
Fig 179
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679andWhich transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Transposons mobile DNA
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Transposons comprise much of human DNA
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Fig 1712C
Retro-transposons move via an RNA intermediate
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Tbl 1 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Humans and chimpanzees shared a common ancestor about 6 million years ago
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
human
chimp
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Humans have more transposons than chimps
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
What affect do transposons have in humans
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Fig 3 Recently Mobilized Transposons in the Human and Chimpanzee Genomes (2006) Ryan E Mills et al The American Journal of Human Genetics 78 671-679
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Does transposition cause disease
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
An active copy of the L1 transposon lsquojumpedrsquo into the factor VIII gene and caused hemophilia
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Diseases caused by transposon insertion
bullDuchenne muscular dystrophy
bullCoffin-Lowry syndrome
bullFukuyama-type congenital muscular dystrophy (FCMD)
bullcolon cancer
bullchronic granulomatous disease
bullX-linked dilated cardiomyopathy
bullfamilial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
bullneurofibromatosis type 1
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Active human transposons have been estimated to generate about one new insertion per 10ndash100 live births
Which transposons are mobile
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Tbl 1 Which transposable elements are active in the human genome (2007) Ryan E Mills et al Trends in Genetics 23 183-191
Which transposons are mobile
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
QuickTimetrade and aTIFF (Uncompressed) decompressor
are needed to see this picture
Comparative genomics also has been used to identify recently mobilized transposons in genetically diverse humans For example over 600 recent transposon insertions were identified by examining DNA resequencing traces from 36 genetically diverse humans
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Conclusions
bullTransposons may play a role in evolution
bullMore abundant transposons in humans show ldquorecentrdquo transposon activity
bullTransposons are still active and can cause mutations and disease
Exam 2 W 79 in class
Exam 2 W 79 in class