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• 11.1 Gregor Mendel
• 11.2 Mendel’s Laws
• 11.3 Mendelian Patterns of Inheritance and Human Disease
• 11.4 Beyond Mendelian Inheritance
Phenylketonuria: A Human Genetic Disorder
• Phenylalanine is an amino acid found in many foods.
• Phenylketonurics are people who lack the enzyme that breaks down phenylalanine. Excess phenylalanine accumulates in their bodies,
causing nervous system disorders. Phenylketonuria is a recessively inherited trait,
which means people have to inherit two copies of the gene to have the disorder.
• Food labels inform phenylketonurics which foods they should avoid.
2
11.1 Gregor Mendel• The Blending Concept of Inheritance:
Parents of contrasting appearance produce offspring of intermediate appearance.
• Over time, variation would decrease as individuals became more alike in their traits.
Blending was a popular concept during Mendel’s time.
• Mendel’s findings were in contrast with this. He formulated the particulate theory of inheritance. Mendel proposed the laws of segregation and independent
assortment.• Inheritance involves reshuffling of genes from generation to generation.
3
Gregor Mendel• Austrian monk
Studied science and mathematics at the University of Vienna Conducted breeding experiments with the garden pea Pisum
sativum Carefully gathered and documented mathematical data from
his experiments
• Formulated fundamental laws of heredity in the early 1860s Had no knowledge of cells or chromosomes Did not have a microscope Experiments on the inheritance of simple traits in the garden
pea disproved the blending hypothesis
4
Gregor Mendel
5
6
Mendel Worked with the Garden Pea
• The garden pea: Organism used in Mendel’s experiments A good choice for several reasons:
• Easy to cultivate
• Short generation
• Normally self-pollinating, but can be cross-pollinated by hand
– Pollen was transferred from the male (anther) of one plant to the female (stigma) parts of another plant.
• True-breeding varieties available
• Simple, objective traits
Garden Pea Anatomy
7
stamenanther
a.
Flower Structure
filament
stigma
style
ovules inovary
carpel
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
8
All peas are yellow whenone parent produces yellowseeds and the other parentproduces green seeds.
Brushingon pollenfrom anotherplant
Cutting awayanthers
Garden Pea AnatomyCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
11.2 Mendel’s Laws
• Mendel performed cross-breeding experiments. Used “true-breeding” (homozygous) plants Chose varieties that differed in only one trait
(monohybrid cross) Performed reciprocal crosses
• Parental generation = P
• First filial generation offspring = F1
• Second filial generation offspring = F2
Formulated the law of segregation9
Monohybrid Cross Done by Mendel
10
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
eggssp
erm
Offspring
P generation
T t
T
t
TT tt
tT
Tt
TT Tt
Tt tt
P gametes
F1 gametes
F2 generation
F1 generation
Phenotypic Ratio
short1tall3
Allele Key
T tall plant=t short plant=
Mendel’s Laws• Law of Segregation:
Each individual has a pair of factors (alleles) for each trait.
The factors (alleles) segregate (separate) during gamete (sperm & egg) formation.
Each gamete contains only one factor (allele) from each pair of factors.
Fertilization gives the offspring two factors for each trait.
Results of the monohybrid cross: All F1 plants were tall, disproved blending hypothesis.
11
Mendel’s Laws
• Classical Genetics and Mendel’s Cross:
Each trait in a pea plant is controlled by two alleles (alternate forms of a gene).
Dominant allele (capital letter) masks the expression of the recessive allele (lowercase).
Alleles occur on a homologous pair of chromosomes at a particular gene locus.
• Homozygous = identical alleles
• Heterozygous = different alleles12
Homologous Chromosomes
13
Replication
alleles at agene locus
sister chromatids
b. Sister chromatids of duplicated chromosomes have same alleles for each gene.
a. Homologous chromosomes have alleles for same genes at specific loci.
G
R
S
t
G
R
S
t
G
R
S
t
g
r
s
T
g
r
s
T
g
r
s
T
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Relationship Between Observed Phenotype and F2 Offspring
Trait
Stem length
Pod shape
Seed shape
Seed color
Flower position
Flower color
Pod color
DominantCharacteristics
Recessive
Tall
Inflated
Round
Yellow
Axial
Purple
Green
Short
Constricted
Wrinkled
Green
Terminal
White
Yellow
Dominant
F2Results
RatioRecessive
Totals:
2.84:1277787
882 299 2.95:1
2.96:1
3.01:1
3.14:1
3.15:1
2.82:1
2.98:1
2,001
1,8505,474
6,022
651
705
428
14,949
207
224
152
5,010
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mendel’s Laws
• Genotype
It refers to the two alleles an individual has for a specific trait.
If identical, genotype is homozygous.
If different, genotype is heterozygous.
• Phenotype
It refers to the physical appearance of the individual.
15
Mendel’s Cross Viewed by Modern Genetics
• The dominant and recessive alleles represent DNA sequences that code for proteins.
• The dominant allele codes for the protein associated with the normal gene function within the cell.
• The recessive allele represents a “loss of function.”• During meiosis I the homologous chromosomes
separate. The two alleles separate from each other.
• The process of meiosis explains Mendel’s law of segregation and why only one allele for each trait is in a gamete.
16
Mendel’s Laws• A dihybrid cross uses true-breeding plants differing in two traits.• Mendel tracked each trait through two generations.
It started with true-breeding plants differing in two traits. The F1 plants showed both dominant characteristics. F1 plants self-pollinated. He observed phenotypes among F2 plants.
• Mendel formulated the law of independent assortment. The pair of factors for one trait segregate independently of the factors for
other traits. All possible combinations of factors can occur in the gametes.
• P generation is the parental generation in a breeding experiment.• F1 generation is the first-generation offspring in a breeding
experiment.• F2 generation is the second-generation offspring in a breeding
experiment. 17
Dihybrid Cross Done by MendelCopyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
×
====
TtGg
9331
ttggTTGG
P generation
P gametes
F1 generation
F1 gametes
F2 generation
sper
m
eggs
TtGg
TG tg
tgtGTgTG
TG
TtGg
Tg
tG
tg
TTGG TTGg TtGG
TtggTtGgTTggTTGg
ttGgttGGTtGgTtGG
ttggttGgTtggTtGg
Allele Key
Offspring
Phenotypic Ratio
Yellow podgreen podshort planttall plant tall plant, green pod
tall plant, yellow podshort plant, green podshort plant, yellow pod
Independent Assortment and Segregation during Meiosis
19
Parent cell has twopairs of homologouschromosomes.
All possible combi -tions of chromosomesand alleles occur inthe gametes assuggested by Mendel'stwo laws.
All orientations of ho-mologous chromosomesare possible at metaphase I in keepingwith the law of Independent assortment.
At metaphase II, eachdaughter cell has onlyone member of eachhomologous pair inkeeping with the law ofsegregation
A
A A
A A
A
A
AB
ab
Ab
aB
a
a
a
a
aa
a
AA
bA
aa aB
B
BB
B
B
B
B
B
Ba
B
b
b b
A A
b b BB
a a
b
b
b
b
b
A
b
b
either
or
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mendel’s Laws
• Punnett Square
Table listing all possible genotypes resulting from a cross
• All possible sperm genotypes are lined up on one side.
• All possible egg genotypes are lined up on the other side.
• All possible zygote genotypes are placed within the squares.
20
Mendel and the Laws of Probability
• Punnett Square It allows us to easily calculate probability of genotypes and
phenotypes among the offspring. Punnett square in next slide shows a 50% (or ½) chance.
• The chance of E = ½• The chance of e = ½
An offspring will inherit:• The chance of EE = ½ ½ = ¼ • The chance of Ee = ½ ½ = ¼ • The chance of eE = ½ ½ = ¼ • The chance of ee = ½ ½ = ¼
The sum rule allows us to add the genotypes that produce the identical phenotype to find out the chance of a particular phenotype.
21
Punnett Square
22
eggs
spem
Pu
nn
ett
squ
are
Offspring
Parents
E e
E
e
Ee
EeEE
Ee Ee
Allele key Phenotypic Ratio
unattached earlobes31
E =
e =
unattached earlobes
attached earlobes attached earlobes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
ee
Mendel’s Laws
• Testcrosses
Individuals with recessive phenotype always have the homozygous recessive genotype.
However, individuals with dominant phenotype have indeterminate genotype.
• May be homozygous dominant, or
• Heterozygous
A testcross determines the genotype of an individual having the dominant phenotype.
23
One-Trait Testcrosses
24
25
Mendel’s Laws
• Two-trait testcross:
An individual with both dominant phenotypes is crossed with an individual with both recessive phenotypes.
If the individual with the dominant phenotypes is heterozygous for both traits, the expected phenotypic ration is 1:1:1:1.
11.3 Mendelian Patterns of Inheritance and Human Disease
• Genetic disorders are medical conditions caused by alleles inherited from parents.
• Autosome is any chromosome other than a sex chromosome (X or Y).
• Genetic disorders caused by genes on autosomes are called autosomal disorders. Some genetic disorders are autosomal dominant.
• An individual with AA has the disorder.• An individual with Aa has the disorder.• An individual with aa does NOT have the disorder.
Other genetic disorders are autosomal recessive.• An individual with AA does NOT have the disorder.• An individual with Aa does NOT have the disorder, but is a carrier.• An individual with aa DOES have the disorder.
26
Autosomal Recessive Pedigree
27
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
I
II
III
IVKey
Gen
erat
ion
s
Autosomal recessive disorders• Most affected children have unaffected parents.
• Heterozygotes (Aa) have an unaffected phenotype.• Two affected parents will always have affected children.• Close relatives who reproduce are more likely to have affected children.
• Both males and females are affected with equal frequency.
A?
aa A?
A? Aa Aa A?
Aa*
Aa A?
A?aaaaaa = affectedAa = carrier (unaffected)AA = unaffectedA? = unaffected (one allele unknown)
Autosomal Dominant Pedigree
28
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• Affected children will usually have anaffected parent.
• Heterozygotes (Aa) are affected.• Two affected parents can produce an unaffected child.• Two unaffected parents will not have affected children.• Both males and females are affected with equal frequency.
AA = affectedAa = affectedA? = affected (one allele unknown)aa = unaffected
I
II
III Aa
aa
Aa
Aa
*
Aa
A?
aa
aa aa aa
aaaaaa
Aa
Key
Gen
erat
ion
s
Autosomal dominant disorders
Mendelian Patterns of Inheritance and Human Disease
• Autosomal Recessive Patterns of Inheritance and Disorders: If both parents carry one copy of a recessive gene they are
unaffected but are capable of having a child with two copies of the gene who is affected.
Methemoglobinemia• It is a relatively harmless disorder.
• Accumulation of methemoglobin in the blood causes skin to appear bluish-purple.
Cystic Fibrosis• Mucus in bronchial tubes and pancreatic ducts is particularly thick and
viscous.
29
Methemoglobinemia
30
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
© Division of Medical Toxicology, University of Virginia
Cystic Fibrosis
31
Mendelian Patterns of Inheritance and Human Disease
• Autosomal Dominant Patterns of Inheritance and Disorders
• Two parents with a dominantly inherited disorder will be affected by one copy of the gene.
• It is possible for them to have unaffected children.
Osteogenesis Imperfecta• Characterized by weakened, brittle bones.• Most cases are caused by mutation in genes required for the synthesis of type I
collagen.
Hereditary Spherocytosis• It is caused by a mutation in the ankyrin-1 gene.• Red blood cells become spherical, are fragile, and burst easily.
32
11.4 Beyond Mendelian Inheritance
• Some traits are controlled by multiple alleles (multiple allelic traits).
• The gene exists in several allelic forms, but each individual only has two alleles.
• ABO blood types The alleles:
• IA = A antigen on red blood cells, anti-B antibody in plasma
• IB = B antigen on red blood cells, anti-A antibody in plasma
• i = Neither A nor B antigens on red blood cells, both anti-A and anti-B antibodies in plasma
• The ABO blood type is also an example of codominance. More than one allele is fully expressed. Both IA and IB are expressed in the presence of the other.
33
ABO Blood Type
34
GenotypeIAIA, IAiIBIB, IBiIAIB
ii
PhenotypeABABO
Figure 14.11
Carbohydrate
Allele
(a) The three alleles for the ABO blood groups and their carbohydrates
(b) Blood group genotypes and phenotypes
Genotype
Red blood cellappearance
Phenotype(blood group)
A
A
B
B AB
none
O
IA IB i
iiIAIBIAIA or IAi IBIB or IBi
Beyond Mendelian Inheritance
• Incomplete Dominance
Heterozygote has a phenotype intermediate between that of either homozygote.
• Homozygous red has red phenotype.
• Homozygous white has white phenotype.
• Heterozygote has pink (intermediate) phenotype.
Phenotype reveals genotype without a testcross.
36
Incomplete Dominance
37
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
R1 R2
R1
R2
R1R2
R1R2R1R1
R2R2
R1R2 R1R2
eggs
sperm
Offspring
Key
1 R1R12 R1R21 R2R2
redpinkwhite
38
Beyond Mendelian Inheritance
• Human examples of incomplete dominance: Familial Hypercholesterolemia (FH)
• Homozygotes for the mutant allele develop fatty deposits in the skin and tendons and may have heart attacks during childhood.
• Heterozygotes may suffer heart attacks during early adulthood.
• Homozygotes for the normal allele do not have the disorder.
39
Beyond Mendelian Inheritance
• Human examples of incomplete dominance:
Incomplete penetrance• The dominant allele may not always lead to the
dominant phenotype in a heterozygote.
• Many dominant alleles exhibit varying degrees of penetrance.
• Example: polydactyly– There are extra digits on hands, feet, or both.
– Not all individuals who inherit the dominant polydactyly allele will exhibit the trait.
Beyond Mendelian Inheritance • Pleiotropy occurs when a single mutant gene
affects two or more distinct and seemingly unrelated traits.
• Marfan syndrome has been linked to a mutated gene FBN1 on chromosome 15 which codes for the fibrillin protein.
• Marfan syndrome is pleiotropic and results in the following phenotypes: Disproportionately long arms, legs, hands, and feet A weakened aorta Poor eyesight
40
Marfan Syndrome
41
Beyond Mendelian Inheritance
• Polygenic Inheritance: Occurs when a trait is governed by two or more sets of
alleles. Each dominant allele has a quantitative effect on the
phenotype. These effects are additive. It results in continuous variation of phenotypes within a
population. The traits may also be affected by the environment. Examples
• Human skin color
• Height
• Eye color
42
Polygenic Inheritance
43
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
aabbcc
Aabbcc
AaBbcc
AaBbCc
AABbCc
AABBCc
AABBCC
20—64
15—64
6—64
164
Pro
po
rtio
n o
f P
op
ula
tio
n
Genotype Examples
F2 generation
—
F1 generation
P generation
Beyond Mendelian Inheritance
• X-Linked Inheritance In mammals
• The X and Y chromosomes determine gender.
• Females are XX.• Males are XY.
44
Extending the Range of Mendelian Genetics
• X-Linked Inheritance The term X-linked is used for genes that have
nothing to do with gender.• X-linked genes are carried on the X chromosome. • The Y chromosome does not carry these genes. • It was discovered in the early 1900s by a group at
Columbia University, headed by Thomas Hunt Morgan.
– Performed experiments with fruit flies» They can be easily and inexpensively raised in simple
laboratory glassware.» Fruit flies have the same sex chromosome pattern as
humans.» Morgan’s experiments with X-linked genes apply
directly to humans.45
46
X-Linked Inheritance
47
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
XrY
XRY
XR
Xr
Y
XrY
Xr XRY
Offspring
eggs
sp
erm
P generation
P gametes
F2 generation
F1 generation
F1 gametes
Allele Key==
XR
Xr red eyes white eyes
Phenotypic Ratioall red-eyedred-eyedwhite-eyed
females:males: 1
1
XRY
XRXrXRXR
XR
XRXr
XRXR
X-Linked Inheritance
Beyond Mendelian Inheritance
• Several X-linked recessive disorders occur in humans: Color blindness
• The allele for the blue-sensitive protein is autosomal.• The alleles for the red- and green-sensitive pigments are on the X chromosome.
Menkes syndrome• It is caused by a defective allele on the X chromosome.
• It disrupts movement of the metal copper in and out of cells.
• Phenotypes include kinky hair, poor muscle tone, seizures, and low body temperature. Muscular dystrophy
• Causes wasting away of the muscle
• It is caused by the absence of the muscle protein dystrophin. Adrenoleukodystrophy
• It is an X-linked recessive disorder.• It is a failure of a carrier protein to move either an enzyme or very long chain fatty acid
into peroxisomes. Hemophilia
• It is an absence or minimal presence of clotting factor VIII or clotting factor IX.
• An affected person’s blood either does not clot or clots very slowly.
49
Hemophilia and the Royal Families of Europe
• Hemophilia is called the bleeder’s disease because the affected person’s blood either doesn’t clot correctly or doesn’t clot at all.
• People with hemophilia bleed internally and externally after injury.
• Blood transfusions or clotting factor injections help with the disorder.
• The pedigree shows why hemophilia is referred to as “the royal disease.” Queen Victoria was the first of the royals to carry the gene. Eventually it was spread throughout the royal families of Europe through
arranged marriages between the English, Spanish, Prussian, and Russian royal families.
50
51
X-Linked Recessive Pedigree
52
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
XBXB XbY grandfather
daughterXBXbXBY XBY XbXb
XbY
XBXb grandsonXBY XBXB XbY
KeyXBXB = Unaffected femaleXBXb = Carrier femaleXbXb = Color-blind femaleXbY = Unaffected maleXbY = Color-blind maleX-Linked Recessive
Disorders
• More males than females are affected.
• An affected son can have parents who have the normal phenotype.
• For a female to have the characteristic, her father must also have it. Her mother must have it or be a carrier.
• The characteristic often skips a generation from the grandfather to the grandson.
• If a woman has the characteristic, all of her sons will have it.
Epistasis
In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus
For example, in Labrador retrievers and many other mammals, coat color depends on two genes
One gene determines the pigment color (with alleles B for black and b for brown)
The other gene (with alleles C for color and c for no color) determines whether the pigment will be deposited in the hair
© 2011 Pearson Education, Inc.
Figure 14.12
Sperm
Eggs
9 : 3 : 4
1/41/4
1/41/4
1/4
1/4
1/4
1/4
BbEe BbEe
BE
BE
bE
bE
Be
Be
be
be
BBEE BbEE BBEe BbEe
BbEE bbEE BbEe bbEe
BBEe BbEe BBee Bbee
BbEe bbEe Bbee bbee
Linked Genes
Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry
• Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome
• Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency
© 2011 Pearson Education, Inc.
• A linkage map is a genetic map of a chromosome based on recombination frequencies
• Distances between genes can be expressed as map units; one map unit represents a 1% recombination frequency
• Map units indicate relative distance and order, not precise locations of genes
© 2011 Pearson Education, Inc.
Figure 15.11
Chromosome
Recombinationfrequencies
9% 9.5%
17%
b cn vg
RESULTS
• Sturtevant used recombination frequencies to make linkage maps of fruit fly genes
• Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes
• Cytogenetic maps indicate the positions of genes with respect to chromosomal features
© 2011 Pearson Education, Inc.
Figure 15.12
Mutant phenotypesShortaristae
Blackbody
Cinnabareyes
Vestigialwings
Browneyes
Long aristae(appendageson head)
Gray body
Red eyes
Normalwings
Redeyes
Wild-type phenotypes
104.567.057.548.50
X Inactivation in Female Mammals
• In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development
• The inactive X condenses into a Barr body• If a female is heterozygous for a particular gene
located on the X chromosome, she will be a mosaic for that character
© 2011 Pearson Education, Inc.
Figure 15.8
Early embryo:
X chromosomesAllele fororange furAllele forblack fur
Two cellpopulationsin adult cat:
Cell division andX chromosomeinactivation
Active X Inactive X Active X
Black fur Orange fur