Chapter 24 Genetics and Genomics

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Chapter 24Lecture

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2402Anatomy and Physiology II

Chapter 24

Susan Gossett

[email protected]

Department of Biology

Paris Junior College

mailto:[email protected]

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Hole’s Human Anatomyand Physiology

Twelfth Edition

Shier Butler Lewis

Chapter 24

Genetics and Genomics


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24.1: Introduction• Packaged into our cells are instruction manuals• The manual is the human genome• It is written in the language of the DNA molecules• DNA consists of a sequence of nucleotide building blocks A, g, C, and T• Sequences of DNA that encode particular proteins are called genes• A gene has different forms and can vary from individual to individual• Genetics is the study of the inheritance of characteristics• A genome is a complete set of genetic instructions• Genomics is the field in which the body is studied in terms of multiple, interacting genes

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DNA

Base pair

Cell

Gene

Nucleus

Chromosome


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Chromosome 7

(a)

Organs affected in cystic fibrosis

(b)

Transcription

Translation

Cellmembrane

DNA

mRNA

Cystic fibrosistransmembraneconductanceregulator (CFTR)protein

AirwaysMucus-clogged bronchiand bronchioles.Respiratory infections.(Common)

LiverBlocked small bile ductsimpair digestion. (Rare)

PancreasBlocked ducts preventrelease of digestiveenzymes, impairing fat digestion. Diabetesis possible. (Common)

IntestinesHard stools may blockintestines. (Rare)

Reproductive tractAbsence of ductus deferens.(Common)

SkinSalty sweat. (Common)


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24.2: Modes of Inheritance

• Genetics has the power of prediction• Knowing how genes are distributed in meiosis and the combinations in which they join at fertilization makes it possible to calculate the probability that a certain trait will appear in the offspring of two particular individuals• These patterns in which genes are transmitted in families are termed modes of inheritance

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Chromosomes and Genes Come in Pairs

• This normal karyotype shows 23 pairs of chromosomes:• Pairs 1-22 are autosomes (they do not determine sex)• Pair 23 are the sex chromosomes

1 2 3 4 5

6 7 8 109 12

13 14 15 16 17 18

19 20 21 22

Sex chromosomes(female)

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© SPL/Photo Researchers, Inc.

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• A gene consists of hundreds of nucleotide building blocks and exists in variant forms called alleles that differ in DNA sequence• An individual who has two identical alleles of a particular gene is homozygous for that gene• A person with two different alleles for a gene is heterozygous• The particular combination of gene variants (alleles) in a person’s genome constitutes the genotype• The appearance or health condition of the individual that develops as a result of the ways the genes are expressed is termed the phenotype• Wild type alleles produce mutations

Chromosomes and Genes Come in Pairs

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Dominant and Recessive Inheritance

• For many genes, in heterozygotes, one allele determines the phenotype• Dominant allele masks the phenotype of the recessive allele• Recessive allele is expressed only if in a double dose (homozygous)• Autosomal conditions are carried on a non-sex chromosome• Sex-linked conditions are carried on a sex chromosome• X-linked conditions are carried on the X chromosome• Y-linked conditions are carried on the Y chromosome

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cf

cf cf cf cf

cf

Punnett Square

Carrier parents

+ + + cf +cf cf cf

(a)

(b) (c)

For each child conceived:

I

II

MaryJoe

Bill Sue Tina


+ = wild type allelecf = cystic fibrosis allele

+ cf + cf

25% chanceunaffectednoncarrier

50% chance unaffected carrier (cf allele inherited

from either parent)

25% chanceaffected

• Recessive Inheritance• 3:1 Phenotype• 1:2:1 Genotype

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(a)

(b) (c)

I

II

AnnDan

EricPam

HDHDHD

Punnett Square

+ = wild typeallele

HD = Huntingtondisease allele

+ HDAffected parent

+ +Unaffected parent

For eachIndividualconceived:

50% chanceunaffected

50% chanceaffected

+ + + HD

• Dominant Inheritance• 1:1 Phenotype• 1:1 Genotype

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Different Dominance Relationships

• Heterozygote has a phenotype intermediate between homozygous dominant and homozygous recessive• Familial hypercholesterolemia is an example here

• Most genes exhibit complete dominance or recessiveness• Exceptions are incomplete dominance and codominance


500

400

300

200

0

100

600

1000

900

800

700

Pla

sm

a c

ho

les

tero

l (m

illig

ram

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ite

r)

Homozygotesfor FH

Heterozygotesfor FH

Generalpopulation

From Genest, Jacques, Jr., Lavoie, Marc-Andre. August 12, 1999. "Images in Clinical Medicine." New England Journal of Medicine, pp 490. ©1999, Massachusetts Medical

Society. All Rights Reserved.

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• Different alleles expressed in a heterozygote are codominant• ABO blood type is an example:

• Three alleles of ABO blood typing are IA, IB, I• A person with type A may have the genotype IA i or IA IA

• A person with type B may have the genotype IB i or IB IB

• A person with type AB must have the genotype IA IB • A person with type O blood must have the genotype ii

• There is an exception – see example later with polygenic traits

Different Dominance Relationships: Codominance

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24.1 Clinical Application

Genetic Counselors Communicate Modes of Inheritance

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24.3: Factors That Affect Expression of Single Genes

• Most genotypes vary somewhat from person to person, due to the effects of the environment and other genes• Penetrance, expressivity, and pleiotropy describe distinctions of genotype

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Penetrance and Expressivity

• Complete penetrance• Everyone who inherits the disease causing alleles has some symptoms

• Incomplete penetrance• Some individuals do not express the phenotype even though they inherit the alleles• An example is polydactyly

• Variable expression• Symptoms vary in intensity in different people• For example, two extra digits versus three extra digits in polydactyly

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Pleiotropy

• Pleiotropy• A single genetic disorder producing several symptoms• Marfan syndrome (an autosomal dominant defect) is an example• People affected produce several symptoms that vary

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Genetic Heterogeneity

• Genetic heterogeneity• The same phenotype resulting from the actions of different genes• Hereditary deafness is an example

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24.4: Multifactorial Traits• Most if not all characteristics and disorders considered “inherited” actually reflect input from the environment as well as genes• Polygenic traits

• Determined by more than one gene• Examples include height, skin color, and eye color• Blood type O without genotype ii. Due to homozygous recessive expression of another gene, therefore blood types A and B are not possible – called Bombay phenotype

• Multifactorial traits• Traits molded by one or more genes plus environmental factors• Examples include height and skin color• Common diseases such as heart disease, diabetes mellitus, hypertension, and cancers are multifactorial

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(a)

(b)


a: © Library of Congress; b: © Peter Morenus/University of Connecticut at Storrs

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Number of dominant alleles

Fre

qu

ency

0 1 2 3 4 5 6

aabbcc aabbCc aabbCC AaBBcc AABbCc AABBCcaaBbcc aaBBcc aaBBCc AaBBCc AABbCCAabbcc AAbbcc AABbcc AaBbCC

aaBbCc AabbCC AABBccAabbCc AAbbCc AAbbCCAaBbcc aaBbCC

AaBbCcaaBBCC

AaBBCC

AABBCC


AABB AABb AaBB

AABb AAbb AaBb

AaBB AaBb

AaBb

AaBb

aaBB

AaBb Aabb aaBb

AaBb

Light blue

1/16

Deep blue or green

Light brown

Medium brown

Dark brown/black

Aabb

aaBb

aabb

AB

AB Ab aB ab

Ab

aB

ab

4/16

6/16

4/16

1/16

0

1

2

3

4

Phenotypefrequency

Number ofdominant

alleles


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24.5: Matters of Sex• Human somatic (nonsex) cells include an X and a Y chromosome in males and two X chromosomes in females

• All eggs carry a single X chromosome• Sperm carry either an X or Y chromosome

• Sex is determined at conception: a Y-bearing sperm fertilizing an egg conceives a male, and an X-bearing sperm conceives a female

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+ +

X

Egg

X

Egg

YX

X-bearingsperm

Y-bearingsperm

XXfemale

XYmale

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Sex Determination

• Maleness derives from a Y chromosome gene called SRY• The SRY gene encodes a type of protein called a transcription factor• The SRY activates transcription of genes that direct development of male structures in the embryo, while suppressing formation of female structures

X chromosome

SRY gene

Y chromosome


© Biophoto Associates/Photo Researchers, Inc.

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Genes of the Sex Chromosomes

• X chromosome• Has over 1,500 genes• Most genes on the X chromosome do not have corresponding alleles on the Y chromosome

• Y chromosome• Has only 231 protein-encoding genes• Some genes are unique only to the Y chromosome

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• Passed from mother (heterozygote) to son

• Each son has a 50% chance of receiving the recessive allele from the mother

• Each son with one recessive allele will have the disease

• Each son has no allele on the Y chromosome to mask the recessive allele

• Each daughter has a 50% chance of receiving the recessive allele from the mother

• Each daughter with one recessive allele will be a carrier

• Each daughter with one recessive allele does not develop the disease because she has another X chromosome with a dominant allele

Hemophilia

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Gender Effects on Phenotype

• Sex-limited trait• Affects a structure or function of the body that is present in only males or only females• Examples are beards or growth of breasts

• Sex-influenced inheritance• An allele is dominant in one sex and recessive in the other• Baldness is an example• Heterozygous males are bald but heterozygous females are not

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24.6: Chromosome Disorders

• Deviations from the normal chromosome number of 46 produce syndromes because of the excess or deficit of genes• Chromosome number abnormalities may involve single chromosomes or entire sets of chromosomes• Euploid is a normal chromosome number

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Polyploidy

• Polyploidy• The most drastic upset in chromosome number• This is an entire extra set of chromosomes• Results from formation of a diploid, rather than a normal haploid, gamete• Most embryos or fetuses die, but occasionally an infant survives a few days with many abnormalities

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Aneuploidy

• Aneuploidy• Cells missing a chromosome or having an extra chromosome• Results from meiotic error called nondisjunction• Here a chromosome pair fails to separate, either at the first or at the second meiotic division, producing a sperm or egg that has two copies of a particular chromosome or none, rather than the normal one copy• When a gamete fuses with its mate at fertilization, the resulting zygote has either 47 or 45 chromosomes, instead of 46 • Trisomy is the condition of having an extra chromosome• Monosomy is the condition of missing a chromosome

Monosomic Monosomic Euploid Euploid Monosomic

Zygotes

Meiosis II

A A a a

A A a a A A a a

Meiosis I

(a) (b)

A A a a

A a A a a aA A


First divisionnondisjunction

Primary spermatocyte

Secondaryspermatocyte

Sperm

Seconddivisionnondisjunction

Fertilization ofeuploid egg

Trisomic Trisomic Trisomic 33

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24.2 Clinical Application

Down Syndrome

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Prenatal Tests Detect Chromosome Abnormalities

Placenta

Catheter

Fetus

Cervix

Syringe

(a) Chorionic villus sampling

Uterus

(c) Fetal cell sorting

Rare fetal cells


Chorionicvilli

Vagina

Amnioticmembrane

Fetus15–16weeks

(b) Amniocentesis

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© Bernard Bennot/SPL/Photo Researchers, Inc.

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24.7: Gene Expression Explains Aspects of Anatomy and Physiology• Gene expression patterns can add to what we know about structure and function of the human body• Identifying which genes are active and inactive in particular cell types, under particular conditions, can add to our understanding of physiology• Gene expression monitors the proteins that a cell produces• The technology used is termed gene expression profiling, and identifying the sets of proteins in a cell is proteomics• DNA microarrays or DNA chips profile gene expression• This is valuable in anatomy and physiology when it allows medical researchers see distinctions their eyes cannot detect

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ALL MLL AML

σ = standard deviation from mean

-3σ -2σ -1σ 0 +1σ +2σ +3σ


© S.A. Armstrong et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nature Genetics Vol. 30, Fig. 5, p. 41-47, January 2002

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Important Points in Chapter 24:Outcomes to be Assessed

24.1: Introduction

Distinguish among genome, gene, and chromosome.

Define genetics.

Explain how genetic information passes from generation to generation.

Explain how the human genome is an economical storehouse of information.

24.2: Modes of Inheritance

State the two bases of genetic predictions.

Define the two types of chromosomes.

Explain the basis of multiple alleles of a gene.

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Distinguish between heterozygous and homozygous; genotype and phenotype; dominant and recessive.

Distinguish between autosomal recessive and autosomal dominant inheritance.

24.3: Factors That Affect Expression of Single Genes

Explain how and why the same genotype can have different phenotypes among individuals.

24.4: Multifactorial Traits

Describe how traits determined by genes and the environment are inherited.

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24.5: Matters of Sex

Describe how and when sex is determined.

Explain how X-linked inheritance differs from inheritance of autosomal traits.

Discuss factors that affect how phenotypes may differ between the sexes.

24.6: Chromosome Disorders

Describe three ways that chromosomes can be abnormal.

Explain how prenatal tests provide information about chromosomes.

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24.7: Gene Expression Explains Aspects of Anatomy and Physiology

What type of information does gene expression profiling provide?

Explain how a DNA microarray works.

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Chapter 24 Genetics and Genomics