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Chapter 24
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Genetics and
genomics
Anatomy and
Physiology
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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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Base pair
DNA
Gene
Cell
Nucleus
Chromosome
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Chromosome 7
Organs affected in cystic fibrosis
Airways
Mucus-clogged bronchi
and bronchioles.
Respiratory infections.
(Common)
DNA
Transcription
Liver
Blocked small bile ducts
impair digestion. (Rare)
mRNA
Pancreas
Blocked ducts prevent
release of digestive
enzymes, impairing fat
digestion. Diabetes
is possible. (Common)
Translation
Intestines
Hard stools may block
intestines. (Rare)
Reproductive tract
Cell
membrane
Absence of ductus deferens.
(Common)
Cystic fibrosis
transmembrane
conductance
regulator (CFTR)
protein
Skin
Salty sweat. (Common)
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(a)
(b)
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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2
3
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4
9
5
11
10
16
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Sex chromosomes
(female)
© SPL/Photo Researchers, Inc.
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Chromosomes and Genes
Come in Pairs
• 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
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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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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
+ = wild type
allele
cf = cystic fibrosis
allele
• Recessive Inheritance
• 3:1 Phenotype
• 1:2:1 Genotype
+ cf
+ cf
Carrier parents
For each child conceived:
+
+ +
25% chance
unaffected
noncarrier
cf
+
cf
cf
cf
50% chance unaffected carrier 25% chance
(cf allele inherited from either
affected
parent)
(a)
cf
I
cf
cf
cf
Joe
Mary
cf cf
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II
(b)
Punnett Square
(c)
Bill
Sue Tina
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• Dominant Inheritance
• 1:1 Phenotype
• 1:1 Genotype
+ = wild type
allele
HD = Huntington
disease
allele
+ HD
Affected parent
++
Unaffected parent
For each
Individual
conceived:
50% chance
unaffected
50% chance
affected
++
+ HD
(a)
I
Dan
HD HD
Ann
HD
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II
(b)
Punnett Square
(c)
Pam
Eric
Different Dominance Relationships
• Most genes exhibit complete dominance or recessiveness
• Exceptions are incomplete dominance and codominance
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Plasma cholesterol (milligrams/deciliter)
1000
Homozygotes
for FH
900
800
• Heterozygote has a phenotype
intermediate between
homozygous dominant and
homozygous recessive
• Familial hypercholesterolemia
is an example here
700
600
500
Heterozygotes
for FH
400
300
200
General
population
100
0
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 Dominance Relationships:
Codominance
• 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
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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)
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(b)
a: © Library of Congress; b: © Peter Morenus/University of Connecticut at Storrs
Frequency
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
aabbcc
Aabbcc
aaBbcc
aabbCc
0
1
AaBbcc
AabbCc
aaBbCc
AAbbcc
aaBBcc
aabbCC
AaBbCc
aaBbCC
AAbbCc
AabbCC
AABbcc
aaBBCc
AaBBcc
aaBBCC
AAbbCC
AABBcc
AaBbCC
AaBBCc
AABbCc
2
3
4
Number of dominant alleles
AaBBCC
AABbCC
AABBCc
AABBCC
5
6
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
AaBb
AB
Ab
aB
ab
AABB
AABb
AaBB
AaBb
AB
Number of
Phenotype dominant
frequency
alleles
Ab
AABb
AAbb
AaBb
Aabb
1/16
0
4/16
1
6/16
2
4/16
3
1/16
4
Light blue
AaBb
aB
AaBB
AaBb
aaBB
aaBb
Deep blue or green
Light brown
ab
AaBb
Aabb
aaBb
aabb
Medium brown
Dark brown/black
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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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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
X
Y
X-bearing
sperm
Y-bearing
sperm
+
+
X
X
Egg
Egg
XX
female
XY
male
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Sex Determination
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• 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
SRY gene
X chromosome
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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Hemophilia
• 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
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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
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
A
A a
a
A
A a
a
Primary spermatocyte
First division
nondisjunction
A
A a
Meiosis I
a
A
Secondary
spermatocyte
a
A
a
Second
division
nondisjunction
Meiosis II
Sperm
A a
A a
A
A
Euploid
Euploid
a
a
Fertilization of
euploid egg
Zygotes
Monosomic
(a)
Monosomic
Trisomic
Trisomic
(b)
Monosomic
Trisomic
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24.2 Clinical Application
Down Syndrome
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Prenatal Tests Detect Chromosome
Abnormalities
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Chorionic
villi
Uterus
Placenta
Amniotic
membrane
Fetus
Catheter
Rare fetal cells
Cervix
Fetus
15–16
weeks
Vagina
(b) Amniocentesis
Syringe
(a) Chorionic villus sampling
(c) Fetal cell sorting
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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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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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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
ALL
MLL
-3σ
-2σ
-1σ
0
+1σ
σ = standard deviation from mean
AML
+2σ
+3σ
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© 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
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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Important Points in Chapter 24:
Outcomes to be Assessed
 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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Important Points in Chapter 24:
Outcomes to be Assessed
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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Important Points in Chapter 24:
Outcomes to be Assessed
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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