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Chapter 13
The Chromosomal
Basis of Inheritance,
and Human Genetics
BIOLOGY
Thirteenth Edition
Raven, Johnson, Mason, Losos,
Duncan

© 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom.
No reproduction or further distribution permitted without the prior written consent of McGraw Hill, LLC.
 Lecture Outline

13.1 Sex Linkage and the

Chromosomal Theory
of Inheritance
13.2 Exceptions to
Mendelian Inheritance
13.3 Genetic Mapping
13.4 Human Genetics
13.5 Human Genetic
Mapping and
Association Studies

Adrian T Sumner/Science Source

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 Chromosomal Theory of Inheritance

Carl Correns – 1900

• First suggests central role for chromosomes
• Authored one of the scientific papers announcing
rediscovery of Mendel’s work
Walter Sutton – 1902
• Chromosomal theory of inheritance
• Based on observations that similar chromosomes paired
with one another during meiosis

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 Inheritance of eye color in fruit flies

Photo Researchers/Science Source

T.H. Morgan – 1910

• Working with fruit fly, Drosophila melanogaster
• Discovered a mutant male fly with white eyes instead of red
• Crossed the mutant male to a normal red-eyed female
• All F1 progeny red eyed = dominant trait

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 The eye color gene resides on the X chromosome

Morgan crossed F1 females × F1 males

F2 generation contained red and white- eyed flies

• But all white-eyed flies were male

Testcross of a F1 female with a white-eyed male showed the

viability of white-eyed females
Morgan concluded that the eye color gene resides on the
female X chromosome
Traits determined by sex chromosome genes are sex-linked

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 Sex chromosomes

Sex chromosomes are a pair of dissimilar chromosomes that

still pair during meiosis and mitosis
Sex determination in Drosophila is based on the number of X
chromosomes
• 2 X chromosomes = female
• 1 X and 1 Y chromosome = male

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 Chromosomal basis of X linkage Figure 13.2 (1)

X chromosome
has allele for
white eyes.

Y chromosome
Both X chromosomes is shorter then
have allele for red the X.
eyes.

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 Chromosomal basis of X linkage Figure 13.2 (2)

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 Chromosomal basis of X linkage Figure 13.2 (3)

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 Sex determination

Sex determination varies across organisms:

Is based on presence of a Y chromosome in humans
• 2 X chromosomes = female
• Having a Y chromosome (XY) = male

In birds, the male has two Z chromosomes and females are

ZW
Some insects are either XX (female) or XO (O indicating
absence of a chromosome) in males

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 Table 13.1

TABLE 13.1 Sex Determination in Some Organisms

Femal Male
e
Humans, Drosophila XX XY

Birds ZW ZZ

Grasshoppers XX XO

Honeybees Diploid Haploi

d
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 Sex chromosomes in humans

Biophoto Associates/Science Source

Humans have 46 total chromosomes

• 22 pairs are autosomes, non-sex chromosomes
• 1 pair of sex chromosomes
• Y chromosome highly condensed
• Recessive alleles on male’s X have no active counterpart on Y
• “Default” for humans is female.
• Requires SRY gene on Y for “maleness”
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 Sex Linkage

In organisms with XY sex-determination (like humans) few

genes from Y chromosome are expressed
Result is that recessive alleles on X chromosome have no
active partner on Y, therefore, a single recessive sex-linked
gene can produce recessive phenotype
Certain genetic diseases affect males to a greater degree
than females as a result
X-linked recessive alleles:
• Red-green color blindness
• Hemophilia

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 Dosage compensation

Ensures equal expression of genes from sex chromosomes

even though number of chromosomes is different between
sexes
In mammalian female cells, 1 X chromosome is randomly
inactivated and is highly condensed into a Barr body
Females heterozygous for genes on the X chromosome are
genetic mosaics
• Example: Calico cat

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 A calico cat

Kenneth Mason

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 Chromosome theory exceptions

• Mitochondria and chloroplasts contain genes

• Traits controlled by these genes do not follow the
chromosomal theory of inheritance
• Genes from mitochondria and chloroplasts are often
passed to the offspring by only one parent, often the
mother, called maternal inheritance
• In plants, chloroplasts are also often inherited from the
mother, although this is species dependent

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 Genomic imprinting

In genomic imprinting, the phenotype exhibited by a mutant

allele depends on which parent contributed the allele to the
offspring
Specific partial deletion of chromosome 15 in humans results
in:
• Angelman syndrome if from the mother
• Prader-Willi syndrome if the chromosome is from the
father

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 The mouse igf 2 gene

insulin-like growth factor 2

(igf 2)

Encodes a growth factor

critical for prenatal
development and growth

Only paternal allele is

expressed
• Phenotypes of
heterozygotes depend on
which parent contributes
the mutant allele

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 Epigenetics

Imprinting is an example of epigenetics

• Epigenetic inheritance
• A mitotically and/or meiotically stable change in gene function that
does not involve a change in DNA sequence

• Mechanisms:
• DNA methylation and histone modification

• Non-coding RNAs

• Nuclear organization

• Alterations to proteins involved in chromosome structure

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 Genetic Mapping

• Early geneticists realized that they could obtain

information about the distance between genes on a
chromosome
• Distance estimates based on patterns of genetic
recombination (crossing over) between genes
• If crossover occurs, parental alleles are recombined
producing recombinant gametes

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 Crossing over exchanges alleles

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 The Creighton and McClintock experiment: Hypothesis

• Hypothesis: Crossing
over involves a physical
exchange of genetic
material
• Prediction:
Recombination of visible
differences in a
chromosome should
correlate with genetic
recombination of alleles

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 The Creighton and McClintock experiment: Test

Two visible chromosome

markers:
• Yellow extension marker
• Green knob marker
combined with two genetic
markers
• Kernel color
• Kernel texture

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 The Creighton and McClintock experiment: Results

• Result:
• Genetically recombinant progeny also have physically
recombinant chromosomes
• Conclusion:
• A physical exchange of genetic material accompanied
genetic recombination

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 Recombination is the basis for genetic maps

Alfred Sturtevant
• Undergraduate in T.H. Morgan’s lab
• Put Morgan’s observation that recombinant progeny
reflected relevant location of genes in quantitative terms
• As physical distance on a chromosome increases, so does
the probability of recombination (crossover) occurring
between the gene loci

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 Constructing maps

The distance between genes is proportional to the

frequency of recombination events

recombinant progency
recombination frequency 
total progeny

1% recombination = 1 map unit (m.u.)

1 map unit = 1 centimorgan (cM)
Perform testcross with doubly heterozygous individuals;
count progeny

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 Two-point cross to map genes

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 Multiple crossovers

If homologues undergo two crossovers between loci, then

the parental combination is restored
Leads to an underestimate of the true genetic distance
• Odd numbers of crossover events (1, 3, etc.) produce
recombinant gametes
• No crossover or even numbers of crossovers (0, 2, 4, etc.)
produce parental gametes
Relationship between true distance on a chromosome and
the recombination frequency is not linear

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 Relationship between true distance and recombination
frequency

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 Three-point testcross

• Uses three loci instead of two to construct maps

• Middle gene allows tracking of recombination events on
either side
• In any three-point cross, the class of offspring with two
crossovers is the least frequent class
• In practice, geneticists use three-point crosses to
determine the order of genes, then use data from the
closest two-point crosses to determine distances

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 A three-point cross to order genes

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 Some human traits exhibit dominant/recessive
inheritance

Some human traits are controlled by a single gene

• Some of these exhibit dominant and recessive inheritance

Pedigree analysis is used to track inheritance patterns in

families
Dominant pedigree example – juvenile glaucoma
Recessive pedigree example - albinism

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 Dominant pedigree for hereditary juvenile glaucoma

• Disease causes
degeneration of optic
nerve leading to
blindness

• Dominant trait appears

in every generation

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 Recessive pedigree for albinism

• Condition in which the

pigment melanin is not
produced
• Form of albinism due to
a nonfunctional allele of
the enzyme tyrosinase
• Males and females
affected equally
• Most affected
individuals have
unaffected parents
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 Sex-linked human genetic disorders

Some genetic disorders affect males more than females (that

is sex-linked)
Hemophilia is a disease that affects a single protein in a
cascade involved in formation of blood clots
Form of hemophilia is caused by an X-linked recessive allele
• Heterozygous females are asymptomatic carriers

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 Human genetic disorder causes

A single amino acid change

in a single protein can result
in clinical syndrome

Example: Sickle cell anemia

• First human disease
shown to be the result of
a mutation in a protein
• Caused by a defect in the
oxygen carrier molecule,
hemoglobin
Jackie Lewin, Royal Free Hospital/Science Source

• Leads to impaired oxygen

delivery to tissues

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 Sickle cell anemia

Homozygotes for sickle cell allele exhibit intermittent illness

and reduced life span
Heterozygotes appear normal
• Do have hemoglobin with reduced ability

Sickle cell allele is particularly prevalent in people of African

descent
• Proportion of heterozygotes higher than expected
• Confers resistance to blood-borne parasite that causes
malaria, explains higher proportion of allele

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 Some important genetic disorders
TABLE 13.2 Some Important Genetic Disorders
Disorder Symptom Defect Dominant/Recessive Frequency Among
Human Births

Cystic fibrosis Mucus clogs lungs, liver, Failure of chloride ion Recessive 1/2500 (Caucasians)
and pancreas. transport mechanism

Sickle cell anemia Blood circulation is poor. Abnormal hemoglobin Recessive 1/600 (African
molecules Americans)

Tay–Sachs disease Central nervous system Defective enzyme Recessive 1/3500 (Ashkenazi
deteriorates in infancy. (hexosaminidase A) Jews)

Phenylketonuria Brain fails to develop in Defective enzyme Recessive 1/12,000

infancy; treatable with (phenylalanine
dietary restriction. hydroxylase)

Hemophilia Blood fails to clot. Defective blood-clotting X-linked recessive 1/10,000 (Caucasian
factor VIII males)

Huntington disease Brain tissue gradually Production of an inhibitor Dominant 1/24,000

deteriorates in middle of brain cell metabolism
age.

Muscular dystrophy Muscles waste away. Degradation of myelin X-linked recessive 1/3700 (males)
(Duchenne) coating of nerves
stimulating muscles

Hypercholesterolemia Excessive cholesterol Abnormal form of Dominant 1/500

levels in blood lead to cholesterol cell surface
heart disease. receptor

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 Nondisjunction changes chromosome number

Nondisjunction is the failure of homologues or sister

chromatids to separate properly during meiosis
Aneuploidy – gain or loss of a chromosome, the result of
nondisjunction
• Monosomy – loss
• Trisomy – gain
• In all but a few cases, do not survive

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 Nondisjunction of autosomes

Human embryos trisomic for five of the smallest autosomes

can survive birth
• Autosomes 13, 15, 18, 21 and 22
• 13, 15, 18 – severe defects, die within a few months
• 21 and 22 – can survive to adulthood
• Down syndrome – trisomy 21
• May be a full, third 21st chromosome

• May be a translocation of a part of chromosome 21

• Mother’s age influences risk

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 Trisomy of chromosome 21

L. Willatt, East Anglian Regional Genetics Service/Science Source

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 Correlation between maternal age and incidence of
Down syndrome

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 Nondisjunction of sex chromosomes

• Do not generally experience severe developmental

abnormalities
• Individuals have somewhat abnormal features, but often
reach maturity and in some cases may be fertile
• XXX – triple-X females
• XXY – males (Klinefelter syndrome)
• XO – females (Turner syndrome)
• OY – nonviable zygotes
• XYY – males (Jacob syndrome)

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 Nondisjunction and sex chromosomes

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 Some genetic defects can be detected early in
pregnancy

Genetic counseling can help identify parents carrying

disease alleles and asses genetic state of early embryos:
• Pedigree analysis used to determine the probability of
genetic disorders in the offspring
• Amniocentesis collects fetal cells from the amniotic fluid
for examination
• Chorionic villi sampling (CVS) collects cells from the
placenta for examination

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 Amniocentesis

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 Chorionic villus sampling

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 Human genome maps

Cannot use techniques from model systems (for example

inducing and tracking mutations) to create human genome
maps
Can use data derived from historical pedigrees
Difficult analysis
• Number of markers was not dense enough for mapping up
to 1980s
• Disease-causing (that is tracible) alleles are rare
Situation changed with the development of anonymous
markers
• Detected using molecular techniques
• No detectable phenotype
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 Molecular markers

Alternative to mutant/disease alleles, some molecular

markers are identifiable via modern genetic techniques and
do not alter phenotype
• Short tandem repeats (STR) are short repeats of 2-4
bases that can differ in repeat number between individuals
• Single-nucleotide polymorphisms (SNPs) affect a single
base of a gene locus
• More than 600 million SNPs identified in human genome
• Used in forensic analysis to ID suspects or for paternity testing

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 The human X-chromosome gene map

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 Genetic maps and genetic disorders

Human genetic maps can be constructed using common

genetic markers
• Data from related individuals is used instead of data from
controlled crosses as in model organisms
• Analysis requires complex statistical analysis and large
amounts of data
Tracking the segregation of possible causal alleles with a
disorder phenotype across multiple families can localize the
disorder alleles on the genome
• Examples: cystic fibrosis (recessive allele), Huntington
disease (dominant allele)

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 Phenotype-to-genotype association studies

Many common diseases are quantitative traits, affected by

many genes, that require different techniques to discover
underlying genes
Genome-wide association study (GWAS) looks for SNPs
associated with a disease phenotype as likely regions of
genome where candidate genes are located
• Requires large amounts of population-level data and is
computationally intensive
Thousands of variants have been identified that impact
complex traits (for example height, coronary artery disease)
but association of a variant does not mean causality

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 Genotype-to-phenotype association studies

Phenotype-wide association study (PheWAS) uses known

genetic variants to find association with phenotypes
• Dependent on large databases of detailed phenotype and
genotype data at population level
• Recently developed method based on use of electronic
health records (EMR) with standardized phenotypic data
Early results indicate high levels of pleiotropy

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