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Molecular Genetics
1450-341
Dr. Abdelaziz Tlili

Class:

Sec 11 MTWR: 02:00-03:40

Office: W8-117

Office hours: MW: 12:00-02:00

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Midterm
June 12, 2024 (TBC)

Final
July 13-18, 2024 (TBA)

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2 or
display Hartwell et al., 4th ed., Chapter 1
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Genetics: From
Genes to Genomes
Seventh Edition
Michael L. Goldberg, Janice
A. Fisher, Leroy Hood, and
Leland H. Hartwell

© 2021 McGraw Hill. 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.
 Because learning changes everything. ®

Chapter 1

Mendel’s Principles of
Heredity
PART I - Basic Principles:
How Traits Are Transmitted

© McGraw Hill Lawrence Manning/Corbis 4

 CHAPTER OUTLINE

1.1 The Puzzle of Inheritance

1.2 Genetic Analysis According to Mendel

1.3 Mendelian Inheritance in Humans

© McGraw Hill 5
 Genetics is the science of heredity

• Why do some children look like only one parent, while

others look more like the great, great grandparents?

• What causes similarities and differences of appearance

and the skipping of generations?

• The study of genetics provides explanations for these

types of questions by connecting the most basic unit of
biological information, genes, with inheritance across
generations

© McGraw Hill 6
 Genetics explains the mechanisms that determine the
inheritance of traits

Genes are the basic units of heredity

• A gene is a region of DNA that encodes a protein or RNA.

• Heredity is the way that genes transmit traits from parents to offspring

Genes underlie the formation of every heritable trait, for

example cleft chin, hair loss, eye color
• Some traits are causes by a single change in a single gene, for
example sickle-cell anemia

• Some traits are caused by complex interactions between many genes,

for example facial features

© McGraw Hill 7
 Four general themes of Mendel’s work

1. Variation is widespread in nature and provides for

continuously evolving diversity

2. Observable variation is essential for following genes from

one generation to another

3. Variation is inherited by genetic laws, which can explain

why like begets like and unlike

4. Mendel’s laws apply to all sexually reproducing organisms

© McGraw Hill 8
 1.1 The Puzzle of Inheritance

Learning Objectives:
• Relate how Mendel’s experimental approach is similar to the process
of modern scientific inquiry

• Describe how Mendel cross-fertilized and self-fertilized pea plants

• Explain why Mendel included reciprocal crosses within his controlled

breeding program of pea plants

• Predict the type of progeny produced by Mendel’s crosses between

pure-breeding plants with discrete, antagonistic traits, such as purple
versus white flowers

© McGraw Hill 9
 Gregor Mendel discovered the basic principles of
genetics

• Mendel was the first

scientist to combine data
collection, analysis, and
theory to understand
heredity

• He inferred genetic laws

about the appearance and
disappearance of traits in
different generations

© McGraw Hill Science Source 10

 Mendel studied the inheritance of alternative traits in pea
plants

• Mendel inferred laws of

genetics that allowed
predictions about which traits
would appear, disappear, and
then reappear.

• Mendel’s paper “Experiments

in plant hybrids” was
published in 1866 and
became the cornerstone of
modern genetics.

© McGraw Hill Biophoto Associates/Science Source 11

 Mendel’s experimental organism: The garden pea

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© McGraw Hill (a): Andrea Jones Images/Alamy 12

 Keys to the success of Mendel’s experiments

Pure-breeding lines of peas (Pisum sativum)

• Controlled breeding via cross-fertilization or selfing
• Large numbers of progeny produced within a short time
• Traits remained constant in crosses within a line

Inheritance of alternative forms of traits

• Antagonistic pairs of “either-or” traits: for example purple or white,
yellow or green

Brilliant experimentalist
• Carefully planned and carried-out experiments
• Controlled the plant breeding, including reciprocal crosses
• Analyzed results mathematically

© McGraw Hill 13
 Mendel studied seven antagonistic pairs of traits in peas

Antagonistic pairs of traits

Mendel used are shown at
right
• Note that each hybrid
resembles only one of the
parents

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© McGraw Hill 14
 1.2 Genetic Analysis According to Mendel 1

Learning Objectives:
• Explain Mendel’s law of segregation and how it predicts the 3:1
dominant-to-recessive phenotypic ratio among the F 2 generation of a
monohybrid cross

• Distinguish between a monohybrid cross and a testcross

• Explain Mendel’s law of independent assortment and how the 9:3:3:1

phenotypic ratio among the F2 of a dihybrid cross provides evidence
for this law

• Interpret phenotypic ratios of progeny to infer how particular traits are

inherited

© McGraw Hill 15
 1.2 Genetic Analysis According to Mendel 2

Learning Objectives (continued):

• Predict the genotypic and phenotypic ratios among progeny of
complex multi hybrid crosses using simple rules of probability.

• Cite the most common molecular explanations for dominant and

recessive alleles.

© McGraw Hill 16
 Monohybrid crosses revealed units of inheritance and
the law of segregation 1

Mendel crossed pure-

breeding lines that differed in
only one trait, for example
seed color
Examined phenotypes of F1
and F2 progeny
• F1 progeny have only one of the
parental traits
• Both parental traits reappear in
F2 progeny in a 3:1 ratio

His results disproved the

blending hypothesis.
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© McGraw Hill 17
 Monohybrid crosses revealed units of inheritance and
the law of segregation 2

Mendel performed reciprocal

crosses
• Pollen from yellow peas
fertilized eggs from green peas
(shown)

• Pollen from green peas fertilized

eggs from yellow peas

The results from reciprocal

crosses produced similar
results, disproving the
blending hypothesis.

© McGraw Hill 18
 Mendel proposed each plant carries two copies of a unit
of inheritance

Traits have two forms that can each breed true

• Trait that appears in F1 progeny is the dominant form

• Trait that is hidden in the F1 progeny is the recessive form

Units of inheritance are now known as genes

• Alternative forms of a single gene are alleles

• Individuals with two different alleles for a single trait are monohybrids

Gametes are the specialized cells (for example eggs or

sperm) that carry genes across generations

© McGraw Hill 19
 Mendel’s law of segregation

How do progeny inherit one unit from the maternal parent

and the other unit from the paternal parent?
• The two alleles for each trait • Two gametes, one from
separate during gamete each parent, unite at
formation random at fertilization

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© McGraw Hill 20
 The Punnett square is a simple way to visualize the
segregation and random union of alleles

Each F1 hybrid produces two

kinds of gametes in a 1:1 ratio
F2 progeny
• 3:1 ratio of phenotypes

• 1/4 will breed true for the dominant

trait

• 1/2 will be hybrids

• 1/4 will breed true for the recessive

trait
Fig. 1.8

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© McGraw Hill 21
 Mendel’s results and the Punnett square reflect the basic
rules of probability

Product rule: probability of two independent events occurring

together is the product of their individual probabilities
• What is the probability that event 1 AND event 2 will occur?

P(1 AND 2) = probability of event 1 × probability of event 2

Sum rule: probability of either of two mutually exclusive

events occurring is the sum of their individual probabilities
• What is the probability that event 1 OR event 2 will occur?

P(1 OR 2) = probability of event 1 + probability of event 2

© McGraw Hill 22
 Applying probability to Mendel’s crosses

From a cross of Yy × Yy peas

• What is the chance of getting YY offspring?

• Chance of Y pollen is 1/2

• Chance of Y ovule is 1/2
• Chance of Y pollen and Y ovule uniting is 1/2 × 1/2 = 1/4

• What is the chance of getting Yy offspring?

• Chance of Y pollen uniting with y ovule is 1/2 × 1/2 = 1/4

• Chance of y pollen uniting with Y ovule is 1/2 × 1/2 = 1/4
• Chance of either event happening is 1/4 + 1/4 = 1/2

© McGraw Hill 23
 Mendel did further crosses to verify the law of
segregation

F2 plants were selfed to produce F3 progeny

• All of the green F2 peas were pure breeding

• 1/3 of the yellow F2 peas were pure breeding

• 2/3 of the yellow F2 peas were hybrids

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© McGraw Hill 24
 Definitions of commonly used terms

Phenotype is an observable characteristic (for example

yellow or green pea seeds)
Genotype is the set of alleles in an individual for given
phenotypes (for example YY or Yy)
Homozygote has two identical alleles (for example YY or yy)
Heterozygote has two different alleles (for example Yy)
• The heterozygous phenotype defines the dominant allele (for example
Yy peas are yellow, so the yellow Y allele is dominant to the green y
allele)

• A dominant allele with a dash represents an unknown genotype (for

example Y− stands for either YY or Yy)

© McGraw Hill 25
 Genotype versus phenotype in homozygotes and
heterozygotes

• From a cross of Yy ×
Yy peas

• Genotypes in F2
progeny are in 1:2:1
ratio (1/4 YY, 1/2 Yy,
1/4 yy)

• Phenotypes in F2
progeny are in 3:1
ratio (3/4 yellow, 1/4
green)

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© McGraw Hill 26
 A testcross can reveal an unknown genotype

Is the genotype of an individual with a dominant phenotype

(for example Y−) heterozygous (Yy) or homozygous (YY)?
• Solution: Testcross to homozygous recessive (yy) and examine
progeny

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© McGraw Hill 27
 Mendel’s dihybrid crosses revealed the law of
independent assortment

Mendel tested simultaneous inheritance of multiple genes

using dihybrids, plants heterozygous for two genes

First, he crossed true-breeding yellow round peas with true-

breeding green wrinkled peas to obtain dihybrid F1 plants:
YY RR × yy rr → F1 Yy Rr

Then, the dihybrid F1 plants were selfed to obtain F2 plants:

F1 Yy Rr × F1 Yy Rr → F2

Mendel asked whether all the F2 progeny would be parental

types (yellow round and green wrinkled) or would some be
recombinant types (yellow wrinkled and green round)?
© McGraw Hill 28
 A dihybrid cross produces parental types and
recombinant types

Fig. 1.12

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© McGraw Hill 29
 Independent assortment in crosses of F1 dihybrids
produces a 9:3:3:1 phenotype ratio

Each F1 dihybrid produces four

possible gametes in a 1:1:1:1
ratio
Yy Rr → 1/4 Y R, 1/4 Y r,
1/4 y R, 1/4 y r

Four phenotypic classes

occurred in the F2 progeny:
• Two are like parents
• Two are recombinant

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© McGraw Hill 30
 Mendel’s law of independent assortment

During gamete formation,

different pairs of alleles
segregate independently of
each other
• Y is just as likely to assort with
R as it is with r

• y is just as likely to assort with

R as it is with r

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© McGraw Hill 31
 Using the product rule to calculate the ratios observed in
the F2 of a dihybrid cross

Each trait is inherited in a 3:1

ratio
• Ratio of yellow (dominant) to
green (recessive) = 3:1
• Ratio of round (dominant) to
wrinkled (recessive) = 3:1

Product rule
P(yellow, wrinkled)
= P(yellow) × P(wrinkled)
= 3/4 × 1/4
= 3/16
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© McGraw Hill 32
 Following crosses with branched-line diagrams

Progeny phenotypes for each gene are shown in different

columns
This gives the same ratios as seen in the Punnett square in
Fig 1.13

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© McGraw Hill 33
 Testcrosses on dihybrids

Testcross can be
performed on
dihybrids by crossing
individuals with
unknown genotype to
individuals
homozygous for both
recessive traits

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© McGraw Hill 34
 Mendel’s laws can be used to predict offspring from
complicated crosses

The number of different gametes  2n n  # of different traits 

Aa Bb Cc Dd  24  16 kinds of gametes
Aa Bb Cc Dd  Aa Bb Cc Dd  16  16  256 genotypes

• To do a Punnett square with this cross involving four

genes, you would need 16 columns and 16 rows

• An easier way is to break down a multihybrid cross into

independently assorting monohybrid crosses

© McGraw Hill 35
 Predicting proportions of progeny from multihybrid
crosses – example 1

Cross Aa Bb Cc Dd × Aa Bb Cc Dd

What proportion of progeny will be AA bb Cc Dd?

• Aa × Aa  1/4 AA

• Bb × Bb  1/4 bb

• Cc × Cc  1/2 Cc

• Dd × Dd  1/2 Dd

So, the expected proportion of AA bb Cc Dd progeny is:

1/4 × 1/4 × 1/2 × 1/2 = 1/64

© McGraw Hill 36
 Predicting proportions of progeny from multihybrid
crosses – example 2

Cross Aa Bb Cc Dd × Aa Bb Cc Dd
How many progeny will show the dominant traits for A, C,
and D and the recessive trait for B?
• Aa × Aa  3/4 A−
• Bb × Bb  1/4 bb
• Cc × Cc  3/4 C−
• Dd × Dd  3/4 D−

So, expected proportion of A− bb C− D− progeny is:

3/4 × 1/4 × 3/4 × 3/4 = 27/256

© McGraw Hill 37
 The science of genetics began with the rediscovery of
Mendel’s work

Despite publishing his results in 1866, it took until 1900 for

three scientists to independently rediscover Mendel’s work,
enabling subsequent connection to Darwin’s theory of
evolution

© McGraw Hill (a): NML/Science Source; (b): INTERFOTO/Alamy; (c): SPL/Science Source; (d): Ullstein Bild/Getty Images 38
 Molecular explanation for Mendel’s pea shape

• The R allele encodes Starch branching enzyme (Sbe1).

• The r allele does not make Sbe1. Sucrose and

unbranched starch build up, leading to wrinkled peas.

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© McGraw Hill 39
 Molecular explanation for Mendel’s pea color

• The Y allele encodes the Stay green enzyme (Sgr). Sgr

helps break down chlorophyll.

• The y allele does not make Sgr. Chlorophyll is not broken

down and the peas remain green.

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© McGraw Hill 40
 Two general molecular principles

1. A specific gene determines a specific protein, whose

activity may affect the phenotype

2. A dominant allele usually determines a normally

functioning protein and a recessive allele usually does
not encode a functional protein

© McGraw Hill 41
 1.3 Mendelian Inheritance in Humans

Learning Objectives:
• Analyze human pedigrees to determine whether a genetic disease
exhibits recessive or dominant inheritance

• Explain why Huntington’s disease is inherited as a dominant allele

while cystic fibrosis is caused by a recessive allele

© McGraw Hill 42
 Mendelian inheritance in humans

Many heritable traits in humans are caused by interaction of

multiple genes and so don't show simple Mendelian
inheritance patterns
In 2016, there were approximately 6000 single-gene traits
known in humans
Even with single-gene traits, determining inheritance pattern
in humans can be tricky compared to peas:
• Long generation time
• Small numbers of progeny
• No controlled matings
• No pure-breeding lines

© McGraw Hill 43
 Some of the most common single-gene traits caused by
recessive alleles in humans

TABLE 1.1 Some of the Most Common Single-Gene Traits in Humans

Incidence of
Disease Effect
Disease
Caused by a Recessive Allele

Thalassemia (chromosome 16 or 11) Reduced amounts of hemoglobin; 1/ 10 in parts of Italy

anemia, bone and spleen enlargement

Sickle-cell anemia (chromosome 11) Abnormal hemoglobin; sickle-shaped 1/625 African-

red cells, anemia, blocked circulation; Americans
increased resistance to malaria

Cystic fibrosis (chromosome 7) Defective cell membrane protein; 1/2000 Caucasians

excessive mucus production; digestive
and respiratory failure

Tay-Sachs disease (chromosome Missing enzyme: buildup of fatty deposit 1/3000 Eastern
15) in brain that disrupts mental European Jews
development

Phenylketonuria (PKU) Missing enzyme; mental deficiency 1/10,000

(chromosome 12) Caucasians

© McGraw Hill 44
 Some of the most common single-gene traits
caused by dominant alleles in humans

TABLE 1.1 Some of the Most Common Single-Gene Traits in Humans

Incidence of
Disease Effect
Disease
Caused by a Dominant Allele
Hypercholesterolemia Missing protein that removes 1/ 122 French
(chromosome 19) cholesterol from the blood; heart Canadians
attack by age 50
Huntington disease Abnormal Huntington protein; 1/ 25,000
(chromosome 4) progressive mental and Caucasians
neurological damage; neurologic
disorders by ages 40 to 70

© McGraw Hill 45
 In humans, pedigrees can be used to study inheritance

Pedigrees are orderly diagrams of a family's relevant genetic

features

Includes as many generations as possible (ideally, at least

both sets of grandparents of an affected person)

Pedigrees can be analyzed using Mendel's laws

• Is a trait determined by alternate alleles of a single gene?

• Is a trait dominant or recessive?

© McGraw Hill 46
 Symbols used in pedigree analysis

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© McGraw Hill 47
 A vertical pattern of inheritance indicates a rare
dominant trait; for example Huntington disease

• Every affected person has at least one affected parent

• Mating between affected person and unaffected person is
effectively a testcross

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© McGraw Hill 48
 The dominant Huntington disease allele produces
abnormal Htt protein

The abnormal protein damages nerve cells, even when the

normal protein is also present.

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© McGraw Hill 49
 A horizontal pattern of inheritance indicates a rare
recessive trait; for example cystic fibrosis

Parents of affected individuals are unaffected but are

heterozygous (carriers) for the recessive allele

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© McGraw Hill 50
 The recessive cystic fibrosis disease allele encodes
abnormal CFTR protein

CFTR protein regulates the passage of chloride ions across the cell
membrane. Heterozygous individuals produce enough CFTR for normal
lung function.

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© McGraw Hill 51
 How to recognize dominant traits in pedigrees

Three key aspects of pedigrees with dominant traits:

1. Affected children always have at least one affected parent

2. As a result, dominant traits show a vertical pattern of inheritance

3. Two affected parents can produce unaffected children, if both parents

are heterozygotes

© McGraw Hill 52
 How to recognize recessive traits in pedigrees

Four keys aspects of pedigrees with recessive traits:

1. Affected individuals can be the children of two unaffected carriers,
particularly as a result of consanguineous (between relatives) mating

2. All the children of two affected parents should be affected

3. Rare recessive traits show a horizontal pattern of inheritance

4. Recessive traits may show a vertical pattern of inheritance if the trait

is extremely common in the population

© McGraw Hill 53
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