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Chapter 05
Lecture Outline
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5.1 Overview of Simple
Inheritance Patterns


Types of inheritance patterns involving single genes
Molecular mechanisms that account for different types of
inheritance patterns for single genes
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Simple Mendelian inheritance describes inheritance
patterns that obey
• The Law of Segregation
• The Law of Independent Assortment
However, many genes have more complex and interesting
inheritance patterns
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Inheritance patterns that deviate from Mendel’s Laws
are seen when
•
•
•
•
•
•
•
•
The alleles do not have a simple dominant/recessive relationship
Phenotype is influenced by the environment
There is more than one gene that controls a single trait
There are more than two alleles for a gene that controls a trait
The genes are on the same chromosome
One allele is lethal
The trait is sex-influenced or sex-limited
There is gene redundancy
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5.2 Dominant and Recessive Alleles



Definition of wild-type allele and polymorphism
Common underlying mechanisms for recessive and
dominant alleles
Alleles can exhibit incomplete penetrance and vary in
expressivity
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Wild-type Alleles
• Wild-type allele – the most prevalent
version of a gene in wild populations (ie,
the “normal” version of a gene)
– Wild-type proteins function normally
– They promote the reproductive success
of the organism
• In large populations, there may be more
than one common allele that can be
considered wild-type – this is known as
genetic polymorphism
– Ex: Yellow and red flower colors in the
elderflower orchid
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Recessive Alleles
• Mutant allele – a less common version of a gene
– Due to random mutations that occur in DNA
– Or, due to mutations induced by a scientist
• Most random mutations produce alleles that are inherited
in a recessive fashion
• Recessive mutant alleles typically produce
less functional protein
• Either because the protein is defective
• Or they produce lower levels of the functional protein
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• Example: Most human disease genes are recessive
– They typically have less functional protein
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Why are most mutants recessive?
• Recall, diploid organisms have two copies of each gene
– A gene is called recessive if the heterozygote has a
normal phenotype
– In other words, one wild-type copy is sufficient
to provide full function... How?
• Two possible explanations:
1. 50% of normal levels of protein are good enough
2. The one wild-type copy is upregulated in expression,
to produce adequate amount of functional protein
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Dominant (functional) allele: P (purple)
Recessive (defective) allele: p (white)
Genotype
PP
Pp
pp
Amount of
functional
protein P
100%
50%
0%
Phenotype
Purple
Purple
White
Simple dominant/
recessive
relationship
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Figure 5.2
Dominant Alleles
• Dominant alleles – Alleles that exert effects on phenotype
in just one copy
• Less common in natural populations, but they do occur
• Three types:
– Gain-of-function mutations
– Dominant-negative mutations
– Haploinsufficiency
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Three Types of Dominant Alleles
• Gain-of-function mutations
– The gene gains a new or abnormal function
– May be overexpressed, producing higher levels of the protein
• Dominant-negative mutations
– The mutant protein acts to antagonize the normal protein
• Haploinsufficiency
– The mutant is a loss-of-function allele, and one wild-type copy
is not enough to provide function
– Example: Polydactyly in humans
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I-1
II-1
I-2
II-2
III-1
IV-1
(a)
IV-2
II-3
III-2
II-4
III-3
II-5
III-4
III-5
IV-3
© Bob Shanley/The Palm Beach Post
(b)
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Incomplete Penetrance
• The term indicates that an allele does not always
“penetrate” into the phenotype of the individual
• Penetrance is described at the population level
– If 60% of heterozygotes carrying a dominant allele
exhibit the trait, the trait is 60% penetrant
– In any individual, the trait is either present or not
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Variable Expressivity
• How affected an individual may be by a mutation
• Example:
– A person with one extra toe is said to have low
expressivity of the polydactyly trait
– A person with several extra fingers and toes is said to
have high expressivity of polydactyly
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What can explain incomplete penetrance
and variable expressivity?
• Two explanations:
1. The environment may affect the outcome of the trait
2. There may be modifier genes that affect the phenotype,
which differ in different individuals
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5.3 Environmental Effects
on Gene Expression


The role of the environment with regard to an individual’s
traits
Definition of norm of reaction
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Environmental Effects
• Environmental conditions may have a great impact on the
phenotype of the individual
– Example: The arctic fox changes coat color
• Grayish brown in summer, white in winter
– Example: Humans with phenylketonuria (PKU)
are unable to metabolize phenylalanine
• Symptoms include mental retardation
• When detected early, individuals can be fed a phenylalanine-free
diet and stay healthy
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Norm of Reaction
• The norm of reaction is the range of phenotypes seen
due to environmental effects (for a given genotype)
• To measure the norm of reaction, researchers start with a
true-breeding strain of animals with the same genotype,
and subject them to different environmental conditions
– Example: Eye facet number in Drosophila
Facet number
1000
Facet
900
800
700
0
0
15
20
25
30
Temperature during development (°C)
© PHOTOTAKE Inc/Alamy
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5.4 Incomplete Dominance,
Overdominance, and Codominance


Predicting the outcome of crosses involving incomplete
dominance, overdominance, and codominance
The underlying molecular mechanisms of incomplete
dominance, overdominance, and codominance
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Incomplete Dominance
Red
P generation
White
CRCR
• In incomplete dominance the heterozygote
exhibits
a phenotype that is intermediate between
the phenotypes of the two homozygotes
CW CW
x
Gametes CR
CW
Pink
F1 generation
CRCW
Gametes C or C
• Example:
Self-fertilization
– Flower color in the four o’clock plant
Sperm
– Two alleles
F generation
C
C
• CR = wild-type allele for red flower color C
C C
C C
Egg
• CW = allele for white flower color
R
W
R
2
W
R
R
R
R
W
CW
CRCW
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CW CW
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Incomplete Dominance
• Whether a trait is dominant or incompletely dominant
may depend on how closely the trait is examined
• Take, for example, the characteristic of pea shape
– Mendel concluded that
• RR and Rr genotypes produced round peas
• rr genotypes produced wrinkled peas
– However, a microscopic examination of round peas
reveals that not all round peas are “created equal
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Dominant (functional) allele: R (round)
Recessive (defective) allele: r (wrinkled)
Genotype
RR
Rr
rr
Amount of functional
(starch-producing)
protein
100%
50%
0%
Phenotype
Round
Round
Wrinkled
With unaided eye
(simple dominant/
recessive relationship)
With microscope
(incomplete
dominance)
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Overdominance
• Overdominance – When a heterozygote is more vigorous
than the two homozygotes
– It is also called heterozygote advantage
• Example: Sickle-cell anemia
– Autosomal recessive disorder
– Affected individuals produce abnormal form of hemoglobin
– Two alleles
• HbA  Encodes the normal hemoglobin, hemoglobin A
• HbS  Encodes the abnormal hemoglobin, hemoglobin S
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• HbS HbS individuals have red blood cells that deform into a
sickle shape under conditions of low oxygen
– Two major ramifications
1. Sickling greatly shortens the life span of the red blood
cells, resulting in anemia
2. Sickle cells form clumps, blocking capillary circulation
– Thus, affected individuals tend to have a shorter life span
than unaffected individuals
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• The sickle cell allele has been found at a fairly high
frequency in parts of Africa where malaria is found
• Malaria is caused by a protozoan, Plasmodium
– This parasite undergoes its life cycle in two
main parts
• One inside the Anopheles mosquito
• The other inside red blood cells
– Red blood cells of heterozygotes are likely to
rupture
when infected by Plasmodium sp.
• Prevents the propagation of the malaria parasite
• Therefore, HbAHbS individuals are “better” than
– HbSHbS, because they do not suffer from sickle cell
anemia
– HbAHbA, because they are more resistant to malaria
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Molecular Mechanisms of Overdominance
• At the molecular level, overdominance is due to two alleles
that produce slightly different proteins
• But how can these two protein variants produce a favorable
phenotype in the heterozygote?
• Three explanations for overdominance at the
molecular/cellular level:
1. Disease resistance
2. Homodimer formation
3. Variation in functional activity
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1. Disease resistance
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Pathogen can
successfully
propagate.
• A microorganism will infect a cell only if
cellular proteins function optimally
• Heterozygotes have one altered copy of the
gene with slightly reduced protein function
– Not enough to cause serious side effects,
but enough to prevent infections
• Examples:
– Sickle-cell anemia and malaria
– Tay-Sachs disease
• Heterozygotes resistant to tuberculosis
A1A1
Normal homozygote
(sensitive to infection)
Pathogen
cannot
successfully
propagate.
A1A2
Heterozygote
(resistant to infection)
(a) Disease resistance
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2. Homodimer formation
• Some proteins function as homodimers
– Composed of two subunits
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• A1A1 homozygotes
– Make only A1A1 homodimers
A1
A1
A2
A2
A1
A2
(b) Homodimer formation
• A2A2 homozygotes
– Make only A2A2 homodimers
• A1A2 heterozygotes
– Make A1A1, A2A2, and A1A2 homodimers
– For some proteins, the A1A2 homodimer may have better functional
activity
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3. Variation in functional activity
• A gene, E, encodes a metabolic enzyme
– Allele E1 encodes an enzyme that functions better at lower temperatures
– Allele E2 encodes an enzyme that functions better at higher
temperatures
E1
27°–32°C
(optimum
temperature
range)
E2
30°–37°C
(optimum
temperature
range)
• E1E2 heterozygotes produce both enzymes
– Therefore they have an advantage under a wider temperature range
than either E1E1 or E2E2 homozygotes
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Multiple Alleles and Codominance
• Many genes have multiple alleles (ie, three or more)
• Example: ABO blood type genes in humans
– The enzyme glycosyl transferase adds sugars to the
carbohydrate tree on the surface of red blood cells
– Antibodies can distinguish between cells with different sugars
added (between the different antigens)
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• Three alleles affect this sugar addition
– The i allele encodes a defective enzyme that can’t add sugars
• The carbohydrate tree is short (called H antigen)
– IA encodes a form of the enzyme that can add the sugar
N-acetylgalactosamine to the carbohydrate tree (makes A antigen)
– IB encodes a form of the enzyme that can add the sugar galactose to the
carbohydrate tree (makes B antigen)
IAi
• A person with IA IB has blood type AB
– Both alleles are expressed, known as codominance
IA
IBi
x
IB
Sperm
i
IAIB
IAi
Type AB Type A
i
IBi
ii
Type B
Type O
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5.5 Sex-Influenced and Sex-Limited
Inheritance


Sex-influenced inheritance vs. sex-limited inheritance
Predicting the outcome of crosses for sex-influenced
inheritance
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Sex and Traits
• The inheritance pattern of certain traits is governed by
the sex of the individual
• There are two main types
– Sex-influenced traits
– Sex-limited traits
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Sex-Influenced Traits
• An allele is dominant in one sex but recessive
in the other
– Thus, sex influence is a phenomenon of heterozygotes
• Sex-influenced does not mean sex-linked
– Most sex-influenced traits are autosomal
• Example: Scurs in cattle
– Small growths on the skull
– Dominant in males, recessive in females
Genotype
Phenotype
Males
Phenotype
Females
Sc Sc
Scurs
Scurs
Sc sc
Scurs
No scurs
sc sc
No scurs
No scurs
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Sex-limited Traits
• Traits that occur in only one of the two sexes
– Responsible for sexual dimorphism
– May be autosomal or sex-linked
• Example: Human sexual dimorphism
– Ovaries in females, testes in males
• Example: Bird plumage and features
– Roosters have more ornate plumage than hens, and larger
comb and wattles
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5.6 Lethal Alleles


Different types of lethal alleles
Predicting how lethal alleles may affect the outcome
of a cross
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Lethal Alleles
• Essential genes – Genes that are required for survival
– Absence of the protein product leads to a lethal phenotype
• It is estimated that about 1/3 of all genes are essential
• So mutations in these genes can form lethal alleles
• Nonessential genes – Those not required for survival
– But nonessential genes still benefit the organism
• A lethal allele is one that has the potential to cause the
death of an organism
– These alleles are typically the result of mutations in
essential genes
– They are usually inherited in a recessive manner
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• Many lethal alleles prevent cell division
– Kill an organism at an early age
• Some lethal alleles exert their effect later in life
– Example: Huntington disease
• Progressive degeneration of the nervous system,
dementia and early death
• The age of onset for the disease is usually between
30 to 50
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• Conditional lethal alleles kill an organism only under
certain environmental conditions
– Temperature-sensitive (ts) lethals
• A developing Drosophila larva may be killed at 30° C
but will survive if grown at 22° C
• Typically, temperature-sensitive proteins misfold at
higher temperatures, becoming nonfunctional
• Semilethal alleles
– Kill some individuals in a population, not all of them
– Environmental factors and other genes may help
prevent the detrimental effects of semilethal genes
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• A lethal allele may produce
ratios that seemingly deviate
from Mendelian ratios
– Example: the Manx cat
• A dominant mutation that
affects the spine
• This mutation shortens
the tail in heterozygotes
• But is lethal as a
homozygote – so M M Egg
are never seen and are
missing from offspring
ratios
x
Mm
(Manx)
Mm
(Manx)
Sperm
M
M
m
m
MM
(early
embryonic
death)
Mm
(Manx)
Mm
(Manx)
mm
(non-Manx)
1:2 ratio
of kittens
that are born
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5.7 Pleiotropy

Explanation of the phenomenon of pleiotropy
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Pleiotropic Effects
• Multiple effects of a single gene on the phenotype of an
organism is called pleiotropy
– Most genes can be pleiotropic
• Occurs because
– The gene product may affect cell function in multiple ways
• Example: Microtubule proteins affect cell division and movement
– The gene may be expressed in different cell types
• Example: Expression in muscle cells and nerve cells
– The gene may be expressed at different stages of
development
• Example: Expression in embryo and later in adult
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• Example: Cystic fibrosis
– Normal allele encodes the cystic fibrosis
transmembrane conductance regulator (CFTR)
– Regulates ionic balance by transporting Cl- ions
– Mutant does not transport Chloride effectively
• In lungs, this causes very thick mucus
• On the skin, causes salty sweat
• Males are often sterile because Cl- transport is needed for
development of the vas deferens
– Thus, defect in CFTR can have multiple effects
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5.8 Gene Interaction



Definition of gene interaction
Epistasis, complementation, modifying genes, and gene
redundancy
Predicting the outcome of crosses that exhibit epistasis,
complementation, and gene redundancy
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Gene Interactions
• Gene interactions occur when two or more different genes
influence the outcome of a single trait
• Indeed, morphological traits such as height, weight and
pigmentation are affected by many different genes in
combination with environmental factors
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A Cross Involving a Two-Gene Interaction Can Produce
Two Distinct Phenotypes Due to Epistasis
• Example: Flower color in the sweet pea
– Lathyrus odoratus normally has purple
flowers
x
• Bateson and Punnett obtained
White variety #1
White variety #2
(CCpp)
(ccPP )
several true-breeding varieties with
F generation
white flowers
• Crossing them together resulted in
purple flowers
All purple
(CcPp)
– The two genes complemented each other
• This is a way of saying the mutations
were in different genes
• Thus each strain contributed a wild-type
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allele
1
• They allowed the purple hybrids to self-fertilize
– This produced interesting results
x
• C is dominant to c
White variety #1
White variety #2
(CCpp)
(ccPP )
• P is dominant to p
• But cc masks the P allele
F generation
Complementation:
• And pp masks the C allele
1
All purple
(CcPp)
Self-fertilization
– We say that cc is epistatic to Pp (or PP)
• And pp is epistatic to Cc (or CC)
– Both enzymes are needed to produce
purple pigment
F2 generation
CP
Cp
cP
cp
CP
CCPP CCPp CcPP CcPp
Purple Purple Purple Purple
Cp
CCPp CCpp CcPp Ccpp
Purple White Purple White
cP
CcPP CcPp ccPP ccPp
Purple Purple White White
cp
CcPp Ccpp ccPp ccpp
Purple White White White
Epistasis:
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• Epistasis – when a gene can mask the phenotypic effects of
another gene
• Epistatic interactions often arise because two different proteins
participate in a common cellular function
– For example, an enzymatic pathway
Colorless
precursor
Enzyme C
Colorless
intermediate
Enzyme P
Purple
pigment
• If an individual is homozygous for either recessive allele
– It will not make a functional enzyme required for the production
of purple pigment: (cc) no enzyme C, (pp) no enzyme P
– Therefore, the flowers remain white
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Gene Redundancy
• Loss of function alleles may have no effect on phenotype
– One gene compensates for the loss of another
– Mechanisms
• Gene duplication creates similar genes, or paralogs
• Genes may be involved in similar cell function
– Example: Homozygous gene knockout mice
sometimes have no visible phenotype
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A
A
A
Normal
phenotype
A
A
Normal
phenotype
B
Normal
phenotype
B
B
Knockout
of gene A
B
Normal
phenotype
Figure 5.14
B
Knockout
of gene B
A
A
B
B
Knockout
of both
gene A
and gene B
A
B
Normal
phenotype
Altered phenotype–
genes A and B are
redundant
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• Example: George Shull’s work in
the weed shepherd’s purse
(Capsella bursa-pastoris)
– Seed capsule shape is normally
triangular
– Ovate seeds were produced by a
double gene knockout (tt vv)
– After crossing to wild-type, in the
F2 generation there was a 15:1
ratio of wild-type to ovate seeds
– This can be explained by gene
redundancy between the T gene
and the V gene
x
TTVV
Triangular
ttvv
Ovate
F1 generation
TtVv
All triangular
F1 (TtVv) x F1 (TtVv)
F2 generation
TV
Tv
tV
tv
TTVV
TTVv
TtVV
TtVv
TTVv
TTvv
TtVv
Ttvv
TtVV
TtVv
ttVV
ttVv
TtVv
Ttvv
ttVv
ttvv
TV
Tv
tV
tv
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