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Chapter 05
Lecture Outline
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5.1 Overview of Simple
Inheritance Patterns
q 
q 
Types of inheritance patterns involving single genes
Simple Mendelian inheritance describes inheritance
patterns that obey
•  The Law of Segregation
•  The Law of Independent Assortment
Molecular mechanisms that account for different types of
inheritance patterns for single genes
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
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5.2 Dominant and Recessive Alleles
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
q 
q 
q 
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
Recessive 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
•  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
•  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
•  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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Why are most mutants recessive?
•  Example: Most human disease genes are recessive
–  They typically have less functional protein
•  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 Alleles
Dominant (functional) allele: P (purple)
Recessive (defective) allele: p (white)
Genotype
PP
Pp
pp
•  Dominant alleles – Alleles that exert effects on phenotype
in just one copy
Amount of
functional
protein P
100%
50%
0%
•  Less common in natural populations, but they do occur
Phenotype
Purple
Purple
White
•  Three types:
–  Gain-of-function mutations
–  Dominant-negative mutations
–  Haploinsufficiency
Simple dominant/
recessive
relationship
Figure 5.2
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Three Types of Dominant Alleles
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•  Gain-of-function mutations
I-1
–  The gene gains a new or abnormal function
–  May be overexpressed, producing higher levels of the protein
II-1
I-2
II-2
II-3
II-4
II-5
•  Dominant-negative mutations
–  The mutant protein acts to antagonize the normal protein
III-1
III-2
III-3
III-4
III-5
•  Haploinsufficiency
–  The mutant is a loss-of-function allele, and one wild-type copy
is not enough to provide function
–  Example: Polydactyly in humans
IV-1
IV-2
IV-3
© Bob Shanley/The Palm Beach Post
(a)
(b)
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Incomplete Penetrance
Variable Expressivity
•  The term indicates that an allele does not always
“penetrate” into the phenotype of the individual
•  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
•  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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What can explain incomplete penetrance
and variable expressivity?
5.3 Environmental Effects
on Gene Expression
•  Two explanations:
q 
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
q 
The role of the environment with regard to an individual’s
traits
Definition of norm of reaction
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Environmental Effects
–  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
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
1000
Facet number
•  Environmental conditions may have a great impact on the
phenotype of the individual
Facet
900
800
700
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0
0
15
20
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Temperature during development (°C)
Incomplete Dominance
5.4 Incomplete Dominance,
Overdominance, and Codominance
q 
Red
P generation
White
C RC R
•  In incomplete dominance the heterozygote
exhibits
a phenotype that is intermediate between
the phenotypes of the two homozygotes
Predicting the outcome of crosses involving incomplete
dominance, overdominance, and codominance
Gametes CR
CW
Pink
F1 generation
C RC W
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
q 
CWCW
x
The underlying molecular mechanisms of incomplete
dominance, overdominance, and codominance
W
R
2
W
R
R
CW
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R
C RC W
R
W
CWCW
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Dominant (functional) allele: R (round)
Recessive (defective) allele: r (wrinkled)
Incomplete Dominance
Genotype
•  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
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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•  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
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
–  Thus, affected individuals tend to have a shorter life span
than unaffected individuals
•  HbA à Encodes the normal hemoglobin, hemoglobin A
•  HbS à Encodes the abnormal hemoglobin, hemoglobin S
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•  The sickle cell allele has been found at a fairly high
frequency in parts of Africa where malaria is found
Molecular Mechanisms of Overdominance
•  Malaria is caused by a protozoan, Plasmodium
–  This parasite undergoes its life cycle in two
main parts
•  At the molecular level, overdominance is due to two alleles
that produce slightly different proteins
•  One inside the Anopheles mosquito
•  The other inside red blood cells
•  But how can these two protein variants produce a favorable
phenotype in the heterozygote?
–  Red blood cells of heterozygotes are likely to
rupture
when infected by Plasmodium sp.
•  Three explanations for overdominance at the molecular/
cellular level:
1. Disease resistance
2. Homodimer formation
3. Variation in functional activity
•  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
1. Disease resistance
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2. Homodimer formation
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
•  Some proteins function as homodimers
A1A1
–  Composed of two subunits
Normal homozygote
(sensitive to infection)
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•  A1A1 homozygotes
–  Make only A1A1 homodimers
Pathogen
cannot
successfully
propagate.
A1
A1
A2
A2
A1
A2
(b) Homodimer formation
•  A2A2 homozygotes
–  Make only A2A2 homodimers
A1A2
•  A1A2 heterozygotes
–  Make A1A1, A2A2, and A1A2 homodimers
–  For some proteins, the A1A2 homodimer may have better functional
activity
Heterozygote
(resistant to infection)
(a) Disease resistance
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Multiple Alleles and Codominance
3. Variation in functional activity
•  Many genes have multiple alleles (ie, three or more)
•  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)
•  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)
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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•  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
x
IBi
q 
IB
Sperm
i
IAIB
IAi
Type AB Type A
i
5.5 Sex-Influenced and Sex-Limited
Inheritance
IBi
ii
Type B
Type O
q 
Sex-influenced inheritance vs. sex-limited inheritance
Predicting the outcome of crosses for sex-influenced
inheritance
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Sex and Traits
Sex-Influenced Traits
•  An allele is dominant in one sex but recessive
in the other
–  Thus, sex influence is a phenomenon of heterozygotes
•  The inheritance pattern of certain traits is governed by
the sex of the individual
•  Sex-influenced does not mean sex-linked
–  Most sex-influenced traits are autosomal
•  There are two main types
–  Sex-influenced traits
–  Sex-limited traits
•  Example: Scurs in cattle
–  Small growths on the skull
–  Dominant in males, recessive in females
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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
5.6 Lethal Alleles
q 
q 
Different types of lethal alleles
Predicting how lethal alleles may affect the outcome
of a cross
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Lethal Alleles
•  Many lethal alleles prevent cell division
–  Kill an organism at an early age
•  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
•  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
•  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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•  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
•  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)
Sperm
M
M
m
MM
(early
embryonic
death)
Mm
(Manx)
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Mm
(Manx)
m
Mm
(Manx)
1:2 ratio
of kittens
that are born
mm
(non-Manx)
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Pleiotropic Effects
5.7 Pleiotropy
•  Multiple effects of a single gene on the phenotype of an
organism is called pleiotropy
–  Most genes can be pleiotropic
q 
Explanation of the phenomenon of pleiotropy
•  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
5.8 Gene Interaction
q 
•  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
q 
q 
–  Thus, defect in CFTR can have multiple effects
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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A Cross Involving a Two-Gene Interaction Can Produce
Two Distinct Phenotypes Due to Epistasis
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
•  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
allele
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1
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•  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
•  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
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
Colorless
precursor
Enzyme C
Colorless
intermediate
Enzyme P
Purple
pigment
CCPP CCPp CcPP CcPp
CP 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:
•  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
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A
•  Loss of function alleles may have no effect on phenotype
–  One gene compensates for the loss of another
A
A
Normal
phenotype
B
–  Mechanisms
B
Knockout
of gene A
B
Normal
phenotype
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Figure 5.14
B
Knockout
of gene B
A
–  Example: Homozygous gene knockout mice
sometimes have no visible phenotype
A
A
Normal
phenotype
B
•  Gene duplication creates similar genes, or paralogs
•  Genes may be involved in similar cell function
•  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
A
Normal
phenotype
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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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
TV
Tv
tV
ttvv
tv
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