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BIO 184
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LECTURE 11
Lecture 11:
Extensions of Mendelian Inheritance
Inheritance of coat color in Labrador Retrievers is under the control of two genes. If both
dominant alleles are present, the dog has a black coat. If the dog lacks “E”, its coat will be
yellow, regardless of its genotype at the other locus. If “E” is present in the absence of
“B”, then the dog has a chocolate coat. http://www.labbies.com/genetics.htm
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BIO 184
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LECTURE 11
I. Extensions Involving the Inheritance of Single Genes
Unlike what Mendel observed, there are many different ways that two alleles can
interact to govern the inheritance of a trait governed by a single gene.
See Table 4.1, Brooker
These extensions of Mendel’s findings will be examined with two things in mind:


Understanding the relationship between the molecular expression of a gene
and the trait itself
Understanding how the extension alters the expected outcome of genetic
crosses
A. Wild-Type versus Mutant Alleles
Prevalent alleles in a population are called wild-type alleles. These typically encode
proteins that are made in the right amount and function normally.
Alleles that are present at less than 1% in the population and have been altered by
mutation are called mutant alleles. Such alleles usually result in a reduction in the
amount or function of the wild-type protein and are most often inherited in a
recessive fashion.
For Mendel’s traits:
Wild-type (dominant) allele Mutant (recessive) allele
Purple flowers
White flowers
Axial flowers
Terminal flowers
Yellow seeds
Green seeds
Round seeds
Wrinkled seeds
Smooth pods
Constricted pods
Green pods
Yellow pods
Tall plants
plants
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LECTURE 11
Human diseases are also caused by mutations, and are also most often inherited in
a recessive fashion because the mutant protein is either non-functional or greatly
reduced compared to the protein coded by the wild-type allele.
See Table 4.2, Brooker
Mendel always chose traits where one of the alleles was completely recessive. At
the molecular level, the most usual explanation for this is that 50% of the normal
level of protein is sufficient to accomplish the protein’s task in the cell. Therefore,
heterozygotes have a normal phenotype.
B. Extension 1: Lethal Alleles
Sometimes, a gene is absolutely essential for survival. The alleles created by
mutations in these genes are called lethal alleles. Although they are usually
recessive (only homozygotes are affected), they are occasionally dominant as well.
Lethal alleles fall into four categories:
1.
Early onset. The gene is necessary for basic cellular functions and
mutants die during embryogenesis.
2.
Late onset. The gene is necessary for life, but not until the individual
is older. Homozygotes for lethal alleles of this kind are born and may
survive for many years but will eventually succumb to the disease.
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LECTURE 11
3.
Conditional. The mutation only kills the organism when certain
environmental conditions prevail.
-In Drosophila, a temperature-sensitive lethal allele kills
larvae at 30 degrees but not at 22 degrees.
4.
Semi-lethal. Kills some mutant individuals in the population, but not
all. This may be due to an unknown environmental influence or other
genes that also influence the phenotype.
-The allele for long-necks in mice is an example (Homework 1)
Lethal alleles may cause a departure from Mendelian ratios, particularly if they are
early onset.
See Brooker, page 78 for an example.
C. Extension 2: Incomplete Dominance of Alleles
In incomplete dominance, the heterozygote exhibits a phenotype that is
intermediate between the two pure-breeding parents. Thus, it appears to be
“blending inheritance” in the F1s. However, in the F2s. both of the original traits
reappear in the homozygotes.
Incomplete dominance is seen in flower color in the four o’clock plant.
 Two alleles
o CR = wild-type allele for red flower color
o CW = allele for white flower color
See Figure 4.2, Brooker
Whether a trait is completely or incompletely dominant can depend on how closely
the trait is examined.
 Take, for example, the characteristic of pea shape
o Mendel visually concluded that
 RR and Rr genotypes produced round peas
 rr genotypes produced wrinkled peas
o However, a microscopic examination of round peas reveals that not all
round peas are “created equal” – the heterozygotes have less starch
than the homozygotes (while the wrinkled peas have very little starch)
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BIO 184
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LECTURE 11
See Figure 4.3, Brooker
D. Extension 3: Multiple Alleles
Genes can be mutated all along their length (nucleotide sequence), and different
mutations can give rise to subtly different phenotypes. When this happens, the
gene is said to have multiple alleles.

An interesting example is coat color in rabbits
o Four different alleles
 C (full coat color)
 cch (chinchilla pattern of coat color)
 Partial defect in pigmentation
 ch (himalayan pattern of coat color)
 Pigmentation in only certain parts of the body
 c (albino)
 Lack of pigmentation
o The dominance hierarchy is as follows:
 C > cch > ch > c
See Figure 4.4, Brooker


The ABO blood group provides another example of multiple alleles
It is determined by the type of antigen present on the surface of red blood
cells
o Antigens are substances that are recognized by antibodies produced
by the immune system

As shown in in the diagram at the top of the next page, there are three
different types of antigens found on red blood
o Antigen A, which is controlled by allele IA
o Antigen B, which is controlled by allele IB
o Antigen O, which is controlled by allele i

Allele i is recessive to both IA and IB

Alleles IA and IB are codominant
o They are both expressed in a heterozygous individual
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LECTURE 11
N-acetylgalactosamin
e


The carbohydrate tree on the surface of RBCs is composed of three sugars
A fourth can be added by the enzyme glycosyl transferase
o The i allele encodes a defective enzyme
 The carbohydrate tree is unchanged
o IA encodes a form of the enzyme that can add the sugar Nacetylgalactosamine to the carbohydrate tree
o IB encodes a form of the enzyme that can add the sugar galactose to
the carbohydrate tree

Thus, the A and B antigens are different enough to be recognized by
different antibodies
For safe blood transfusions to occur, the donor’s blood must be an
appropriate match with the recipient’s blood
For example, if a type O individual received blood from a type A, type B or
type AB blood
o Antibodies in the recipient blood will react with antigens in the
donated blood cells
o This causes the donated blood to agglutinate
o A life-threatening situation may result because of clogging of blood
vessels


E. Extension 4: Overdominance

Overdominance is the phenomenon in which a heterozygote is more vigorous
than both of the corresponding homozygotes
o It is also called heterozygote advantage

Example = Sickle-cell anemia
o Autosomal recessive disorder
o Affected individuals produce abnormal form of hemoglobin
o Two alleles
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HbA  Encodes the normal hemoglobin, hemoglobin A
HbS  Encodes the abnormal hemoglobin, hemoglobin S
HbSHbS individuals have red blood cells that deform into a sickle shape
under conditions of low oxygen tension
o Refer to Figure 4.9
o This has two major ramifications
 1. Sickling phenomenon greatly shortens the life span of the
red blood cells
 Anemia results
 2. Odd-shaped cells clump
 Partial or complete blocks in capillary circulation
o Thus, affected individuals tend to have a shorter life span than
unaffected ones


The sickle cell allele has been found at a fairly high frequency in parts of
Africa where malaria is found
o How come?
Malaria is caused by a protozoan, Plasmodium
o This parasite undergoes its life cycle in two main parts
 One inside the Anopheles mosquito
 The other inside red blood cells
o Red blood cells of heterozygotes, are likely to rupture when infected
by Pasmodium sp.
 This prevents the propagation of the parasite

Therefore, HbAHbS individuals are “better” than
o HbSHbS, because they do not suffer from sickle cell anemia
o HbAHbA, because they are more resistant to malaria

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
Well, there are three possible explanations for overdominance at the
molecular/cellular level
o 1. Disease resistance


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2. Homodimer formation
3. Variation in functional activity
See Figure 4.10, Brooker
F. Extension 5: Incomplete Penetrance


In some instances, a dominant allele is not expressed in a heterozygote
individual
Example = Polydactyly
o Autosomal dominant trait
o Affected individuals have additional fingers and/or toes
 See Figure 4.11 and 4.12, Brooker
o A single copy of the polydactyly allele is usually sufficient to cause
this condition
o In some cases, however, individuals carry the dominant allele but do
not exhibit the trait

The term indicates that a dominant allele does not always “penetrate” into
the phenotype of the individual

The measure of penetrance is described at the population level
o If 60% of heterozygotes carrying a dominant allele exhibit the trait
allele, the trait is 60% penetrant
NOTE:
o In any particular individual, the trait is either penetrant or not

G. Extension 6: Expressivity


Expressivity is the degree to which a trait is expressed
In the case of polydactyly, the number of digits can vary
o A person with several extra digits has high expressivity of this trait
o A person with a single extra digit has low expressivity

The molecular explanation of expressivity and incomplete penetrance may
not always be understood
In most cases, the range of phenotypes is thought to be due to influences of
the

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LECTURE 11
Environment, and/or
Other genes
Environmental conditions may have a great impact on the phenotype of the
individual. Example: Snapdragon flower color vs. Temperature and degree of
sunlight
H. Extension 7: Sex-Limited and Sex-Influenced Traits
Sex-influenced traits are ones in which an allele is dominant in one sex but
recessive in the opposite sex. Thus, sex influence is a phenomenon of
heterozygotes.

Example: Pattern baldness in humans
o Caused by an autosomal gene
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Allele B behaves as dominant in males, but recessive in females
Genotype
Phenotype
in Females
Phenotype
in Males
BB
bald
bald
Bb
nonbald
bald
bb
nonbald
nonbald

Pattern baldness appears to be related to the level of male sex hormones

In females, a rare tumor of the adrenal gland can cause the secretion of
large amounts of male sex hormones
o If this case a heterozygous Bb female will become bald
o When the tumor is removed surgically, her hair returns to its normal
condition
The autosomal nature of pattern baldness has been revealed by analysis of
human pedigrees

Bald fathers can pass
the trait to their sons


Sex-limited traits occur in only one of the two sexes
For example in humans, breast development is normally limited to females
and beard growth is normally limited to males
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LECTURE 11
II. Extensions Involving the Inheritance of More than One Gene
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




We will next examine two different cases, both involving two genes that two
alternative alleles
The two crosses we will perform can be illustrated in this general pattern
o AaBb X AaBb
 Where A is dominant to a and B is dominant to b
If these two genes govern two different traits
o A 9:3:3:1 ratio is predicted among the offspring
However, the two genes in this section do affect the same trait
o In the first case, the 9:3:3:1 ratio is not affected, but in the second
case, it is altered.
A. Situation in Which the 9:3:3:1 Ratio is Not Affected

Example: Inheritance of comb morphology in chicken
o First example of gene interaction
o Discovered by William Bateson and Reginald Punnett in 1906
o Comb types come in four different morphologies
See Figure 14.7b in Brooker


Thus, the F2 generation consisted of chickens with four types of combs
o 9 walnut : 3 rose : 3 pea : 1 single
Bateson and Punnett reasoned that comb morphology is determined by two
different genes
o R (rose comb) is dominant to r
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LECTURE 11
o P (pea comb) is dominant to
o R and P are codominant (walnut comb)
o rrpp produces single comb

Note:
o Mendel’s laws of segregation and independent assortment still hold!
B. A Cross Involving a Two-Gene Interaction Can Produce a 9:7 ratio

Inheritance of flower color in the sweet pea
o Also discovered by Bateson and Punnett
o Lathyrus odoratus normally has purple flowers
o Bateson and Punnett obtained several true-breeding varieties with
white flowers
o They carried out the following cross
P: True-breeding purple X true-breeding white
F1: Purple flowered plants
F2: Purple- and white-flowered in a 3:1 ratio

These results were not surprising, but the results shown in Figure 4.18
(Brooker) were.

Thus, the F2 generation contained purple and white flowers in a ratio of 9
purple : 7 white
o Bateson and Punnett reasoned that flower color is determined by two
different genes
 C (one purple-color-producing) allele is dominant to c (white)
 P (another purple-color-producing) allele is dominant to p
(white)
 cc or pp masks P or C alleles, producing white color

Thus, a plant that is homozygous for either recessive white allele, would
develop a white flower, regardless whether of not the other gene contains a
purple-producing allele

The term epistasis describes the situation in which a gene can mask the
phenotypic effects of another gene.
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LECTURE 11

Epistatic interactions often arise because two (or more) different proteins
participate in a common cellular function

For example, an enzymatic pathway
Colorless
precursor
Enzyme C
Colorless
intermediate
The recessive c allele
encodes an inactive enzyme


Enzyme P
Purple
pigment
The recessive p allele
encodes an inactive enzyme
If an individual is homozygous for either recessive allele
o It will lack one of the enzymes required to make purple pigment
o Therefore, the flowers remain white
Thus, there is an alteration in the phenotypes seen by Mendel:
9
3
3
1
C_P_
C_pp
ccP_
ccpp
purple
white
white
white
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7 white