4.

6 Lethal Alleles Represent Essential Genes

• Essential genes are those that are absolutely required for survival
• Mutations resulting in the synthesis of a nonfunctional protein can often be tolerated in heterozygote
• Recessive lethal alleles result in homozygous recessive individuals that don’t survive
• A mutation in mice causes a yellow coat color that varies from the normal agouti (wild-type) coat
phenotype
• Crosses between the two strains lead to several phenotypes
• Homozygous yellow coats are lethal in mice
• Mice die before birth (embryonic lethal)

Lethal yellow (Ay) is a mutation at

the mouse agouti (a) locus that is
associated with an all-yellow coat color,
obesity, diabetes, tumors in heterozygotes,
and preimplantation embryonic lethality in
homozygotes

Figure 4-3
 Huntington’s disease: a neurodegenerative genetic disorder that affects muscle
coordination

https://www.youtube.com/watch?v=rcFlo2fDMMs
• Dominant lethal allele
• Presence of one copy of allele results in death
• Huntington Disease is due to an autosomal dominant allele (H)
• In the heterozygote (Hh), the onset of the disease is delayed well into adulthood
• Affected individuals undergo gradual nervous degeneration until they die
• Typical onset is about 40 years of age, by which time the affected individual has
already had a family
• Each child has a 50 percent chance of inheriting the disorder
• Huntington's disease is caused by a dominant lethal allele and even though it is not
described as lethal, it is invariably lethal in that the victim experiences gradual neural
degeneration and mental deterioration for some years before death occurs
 Revision

Both sickle cell anemia and Huntington follow Mendelian inheritance (autosomal
dominant, autosomal recessive). However, their alleles are codominant.

Codominant

https://blog.prepscholar.com/difference-between-
incomplete-dominance-and-codominance

https://genetics.thetech.org/ask-a-
geneticist/genotype-vs-phenotype
 Punnett square of a dihybrid cross

• Mendel’s 9:3:3:1 dihybrid ratio is an ideal ratio based on probability events involving
segregation, independent assortment, and random fertilization.
4.7 Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the
9:3:3:1 Ratio
 Do you know?

• Human skin color is determined by 376 genetic loci

• Human Eye color is determined by 15 genes

 4.8 Phenotypes Are Often Affected by More Than One Gene

• Phenotypic characters are influenced by many different genes and their products
• Gene interaction
• Several genes influence a particular characteristic
• Cellular function of numerous gene products contributes to development of
common phenotype (eye color, hair color, or fruit shape )
• This does not mean, however, that two or more genes or their products necessarily
interact directly with one another to influence a particular phenotype

• Epigenesis is a development concept whereby each step of development increases the

complexity of the sensory organ and is under the control and influence of one or more
genes
• Example: The compound eye of an insect (colour, texture, shape and size)
• The formation of the inner ear in mammals (multiple gene action)
• Mutations that interrupt the many steps of development lead to hereditary
deafness, and the trait is referred to as a heterogeneous trait (over 50 genes are
involved in development of the ability to discern/recognize sound……..many
genes “interact” to produce a common phenotype)
 Section 4.8 Epistasis

• In epistasis, the expression of gene or gene pairs masks or modifies the expression of
another gene or gene pair
• Sometimes the effect is antagonistic (masking)
• The expression of one gene pair masks or modifies the effect of another. In this
case, the alleles at the first locus are said to be epistatic to those at the second
locus, and the alleles at the second locus are hypostatic to those at the first locus.
The alleles at the epistatic gene mask or repress the
effects of alleles at another gene. The gene whose alleles
are masked or repressed is called the hypostatic gene.

• Sometimes the effect is complementary or cooperative

• Two gene pairs complement one another wherein one dominant allele is required
at each locus for phenotype expression
 BbEe BbEe

The gene for pigment Sperm

1/ BE 1/ bE 1/ 1/
deposition (E/e) is said to be 4 4 4 Be 4 be
epistatic to the gene that Eggs
codes for black or brown 1/
4 BE
pigment (B/b). BBEE BbEE BBEe BbEe

1/
4 bE
BbEE bbEE BbEe bbEe

1/
4 Be #
BBEe BbEe BBee Bbee

1/ be
4
BbEe bbEe Bbee bbee

9 : 3 : 4
 Epistasis Example – Blood Types

• The Bombay phenotype is an example of the homozygous recessive condition

• First locus masks expression of second locus
• The mutant form of the FUT1 gene masks the expression of IA and IB alleles
• A and B antigen forms only when individual has one wild-type allele (FUT1)
 Recessive Epistasis

• Case 1, demonstrates the effect of recessive epistasis on coat color inheritance in mice.
• B allele: black pigment
• A allele: agouti phenotype
• aa genotype: all black
• B locus mutation (recessive, b) can eliminate pigmentation, yielding albino mice
(bb) regardless of the genotype at the other locus.

Figure 4-7

bb genotype MASKS expression of A allele = recessive epistasis

 Dominant Epistasis

• Dominant epistasis: dominant allele at one genetic locus masks the expression of the
alleles in the second locus
• Example: Summer squash fruit color
• Dominant allele A = White fruit
• Regardless of second loci allele
• Absence of A allele = Yellow fruit
• Genotypes aa, BB, Bb = yellow fruit
• Genotype bb = green
https://www.thekitchn.com/
• Crossing two heterozygotes results in a 12:3:1 modified ratio.

A genotype MASKS expression of B allele = Dominant epistasis

 Complementary gene interaction

• The third type of gene interaction is complementary gene interaction

• At least one dominant allele for each locus is needed for purple flowers, which ensures
proper biochemical conversions
 Novel Phenotypes (Alleles and Loci) in summer squash

Other cases of gene interaction result in new or novel

phenotypes in the F2 generation.

Both gene pairs influence fruit shape equally

• Disc fruits
• Require dominant alleles at both loci
• Sphere fruits
• Require dominant allele at one/either locus
• Long fruits Figure 4-8

• Occur when no dominant alleles at either locus

Both gene pairs influence fruit shape equally

4.9 Complementation Analysis Can Determine If Two Mutations Causing a Similar
Phenotype Are Alleles of the Same Gene

• Complementation analysis allows the determination of whether two mutations

yielding similar phenotypes are on the same gene or on separate genes

Figure 4-9x
 4.10 Expression of a Single Gene May Have Multiple Effects

Polygenic traits = trait influenced by several genes; genes may be on same chromosome
or on different one (ex. Human eye color, weight, skin tone)
Pleiotropy occurs when expression of a single gene has multiple phenotypic effects
Marfan syndrome results from an autosomal dominant mutation in the gene encoding
connective tissue protein, fibrillin
Affects the eye, aorta, bones, and other tissue
It is speculated that Abraham Lincoln had Marfan syndrome

• Example: Porphyria variegata

• Autosomal disorder
• Toxic buildup of porphyrins organic compounds in body
• Numerous phenotypic effects
• Abdominal pain
• Muscular weakness
• Fever King George III of England may
• Racing pulse have suffered from this condition. He
became blind and senile prior to dying
• Insomnia
• Vision issues
 4.11 X-Linkage Describes Genes on the X Chromosome

• Drosophila and humans

• Males: XY
• Females: XX
• Hemizygous: males XY
• Homozygous: females XX

• X-linkage
• Genes present on X chromosome exhibit patterns of inheritance
• Different from autosomal genes
• Y chromosome
• Relatively inert genetically (few genes)
• Male-specific genes on human Y chromosome
 Section 4.11: X-linkage in Drosophila

• White eye mutation in Drosophila

• Wild-type red eye color is dominant to white
• Inheritance pattern of white eye related to sex
of parent
• Reciprocal crosses between white- and red-eyed flies
did not yield identical results
• White locus present on X chromosome (X-linked)

Figure 4-10

© 2015 Pearson Education, Inc.

 Section 4.11: X-linkage in Drosophila

• Whatever alleles are present on the X chromosome of the male will be expressed
• Males cannot be homozygous or heterozygous but are hemizygous

Figure 4-11
 Section 4.11: X-linked in Humans

• Color blindness: X chromosome-linked

• Red/green color blindness
• Mother passes to all sons
• Mother passes to no daughters
Color blindness is due to the X-linked recessive allele b, while the X-linked
dominant allele B leads to full color vision

© 2015 Pearson Education, Inc.

Figure 4-12
 Section 4.11: Lethal X-linked Recessive

• Lethal X-linked recessive disorders

• Observed only in males
• Females can only be heterozygous carriers who do not develop the disorders
• Example: Duchenne muscular dystrophy
• Onset prior to age 6
• Lethal around age 20
• Occurs only in males

© 2015 Pearson Education, Inc.

 4.12 In Sex-Limited and Sex-Influenced Inheritance, an Individual's Sex
Influences the Phenotype

• Sex-limited inheritance: occurs in cases where the expression of a specific phenotype is

absolutely limited to one sex even when the genes are not on X chromosome
• Genes for milk production are only expressed in females
• Sex-influenced inheritance: the sex of an individual influences the expression of a phenotype
that is not limited to one sex or the other
 4.12 In Sex-Limited and Sex-Influenced Inheritance, an Individual's Sex
Influences the Phenotype

• Feather plumage in chicken

• Caused by an autosomal gene
• Hen-feathering controlled by dominant allele expressed in both sexes
• Cock-feathering controlled by recessive allele only expressed in males (sex-
limited)
• But actual expression can be modified by the individual’s sex hormones
Figure 4-13
 Sex-influenced inheritance

Pattern baldness in humans

• Allele B behaves dominant in males and recessive in females
• In BB genotype in females, phenotype is less pronounced

© 2015 Pearson Education, Inc. Figure 4-14

4.13 Genetic Background and the Environment May Alter Phenotypic Expression

• Penetrance—the percentage (%) of individuals that show at least some degree of

expression of the mutant genotype in a population
• Expressivity—the range (degree) of expression of the mutant phenotype
• Drosophila homozygous for the recessive mutant eyeless gene yield phenotypes
that range from the presence of normal eyes to a partial reduction in size to the
complete absence of one or both eyes (Can be the result of genetic background
differences and/or environmental effects as temperature, humidity, and
nutrition maybe involved). The is a range of phenotypes including different sizes
or complete absence.
 Genetic background: Position effect

• Physical location of gene influences expression

• Translocation or inversion events modify expression
• Gene relocated to condensed or genetically inert chromosome (heterochromatin)

• loss-of-function mutation in the white+ gene (white-) has white eyes.

© 2015 Pearson Education, Inc.

 Section 4.14

Johann E.Gudjonsson et. al. 2012

Acetylation of K9 and methylation of K4 of H3 have been associated

with an open chromatin (transcriptionally active promoters). In contrast,
methylation of K9 of H3 is a marker of condensed, inactive chromatin
 Section 4.13: Conditional Mutations

• Temperature effects: Temperature can affect the kinetic energy of the reacting substances
• Evening primrose
• Red flowers at 23°C
• White flowers at 18°C
• Siamese cats and Himalayan rabbits
• Darker fur on cooler areas of body (tail, feet, ears)
• Enzymes (tyrosinase) responsible for pigment production lose catalytic function at
higher temperature

Figure 4-16
 Onset of Phenotypic Expression

• Genetic traits become apparent at different times during an organism's life span
• In humans, the prenatal, infant, preadult, and adult phases require different genetic information; thus
many severe inherited disorders are not manifested until after birth
Delayed onset of phenotypic expression
• Tay-Sachs disease
• Inherited autosomal recessive/Lethal lipid-metabolism disease
(hexosaminidase A)
• Baby normal for a few months, dies by age 3
• Lesch-Nyhan syndrome
• Inherited X-linked recessive/Purine salvage enzyme defect (HPRTase)
• Normal for about 6 months
• Duchene muscular dystrophy (DMD)
• X-linked recessive disorder
• Diagnosis at 3–5 years old, fatal by age 20
• Huntington disease
• Variable age of onset in humans
• Autosomal dominant disorder
• Affects frontal lobes of cerebral cortex
• Progressive cell death – brain deterioration
• Age range 30–50 years old