2. Genes Interact!
• So far we have looked at
dominant/recessive, but the real story
is more complicated…
• EPISTASIS: How genes interact
to express phenotypes
• There may be more than two alleles
for a given locus within a population
How many alleles per gene are
present in a diploid individual?
• Dominance of one allele over another
may not be complete
• Two or more genes may affect a
single trait
• The expression of a trait may
depend on the interaction of
more than one gene and/or
the interaction of genes with
nongenic factors
3. Gene Interaction
• The phrase gene
interactions refers to
the ways genes
collaborate or
interact to influence
a phenotype
• There are several
important types of
interactions
5. The Molecular Basis of Dominance
• The terms dominant and
recessive have a phenotypic
basis
• However, the dominance of
one allele over another is
determined by the protein
product of that allele
• The overall phenotype is the
consequence of the activities
of the protein products of the
alleles of the gene
http://hereausclasses.weebly.com
6. Mutations of haplosufficient genes are recessive
Haplosufficient: a wild-type allele that supports wild type function in
a heterozygous organisms (dominant wild-type allele).
7. Haploinsufficiency: when one copy of an allele
is not enough
The mutant allele is
dominant to the wild
type allele because
individuals heterozygous
or homozygous for the
mutant allele are both
mutant in phenotype
8. Dominance is the interaction of Genes
at the Same Locus
• Genes at the same locus – two
versions of the same gene; each
version of the same gene is
defined as allele.
• Dominance can be complete or
incomplete
• Incomplete: heterozygous falls in the
range between two homozygous
• Not always a perfect ‘pink’
• Codominance: offspring express
the phenotype of both parents
equally
• Phenotypic ratios are the same as
genotypic ratios (blood type)
9. Incomplete Dominance
• Often the dominance of one allele
over the other is not complete,
• allele designations such as A1, A2
or B1, B2 are used instead of A, a or
B, b
• Incomplete dominance, or
partial dominance
• heterozygous individuals display
intermediate phenotypes between
either homozygous type
• Typically the heterozygote is more
similar to one of the homozygous
types than the other
11. Codominance
• Codominance leads to heterozygotes
with a different phenotype than that
of either homozygote
• In this case, there is detectable
expression of both alleles in the
heterozygotes
• More than one pattern of dominance
may exist between different alleles of
a gene, e.g. ABO blood type
12. Dominance Relationships of ABO Alleles
• The ABO blood type has 4
different types, resulting from
different combinations of 3
alleles
• The alleles are: IA, IB and i; the
IA and IB alleles are completely
dominant over the i allele, but
they are codominant with each
other
• The A blood type involves the
presence of one antigen on the
blood cell surfaces; type B the
presence of a different antigen
• Type AB people have both
antigens and type O people
have neither
13. Blood Types and Genotypes
• Type A: IAIA or IAi
• Type B: IBIB or IBi
• Type AB: IBIA
• Type O: ii
Antiserum
14.
15.
16.
17. Allelic Series
• In populations the number of
alleles is theoretically unlimited
and some genes have many
• A locus with more than two
alleles is said to have multiple
alleles
• An order of dominance among
the alleles may form a sequential
series referred to as an allelic
series
www.mun.ca
18. The C-Gene System for Mammalian Coat
Color
• Many genes are required to
produce and distribute pigment to
the hair follicles or skin cells,
where they give rise to skin or
coat color
• The C gene is responsible for
coat color in mammals like cats,
rabbits and mice, etc.
• It produces an enzyme active in
the production of melanin
• There are dozens of alleles of the
gene, but four that form an allelic
series
cnx.org
19. The Allelic Series of the C Gene
• The wild type allele, C, produces a functional enzyme and full coat color
• cch produces a “dilute” phenotype called chinchilla
• ch produces a phenotype called Himalayan with little pigment on the body
but full color on the extremities
• c is a fully recessive null allele and produces an albino phenotype
20. Therefore, C is dominant over cch, ch, and c
Let’s test for dominance….
21. How do the rest interact with each other?….
Therefore, C > cch > ch > c
Chinchilla is partially
dominant over Himalayan
23. The Molecular Basis of the C-Gene Allelic
Series
• The C allele produces a tyrosinase enzyme that is
100% active, whereas that of the cch allele is less
than 20% active
• The ch allele enzyme is temperature-sensitive;
functional at lower temperatures (like the paws, ears
and tail) and non-functional at higher temperatures
(the trunk)
• The c allele produces no functional enzyme
24. Lethal Alleles
• Some single-gene mutations are so detrimental that
they cause death in the organism
• These are caused by lethal mutations, which are
inherited as recessive alleles (only the homozygotes
die)
• Lethal alleles can be detected as distortions in
segregation ratios caused by one or more missing
classes of progeny
25.
26.
27. Molecular Basis of the AY Lethality
• The AY mutation is caused
by a deletion that affects two
genes, Agouti and Raly
• Raly produces a protein
essential for mouse
development; the deletion
connects the Raly promoter
to the Agouti gene
• In heterozygotes, the Raly
promoter drives a high level
of Agouti gene transcription,
resulting in an excess of
yellow pigment is produced
(displaces black pigment),
whereas homozygotes die
due to lack of the Raly
protein
28. LETHAL ALLELES MAY ALTER PHENOTYPIC RATIOS
• A lethal allele: causes death at an early stage
of development, and so some genotypes may
not appear among the progeny
• Alleles that affect viability often produce
deviations from a 1:2:1 genoptypic and 3:1
phenotypic ratio predicted by Mendel’s Laws.
29. PLEIOTROPIC GENES
• Pleiotropy is the alteration of multiple
distinct traits of an organism by a
mutation in a single gene.
• Two main mechanisms:
• Direct action of a mutant protein
• Ex. Mendel’s white flowers had mutated
anthocyanin, which also produces gray
seed coats & lack of color at leaf axils
• Secondary result of a cascade of problems
stemming from the mutation
• Ex. Sickle cell disease
30. SICKLE CELL DISEASE (SCD)
• SCD is an autosomal recessive
condition caused by mutation of the
β-globin gene that, in turn, affects the
structure and function of hemoglobin
(the main oxygen-carrying molecule
in red blood cells)
• Mutation in β-globin cause the
red blood cells to take on a sickle
shape
• Causes a wide range of physical
complications
31. SICKLE-CELL SYNDROME
• Multiple alleles for β-globin gene of hemoglobin
• Normal wild-type is HbbA
• More than 400 mutant alleles identified so far
• HbbS allele specifies abnormal peptide causing sickling
among red blood cells
• Pleitropy
• HbbS affects more than one trait
• Sickling
• Resistance to malaria
• Numerous disease symptoms
• Recessive lethality
• Different dominance relations
Hemoglobin:
iron-containing oxygen-transport
metalloprotein in the red blood cells
of all vertebrates
-Beta subunit in blue
-Alpha subunit in red
34. Sex-Limited Traits
• The sex of an organism can influence gene
expression
• Sex-limited gene expression is a pattern of
expression limited to one sex or the other
• The traits involved are called sex-limited traits;
both sexes carry the genes for such traits, but they
are expressed in just one sex
35. Sex-Limited Traits: Examples
• Mammalian breast and ability to
produce milk are female-specific
traits
• Horn development is limited to males
in some sheep, cows and other
hoofed animals
• Behavioral traits, especially related to
mating are strongly influenced by sex
• Sex hormones differentially influence
expression of genes related to these
and other sex-limited traits
36. Sex-Influenced Traits; Baldness
• Sex-influenced traits are those in which the
phenotype corresponding to a particular genotype
differs depending on the sex of the organism
• Male pattern baldness is an example:
• In males and females, BB individuals have full hair
• bb individuals experience hair loss but males have much more hair loss due to
the effect of male hormones
• Bb males experience hair loss just like bb males, while females have full hair
Male hair loss: Bb or bb Female hair loss: bb
38. Dominant Lethal Alleles & Delayed Age of
Onset
• Dominant lethal alleles can sidestep natural selection if they
have a delayed age of onset
• The abnormalities they produce are not expressed until
after the affected individual has reproduced
• A prominent example is Huntington Disease (HD), a fatal
neurodegenerative disorder which does not usually show
symptoms until the late 30s or 40s
• Neurodegenerative disorder causing cognitive
• decline & psychiatric issues
• Causes writhing movements call chorea,
• used to be called Huntington’s Chorea
http://learn.genetics.utah.edu
39.
40. • So far, phenotypes can be distinguished with
100% certainty
• All individuals with certain genotype express the
expected phenotype
• But… some individuals do not express the genotype
• Penetrance: percentage of individuals having a
particular genotype that express the expected
phenotype
Penetrance and Expressivity Describe
How Genes Are Expressed as
Phenotype
41. • Why not to express the corresponding
genotype?
• Influence of the environment: same genotype may
result in range of phenotypes.
• Influence of other interacting genes: more on this
through the following lectures
Penetrance and Expressivity Describe
How Genes Are Expressed as
Phenotype
42. • Penetrance: percentage of
individuals having a particular
genotype that express the
expected phenotype
• Measures how often the
phenotype occurs
• Expressivity: the degree to
which a character is
expressed
• Measures the intensity of the
phenotype
• Both examine how gene
expression is affected by
environment and genetic
background.
Penetrance and Expressivity Describe
How Genes Are Expressed as Phenotype
www.mun.ca
43. Incomplete Penetrance
• An organism is
penetrant for a trait
when the phenotype is
consistent with the
genotype
• An organism which
does not produce the
phenotype generally
associated with the
genotype is
nonpenetrant
• Traits for which
nonpenetrant
individuals routinely
occur are said to
display incomplete
penetrance
www.cancer.gov
44. Incomplete Penetrance: Polydactyly
• Polydactyly is an autosomal dominant condition, in
which affected individuals have more than 5
fingers and toes
• The dominant allele is nonpenetrant in about 25 –
30% of individuals carrying it
46. Variable Expressivity
• In variable expressivity individuals
who carry the alleles for a trait show
a phenotype but to a varying degree
of severity
• Waardenburg syndrome has four
principle features
• Premature graying, hearing loss, white
forelock, different colored eyes
• Each family member with
Waardenburg syndrome has the
same genotype but shows a different
combination of symptoms
48. Gene-Environment Interactions
• Genes alone are not responsible for all the
variation seen between organisms
• Gene-environment interaction is the result of the
influence of the environment on the expression of
genes and on the phenotype of the organism
• Ex: Drug use can change gene expression!
http://www.niehs.nih.gov
National Institute of Environmental Health
Sciences
-carcinogens, fetal alcohol syndrome,
Autism risks and the environment,
climate change & human health,
respiratory disease and pollution, etc.
49. Environmental Modification to Prevent
Hereditary Disease
• The human autosomal recessive condition, PKU (phenylketonuria) is
caused by the absence of an enzyme involved in phenylalanine
breakdown
• Infants with PKU are normal at birth, but over time, the inability to break
down phenylalanine is toxic to developing neurons
• PKU is one of the hereditary disorders infants are routinely screened for
50. Preventing Symptoms of PKU
• The key to preventing PKU is restricting
phenylalanine in the diet of infants found to have
PKU
• Thousands of people with PKU are living normal
lives due to the simple dietary modification that
prevents the expression of the PKU phenotype
depts.washington.edu
www.pku.com
