BIOL 2110 - Genetics

LECTURE 4
Allelic variation & gene function
Chapter 5

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 Allelic variation,
gene interactions and function
• Why?
As geneticists, we should understand the basics
of heredity – how genes are passed on and
expressed across generations.

• What you see is not what you get…

• Genes interact in different ways!

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 Allelic variation,
gene interactions and function

• Incomplete Dominance and Codominance

• Multiple alleles

• Gene action: environment, gene interactions

• Epigenetics

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Reminder:
Mendel s main findings
=monohybrid crosses (1 trait)
• Alleles exist in pairs
• With two alleles one will be dominant to the other
• Alleles segregate randomly into gametes – one
male, one female
• Allele pairs assort independently of other loci–
during meiosis – for two phenotypic traits

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Are all of Mendel’s conclusions right?
Is it the full story? 5
Allelic variation
& gene function

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 Note: What is an allele anyway?

• Alleles, like R and r that code for Mendel’s

round and wrinkled peas represent specific
DNA sequences on a particular chromosome.

• E.g. The R allele codes for the SBEI enzyme

that converts a linear form of starch to a
branched form, causing round peas. Just one
copy of R is needed to dominate r.

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 Complete dominance

Mendel’s idea that the phenotype of the heterozygote is

the same as that of the homozygous dominant
(e.g. Aa and AA are phenotypically indistinguishable)

Incomplete (partial) dominance

Phenotype of heterozygote is intermediate between
the phenotypes of the homozygotes
(Aa and AA are phenotypically distinguishable)

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Incomplete (partial) dominance

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Incomplete (partial) dominance

F1 intercross: 1:2:1 genotypic AND phenotypic ratios

complete dominance 3:1!!
The allele R is incompletely dominant over W
(RW heterozygote produces less pigment) 10
Incomplete vs. co-dominance

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 Codominance, dominance and multiple
alleles: e.g. ABO blood types
The two alleles (IA & IB) contribute equally to the heterozygous phenotype
but is dominant over allele i = ‘O’

IA > i, IB > i, IA = IB

The ‘A’ and ‘B’ code for

different enzymes that
attach different types of
sugars to red blood cells
(antigens)
AB = both enzymes
i = O = inactive enzyme12
 Incomplete vs co-dominance
Difference Incomplete co-dominance
dominance
Allele expression One is not Both are completely
completely expressed
expressed
Allele dependence The effect of an The effect of an
allele is dependent allele is
on its paired alleleindependent of its
paired allele
Observed A third phenotype Both alleles are
phenotype showing a mixture expressed showing a
of the dominant and combination of both
recessive phenotypes
phenotypes 13
 Multiple alleles => 3 alleles at a gene
Mendel’s concept of inheritance dealt with only 2
different alleles for a particular gene

In a diploid individual, there can be a maximum of 2

of these alleles
But, in a population/species there may be more than
2 alleles for a particular gene

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 Multiple alleles at a
single locus = lots of
variation.
White clover, 7 alleles = 22
phenotypes

•With 2 alleles, the number of genotypes is 1 + 2 = 3

•3 alleles there are 1 + 2 + 3 = 6 genotypes
•7 alleles there are 1 + 2 + 3 + 4 + 5 +6 +7 = 28 genotypes.
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 Multiple alleles

• e.g. ABO blood: co-dominant with multiple alleles

The allele, and phenotype, predominant in the

population (in nature) is called the wild type

Example of a particular gene c: wild type c+

-‘+’ denotes wild type
All the others are mutant alleles or phenotypes
(implies they appeared after the wild type allele)
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 Functional relationships and multiple
alleles

Coat colour in
rabbits cc
c is colourless
(albino) chch

Studied by making cchcch

heterozygous
combinations by c+c+
crossing
homozygotes
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Functional relationships among
members of allele series

cc c+ is completely dominant over all alleles

cch is partially dominant over ch & c
ch is completely dominant over c,
chch but only under certain environmental
conditions!
cchcch
Hierarchy of
dominance:
c+c+
or c+cch ; c+ > cch > ch > c
c+ch
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 Gene interactions: Pleiotropy
A single gene influences many aspects of the phenotype
From the Greek “to take many turns”
Example: the silver fox experiments

Selection for tameness - raised tail

- heat every 6 months
- mottled coat

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 Getting more complicated…

Gene action/interaction

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 Gene action: from genotype to
phenotype
• Environment and other genes may have an
influence on gene action
-combinations of genes at different loci can affect
phenotypes
-environmental cues/tolerances may determine
gene expression
• Many genes don’t act in isolation
• Potentially, a particular gene can influence
many traits
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 Environmental influence on
gene function

Himalayan phenotype only at cooler temperature,

otherwise albino

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 Penetrance vs. expressivity

• Penetrance: the percentage of individuals with a

given genotype who exhibit the phenotype
associated with that genotype
- e.g. affected by gene suppressors, environment

• Expressivity: measures the extent to which a given

genotype is expressed at the phenotypic level
- e.g. affected by environment, genomic background
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 Incomplete (variable) penetrance

Mothers in generation III do not appear to pass the disease

on to their children in generation IV, but the disease
reappears in their grandchildren in generation V through their
mothers.
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 Variable expressivity
Piebald spotting in beagles,
Each dog carries the gene
SP - for piebald spotting in
dogs

WHY?
Environmental factors, as well as
the effects of other genes, may
alter the phenotypic expression of
a particular genotype

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 Variable expressivity
Degree of manifestation of a trait controlled by a gene

• One gene may

produce different
degrees of expression
in different
individuals
• Extremely variable
phenotype
e.g. ‘eye’ lobe mutation in
Drosophila 27
 Lethal alleles

Yellow x non-yellow = 50:50

Non-yellow x non-yellow = 100% NY
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Lethal alleles

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 Gene Interactions

• When genes at multiple loci determine a single

phenotype
• Mendel looked at two distinct phenotypes – pea
shape and colour – genes were independent in
their phenotypic expression
• With gene interactions, many phenotypes are
possible – unpredictable based on single genes
• Can have 2,3 4 or ?? genes interacting…

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 Gene interactions
Two independently assorting genes can affect a trait
P (rose) X (pea) Phenotype of F2 (RrAa x RrAa):
RR aa rrAA R-A- = walnut (9)
R-aa = rose (3)
F1 (walnut) rrA- = pea (3)
Rr Aa
rraa = single (1)

Comb
formation

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Rose Pea walnut Single
 Gene interactions: Epistasis
When two or more genes influence a trait, an
allele from one of them has an overriding effect
on the phenotype
Can have a recessive epistatic gene (2 copies needed) or
a dominant (1 copy needed) epistatic gene

Epistasis is interaction between products of two

or more genes (from the Greek “to stand above”)
-with a heterozygote/heterozygote cross you do
not expect a 9:3:3:1 ratio….why?

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 Gene interactions: Epistasis

• Epistasis is inferred when an allele of

one gene masks expression of alleles of
another gene – then expresses its own
phenotype instead.

• Epistasis indicates an interaction of genes

involved in some biochemical or
developmental sequence.
- Often inhibits biochemical pathways

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 Example of Epistasis – coat-colour
inheritance in Labrador retrievers

Gene 1:
Allele B (black coat) and allele b (brown coat)
Gene 2:
Alleles E and e are epistatic on alleles A and b (E allows
colour deposition in the coat, ee prevents deposition)
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 Recessive epistasis – coat-colour
inheritance in Labrador retrievers

When recessive alleles at one locus mask the expression of

both (dominant and recessive) alleles at another

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Phenotypic ratio- Labrador Dog colour
BbEe X BbEe
BE bE B e b e
BE BBEE BbEE BBEe BbEe
Black Black Black Black
bE BbEE bbEE BbEe bbEe
Black Brown Black Brown
Be BBEe BbEe BBee Bbee
Black Black Yellow Yellow
be BbEe bbEe Bbee bbee
Black Brown Yellow Yellow

Bl = 9; Br = 3; Y = 4
(i.e. not 9:3:3:1) 36
 Duplicate dominant epistasis
Epistasis in the rice

Awnless Awned Some genes may be present more

than once in the genome and co-
determine phenotypes/ code for the
same phenotype

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Duplicate dominant epistasis
When there is a dominant allele masking the
expression of recessive alleles at two loci

Awnless Awned

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 Dominant epistasis
When a dominant allele at one locus can mask the
expression of both alleles (dominant and recessive) at
another locus,

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 Duplicate recessive epistasis
2 recessive alleles at either locus, suppress phenotype
 Duplicate interaction epistasis
2 recessive alleles at either locus, suppress phenotype, but
not when both loci are homozygous

[Y]

, Y = Yellow flower
9:6:1 instead of 9:3:3:1
Inhibitory/ Dominant and Recessive
Epistasis…
a dominant allele at one locus can mask the expression of
both (dominant and recessive) alleles at second locus

I>P 42
 TABLE 5.2 Modified dihybrid phenotypic ratios due to gene interaction

Genotype
Example Discussed in
Ratio* A_ B_ A_ bb aa B_ aa bb Type of Interaction Chapter
Seed shape and seed
9:3:3:1 9 3 3 1 None
color in peas

Coat color in Labrador

9:3:4 9 3 4 Recessive epistasis
retrievers

12 : 3 : 1 12 3 1 Dominant epistasis Color in squash

9:7 9 7 Duplicate recessive epistasis Albinism in snails

9:6:1 9 6 1 Duplicate interaction —

15 : 1 15 1 Duplicate dominant epistasis —

Dominant and recessive

13 : 3 13 3 —
epistasis

*Each ratio is produced by a dihybrid cross (Aa Bb × Aa Bb). Shaded bars represent combinations of genotypes that give
the same phenotype.
 Testing for different inheritance
patterns
• To find out how statistically probable a given
inheritance pattern is: Chi-Square (X2) test
• Most widely used probability test in the life
sciences
• Useful when offspring ratios do not fit a clear
expected pattern
• Need to know numbers of progeny to do test

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 The Chi-Square Test

• Predict expected numbers based on hypothesis

• Experimentally obtain (observe) numbers
• Calculate the c2 statistic.
• Determine the degrees of freedom.
• Compare the c2 statistic to the critical value

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 X2 test for inheritance patterns

E.g. Are the phenotype frequencies of

182 orange:61 red:77 yellow due to R r
R AA Aa
1. Incomplete dominance? r Aa aa

•Test against expected ratio 1:2:1 160/80/80

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 X2 Test for inheritance patterns

E.g. Are the phenotype frequencies of

182 orange:61 red:77 yellow due to R r
R AA Aa
1. Incomplete dominance? r Aa aa

•Test against expected ratio 1:2:1 160/80/80

YR yR Y r y r

2. Recessive epistasis of red YR YYRR YyRR YYRr YyRr

on orange and yellow?? YR YyRR yyRR YYRr yyRr

•Test with expected ratio 9:3:4 Yr YYRr YyRr YYrr Yyrr

yr YyRr yyRr Yyrr yyrr

180/80/60 47
 Influence of sex on inheritance
and gene expression
• Autosomal traits may differ in penetrance
between sexes
• Cytoplasmic inheritance
• Genetic maternal effect (dextral vs sinistral –
biallelic dominant system)
• Genomic imprinting (preferential expression of
allele depending from which parent it originated –
epigenetic mechanisms)

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Differences in penetrance

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Cytoplasmic inheritance
 TABLE 5.4 Characteristics of cytoplasmically inherited
traits
1. Present in males and females.

2. Usually inherited from one parent, typically the maternal parent.

3. Reciprocal crosses give different results.

4. Exhibit extensive phenotypic variation, even within a single

family.
Insulin-like growth factor 2 in humans
Next Lecture:
Linkage and crossing over

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