BMS2042 Lecture 4

Extensions to Mendelian Inheritance II

Gene and environmental interactions

References: Associate Professor Francine Marques

Klug 12th ed, Chapter 4 @FZMarques
Strachan & Read 4th ed, Chapter 3

© 2017 Pearson Education, Ltd.

 Autosomal dominant
Affected: Aa
Unaffected: aa
© 2017 Pearson Education, Ltd.
 X-linked recessive
Affected X^aY or XaY
Carriers: X^AX^a or XAXa
Unaffected: X^AY or XAY, X^AX^_ or XAX_
https://www.researchgate.net/publication/13759773_Dystrophin_gene_abnormalities_in_two_patients_with_idiopathic_dilated_cardioyopathy/figures?lo=1
 Autosomal recessive
Affected: aa
Carriers: Aa
© 2017 Pearson Education, Ltd. Unaffected: A_
If a father has type O blood and his son has type A blood,
what are the possible blood types of his son’s mother?

a) type O
b) type A
c) type B
d) types A, B, or O
e) any blood type

Father iOiO
Son iAiO
Mother needs to have at least one iA allele
You are studying an autosomal dominant disease. Symptoms
include the formation of lesions on the skin. Symptoms range from
mild to severe, but all individuals with the dominant allele show
symptoms. This is an example of:

a) incomplete penetrance and variable expressivity

b) full penetrance and variable expressivity
c) incomplete penetrance and uniform expressivity
d) full penetrance and uniform expressivity
e) incomplete penetrance and incomplete dominance

Since all individuals who have the mutation show the

phenotype, penetrance is 100%. The severity of symptoms
varies so expressivity is variable.
The genes that Mendel worked with were__________________

a) Variable in penetrance and expressivity

b) Variable in penetrance only
c) Variable in expressivity only
d) 100% penetrant with 100% expressivity

The 7 sets of pea genes that Mendel worked with showed 100%
penetrance and 100% expressivity. Due to this the dominant and
recessive genes always expressed the different phenotype to the
full degree of expression.
 What we will learn today:
• Complementary gene action
• Epistasis
• Duplicate genes
• Sex-influenced and sex-limited traits
• Environmental influence
• Genetic imprinting
• Mitochondrial inheritance

Problem
Tools &
identification
Technology
& solution
 Extensions to Mendel 2:
Gene-gene and gene-environmental interactions
Many traits are genetically heterogeneous – they are controlled by multiple
genes

e.g. deafness in humans

When genes interact in pathways, mutation of >1 gene can produce exactly
the same mutant phenotype  locus heterogeneity

When two genes affect different traits, a dihybrid cross gives an F2 9:3:3:1
phenotypic ratio = dihybrid ratio.

However, most traits are controlled by two or more genes, therefore we need
to consider gene interactions.
 2.1. Complementary gene action

Distinguished by a 9:7 F2 dihybrid ratio

Example: Colour in sweet peas.

Normally purple, but Bateson and

Punnett had several true breeding
white varieties.

Crossed two together and all F1 were

purple.

F2 had purple: white in a 9:7 ratio.

Brooker Fig 4.20

 2.1. Complementary gene action
Need a dominant allele for each gene to produce the trait

Gene C Gene P

C_ P_

Two genes: C dominant to c, P dominant to p

If either cc or pp will be white. Need a dominant allele for both genes to get
purple.
F2 9 : 7
purple : white
C_;P_ : C_;pp or cc;P_ or cc;pp
© 2017 Pearson Education, Ltd.
 Gene C Gene P
Colourless Colourless Purple
precursor 1 precursor 2 Pigment?
C_ P_

Colourless Colourless Purple

precursor 1 precursor 2 Pigment?
C_ pp

Colourless Colourless Purple

precursor 1 precursor 2 Pigment?
cc P_

Colourless Colourless Purple

precursor 1 precursor 2 Pigment?
cc pp

F2 9 : 7
purple : white
C_;P_ : C_;pp or cc;P_ or cc;pp
 Extensions to Mendel II: 2.2 Epistasis

Klug 10, Chapter 4

 2.2 Epistasis
The phenotype produced by a variant of one gene (called the
epistatic allele) blocks or masks the phenotype produced by
alleles of another gene.

Usually occurs because genes act in the same pathway for

producing trait.

No new phenotypes are produced, but fewer than four

phenotypes expected by two separate genes

Recessive epistasis - distinguishing F2 ratio is 9:3:4

A recessive epistatic allele blocks or masks phenotypic effects

of alleles of other genes only when it is homozygous.
e.g. Recessive epistasis

Coat colour in Labrador

retrievers,
ee is epistatic to B gene.

yellow brown black

E gene B gene
Hartwell Fig 3.13a
yellow brown black 9 B_E_ (black)
E gene B gene 3 bbE_ (brown)
4 __ee (yellow)

E_ B_
yellow brown black

E_ bb
yellow brown black

ee B_
yellow brown black

ee bb
yellow brown black
The case of Charlie Chaplin’s
paternity suit
Joan Berry

A O

AB
Carol Ann

Question: Was he the father?

Changed paternity laws in America

 Bombay phenotype

India 1:10,000
Caucasians 1:250,000
What is wrong with this pedigree?
Hartwell Fig 3.13b
 Bombay phenotype explained
• H substance
– One or two terminal sugars are added
– O blood types (ii) only have the H substance protruding
from red blood cells

• In 1952, a female in Bombay was found to be homozygous for

FUT1 at the fucosyl transferase locus, which masks expression
of IA and IB alleles
– Prevents her from producing H substance
– No substrate to make A or B antigens
– Results functionally in type O
 Dominant epistasis
• Dominant allele at one loci
masks an allele at second loci
• Ratio 12 : 3 : 1
• Example: Summer squash fruit
colour
– Dominant allele B  White fruit
• Regardless of second loci allele
– Absence of B allele  Yellow fruit
• Genotypes bb, Aa, AA  yellow fruit
• Genotype aa  green
 Extensions to Mendel II
2.3 Duplicate genes
Distinguished by 15:1 F2 dihybrid ratio

Either A or B is required
e.g. fruit shape in Shepherd’s purse (weed)
- two genes, each with two alleles
- dominant allele of either  triangular
shape.

15 T - ; - - or - - ; V –
1 tt;vv

Brooker Fig 4.24

http://www.uaex.edu/yard-garden/images/weed_id/shepherds_purse_fruit.jpg
 Extensions to Mendel II
2.4 Effect of environment on phenotype
The environment can affect the phenotypic expression of a
genotype

Examples:
1. Temperature
e.g. Coat colour in the arctic fox

2. Chemicals
e.g. Phenylketonuria (PKU) in humans
Loss of enzyme to metabolize amino acid phenylalanine (Phe)
Severe problems unless low-Phe diet
Alter physical environment by removal of phenylalanine from diet
 Temperature-sensitive variants:
Siamese cats
• Temperature-sensitive allele is
responsible for pigment
production.
• They work as conditional
variants.
• Variant in tyrosinase (that makes
melanin) in Siamese cats causes
it work best at room temperature.
• Thus, body extremities that are
closer to room temperature
compared to the warmer body
have darker hair colour.
 Phenylketonuria (PKU)
Autosomal recessive, PAH gene
Affects 1:15,000 in Australia (20-25 babies a year, tested at birth)

Phenylalanine hydroxylase

Neurotoxic, leading to intellectual disability

https://wiki.ubc.ca/File:How_does_PKU_occur%3F.png
 Congenital lactase deficiency
(variant in the LCT gene, AR)
• Also called congenital alactasia, is a disorder in which infants are
unable to break down lactose in breast milk or formula.
• The LCT gene provides instructions for making the lactase enzyme.
• Variants that cause congenital lactase deficiency are believed to
interfere with the function of lactase, causing affected infants to
have a severely impaired ability to digest lactose in breast milk or
formula.

https://www.gbhealthwatch.com/Trait-Lactose-Intolerance.php
 Extensions to Mendel II
2.5 Genomic (parental) imprinting
• For some human genes, one of the alleles is transcriptionally
inactive (no mRNA is produced), depending upon the parent from
whom the allele was received.
• This process of gene silencing is known as imprinting, and the
transcriptionally silenced genes are said to be imprinted.
• Imprinted alleles tend to be heavily methylated or have
modifications in chromatin of specific histone types (epigenetic
changes).
• Selective gene silencing impacts phenotypic expression.
• Silencing depends on parental origin of genes and occurs in early
development.
 Example: deletion of chromosomal region
15q11-q13

Inheritance of the deletion from the father Inheritance of the deletion from the
produces Prader-Willi syndrome (PWS) mother produces Angelman syndrome
(paternally expressed genes SNRPN and NDN) (maternally expressed gene UBE3A)
 Inheritance pattern of this deletion and the
activation status of genes in the critical region
 Extensions to Mendel II
2.6 Sex-influenced and sex-limited traits
• Sex influences the inheritance and expression of genes in a variety of
ways

• Sex-influenced characteristics
– Inherited characteristics that are conditioned by the sex of the
individual
– Example: baldness behaves as an autosomic dominant condition
in males, and as a recessive in females

• Sex-limited characteristics
– Characteristic only appears (or develops) in one of the sexes
– Example: Ovary development and milk yield in females; sperm
development in males
 Pattern of baldness in the Adams family line

John Adams John Quincy Charles Francis Henry Adams

Adams Adams
(father) (great-grandson)
(son) (grandson)

Brooker Fig 4.15

Sex-influenced does not mean trait is sex-linked!!
Allele B behaves dominant in males and recessive in females
In BB genotype in females, phenotype is less pronounced

Brooker Fig 4.16

 Extensions to Mendel II
2.7 Cytoplasmic inheritance
• Inheritance of parental characters through non-chromosome DNA.

• Mitochondrial DNA is cytoplasmically inherited since the

information is not segregated at mitosis.

• Inheritance is matrilineal only and can be initially seen as

autosomal dominant because affects either sex.

• Human mitochondrial genome is small (16.5kb).

• These encode only 37 genes that are important in mitochondrial

development.
 Mitochondrial genes
• The mitochondria, which
produce ATP, have their
own unique DNA.

• Mitochondrial DNA is
maternally inherited and
has a high mutation rate.

• A number of diseases are

known to be caused by
mutations in mitochondrial
DNA.
Homoplasmy: every
mitochondrial
genome carries the
causative mutation

Heteroplasmy:
contain a mixed
population of normal
and mutant genomes
in each cell
Learning outcomes
• Explain how complementary gene action works
• Describe epistasis, giving examples (e.g. Bombay
phenotype)
• Explain the impact of gene duplication in inheritance
patterns
• Describe interaction of genes with environment, and
give examples
• Understand the concept of genetic imprinting and
sex-influenced/limited traits
• Identify a pedigree affected by mitochondrial DNA
mutation
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