Lecture #6 – Bombay Phenotype & Epistasis

Wheeler High SchoolThe Center for Advanced Studies in Science, Math & Technology

Post-AP DNA/Genetics – Ms. Kelavkar

The Bombay Phenotype

• Discovered in 1952

• Woman from Bombay who was genetically blood type B but phenotypically O– Homozygous for recessive mutation in gene

known as FUT1• Having this mutation meant she could not make any

H substance

What type of mutation is this?

Bombay Phenotype = Has the genes to make and

but has a mutation in the gene that makes

Bombay Woman’s PedigreeWhat does it mean to lack the H substance?

•Must have the H substance to make antigen A or B

•Can only receive a blood transfusion from other individuals with the Bombay phenotype

–OhOh

Figure 4-3 Copyright © 2006 Pearson Prentice Hall, Inc.

Bombay Phenotype & Epistasis

• Many traits characterized by a distinct phenotype are affected by more than one gene

• Epistasis occurs when one gene masks the effect of another gene or when two gene pairs complement each other such that one dominant allele is required at each locus to express a certain phenotype.

Bombay Phenotype & Epistasis• The Bombay phenotype for ABO blood groups is

an example of epistasis – homozygous recessive condition at one locus masks the

expression of a second locus• A locus is a position on a chromosome

• Individuals with the Bombay Phenotype have the genes to make the A or B antigen at one loci but lack the genes that produce the H substance produced at another loci. – No H antigen gives you the O phenotype!

A ratio expressed in 16 parts (e.g., 3:6:3:4)

suggests that epistasis is occurring which means

genes are ‘interacting’ to give a particular

phenotype.

Epistasis in MiceB is the pigment gene!

•wt coat color in mice is called agouti (A-)

•Agouti is dominant to black (aa)

•When a recessive mutation, bb, at a separate locus is homozygous, all pigmentation is eliminated giving albino mice

F1: AaBb x AaBbF2 Ratio Genotype Phenotype Phenotypic

Ratios

9/16 A-B- Agouti 9/16 agouti

3/16 A-bb Albino 4/16 albino

3/16 aaB- Black 3/16 black

1/16 aabb albino

Agouti = A-

Black = aa

Pigment = B-

No pigment = bb

Agouti = A-

Black = aa

Pigment = B-

No pigment = bb

Epistasis in Mice

Mouse color is dependent on 2 different genes that interact (A- and B-)…

B- Black

Pigment A- Agouti

Gene B Gene A

Agouti = A-

Black = aa

Pigment = B-

No pigment = bb

bbNo

Pigment A- Albino Mouse

B- Black Pigment aa Black

So there are 3

possibilities

Gene Interaction Diagram

Try One Out!!

F1: Aabb x AaBb

F2 Aa x Aa F2 bb x Bb F2 phenotypic proportions

¾ A-

¼ aa

½ B-

½ bb

½ bb

½ B-

3/8 A-B- (Agouti)

3/8 A-bb (Albino)

1/8 aaB- (Black)

1/8 aabb (Albino)

Agouti = A-

Black = aa

Pigment = B-

No pigment = bb

Lethal Mutations

• A loss of function mutation can sometimes be tolerated in the heterozygous state but may behave as a recessive lethal allele in the homozygous state, in which case homozygous recessive individuals will not survive.– This is a lethal mutation!

Inheritance patterns in 3 crosses involving the

normal wt agouti allele (A) and the mutant yellow (AY) allele in the mouse. Note

that the mutant allele behaves dominantly to the normal allele in controlling

coat color, but it also behaves as a

homozygous recessive lethal allele. The

genotype AYAY does not exist.

Any Questions?

I am an Agouti mouse

I’m an Albino

I’m a Black mouse