Epistasis

 Epistasis

The term epistasis is Greek word mean “standing upon”. It is a type of intergenic interaction in which a gene masks or modifies the expression of another gene present at a different locus.

Genes

Epistatic Gene: The gene which modifies or mask the phenotypic expression of another gene called epistatic gene.

Hypostatic Gene: It is a gene whose phenotypic expression is affected by a epistatic gene.

Example:

Epistasis can be best demonstrated in Bombay phenotype and coat color of Labrador retrievers.

 

Bombay phenotype:

Bombay phenotype is a rare blood group phenotype in which individuals are genetically of type A, B, or AB blood group but phenotypically O type blood group. This blood phenotype was first discovered in Bombay (Mumbai) in India by Dr. Y.M. Bhende in 1952.

In 1952, A woman was found to be genetically type B but functionally type O. she was found to lack both the A and B antigens and was thus typed as O. Her mother was type AB while her father was type A. This woman was carrying a homozygous recessive mutation in a gene designated FUT1 (encoding an enzyme, fucosyl transferase), which prevented her from synthesizing the complete H substance. 

The enzymes produced by the IA and IB alleles are unable to recognize the incomplete H substance. Thus, neither the terminal galactose nor N-acetylgalactosamine can be added.

Genetic basis of Bombay Phenotype:

The ABO blood groups are determined by antigen A and antigen B present on the surface of RBC. The production of antigen A and antigen B antigen is controlled by gene I^A and I^B and is also dependent upon gene H (present on chromosome 19). The dominant H gene allele produces H substance, a precursor for the antigen A and antigen B. Antigen A and antigen B will only be produced if the H substance is present. The allele I^A and I^B modifies the H substance to antigen A and antigen B respectively.

 

Genotype		H Substance	Type of Antigen	Blood group
I gene	H gene
IA IA ,  IAi	HH, Hh	Produced	A	A
IB IB , IBi	HH, Hh	Produced	B	B
IA IB	HH, Hh	Produced	A and B	AB
IA IA ,  IAi	hh	Not produced	None	O (Bombay)
IB IB , IBi	hh	Not produced	None	O (Bombay)
IA IB	hh	Not produced	None	O (Bombay)

Antigen A and Antigen B

The A and B antigens are sugars that are bound to membrane lipid molecules (fatty acids) of the red blood cell. The specificity of the A and B antigens is based on the terminal sugar.

 Antigen A and B are produced by adding a specific terminal sugar to the H substance. The H substance itself contains three sugar molecules—galactose (Gal), N-acetylglucosamine (AcGluNH), and fucose.  

The IA allele is responsible for an enzyme that can add the terminal sugar N-acetylgalactosamine (AcGalNH) to the H substance. The IB allele is responsible for an enzyme that can add a terminal galactose. Heterozygotes (IAIB) add either one or the other sugar to the H substance. Persons of type O (ii) cannot add either terminal sugar; these persons have only the H substance protruding from the surface of their red blood cells.