Blood group genetics and Bombay phenotype

 The gene I encode a glycosyltransferase, an enzyme that modifies the carbohydrate content of the red blood cell antigens. Allele IA codes for N-acetylgalactosamine transferase, allele IB codes for galactose transferase. These alleles vary at four nucleotides leading to two different proteins (enzymes) differing in four amino acids. Allele i has single nucleotide deletion in the initial coding region, leading to a frameshift and no formation of glycosyltransferase enzyme.

Allele IA IB codes for both the enzymes and produce both N-acetylgalactosamine transferase and galactose transferase.

These sugars (N-acetylgalactosamine and galactose) are added to a basic sugar molecule on RBC called mucopolysaccharide or H antigen which is made of galactose, N-acetyl glucosamine, and fucose. The production of mucopolysaccharide is controlled by another gene called H. The individual with genotype HH and Hh will produce functional mucopolysaccharide on the surface of RBC, whereas an individual with hh will fail to produce mucopolysaccharide, especially fucose moiety. This individual is called as Bombay phenotype.

The individual lacking functional mucopolysaccharide on its RBC and hence fail to add antigen-specific sugar is called Bombay phenotype. Their blood will not react with anti-A and anti-B antibodies as they lack their respective antigens on RBC.

Synthesis of blood group antigens

Production of H antigen or mucopolysaccharide

Table showing possible blood types of children from parents of various blood groups.