The Bombay Phenotype

In 1952, a very unusual situation provided information concerning the

genetic basis of the H substance. A woman in Bombay displayed a unique
genetic history inconsistent with her blood type. In need of a transfusion, she
was found to lack both the A and B antigens and was thus typed as O. However
one of her parents was type AB, and she herself was the obvious donor of an IB
allele to two of her offspring. Thus, she was genetically type B but functionally
type O!
This woman was subsequently shown to be homozygous for a rare
recessive mutation in a gene designated FUT1 (encoding an enzyme, fucosyl
transferase), which prevented her from synthesizing the complete H substance.
In this mutation, the terminal portion of the carbohydrate chain protruding from
the red cell membrane lacks fucose, normally added by the enzyme. In the
absence of fucose, the enzymes specified by the I A and IB alleles apparently are
unable to recognize the incomplete H substance as a proper substrate. Thus,
neither the terminal galactose nor N-acetylgalactosamine can be added, even
though the appropriate enzymes capable of doing so are present and functional.
As a result, the ABO system genotype cannot be expressed in individuals
homozygous for the mutant form of the FUT1 gene; even though they may have
the IA and/ or the IB alleles, neither antigen is added to the cell surface, and they
are functionally type O. To distinguish them from the rest of the population, they
are said to demonstrate the Bombay phenotype. The frequency of the mutant
FUT1 allele is exceedingly low. Hence, the vast majority of the human population
can synthesize the H substance.