Genetics of the Bombay Phenotype

Seven individuals with the Bombay phenotype have been found among the thirty-three members of an Indian family spanning three generations. This is the first report of children resulting from the union of an individual of the Bombay phenotype hh and an individual heterozygous Hh at the Bombay locus. This family again demonstrates the effective suppression of the A-B-O phenotype by the Bombay genotype. Three Bombay individuals of this family were shown to be heterozygous at the Lewis locus. This had not been determinable in previously reported cases. This is consistent with the concept that there are two kinds of Bombay genotypes. We propose that the Lewis gene has evolved from a duplication of the H gene. Such duplication predisposes to both higher orders of duplication and to deletion. Deletions in this system would then provide the genetic basis for the Lewis-negative and the Bombay phenotype. In order to explain the rarity of the Lewis-negative Bombay phenotype by the proposed mechanism, we postulate that it would only arise by crossing over at the position determining the active site of the transferase enzymes which determine the Lewis and the H specificities.