ABO is clinically the most important blood group system in transfusion
medicine and includes many variant phenotypes. To understand the mole
cular genetic basis of this polymorphic system, we have analyzed genom
ic DNAs obtained from Japanese individuals possessing variant ABO phen
otypes including A(2), A(x), A(el), cis-AB, B-x, and B-el. By polymera
se chain reaction-single-strand conformation polymorphism (SSCP) and n
ucleotide sequence analyses, we identified 11 different alleles, These
alleles had nucleotide sequences different from those of the previous
ly described 13 different alleles responsible for the common ABO pheno
types. Analysis of the nucleotide sequences of the alleles responsible
for those variant phenotypes showed that the amino acid residues at p
ositions 266 and 268 may be crucial for transferase specificity, where
as those at positions 214, 216, 223, 291, and 352 may be critical for
the activity level. Nine of the 11 alleles, responsible for the A(2),
A(x), A(el), cis-AB, B-x, and B-al phenotypes, were presumed to be gen
erated from common ABO alleles by single nucleotide mutations such as
nonsynonymous substitution, deletion, or insertion. Two other alleles,
responsible for the A(2) and A(el) phenotypes, may have originated by
recombination, gene conversionlike events or accumulation of nucleoti
de substitutions, Our data indicate that different alleles could cause
the same ABO variant phenotypes, and that these alleles do not necess
arily belong to a single evolutionary lineage. (C) 1996 by The America
n Society of Hematology.