POLYMORPHISMS AT THE ABO LOCUS IN SUBGROUP A INDIVIDUALS

Background: The common ABO allele sequences are known, but little or n o genetic information is available on the rare but important A subgrou ps. Study Design and Methods: Blood group ABO polymorphism was analyze d in genomic DNA from 45 rare subgroup A individuals by sequence-speci fic primer polymerase chain reaction and amplified fragment length pol ymorphism investigating exons VI and VII in the ABO genes, These metho ds are used to detect specific mutations only, and not all changes tha t might be present can be detected. ABO genotypes discriminating six a lleles (A', A(2), B, O-1, O-1var, and O-2) were determined. Results: T he C-->T substitution at nucleotide position 467 (C467T) is not restri cted to A(2) and cis-AB individuals, but was found also in some A subg roups. Detection of the functionally more relevant C1060- single-point deletion in A(2) was accomplished by a novel sequence-specific primer polymerase chain reaction approach. A 100-percent correlation between the C467T and the C1060- mutations was found, Fifteen of 17 samples s howing the T646A mutation (described earlier in one case of A(x)) show ed a positive correlation with the C771T mutation in a frequently occu rring O-1var allele. The two exceptions were defined serologically as A(x). Conclusion: Indications have been found of an evolutionary relat ionship between A(1) alleles and A(el) and A(3) subgroups as well as b etween A(2) alleles and A(end) and A(weak) subgroups. Genetic heteroge neity within the A(x) and A(int) subgroups was also seen.