Recombination and gene conversion-like events may contribute to ABO gene diversity causing various phenotypes

We identified five different alleles, tentatively named ABO*O301, *O302, "R 102, "R103, and *A110, in Japanese individuals possessing the blood group O phenotype. These alleles lack the guanine deletion at nucleotide position 261 which is shared by a majority of O alleles. Nucleotide sequence analysi s revealed that *O301 and *O302 had single nonsynonymous substitutions comp ared with *A101 or *A102 responsible for the A(1) phenotype. Analysis of in tron 6 at the ABO gene by polymerase chain reaction-single-strand conformat ion polymorphism and direct sequencing revealed that *DR102 and *R103 had c himeric sequences of A-O2 and B-O2, respectively, from exons 6 to 7. In the analysis of five other chimeric alleles detected in the same manner, we id entified a total of four different recombination-breakpoints within or near intron 6. When 510 unrelated Japanese were examined, the frequency of the chimeric alleles generated by recombination in intron 6 or exon 7 was estim ated to be 1.7%. In addition, we found that *O301, *A110, *C101, *A111, and 35% of *A102 had a unique A-B-A chimeric sequence at intron 6, presumed to originate from a gene conversion-like event. We had previously established that *A110 also had an A-O2-A chimeric sequence around nucleotide position 646 in exon 7. Thus this allele has an A-B-A-O2-A chimeric sequence from i ntron 6 to exon 7 probably generated by two different gene conversions. Sim ilar patchwork sequences around nucleotide position 646 in exon 7 were obse rved in two other new alleles responsible for the A(x) and B-3 phenotypes. Thus, the site is presumably a hotspot for gene conversion. These results i ndicate that both recombination and gene conversion-like events play import ant roles in generating ABO gene diversity.