title: Recombination and gene conversion-like events may contribute to ABO gene diversity causing various phenotypes.
abstract: We identified five different alleles, tentatively named ABO*O301, *0302, *R102, *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 analysis revealed that *0301 and *0302 had single nonsynonymous substitutions compared with *A101 or *A102 responsible for the A1 phenotype. Analysis of intron 6 at the ABO gene by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing revealed that *R102 and *R103 had chimeric sequences of A-02 and B-02, respectively, from exons 6 to 7. In the analysis of five other chimeric alleles detected in the same manner, we identified 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 estimated 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 intron 6 to exon 7 probably generated by two different gene conversions. Similar patchwork sequences around nucleotide position 646 in exon 7 were observed in two other new alleles responsible for the Ax and B3 phenotypes. Thus, the site is presumably a hotspot for gene conversion. These results indicate that both recombination and gene conversion-like events play important roles in generating ABO gene diversity.
authors.affiliation: Japanese Red Cross Central Blood Center, Tokyo. ogasawara@cbc.jrc.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Ogasawara
authors.forename: R
authors.initials: R
authors.lastname: Yabe
authors.forename: M
authors.initials: M
authors.lastname: Uchikawa
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D005785:Gene Conversion; D017353:Gene Deletion; D005787:Gene Frequency; D014644:Genetic Variation; D006147:Guanine; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D011995:Recombination, Genetic
chemical_list: D000017:ABO Blood-Group System; D018076:DNA, Complementary; D006147:Guanine