HETEROGENEITY OF THE BLOOD-GROUP A(X) ALLELE - GENETIC-RECOMBINATION OF COMMON ALLELES CAN RESULT IN THE A(X) PHENOTYPE

The A, phenotype is an important subgroup of the ABO blood group syste m. Its inheritance does not always follow Mendelian rules and recent s tudies suggested that different alleles can result in this phenotype. This suggestion has been explored by cloning and sequencing exons 6 an d 7 of the ABO gene and the intervening intron from members of six unr elated families expressing the A, phenotype. Two families showed the p reviously described T646A 'A(x)' mutation as the only deviation from t he consensus A(1) allele. In two other families the A(x) phenotype was inherited as two different recombinational gene products. Combination of exon 6 derived from A or B/O-2 alleles with exon 7 from the O-1v a llele created two novel alleles that have four O-1v-characteristic nuc leotide substitutions in exon 7, including T646A. Sequencing and analy sis of polymorphisms in intron 6 defined the crossing-over zones of th ese hybrid alleles. Southern blot confirmed the hybrid formation by de tecting ABO-related polymorphisms approximate to 1.35 kb downstream fr om the ABO reading frame. The remaining two families expressed the A(x ) phenotype via an allele having A(2)-specific mutations. Thus, a hete rogeneous molecular background leads to the serologically defined A, p henotype and may well explain the different modes of inheritance obser ved.