DNA polymorphisms and haplotypes in the 5'-upstream region of the ABO blood group gene

We investigated the polymorphisms in the 5'-upstream region between nucleotide position (nt) -9600 and nt-4105 of the ABO blood group gene using PCR and direct sequencing methods. We found 16 single nucleotide polymorphisms, two insertion-deletion polymorphisms and two sequence polymorphisms. One of the insertion-deletion polymorphisms was found at nts from -9605 to -9204, and the alleles of that locus were named ABORR*L (non-deletion) and ABORR*S (52-base-deletion). There were two haplotypes constructed from 14 polymorphisms in the region between nt-9600 and nt-7565; they were tentatively named ABORR*L-associated and ABORR*S-associated haplotypes. The ABORR*L-associated haplotype may link with ABO*O(A) (also known as ABO*O201), and the ABORR*S-associated haplotype links with the other common alleles. This indicates the existence of two major lineages of the Japanese ABO alleles in the 5'-upstream region from nt-7565. In contrast to these findings, we observed six haplotypes in the region between nt-6371 and nt-4105, and we assume that the sequence in that region is variable as compared with those in the other 5'-upstream regions. We examined the generation of two sequence polymorphisms found in the present study. In the both cases, the formation of a hairpin loop caused by palindrome in a single-stranded DNA molecule may play an important role in generating the polymorphism.