Allele-related variation in minisatellite repeats involved in the transcription of the blood group ABO gene

Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood group ABO locus, polymorphisms at the ABO locus and phenotype-genotype correlation have been analysed by several investigators. An enhancer-active minisatellite motif reported to contain four 43-bp repeats has been analysed by PCR in blood samples from 160 random Swedish blood donors. Different sizes of the DNA fragments obtained led to further analysis by direct sequencing. Fragments with either one or four 43-bp repeats were identified. A nucleotide substitution (G-->A) at nt. 41 of 43 was found in all alleles with only one repeat. Correlation with the ABO genotypes of the samples, as determined by a panel of ABO genotyping techniques, revealed an allele-related variable number of tandem repeats (VNTR). The A1 and the infrequent O2 allele had only one repeat whilst A2, B, O1 and O1v had four repeats and thus generated longer (by 129 bp) fragments. A further 74 samples obtained from various geographical areas/ethnic groups indicated a widespread correlation with few exceptions. In conclusion, a novel ABO polymorphism located in the 5'-nontranslated region involved in transcriptional regulation of the ABO gene is reported and its relationship to common alleles at this locus defined