The Abantu phenotype in the ABO blood group system is due to a splice-site mutation in a hybrid between a new O1-like allelic lineage and the A2 allele.

BACKGROUND AND OBJECTIVES: Many phenotypic variations in the expression of blood group A have been explained by variations in gene structure, but unresolved samples are frequently encountered in the reference laboratory. Among ABO subgroups, A(bantu) has the highest frequency in a specified population. The molecular basis of this phenotype is now described. MATERIALS AND METHODS: Blood from Black donors phenotyped as A(bantu) was subjected to genomic ABO screening and direct sequencing of polymerase chain reaction (PCR)-amplified ABO exons 1-7 and introns 2-6. Total RNA was extracted and ABO cDNA was synthesized by reverse transcription (RT)-PCR. Control material comprised Black South African, Swedish, Jordanian and Brazilian blood samples with common phenotypes. RESULTS: Genomic ABO typing indicated the presence of an A(2) allele in each A(bantu) donor, in combination with an O allele. No previously reported mutations associated with weak A or B expression were found. Direct sequencing indicated the common A(2) sequence with a single nucleotide deletion (AGGT>AGT) at the exon 4/intron 4 junction, predicted either to disrupt the reading frame (resulting in a premature stop codon) or to cause erroneous splicing (resulting in the exclusion of exon 4 from the mRNA). O mRNA, but no transcripts from the A(bantu) allele, could be detected. Surprisingly, the splice-site mutation was also found in approximately 5% of O alleles in Black South Africans, but not in other blood donors, or in non-O(1) alleles. Utilizing intron polymorphisms, the A(bantu) allele was shown to be a recombination between a new allelic lineage (O(1bantu)) and A(2), with a cross-over region near exon 5. CONCLUSION: The A(bantu) phenotype is caused by an O(1bantu)-A(2) hybrid at the ABO locus.