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The A bantu phenotype in the ABO blood group system is due to a splice‐site mutation in a hybrid between a new O 1 ‐like allelic lineage and the A 2 allele
Author(s) -
HosseiniMaaf B.,
Smart E.,
Chester M. A.,
Olsson M. L.
Publication year - 2005
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.2005.00626.x
Subject(s) - abo blood group system , splice , mutation , genetics , bantu languages , splice site mutation , phenotype , medicine , biology , exon , gene , alternative splicing , philosophy , linguistics
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 ≈ 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.