title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The A(bantu) phenotype is caused by an O(1bantu)-A(2) hybrid at the ABO locus.
authors.affiliation: Blood Centre, Lund University Hospital, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Hosseini-Maaf
authors.forename: E
authors.initials: E
authors.lastname: Smart
authors.forename: M A
authors.initials: MA
authors.lastname: Chester
authors.forename: M L
authors.initials: ML
authors.lastname: Olsson
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D044383:Black People / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D016368:Frameshift Mutation; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D007438:Introns; D009154:Mutation; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011995:Recombination, Genetic
chemical_list: D000017:ABO Blood-Group System; D022821:RNA Splice Sites; D012333:RNA, Messenger