New and unusual O alleles at the ABO locus are implicated in unexpected blood group phenotypes

Transfusion. 2005 Jan;45(1):70-81. doi: 10.1111/j.1537-2995.2005.04195.x.


Background: In the ABO blood group system mutations in the A gene may lead to weak A subgroups owing to a dysfunctional 3-alpha-N-acetylgalactosaminyltransferase.

Study design and methods: Blood and DNA were investigated to correlate weak A phenotypes with genotype, and an overrepresentation of the infrequent O2 allele was observed. Consequently, 57 available O2 alleles were examined in detail.

Results: Two new O2 alleles were identified having mutations resulting in Gly229Asp with or without Arg217Cys. A recently described O2 variant (488C>T; Thr163Met) was also found. Surprisingly, both the original and the variant O2 alleles were associated with either O or Aweak phenotypes. Three novel O alleles surfaced in six other samples with suspected A subgroups. These were A1-like alleles having nonsense mutations causing premature truncation at codons 56, 107, or 181. A second example of the rare O3 allele was also identified. A newly described O1 allele having 768C>A was found to be the third most frequent O allele among Swedish donors. Of the five novel O alleles, three were incorrectly interpreted as A1 following routine ABO genotyping.

Conclusion: Apparent O alleles lacking 261delG may cause weak A expression on red blood cells and/or inhibit anti-A production. A hypothesis that exchange of genetic material between principally dissimilar O alleles during mitosis ("autologous chimerism") restores glycosyltransferase activity in some cells would explain this interesting phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / genetics*
  • Alleles*
  • Base Sequence
  • Chromosome Mapping
  • Exons
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Polymorphism, Genetic
  • Sequence Analysis, DNA


  • ABO Blood-Group System

Associated data

  • GENBANK/AY611637
  • GENBANK/AY611638
  • GENBANK/AY611639
  • GENBANK/AY611640
  • GENBANK/AY611641