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


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.


CONCLUSIONS
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.
Hosseini-Maaf
Bahram
B
Blood Center, Lund University Hospital and Department of Transfusion Medicine, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
Irshaid
Nidal M
NM
Hellberg
Asa
A
Wagner
Thomas
T
Levene
Cyril
C
Hustinx
Hein
H
Steffensen
Rudi
R
Chester
M Alan
MA
Olsson
Martin L
ML
D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D005091:Exons; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D000017:ABO Blood-Group System