A clue to the basis of allelic enhancement: occurrence of the Ax subgroup in the offspring of blood group O parents

Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analys...

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Bibliographic Details
Published in:Transfusion medicine (Oxford, England) England), 2005-10, Vol.15 (5), p.435-442
Main Authors: Olsson, M. L., Michalewska, B., Hellberg, Å., Walaszczyk, A., Chester, M. A.
Format: Article
Language:English
Subjects:
ABO blood group
ABO Blood-Group System - genetics
allele
Alleles
allelic enhancement
Ax subgroup
Crossing Over, Genetic
Family
Female
Gene Expression
Genotype
Humans
inheritance
Male
Polymorphism, Restriction Fragment Length
Quantitative Trait Loci
serology
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Summary:Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analysed by PCR‐ASP/restriction fragment length polymorphism genotyping and DNA sequencing. The propositus' RBCs were very weakly agglutinated with monoclonal anti‐A but distinctly with polyclonal anti‐A,B, i.e. typical for Ax. Serum anti‐A1 (titre 4) and ‐B were present. Her parents' blood groups were both clearly O, with titres of serum anti‐A1, and ‐A at 16 and 4, respectively. Adsorption/ elution studies demonstrated A antigen on the daughter's cells only. The ABO genotypes were: mother, AxO1; father, O1vO2; and propositus, AxO2. The Ax allele was an A1‐O1v hybrid allele with a crossing‐over breakpoint between positions 235 and 446 in intron 6 (Ax‐4). Compared to the A1 glycosyltransferase, this allele predicts a protein with two amino acid substitutions (Phe216Ile and Met277Val) known to yield either weakly expressed or no A antigen on RBCs. This study suggests that the nature of the ABO allele in trans can influence A antigen expression, a phenomenon previously described as allelic enhancement (or reinforcement). Potential mechanisms for this are discussed.
ISSN:0958-7578
1365-3148
DOI:10.1111/j.1365-3148.2005.00603.x