Gene conversion events between GYPB and GYPE abolish expression of the S and s blood group antigens.
OBJECTIVE
The locus specifying the MNS blood group system is composed of three highly homologous genes, glycophorin A (GYPA), B (GYPB) and E (GYPE). While more than 20 hybrid genes between GYPA and GYPB have been identified, no hybrid genes between GYPB and GYPE have been reported so far. We serendipitously identified GYPB-E-B hybrid genes by studying three individuals whose rare S-s- blood phenotype failed to be predicted by our genotyping platform.


METHODS
Long-range PCR amplification and extended Sanger sequencing were required to identify and characterize these GYPB-E-B hybrid genes. A PCR assay was developed to detect them in individual or pooled gDNA samples.


RESULTS
The first S-s- proband appeared to have two silenced GYPB alleles, one harbouring the so-called P2 mutation and one harbouring GYPE Pseudoexon E4 in place of GYPB Exon B4 (GYPB-E-B hybrid). The two other S-s- probands were homozygous or hemizygous for other GYPB-E-B hybrid alleles, which also lack GYPB Exon B4 and thus do not carry the S/s polymorphism.


CONCLUSIONS
The three GYPB-E-B hybrid genes reported here constitute the first evidence of recombination events between GYPB and GYPE. As these GYPB-E-B hybrid genes drive the S-s- blood phenotype, it is important to know they are a limitation for the current blood group genotyping methods, including those performed by commercial platforms.
Département Centre National de Référence pour les Groupes Sanguins (CNRGS), Institut National de la Transfusion Sanguine (INTS), Paris, France.
A
A
Willemetz
J
J
Nataf
V
V
Thonier
T
T
Peyrard
L
L
Arnaud
D005785:Gene Conversion; D006021:Glycophorins / Q000235:genetics*; D006801:Humans; D008951:MNSs Blood-Group System / Q000097:blood*; D011110:Polymorphism, Genetic
C409973:GYPB protein, human; D006021:Glycophorins; D008951:MNSs Blood-Group System
MNS blood group system; gene conversion; genotyping; glycophorin