Gene conversion events between GYPB and GYPE abolish expression of the S and s blood group antigens.
BACKGROUND AND 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.


MATERIALS AND 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.


CONCLUSION
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.
['Willemetz|A|A|', 'Nataf|J|J|', 'Thonier|V|V|', 'Peyrard|T|T|', 'Arnaud|L|L|']
D005785:Gene Conversion D006021:Glycophorins D006801:Humans D008951:MNSs Blood-Group System D011110:Polymorphism, Genetic
gene conversion MNS blood group system glycophorin genotyping