Gene conversion events between GYPB and GYPE abolish expression of the S and s blood group antigens. Issue 4 (4th March 2015)

• Record Type: Journal Article
• Authors: Willemetz, A.; Nataf, J.; Thonier, V.; Peyrard, T.; Arnaud, L.
• Is Part Of: Vox sanguinis. Volume 108:Issue 4(2015)
• Page Start: 410
• Page End: 416
• Publication Date: 2015-03-04
• Subjects: Blood -- Periodicals; Blood -- Transfusion -- Periodicals; Immunohematology -- Periodicals; Immunopathology -- Periodicals; 615.39
• DOI: 10.1111/vox.12244
• Languages: English
• ISSNs: 0042-9007

Abstract

<abstract abstract-type="main" id="vox12244-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="vox12244-sec-0001" sec-type="section"> <title>Background and Objective</title> <p>The locus specifying the MNS blood group system is composed of three highly homologous genes, <italic>glycophorin A</italic> (<italic>GYPA</italic>), <italic>B</italic> (<italic>GYPB</italic>) and <italic>E</italic> (<italic>GYPE</italic>). While more than 20 hybrid genes between <italic>GYPA</italic> and <italic>GYPB</italic> have been identified, no hybrid genes between <italic>GYPB</italic> and <italic>GYPE</italic> have been reported so far. We serendipitously identified <italic>GYPB‐E‐B</italic> hybrid genes by studying three individuals whose rare S−s− blood phenotype failed to be predicted by our genotyping platform.</p> </sec> <sec id="vox12244-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Long‐range PCR amplification and extended Sanger sequencing were required to identify and characterize these <italic>GYPB‐E‐B</italic> hybrid genes. A PCR assay was developed to detect them in individual or pooled gDNA samples.</p> </sec> <sec id="vox12244-sec-0003" sec-type="section"> <title>Results</title> <p>The first S−s− proband appeared to have two silenced <italic>GYPB</italic> alleles, one harbouring the so‐called P2 mutation and one harbouring <italic>GYPE</italic> Pseudoexon E4 in place of <italic>GYPB</italic> Exon B4 (<italic>GYPB‐E‐B</italic> hybrid). The two other S−s− probands were homozygous or hemizygous for other <italic>GYPB‐E‐B</italic> hybrid alleles, which also lack <italic>GYPB</italic> Exon B4 and thus do not carry the S/s polymorphism.</p> </sec> <sec id="vox12244-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The three <italic>GYPB‐E‐B</italic> hybrid genes reported here constitute the first evidence of recombination events between <italic>GYPB</italic> and <italic>GYPE</italic>. As these <italic>GYPB‐E‐B</italic> 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.</p> </sec> </abstract>