MN typing discrepancies based on GYPA‐B‐A hybrid. Issue 4 (11th June 2014)

• Record Type: Journal Article
• Authors: Polin, H.; Danzer, M.; Reiter, A.; Brisner, M.; Gaszner, W.; Weinberger, J.; Gabriel, C.
• Is Part Of: Vox sanguinis. Volume 107:Issue 4(2014)
• Page Start: 393
• Page End: 398
• Publication Date: 2014-06-11
• Subjects: Blood -- Periodicals; Blood -- Transfusion -- Periodicals; Immunohematology -- Periodicals; Immunopathology -- Periodicals; 615.39
• DOI: 10.1111/vox.12168
• Languages: English
• ISSNs: 0042-9007

Abstract

<abstract abstract-type="main" id="vox12168-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="vox12168-sec-0001" sec-type="section"> <title>Background and Objectives</title> <p>Gene conversion events between <italic>GYPA</italic> and <italic>GYPB</italic> or <italic>GYPA</italic> and <italic>GYPE</italic> are facilitated by the close chromosomal proximity and high degree of sequence homology and can lead to the formation of GP hybrid genes. Discrepant results between blood group genotyping and haemagglutination in 22 random blood donors induced molecular characterization.</p> </sec> <sec id="vox12168-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Sequence analysis of <italic>GYPA</italic> exons 1–7 and <italic>GYPB</italic> exons 1–5 was performed for gDNA and cDNA. The linkage of the nucleotide alterations was defined by haplotype separation.</p> </sec> <sec id="vox12168-sec-0003" sec-type="section"> <title>Results</title> <p>DNA analysis demonstrated a normal <italic>GYPA</italic> haplotype (<italic>GYPA*N n</italic> = 20, <italic>GYPA*M n</italic> = 2) with an altered GP hybrid nucleotide sequence in trans. A <italic>GYPB</italic> homologue sequence of minimal 10‐bp encompassing intron 1 and exon 2 was translated into <italic>GYPA</italic>, accounting for an amino acid substitution from arginine to glutamic acid at position 13 (38 C>A). Genomic DNA analysis demonstrated the cis‐linkage of the hybrid nucleotide sequence with each <italic>GYPA</italic>(<italic>Ser20, Gly24</italic>) (<italic>n</italic> = 20) associated with the expression of M and <italic>GYPA</italic>(<italic>Leu20, Glu24</italic>) (<italic>n</italic> = 2) encoding the N phenotype. The serologic data indicate that the changes do not affect the expression of a normal M and N antigen. cDNA sequences confirmed the gDNA results and furthermore identified a heterozygous deletion of <italic>GYPB</italic> exon 2 in all probands.</p> </sec> <sec id="vox12168-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The results document a <italic>GYPA‐B‐A</italic> hybrid gene, probably produced via a single unequal homologous recombination event. A segmental transfer of <italic>GYPB</italic> seems most likely accounting for the allelic dropout.</p> </sec> </abstract>