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MN typing discrepancies based on GYPA ‐ B ‐ A hybrid
Author(s) -
Polin H.,
Danzer M.,
Reiter A.,
Brisner M.,
Gaszner W.,
Weinberger J.,
Gabriel C.
Publication year - 2014
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12168
Subject(s) - genetics , biology , microbiology and biotechnology , haplotype , exon , gene , genotype
Background and Objectives Gene conversion events between GYPA and GYPB or GYPA and GYPE 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. Materials and Methods Sequence analysis of GYPA exons 1–7 and GYPB exons 1–5 was performed for g DNA and c DNA . The linkage of the nucleotide alterations was defined by haplotype separation. Results DNA analysis demonstrated a normal GYPA haplotype ( GYPA * N n = 20, GYPA * M n = 2) with an altered GP hybrid nucleotide sequence in trans. A GYPB homologue sequence of minimal 10‐bp encompassing intron 1 and exon 2 was translated into GYPA , 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 GYPA ( S er20, G ly24 ) ( n = 20) associated with the expression of M and GYPA ( L eu20, G lu24 ) ( n = 2) encoding the N phenotype. The serologic data indicate that the changes do not affect the expression of a normal M and N antigen. c DNA sequences confirmed the g DNA results and furthermore identified a heterozygous deletion of GYPB exon 2 in all probands. Conclusion The results document a GYPA ‐ B ‐ A hybrid gene, probably produced via a single unequal homologous recombination event. A segmental transfer of GYPB seems most likely accounting for the allelic dropout.