title: MN typing discrepancies based on GYPA-B-A hybrid.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Sequence analysis of GYPA exons 1-7 and GYPB exons 1-5 was performed for gDNA and cDNA. 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(Ser20, Gly24) (n = 20) associated with the expression of M and GYPA(Leu20, Glu24) (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. cDNA sequences confirmed the gDNA results and furthermore identified a heterozygous deletion of GYPB exon 2 in all probands.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Red Cross Transfusion Service of Upper Austria, Linz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Polin
authors.forename: M
authors.initials: M
authors.lastname: Danzer
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.forename: M
authors.initials: M
authors.lastname: Brisner
authors.forename: W
authors.initials: W
authors.lastname: Gaszner
authors.forename: J
authors.initials: J
authors.lastname: Weinberger
authors.forename: C
authors.initials: C
authors.lastname: Gabriel
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001782:Blood Donors; D001789:Blood Group Antigens / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006021:Glycophorins / Q000235:genetics*; D006239:Haplotypes; D006384:Hemagglutination / Q000235:genetics; D006801:Humans; D008951:MNSs Blood-Group System / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment
chemical_list: D001789:Blood Group Antigens; D018076:DNA, Complementary; D006021:Glycophorins; D008951:MNSs Blood-Group System
keywords: GYPA; GYPB; MNS blood group; glycophorin