title: The MNS blood group antigens, Vr (MNS12) and Mt(a) (MNS14), each arise from an amino acid substitution on glycophorin A.
abstract: OBJECTIVE
  The antigens, Vr (MNS12) and Mt(a) (MNS14), are low-incidence antigens of the MNS blood group system. The Vr antigen has been found only on the red blood cells (RBCs) of persons of Dutch ancestry whereas the Mt(a) antigen has been found on the RBCs of persons from a wide geographic distribution. The objective of this study was to determine the molecular basis of Vr and Mt(a).
  
  
  METHODS
  Following RT-PCR amplification of total RNA isolated from one Vr+ person (G488) and one Mt(a+) person (GH), the genes encoding glycophorin A (GYPA) and glycophorin B (GYPB) were cloned and sequenced. To confirm the point mutation observed in the cDNA from G488 (Vr+), GYPA exon 3 was cloned and sequenced from the genomic DNA of G488 and a second unrelated Vr+ person (MU). A restriction fragment length polymorphism (RFLP) assay was used to analyze genomic DNA from 11 Mt(a+) persons (10 unrelated) following PCR amplification of GYPA exon 3.
  
  
  RESULTS
  The coding sequence of GYPB was normal in both G488 (Vr+) and GH (Mt(a+)). Sequencing data from GYPA clones derived from G488 showed to full length GYPA sequences: A normal GYPA M allele and a GYPA M allele with a point mutation 197C-->A. Sequencing of GYPA exon 3 from G488 and MU confirmed the point mutation. Sequencing data drom GYPA clones derived from GH showed two full length GYPA sequences: a normal GYPA M allele and a GYPA N allele with a point mutation 230C-->T. RFLP analysis based on the point mutation showed that DNA from 11 Mt(a+) samples were heterozygous for the point mutation.
  
  
  CONCLUSIONS
  The Vr antigen arises from a point mutation 197C-->A on GYPA which is predicted to change serine at position 47 to tyrosine. This change introduces a new alpha-chymotrypsin cleavage site. The Mt(a) antigen arises from a point mutation 230C-->T which is predicted to change threonine at position 58 to isoleucine.
authors.affiliation: New York Blood Center, New York, NY 10021, USA. jstorry@nybc.og
authors.forename: J R
authors.initials: JR
authors.lastname: Storry
authors.forename: G
authors.initials: G
authors.lastname: Coghlan
authors.forename: J
authors.initials: J
authors.lastname: Poole
authors.forename: D
authors.initials: D
authors.lastname: Figueroa
authors.forename: M E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal; D002918:Chymotrypsin / Q000378:metabolism / Q000494:pharmacology; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis; D004229:Dithiothreitol / Q000494:pharmacology; D005091:Exons; D006021:Glycophorins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008951:MNSs Blood-Group System / Q000235:genetics* / Q000276:immunology; D009439:Neuraminidase / Q000378:metabolism / Q000494:pharmacology; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011402:Pronase / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D006021:Glycophorins; D008951:MNSs Blood-Group System; D009439:Neuraminidase; D002918:Chymotrypsin; D011402:Pronase; D004229:Dithiothreitol