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The MNS Blood Group Antigens, Vr (MNS12) and Mt a (MNS14), Each Arise from an Amino Acid Substitution on Glycophorin A
Author(s) -
Storry Jill R.,
Coghlan Gail,
Poole Joyce,
Figueroa Dolores,
Reid Marion E.
Publication year - 2000
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 - 10.1046/j.1423-0410.2000.7810052.x
Subject(s) - genetics , glycophorin , biology , exon , microbiology and biotechnology , point mutation , restriction fragment length polymorphism , mutation , antigen , gene , polymerase chain reaction
Background and Objectives: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 . Materials and 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 ot 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. Conclusion: 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 α‐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.