Novel hybrid genes and a splice site mutation encoding the St^a antigen among Japanese blood donors

Abstract

Background The low-incidence antigen St a of the MNS system is usually associated with the GP(B-A) hybrid molecule, which carries the 'N' antigen at the N terminus. The GP(A-A) molecule with trypsin-resistant M antigen has been found in a few St(a+) individuals. Materials and Methods Among Japanese blood donors, we screened 24 292 individuals for the presence of St(a+) with trypsin-resistant 'N' antigen and 193 009 individuals for the presence of St(a+) with trypsin-resistant M antigen. The breakpoints responsible for the St a antigen were analysed by sequencing the genomic DNAs. Results A total of 1001 (4Á1%) individuals were identified as St(a+) with trypsinresistant 'N' antigen. Out of 1001 individuals, 115 were selected randomly for sequencing. Two novel GYP*Sch (GYP*401) variants with new intron 3 breakpoints of GYPA were detected in three cases. Twenty-five (0Á013%) individuals were identified as St(a+) with trypsin-resistant M antigen. Five individuals had the GYP(A-wB-A) hybrid allele; two of these five individuals were GYP*Zan (GYP*101.01), and the remaining three had a novel GYP(A-wB-A) allele with the first breakpoint in GYPA exon A3 between c.178 and c.203. Nine individuals had a novel GYP(A-E-A) allele with GYPE exon E2 and pseudoexon E3 instead of GYPA exon A2 and A3. The 11 remaining individuals had a novel GYP(A-A) allele with a 9-bp deletion that included the donor splice site of intron 3 of GYPA. Conclusion Our finding on diversity of glycophorin genes responsible for St a antigen provides evidence for further complexity in the MNS system.