Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group and collection

Abstract

The aim of this study was to further explore the molecular genetic bases of the clinically important but rare blood group phenotypes p, P1k and P2k by analysis of the 4-α-galactosyltransferase (Pk) and 3-β-N- acetylgalactosaminyltransferase (P) genes responsible for synthesis of the related Pk (Gb3) and P (Gb4) antigens respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against certain infectious agents. Blood samples from 20 p and 11 P1k or P2k individuals of different geographic and ethnic origin were investigated. DNA sequencing by capillary electrophoresis was performed following amplification of the coding regions in the Pk or P genes. In the Pk gene, nine novel and five previously described mutations were detected. One of the newly found mutations introduced an immediate stop, five shifted the reading frame introducing premature stop codons and three were missense mutations causing amino acid substitutions in conserved regions of the transferase. Four new and two previously described mutations in the P gene were found. Three of the novel alleles reported here carried nonsense mutations whilst the fourth allele had a missense mutation. The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection. © 2004 Blackwell Publishing Ltd.