MOLECULAR-BASIS OF GLYCOPHORIN-C VARIANTS AND THEIR ASSOCIATED BLOOD-GROUP ANTIGENS

The normal and variant forms of GPC and GPD molecules carry antigens o f the Gerbich blood group system. This blood group system comprises th ree high-incidence antigens (Ge2, Ge3 and Ge4) and four low-incidence antigens (Wb, Ls(a), Dh(a) and An(a)). Erythrocytes of the Ge and Yus phenotypes lack normal GPC and GPD molecules but express variant molec ules (denoted GPC.Ge, GPC.Yus, respectively) that functionally substit ute for normal GPC and GPD in the membrane. Leach phenotype cells lack GPC and GPD molecules and are elliptocytic in shape with a membrane t hat is less deformable than that of normal cells. The LSa antigen is e xpressed on higher molecular-weight variants of GPC (GPC.Ls(a)) and GP D (GPD.LS(a)). Wb, Dh(a) and An(a) antigens arise from point mutations in the GYPC gene and are expressed on GPC.Wb, GPC.Dh(a) and GPD.An(a) , respectively. The structure of each of the variant GPC and GPD molec ules and the location of the Gerbich blood group system antigens is di scussed. The GYPC gene, located on chromosome 2q14 q21, is 13.5 kb lon g and comprises four exons. Exons 1, 2 and most of exon 3 encode the N -terminal extracellular domain while the remainder of exon 3 and exon 4 encode transmembrane and cytoplasmic domains of GPC. Exons 2 and 3 a re highly homologous, with less than 5% nucleotide divergence. The mol ecular basis of generation of variation GPC and GPD molecules, and the structure of the GYPC gene from different Leach phenotype individuals , is discussed.