Molecular Basis and Investigation of Blood Group Genes

There are 284 blood group antigens recognized by the ISBT Committee on Terminology for Red Cell Surface Antigens. Of these, 244 antigens are included in one of 29 blood groups systems. The rest are included in collections of similar antigens, or in a series of either low incidence or high incidence antigens. The biochemical work of the middle of the last century revealed these antigens to be carried on different glycoproteins and glycolipids on the surface of the red blood cell (RBC). Their usefulness as protein markers recognized by highly specific immune antibodies permitted functional studies of many of these membrane components. In the last twenty years, the genes encoding all but one of the 29 blood group systems have been sequenced, and the molecular basis identified. These studies have shown that the majority of blood group antigens are encoded by simple single nucleotide polymorphisms within the coding sequence of the gene. Where gene families exist such as at the Rh and MNS loci, high nucleotide identity between related genes has resulted in the formation of hybrid genes that encode novel antigens and create unusual phenotypes. Mutations and other alterations in the non-coding regions of genes are also responsible for creating blood group antigen diversity. The molecular identity of blood groups has many different applications. From a clinical perspective, molecular assays can be used to determine likely RBC phenotype in situations where it is difficult or undesirable to obtain RBCs. It also provides a model for the study of diversity within humans and enabled scientists to look at ancestral genes. These studies not only tell more about who we are but also map the influences of different external factors such as disease, on our evolution.