Rhesus Gene Family and Blood Group Antigens—Molecular Aspects in Relation to Genomic Transfusion Medicine

Abstract

The Rhesus (Rh) antigens form a blood group system of major significance in transfusion medicine due to their polymorphic nature at a population level and their potency as protein immunogens, which in response to incompatibility induce harmful hemolytic reactions. For seven decades, the Rh family has undergone extensive investigation and has served as a model for studies on membrane biology with a focus on biochemistry and genetics. The past decade has seen a rapid growth of molecular data on Rh allelic diversity and a major effort in probing the function of Rh proteins as gas channels in the membrane. It is now established that the antigen carrier RhD or RhCE and its regulator RhAG, the erythroid branches of the Rh family, dictate antigen expression, which together with RhBG and RhCG, the epithelial branches of the Rh family, penetrate all vertebrate animals and arise from a common ancestor of unicellular origin. Hematology and immunohematology, similar to other clinical disciplines, are on the horizon of genomic medicine, being transformed by the new knowledge of chromosome biology and gene expression. This article addresses the molecular aspects of the Rh protein family with an emphasis on its blood group system, relating translation research to genomic transfusion medicine.