Blood Groups: Molecular Genetic Basis

Abstract

Abstract Human blood groups are of clinical significance in transfusion medicine and blood group incompatible pregnancy. Blood groups are due to polymorphic structures on human red cells, may arise from carbohydrates or proteins and include most species of proteins found in red cell membranes including transporters, adhesion molecules, structural proteins, complement control proteins, receptors and membrane‐bound enzymes. The molecular background of most clinically significant blood group antigens has been defined at the level of the gene, and there are (as of 2017) 36 blood group systems, with the clinically relevant VEL system being described in 2015 being the most important recent addition. Mass‐scale sequencing projects have revealed yet further complexities in the blood group genes, indicating the possibility for alloimmunisation by these variants. Despite significant advances in SNP genotyping and next‐generation sequencing, routine sequencing of blood donors and patients has not yet materialised. Key Concepts Blood group antigen expression can be divided into two broad categories: carbohydrate and protein. Protein‐based blood group antigens can be further divided by their functional consequences as membrane transporters, adhesion molecules, receptors/structural components, complement control proteins and membrane‐bound enzymes. The accrual of thousands of complete genome sequences has indicated the occurrence of large numbers of blood group alleles in all blood groups. These may or may not include antigenic polymorphisms that have yet to be identified clinically. Blood group antigen classification and identification of null phenotypes in particular have acted as naturally occurring human knockouts and have revealed the functional significance of the carrier molecules. Blood group genotyping (BGG) has emerged as a useful supplementary analysis for fetuses and patients that are multi‐transfused, e.g. sickle cell patients