Blood Groups: Molecular Genetic Basis


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 membraneā€bound enzymes.

Keywords: blood group polymorphisms; single nucleotide polymorphisms; genotyping; red cell membrane; blood groups; molecular basis; erythrocyte membrane

Figure 1.

Biosynthesis of the carbohydrate‐dependent antigens of the erythrocyte. The left‐hand panel indicates the glycosyltransferases involved in the biosynthesis of the ABH blood group active carbohydrates, indicated by arrows. The genetic basis of these differences is indicated in the text, but A→B transferases (α1,3‐N‐acetylgalactosaminyl and α1,3‐galactosaminyl transferases respectively) differ by four amino acids and group O individuals are devoid of any A/B transferase. The A/B transferase transfers UDP‐GalNAc/UDP‐Gal to H substance, generated by action of the H‐transferase (FUT1; an α1,2‐fucosyltransferase) that can act on a wide variety of precursor carbohydrate chains attached to type 2, 3 and 4 chain glycosphingolipids (Lacto‐series), to O‐ and N‐glycosylated proteins. The right‐hand panel depicts the biosynthesis of Lewis antigens from type 1 precursor. The Lea antigen is synthesized by the action of the Le glycosyltransferase (FUT3), an α1,3/4‐fucosyltransferase that adds fucose to the subterminal GlcNAc. Sequential additions by Se (FUT2) or A transferase can yield Leb, Led or ALeb substances as depicted above. Fuc: fucose; GlcNAc: N‐acetylglucosamine; Gal: galactose, GalNAc: N‐acetylgalactosamine.

Figure 2.

Protein antigens of the red cell membrane. This figure depicts representations of the 19 human blood groups that arise from proteins of the red cell. Two further blood groups (Scianna and RAPH) are absent from this figure as the precise identities of their protein carriers remain to be defined. The broad functional classes of each blood group system are shown (adhesion molecule, receptor, membrane‐bound enzyme, structural protein or membrane transporter). The identity of each protein species is shown above each cartoon, while the blood group system that it carries lies beneath. N‐ and O‐glycans are represented as branches and circles respectively, while polymorphic amino acids are shown as circles (the major clinically relevant antigens are shown only for clarity).



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Web Links

Genew: Human Gene Nomenclature Database Search Engine. Approved gene names and symbols plus links to further information‐bin/nomenclature/

Human blood group antigen mutation database

ISBT nomenclature (blood group terminology)

LocusLink. A single query interface to curated sequence and descriptive information about genetic loci. Information on official nomenclature, aliases, sequence accessions, phenotypes, map locations etc. and related websites

NCBI mapview. Enter gene symbol in search engine and obtain information about chromosomal location

NCBI nucleotide database. Enter the accession number given in Table 1 (for example NM_020469) and search

ABO blood group (transferase A, alpha 1‐3‐N‐acetylgalactosaminyltransferase; transferase B, alpha 1‐3‐galactosyltransferase) (ABO); Locus ID: 28. LocusLink:

Fucosyltransferase 3 (galactoside 3(4)‐L‐fucosyltransferase, Lewis blood group included) (FUT3); Locus ID: 2525. LocusLink:

Rhesus blood group, D antigen (RHD); Locus ID: 6007. LocusLink:

Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group) (SLC4A1); Locus ID: 6521. LocusLink

Xg blood group (pseudoautosomal boundary‐divided on the X chromosome) (XG); Locus ID: 7499. LocusLink:

ABO blood group (transferase A, alpha 1‐3‐N‐acetylgalactosaminyltransferase; transferase B, alpha 1‐3‐galactosyltransferase) (ABO); MIM number: 110300. OMIM:‐post/Omim/dispmim?110300

Fucosyltransferase 3 (galactoside 3(4)‐L‐fucosyltransferase, Lewis blood group included) (FUT3); MIM number: 111100. OMIM:‐post/Omim/dispmim?111100

Rhesus blood group, D antigen (RHD); MIM number: 111680. OMIM:‐post/Omim/dispmim?111680

Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group) (SLC4A1); MIM number: 109270. OMIM:‐post/Omim/dispmim?109270

Xg blood group (pseudoautosomal boundary‐divided on the X chromosome) (XG); MIM number: 314700. OMIM:‐post/Omim/dispmim?314700

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Avent, Neil D(Jan 2006) Blood Groups: Molecular Genetic Basis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0006034]