Blood Groups: Molecular Genetic Basis

Neil D Avent, University of the West of England, Bristol, UK

Published online: January 2006

DOI: 10.1038/npg.els.0006034

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.

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 AB transferases (1,3-N-acetylgalactosaminyl and 1,3-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 1,2-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 1,3/4-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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 References
    Avent ND and Reid ME (2000) The Rh blood group system: a review. Blood 95: 375–387.
    Blumenfeld OO and Huang CH (1997) Molecular genetics of glycophorin MNS variants. Transfusion Clinique et Biologique 4: 357–365.
    Cartron JP and Colin Y (2001) Structural and functional diversity of blood group antigens. Transfusion Clinique et Biologique 8: 163–199.
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 Further Reading
    Daniels G (1999) Functional aspects of red cell antigens. Blood Reviews 13(1): 14–35.
    book Reid ME and Lomas-Francis C (eds.) (1997) The Blood Group Antigen Factsbook 1997 New York: Academic Press.
    Reid ME and Yahalom V (2000) Blood groups and their function. Baillières Best Practice and Research, Clinical Haematology 13(4): 485–509.
    book Schenkel-Brunner H (2000) Human Blood Groups: Chemical and Biochemical Basis of Antigen Specificity. Vienna: Springer-Verlag.
 Web Links
    ePath Genew: Human Gene Nomenclature Database Search Engine. Approved gene names and symbols plus links to further information http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl
    ePath Human blood group antigen mutation database http://www.bioc.aecom.yu.edu/bgmut/
    ePath ISBT nomenclature (blood group terminology) http://www.iccbba.com/page27.htm
    ePath 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 http://www.ncbi.nlm.nih.gov/LocusLink/
    ePath NCBI mapview. Enter gene symbol in search engine and obtain information about chromosomal location http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi
    ePath NCBI nucleotide database. Enter the accession number given in Table 1 (for example NM_020469) and search http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
    ePath ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase) (ABO); Locus ID: 28. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=28
    ePath Fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group included) (FUT3); Locus ID: 2525. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2525
    ePath Rhesus blood group, D antigen (RHD); Locus ID: 6007. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6007
    ePath Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group) (SLC4A1); Locus ID: 6521. LocusLink http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6521
    ePath Xg blood group (pseudoautosomal boundary-divided on the X chromosome) (XG); Locus ID: 7499. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7499
    ePath ABO blood group (transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3-galactosyltransferase) (ABO); MIM number: 110300. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?110300
    ePath Fucosyltransferase 3 (galactoside 3(4)-L-fucosyltransferase, Lewis blood group included) (FUT3); MIM number: 111100. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?111100
    ePath Rhesus blood group, D antigen (RHD); MIM number: 111680. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?111680
    ePath Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group) (SLC4A1); MIM number: 109270. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?109270
    ePath Xg blood group (pseudoautosomal boundary-divided on the X chromosome) (XG); MIM number: 314700. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?314700

Related Sub-Topics:

Innate Immunity | Antigens | Membrane Proteins | Structure of Cell–Cell Interactions | Lipids and Membrane Structure | Mutational Mechanisms of Genetic Disease | Inter-Individual Variation and Polymorphism
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Article Title: Blood Groups: Molecular Genetic Basis
 
How to Cite close
Avent, Neil D(Jan 2006) Blood Groups: Molecular Genetic Basis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006034]