The molecular genetics of blood group polymorphism

Abstract

Over 300 blood group specificities on red cells have been identified, many of which are polymorphic. The molecular mechanisms responsible for these polymorphisms are diverse, though many simply represent single nucleotide polymorphisms (SNPs). Other mechanisms include the following: gene deletion; single nucleotide deletion and sequence duplication, which introduce reading-frame shifts; nonsense mutation; intergenic recombination between closely linked genes, giving rise to hybrid genes and hybrid proteins; and a SNP in the promoter region of a blood group gene. Examples of these various genetic mechanisms are taken from the ABO, Rh, Kell, and Duffy blood group systems. Null phenotypes, in which no antigens of a blood group system are expressed, are not generally polymorphic, but provide good examples of the effect of inactivating mutations on blood group expression. As natural human 'knock-outs', null phenotypes provide useful clues to the functions of blood group antigens. Knowledge of the molecular backgrounds of blood group polymorphisms provides a means to predict blood group phenotypes from genomic DNA. This has two main applications in transfusion medicine: determination of foetal blood groups to assess whether the foetus is at risk from haemolytic disease and ascertainment of blood group phenotypes in multiply transfused, transfusion-dependent patients, where serological tests are precluded by the presence of donor red cells. Other applications are being developed for the future.

Noninvasive fetal RhCE genotyping from maternal blood

“…The RHCE gene encodes the C/c and E/e antigens and many others such as C w (RH8), C x (RH9) and VS (RH20). 25 A significant number of exon 5 mutations are known that generate E and e variants in individuals of African descent too. Variants of RHCE gene coincide with antigen variations and effect accurate genotyping and phenotyping.…”

“…For example, C has a frequency of 70% and c a frequency of 80% in Europeans, whereas in Africans the frequency of c is much higher (99%) and the frequency of C much lower (17%). 25 However, some of the articles were reported before the publication of the STARD checklist and all of them reported on an innovative test that needs special evaluation as reflected in a suggested specific proforma (checklist) to evaluate the articles describing noninvasive fetal Rh genotyping (K. Freeman et al, submitted). In addition, a larger study is needed for this test to become qualified as a diagnostic standard test.…”

Blood group does not appear to affect longevity a pilot study in centenarians from Western Sicily

“…The most significant mutations are located on exons 6 and 7 that contain 77% of the full coding regions. There are 5 main alleles described in literature: A1, A2, B1, O1 and O2; there are many variations and subgroups (Daniels, 2009). …”

High ratio of Duffy (a+b+) phenotype in patients with multiple myeloma compared to healthy controls

“…The Duffy blood group antigens have receptor functions for cytokines and parasites, such as Plasmodium vivax [1]. Duffy antigens act as receptors for chemokines [2].…”

“…DARC shows high similarity in protein sequence for both human and rabbit IL-8 receptors [1]. After the binding of IL-8 to DARC, it loses its ability to function as a chemokine [3].…”