The INDIVIDUALIST

A Wiki about biochemical individuality

Polymorphism

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Description

The most important of blood-typing systems, the ABO blood group is the determinant for transfusion reactions and organ transplantation. Unlike the other blood-typing systems, the ABO blood types have far-ranging significance other than transfusion or transplantation, including the determination of many of the digestive and immunologic characteristics of the body.

Despite the recognized importance of the ABO antigens in blood typing, few physicians appreciate the extraordinary complexity of this system, its association with human disease, fascinating phylogenetic heritage and usefulness in describing physiologic parameters, especially digestive and secretory. These antigens are found in secretions throughout the body and on the surface of endothelial and epithelial cells.

The first description of a human blood group system was published by Karl Landsteiner in 1900, working to understand the unpredictability of hemolytic reactions resulting from early attempts at transfusion. Using the newly discovered lectins abrin and ricin, recently isolated by Stillmark, he was able to describe classically what has still remained the major blood group of clinical interest.

The ABO blood group is comprised of four blood types: O, A, B and AB. Type O has no true antigen, but carries antibodies to both A and B blood. Type A and type B carry the antigen named for their blood type and make antibodies to each other. Type AB does not manufacture any antibodies to other blood types because it has both A and B antigens.

Discussion

Anthropologists use the ABO blood types extensively as a guide to the development of early peoples. Many diseases, especially digestive disorders, cancer, and infection, express preferences, choosing between the ABO blood types. These expressions are not generally understood or appreciated by either physicians or the general population.

Disease association

See:

The Genes

ABO genes consist of at least 7 exons, and the coding sequence in the seven coding exons spans over 18kb of genomic DNA. The single nucleotide deletion, found in a large number (but not all) of O alleles and responsible for the loss of the activity of the enzyme, is located in exon 6. The first of the seven nucleotide substitutions which distinguish the A and B transferases, resides in coding exon 6; exon 7, the largest of all, contains the other six nucleotide substitutions which result in four amino acid substitutions that differentiate the A and B transferases. Among those, substitutions responsible for alterations at two sites (residues 266 and 268) determine the A or B specificity of the enzyme (Yamamoto and Hakamori). In addition to four common alleles (A1, A2, B and O), numerous alleles which encode glycosyltransferases with changes in activity and/or specificity have been identified. Function of proteins

The primary gene products of functional alleles are glycosyltransferases. The A alleles encode UDP-GalNAc: Fuc alpha1->2 Gal alpha1->3 N-acetyl-D-galactosaminyltransferase (alpha 1->3 GalNAc transferase or histo-blood group A transferase). The B alleles encode UDP-Gal: Fuc alpha1->2 Gal alpha 1->3 galactosyltransferase (alpha 1->3 galactosyltransferase or histo-blood group B transferase). O alleles encode proteins without glycosyltransferase function.

Tissue distribution

Gene expression is not restricted to erythroid tissues but occurs universally in most epithelial and endothelial cells. Expression of the antigens may undergo changes during development, differentiation and maturation. Aberrant expression is often observed in human pre-malignant and malignant cells.

The Alleles

As will become apparent in the list of alleles, subgroups of each category of ABO alleles (A, B or O) have been documented, first serologically, as they exhibited unique phenotypes under defined conditions; also by characteristic transferase activities, and more recently, at the nucleotide sequence level. The latter studies are revealing that DNA variation (single or multiple mutations, rearrangements) occur in each category, often in a recurrent fashion, i.e. in a number of alleles, identical mutations occur at one or more identical sites. The incidence of the occurrence of the various alleles in world populations is not known (except for selected populations, such as the Japanese, see Ogasawara K. et al.) and there seems to be a difference in frequency among different ethnic groups. In the Table below, percent allelic frequency for each allele represents the sum of all the alleles in that category.

When referring to the list of alleles, allele A101 is taken as reference. For intronic sequences described in Seltsam et al. or Roubinet et al. nucleotide positions are numbered starting from the first nucleotide of each intron. Results, for the same allele, originating from different laboratories (as different regions of the allele may have been sequenced) are referred to when they are not identical; exonic mutations are similarly referred to for the origin of their documentation.

AlleleProteincaucasians blacks orientals
A1A1 transferase 221218
A2A2 transferase 76rare
B B transferase 61217
O non-functional 657065

Among South American Indians, whereas the incidence of A1, A2 or B allele is rare, that of the O allele is 90-100%. The distribution of ABO genotypes including allele frequencies in a sample of Chinese or white European population was recently documented. (1)

Attribution

Sections excerpted from the Blood Group Antigen Gene Mutation Database. See: Blumenfeld OO, Patnaik SK. Allelic genes of blood group antigens: a source of human mutations and cSNPs documented in the Blood Group Antigen Gene Mutation Database. Human Mutation. 2004 Jan; 23(1):8-16. PubMed ID: 14695527

Other database IDs and links

NCBI genes

Uniprot ID Genbank proteins Gene nomenclature database ID

Genbank nucleic acids

NCBI homologenes for homologs and orthologs NCBI dbSNP for single nucleotide polymorphisms HGMD ID - at the Human Gene Mutation Database

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References


1. SP Yip, Blood, 95:1487, 2000.

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