Alternative titles; symbols
SNOMEDCT: 63915006;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q34.2 | [Blood group, ABO system] | 616093 | 3 | ABO | 110300 |
A number sign (#) is used with this entry because the ABO blood group system is based on variation in the ABO gene (110300) on chromosome 9q34.
The ABO system, discovered in 1900 by Landsteiner (1900), is one of the most important blood group systems in transfusion medicine. The ABO system consists of A and B antigens and antibodies against these antigens. There are 4 major groups in the ABO system (A, B, AB, and O) that result from 3 major alleles (A, B, and O) of the ABO gene (110300). Additional ABO subgroups are produced by dozens of ABO subgroup alleles. The A and B antigens are carbohydrate rather than protein antigens and are synthesized by a series of reactions catalyzed by glycosyltransferases. The final step in their biosynthesis is catalyzed by the A and B glycosyltransferases, which are encoded by the A and B alleles of the ABO gene, respectively. Individuals with blood group O do not produce functional A or B glycosyltransferases and therefore lack A and B antigens. Unlike many other blood group systems, the presence of naturally occurring antibodies against A and B antigens in individuals who do not express those antigens causes an adverse and potentially fatal outcome at the first mismatched transfusion. Because the A and B antigens exist in cells other than red blood cells, ABO matching is also important in cell, tissue, and organ transplantation, and ABO blood groups are important in forensic science (review by Yamamoto, 2004).
In his review, Yamamoto (2004) noted that the A and B alleles of ABO are codominant over the recessive O allele.
Yamamoto et al. (1990) detected bands in Northern hybridization of mRNAs from cell lines expressing A, B, AB, or H antigens, suggesting that sequences of ABO genes have only minimal differences and that the inability of the O gene to encode A or B transferases is probably due to a structural difference rather than to failure of expression of the A or B transferases. Yamamoto et al. (1990) showed that cells of the histo-blood group phenotype O express a message similar to that of A and B alleles. Indeed, they found that the O allele is identical in DNA sequence to the A allele, except for a single-base deletion, 258G, in the coding region close to the N terminus of the protein (110300.0001). The deletion shifts the reading frame, resulting in translation of an entirely different protein. It is therefore unlikely that O individuals express a protein immunologically related to the A and B transferases, which agrees with the absence of crossreacting protein in O cells when specific monoclonal antibody directed toward soluble A transferase is used. Yamamoto et al. (1990) also reported the single-base substitutions responsible for the 4 amino acid substitutions that distinguish the A and B glycosyltransferases. Thus, the ABO polymorphism, discovered by Landsteiner (1900), was finally elucidated 90 years later.
Ugozzoli and Wallace (1992) applied allele-specific PCR to the determination of ABO blood type. Johnson and Hopkinson (1992) showed that one could use PCR followed by denaturing gradient gel electrophoresis (DGGE) for rapid identification of the 6 major ABO genotypes. The procedure also distinguished hitherto undescribed polymorphisms associated with the O and B alleles, thereby elevating the information content of the locus as a genetic marker from 3 to 70%. Its usefulness in the study of disease associations and in forensic identification was also emphasized.
See 110300 for information on possible associations of ABO blood groups with infectious disease susceptibility, pancreatic cancer susceptibility, and blood soluble E-selectin (SELE; 131210) levels.
ABO was the first blood group system discovered, by Landsteiner at the beginning of the 20th century (Landsteiner, 1900). The occurrence of natural antibody permitted identification of red cell types by agglutination of red cells when mixed with serum from some, but not all, other persons. At first the alternative genetic hypotheses were mainly (1) multiple alleles at a single locus, and (2) two loci with two alleles each, one locus determining A and non-A and the other B and non-B. Application of the Hardy-Weinberg principle to population data by Felix Bernstein (1878-1956) and analysis of family data excluded the second alternative and established the former. Crow (1993) reviewed this history. He introduced his review with the following words: 'Accustomed as we now are to thousands of polymorphisms useful as human chromosome markers, it is hard to realize that in the first quarter century of Mendelism there was only one good marker. It is all the more remarkable that its simple mode of inheritance was not understood until the trait had been known for 25 years.'
Developments in the 1950s and 1960s included (1) demonstration of associations between particular disorders (peptic ulcer, gastric cancer, thromboembolic disease) and particular ABO phenotypes, and (2) discovery of the biochemical basis of ABO specificity. It is known that the A and B alleles determine a specific glycosyl-transferring enzyme. The specificity of the enzyme formed by the A allele is to add N-acetylgalactosaminosyl units to the ends of the oligosaccharide chains in the final stages of the synthesis of the ABO blood group macromolecule. The enzyme determined by the B allele may differ from that determined by the A allele by only a single amino acid, but its function is to add D-galactosyl units to the end. The O allele appears to be functionless.
In a manner similar to the elucidation of the origin of the ABO blood groups, the colorblindness polymorphism, which can be said to have been described first by John Dalton in 1798, was elucidated in molecular terms in 1986 (see 303800), and the wrinkled/round polymorphism of the garden pea, which was studied by Mendel (1865), was explained at the molecular level by Bhattacharyya et al. (1990). The wrinkled trait is called 'rugosus' (symbolized r); the pea seeds of RR or Rr genotype are round. Wrinkled seeds lack 1 isoform of starch-branching enzyme (SBEI), present in round seeds. Bhattacharyya et al. (1990) demonstrated that the SBEI gene in the rr genotype is interrupted by a 0.8-kb insertion that appears to be a transposable element. Loss of activity of SBEI leads to reduction in starch synthesis, accompanied by failure to convert amylose to amylopectin. In rr seeds, the levels of free sucrose are higher than in RR seeds, and this apparently leads to the observed higher osmotic pressure and, hence, higher water content. The seeds lose a larger proportion of their volume during maturation, which results in the wrinkled phenotype. See comment by Fincham (1990).
In studies of a familial 15p+ chromosomal variant, Yoder et al. (1974) calculated a lod score of 1.428 at theta 0.32 for linkage between the p+ region and the ABO blood group locus. This suggested linkage to 15p did not subsequently hold up.
Occasionally, an O mother and an AB father may give birth to an AB child. The interpretation is cis-AB, i.e., both alleles on the same chromosome, or an allele with both specificities. Hummel et al. (1977) traced such through 3 generations. Inherited mosaicism in the ABO system consists of a situation in which, in an autosomal dominant pedigree pattern, family members show mosaicism of A cells and O cells, or B cells and O cells. A 'mixed field' agglutination pattern results. This phenotype is probably caused by a weak allele rather than by a modifier gene. Bird et al. (1978) found that in a B-O mosaic family affected persons had low levels of B-specific transferase. A curious feature was that one class of cells had nearly normal B antigen, whereas the second class had none.
Watkins et al. (1981) reviewed the evidence to refute the arguments that the genes coding for the A antigen-associated alpha-3-N-acetyl-D-galactosaminyltransferase and the B antigen-associated alpha-3-D-galactosyltransferase are not allelic. They suggested that the final answer may need to await the isolation of the pure enzymes in sufficient quantities for amino acid sequencing and examination of the active sites (or, one might add, sequencing of the genes themselves). The demonstration of immunologic homology of the 2 transferases indicates that the differences in structure of the 2 enzymes are relatively small and hence not incompatible with those to be expected of the products of allelic genes. Yoshida et al. (1982) concluded that the blood group A allele can take any of 3 common forms, A1, A2, and Aint (for intermediate), each determining a different type of blood group GalNAc transferase.
Badet, J., Ropars, C., Salmon, C. Alpha-N-acetyl-D-galactosaminyl- and alpha-D-galactosyltransferase activities in sera of cis AB blood group individuals. J. Immunogenet. 5: 221-231, 1978. [PubMed: 731066] [Full Text: https://doi.org/10.1111/j.1744-313x.1978.tb00650.x]
Bhattacharyya, M. K., Smith, A. M., Ellis, T. H. N., Hedley, C., Martin, C. The wrinkled-seed character of pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme. Cell 60: 115-122, 1990. [PubMed: 2153053] [Full Text: https://doi.org/10.1016/0092-8674(90)90721-p]
Bird, G. W. G., Wingham, J., Watkins, W. M., Greenwell, P., Cameron, A. H. Inherited 'mosaicism' within the ABO blood group system. J. Immunogenet. 5: 215-219, 1978. [PubMed: 569677] [Full Text: https://doi.org/10.1111/j.1744-313x.1978.tb00649.x]
Crow, J. F. Felix Bernstein and the first human marker locus. Genetics 133: 4-7, 1993. [PubMed: 8417988] [Full Text: https://doi.org/10.1093/genetics/133.1.4]
Fincham, J. R. S. Mendel--now down to the molecular level. Nature 343: 208-209, 1990. [PubMed: 2405276] [Full Text: https://doi.org/10.1038/343208a0]
Hummel, K., Badet, J., Bauermeister, W., Bender, K., Duffner, G., Lopez, M., Mauff, G., Pulverer, G., Salmon, C., Schmidts, W. Inheritance of cis-AB in three generations (family Lam.). Vox Sang. 33: 290-298, 1977. [PubMed: 919419] [Full Text: https://doi.org/10.1111/j.1423-0410.1977.tb04478.x]
Johnson, P. H., Hopkinson, D. A. Detection of ABO blood group polymorphism by denaturing gradient gel electrophoresis. Hum. Molec. Genet. 1: 341-344, 1992. [PubMed: 1303212] [Full Text: https://doi.org/10.1093/hmg/1.5.341]
Landsteiner, K. Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe. Zbl. Bakt. 27: 357-362, 1900.
Landsteiner, K. Ueber Agglutinationserscheinungen normalen menschlichen Blutes. Wien. Klin. Wschr. 14: 1132-1134, 1901.
Mendel, G. Versuche ueber Pflanzen-Hybriden. Verh. Naturforsch. Ver. Brunn. 4: 3-47, 1865.
Nagai, M., Yoshida, A. Possible existence of hybrid glycosyltransferase in heterozygous blood group AB subjects. Vox Sang. 35: 378-381, 1978. [PubMed: 746631] [Full Text: https://doi.org/10.1111/j.1423-0410.1978.tb02951.x]
Oka, Y., Niikawa, N., Yoshida, A., Matsumoto, H. An unusual case of blood group ABO inheritance: O from AB x O. Am. J. Hum. Genet. 34: 134-141, 1982. [PubMed: 6805318]
Oriol, R., Le Pendu, J., Mollicone, R. Genetics of ABO, H, Lewis, X and related antigens. Vox Sang. 51: 161-171, 1986. [PubMed: 2433836] [Full Text: https://doi.org/10.1111/j.1423-0410.1986.tb01946.x]
Salmon, C., Seger, J., Mannoni, P., Bahno-Duchery, J., Liberge, G. Une population d'erythrocytes avec anomalie simultanee des phenotypes induits par les genes des locus A B O et adenylate kinase. Rev. Franc. Etud. Clin. Biol. 13: 296-298, 1968. [PubMed: 5682079]
Ugozzoli, L., Wallace, R. B. Application of an allele-specific polymerase chain reaction to the direct determination of ABO blood group genotypes. Genomics 12: 670-674, 1992. [PubMed: 1572640] [Full Text: https://doi.org/10.1016/0888-7543(92)90292-z]
Watkins, W. M., Greenwell, P., Yates, A. D. The genetic and enzymic regulation of the synthesis of the A and B determinants in the ABO blood group system. Immun. Commun. 10: 83-100, 1981. [PubMed: 6169633] [Full Text: https://doi.org/10.3109/08820138109050691]
Yamamoto, F., Clausen, H., White, T., Marken, J., Hakomori, S. Molecular genetic basis of the histo-blood group ABO system. Nature 345: 229-233, 1990. [PubMed: 2333095] [Full Text: https://doi.org/10.1038/345229a0]
Yamamoto, F., Marken, J., Tsuji, T., White, T., Clausen, H., Hakomori, S. Cloning and characterization of DNA complementary to human UDP-GalNAc:Fuc alpha 1--2Gal alpha 1--3GalNAc transferase (histo-blood group A transferase) mRNA. J. Biol. Chem. 265: 1146-1151, 1990. [PubMed: 2104828]
Yamamoto, F. Review: ABO blood group system--ABH oligosaccharide antigens, anti-A and anti-B, A and B glycosyltransferases, and ABO genes. Immunohematology 20: 3-22, 2004. [PubMed: 15373665]
Yoder, F. E., Bias, W. B., Borgaonkar, D. S., Bahr, G. F., Yoder, I. I., Yoder, O. C., Golomb, H. M. Cytogenetics and linkage studies of a familial 15p+ variant. Am. J. Hum. Genet. 26: 535-548, 1974. [PubMed: 4138462]
Yoshida, A., Dave, V., Branch, D. R., Yamaguchi, H., Okubo, Y. An enzyme basis for blood type A intermediate status. Am. J. Hum. Genet. 34: 919-924, 1982. [PubMed: 6817633]
Yoshida, A., Yamaguchi, H., Okubo, Y. Genetic mechanism of cis-AB inheritance. I. A case associated with unequal chromosomal crossing over. Am. J. Hum. Genet. 32: 332-338, 1980. [PubMed: 6770676]
Yoshida, A. Biochemical genetics of human blood group ABO system. Am. J. Hum. Genet. 34: 1-14, 1982. [PubMed: 6805317]