This website was created by Fumiichiro Yamamoto, Ph.D., to disseminate knowledge on the molecular genetic basis of the ABO system.
Karl Landsteiner discovered the ABO system in 1900, distinguishing it as one of the most important blood group systems in transfusion medicine. The system consists of A and B antigens and their corresponding antibodies. The underlying factor differentiating the ABO system from others, such as the Rh system, is the presence of antibodies against A and B antigens. These antibodies are present in individuals who do not express A and B antigens, and cause the first mismatched blood transfusion to be possibly fatal. The discovery of the ABO blood group system paved the way for safe blood transfusion.
Due to its complexity, exploration of the ABO system peaks interest not only in transfusion medicine, but also in a variety of scientific fields. In addition to the four major groups (A, B, AB, O), we know of more than a dozen existing subgroups that exhibit different patterns and degrees of agglutination. Additionally, A and B antigens are found not only on red blood cells (RBCs) but also on the surface of other cell types and in secretions. As such, the system is often referred to as the “histo-blood group system.” The presence of A and B antigens on cells other than RBCs emphasizes the importance of ABO blood type matching not only in blood transfusions, but also in cell, tissue, and organ transplantations.
Both the synthesis and properties of A and B antigens raises many important questions on their roles not only in medicine but also in many aspects of biology. A and B antigens are synthesized by a series of enzymatic reactions catalyzed by enzymes called glycosyltransferases. In fact, the final step in producing these antigens requires a glycosyltransferase, which is encoded by the functional A and B alleles at the ABO genetic locus. The fact that allele frequencies vary amongst different races raises interesting questions on the relevance of ABO blood type on population studies, anthropology and human genetics. Another interesting characteristic of A and B antigens is their presence in animals other than human beings. The glycosyltransferases involved in A/B antigen production in humans also exhibit the same enzymatic purposes in animals. Therefore, the ABO blood group system is also of evolutionary and enzymatic significance. A/B antigens also exhibit dynamic changes during development and pathogenesis, suggesting their importance in cancer, molecular, cellular and developmental biology.
Safer blood transfusion, conceived by Landsteiner and improved upon by many others, primarily immunohematologists, has become a routine medical practice. Since our cloning of the ABO gene in 1990, progress has been made in the structural and functional analyses of ABO genes and A/B transferases at the molecular level. I hope that readers find these web pages interesting and useful, and that they both help facilitate a better understanding of the scientific bases of the ABO system, oligosaccharide ABH antigens, A and B transferases, and ABO genes, and aid in applying this information to clinical applications.
02. Immunogenetics of the Histo-blood group ABO System
03. Discovery of ABO Blood Group System
06. A transferase cDNA cloning
07. Northern Hybridization Results
09. Deduced Amino Acid Sequences of A/B/O Alleles
10. Restriction Fragment Length Polymorphism (A/B Allele vs. O Allele)
11. RFLP (A/O Alleles vs. B Allele)
12. ABO Genotyping of Blood Specimens
13. ABO Alleles (A and B Alleles)
15. ABO Alleles (A and B Subgroup Alleles)
16. ABO Alleles (cis-AB & B(A) Alleles)
21. Transfection Results (A/B transferase)
22. Transfection Results (A2 and A3 Alleles)
23. Transfection Results (O Alleles)
24. Transfection Results (A-B Transferase Chimeras --AA)
25. Transfection Results (A-B Transferase Chimeras --BB)
26. Transfection Results (A-B Transferase Chimeras --AB)
27. Transfection Results (A-B Transferase Chimeras --BA)
28. Transfection Results (A transferase Codon 268)
29. Nucleotide-Sugar Specificity (A transferase Codons 266-268)
30. Transfection Results (B transferase Codon 268)
31. Nucleotide-Sugar Specificity (B Transferase Codons 266-268)
32. Three-Dimensional Structure of A Transferase
33.Homologous Sequences in Other Species
34. Primate ABO Gene Sequence Comparison
35. Evolution of ABO Genes in Primates
36. Evolution of ABO Genes (2008)
37. Alpha 1-3 Gal(NAc) Transferase Family
38. Evolutionary Tree of ABO and Related Genes (2001)
39. Partial Amino Acid Sequence Comparison (2001)
40. Evolutionary Tree of ABO and Related Genes (2008)
41. Partial Amino Acid Sequence Comparison (2008)
42. Partial Amino Acid Sequence Comparison (GGTA1 Genes)
43. Partial Amino Acid Sequence Comparison (A3GALT2 Genes)
44. Partial Amino Acid Sequence Comparison (GBGT1 Genes)
45. Partial Amino Acid Sequence Comparison (ABO Genes)
46. Partial Amino Acid Sequence Comparison (GLT6D1 Genes)
47. Glycosyltransferase Gene Family
48. Glycosyltransferase Gene Expression in Human Tissues
49. Glycosyltransferase Gene Expression Analyzed by Hierarchical Clustering Algorithm
Appendix 01.Discovery of the ABO blood group system
Appendix 02. Four major groups
Appendix 03. Genetic basis of ABO blood grouping
Appendix 04. ABH(O) substances
Appendix 05. Immuno-determinant structures of ABH(O) antigens
Appendix 06. The immuno-dominant sugars of the A and B antigens are GalNAc (N-acetyl-D-galactosamine
Appendix 07. The Biosynthetic pathways of the A and B antigens
Appendix 08. Linkage analysis of the ABO genes
Appendix 09. ABO blood groups and A and B transferase activity
Appendix 10. History of the purification attempt of A transferase
Appendix 11. A and B subgroups
Appendix 12. A1 and A2 subgroups
Appendix 13. A3, Ax, and B3 weak subgroups
Appendix 14. Discovery of cis-AB
Appendix 15. Two examples of cis-AB inheritance
Appendix 16. Discovery of B(A) phenotype
Appendix 17. Mapping of the ABO gene using the radiation hybrid panel
Appendix 18. ABH and related antigens
Appendix 19. The genomic structure of the human ABO gene
Appendix 20. Comparison of amino acid sequences of the ABO and related genes
Appendix 21. Comparison of gene organization between human and mouse ABO genes
Appendix 22. Polymorphism in the ABO gene that was observed among different species and subspecies o