HomeMolecular Genetic Basis of ABO Blood Group System This website was created by Fumiichiro Yamamoto, Ph.D., to disseminate knowledge on the molecular genetic basis of the ABO system.
Link to the Spanish site is as follows. Home Link to the Japanese site is as follows. ABO血液型の分子遺伝学
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.
The basic information on the ABO blood group system may also be found in the link below.
ABO BLOOD GROUP SITES 02. Immunogenetics of the Histo-blood group ABO System 03. Discovery of ABO Blood Group System 04. A and B Antigens 05. A and B transferases 06. A transferase cDNA cloning 07. Northern Hybridization Results 08. A/B/O Allelic cDNAs 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) 14. ABO Alleles (O Alleles) 15. ABO Alleles (A and B Subgroup Alleles) 16. ABO Alleles (cis-AB & B(A) Alleles) 17. ABO Alleles 2008 18. ABO Alleles (BGAGMD) 19. ABO Allele Mutations 20. Transfection Analysis 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 50. Summary 51. Acknowledgment 52. Yamamoto Biosketch Sitemap 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 Appendix 23. The specificity of the murine enzyme Appendix 24. Porcine ABO gene Appendix 25. A variety of methods for the ABO genotyping Appendix 26 ABO & Infectious disease-1
Appendix 27 ABO & Infectious disease-2
Appendix 28 ABO & Cancer Susceptibility
Appendix 29 ABH Expression in Cancer
Appendix 30 ABO & Pancreatic Cancer
Appendix 31 ABO & Diet
Appendix 32 ABO Blood Type Diets
Appendix 33 ABH Antigens in Neurobiology
Appendix 34 ABO & Personality
"What You Had Better Know About ABO Blood Groups" From History to Modern Genetics From Red Blood Cell to Kidney, Hair, Seminal Fluid From Blood Transfusion, Cell/Tissue/Organ Transplantation to Crime Scene Investigation From Humans to Animals
ABO BLOOD TYPE SITES 02. Immunogenetics of the Histo-blood group ABO System
03. Discovery of ABO Blood Group System
04. A and B Antigens
05. A and B transferases
06. A transferase cDNA cloning
07. Northern Hybridization Results
08. A/B/O Allelic cDNAs
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)
14. ABO Alleles (O Alleles)
15. ABO Alleles (A and B Subgroup Alleles)
16. ABO Alleles (cis-AB & B(A) Alleles)
17. ABO Alleles 2008
18. ABO Alleles (BGAGMD)
19. ABO Allele Mutations
20. Transfection Analysis
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
50. Summary
Acknowledgment
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) and galactose, respectively.
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 of mice
Appendix 23. The specificity of the murine enzyme
Appendix 24. Porcine ABO gene
Appendix 25. A variety of methods for the ABO genotyping
Appendix 26. ABO Polymorphism & Infectious Disease Susceptibility
Appendix 27. ABO Polymorphism & Infectious Disease Susceptibility-2
Appendix 28. ABO Polymorphism & Cancer Susceptibility
Appendix 29. ABH Antigen Expression & Cancer
Appendix 30. ABO & Pancreatic Cancer
Appendix 31. ABO & Diet
Appendix 32. ABO Blood Type Diets
Appendix 33. ABH Antigens in Neurobiology
Appendix 34. ABO & Personality
Keywords Histo-blood group ABO system, blood group ABO system, ABO system, AB0 system, ABO blood groups, AB0 blood groups, ABO blood types, AB0 blood types, ABO genetic locus, ABO genes, ABO, AB0, A glycosyltransferases, B glycosyltransferases, glycosyltransferases, A transferase, B transferase, cell surface antigens, carbohydrate antigens, oligosaccharide antigens, oligosaccharides, complex carbohydrate antigens, complex carbohydrates, A antigen, B antigen, H antigen, red blood cell antigens, A/B antigens, ABH antigens, glycolipid, glycosphingolipids, glycoproteins, oligo sugars, red blood cells, RBC, blood transfusion, transfusion medicine, cell/tissue/organ transplantation, transplantation medicine, immunohematology, immunohaematology, immuno-hematology, immunology, ABO genotyping, forensic sciences, legal medicine, human genetics, population genetics, evolution, enzymology, glycobiology, glycosciences, human genes, primate genes, mouse gene, pig genes, alpha 1,3-Gal(NAc) transferases, a1,3-galactosyl transferase, a1,3-GalNAc transferase, structural basis, molecular genetic basis of ABO, ABO polymorphism, single nucleotide polymorphism, SNP, A, B, AB, O, A2, A3, Ax, B3, alleles, weak subgroups, homo sapiens, pig AO genes, cis-AB, B(A), mouse cis-AB gene, ABO genotype, ABO phenotype, DNA methylation, transcription, alternative splicing, Golgi apparatus, transferase chimeras, GBGT1, GGTA1, A3GALT2, monoclonal antibody, sera, plant lectins, Fumi-ichiro Yamamoto, Fumiichiro Yamamoto, F. Yamamoto, Landsteiner, enzyme, kinetics, sugar specificity, acceptor substrate specificity, acceptors, donors, sugars, nucleotide-sugars, genetic engineering, differential susceptibility to infectious diseases, differential cancer susceptibility, alterations in glycosylation in cancer, pancreatic cancer, diets, Peter D'Adamo, Blood type diets, neurobiology, Masahiko Nomi, personality, Burnham Institute, Burnham Institute for Medical Research, Biomembrane Institute, IMPPC, IMPPC Institute of Predictive and Personalized Medicine of Cancer, Institut de Medicina Predictiva i Personalitzada del Càncer, AABB, ISBT, dbRBC - Blood Group Antigen Gene Mutation Database Fumiichiro Yamamoto, Ph.D. Josep Carreras Leukaemia Research Institute (IJC) Important Links: Dr. Yamamoto's home page at Josep Carreras Leukaemia Research Institute (IJC) http://www.carrerasresearch.org/en/immunohematology-and-glycobiology_23995
Some of Dr. Yamamoto's publications Yamamoto, F., Marken, J., Tsuji, T., White, T., Clausen, H., and Hakomori, S. (1990). Cloning and characterization of DNA complementary to human UDP-GalNAc:Fuc alpha1->2Gal alpha 1>3 GalNAc transferase (histo-blood group A transferase) mRNA. J. Biol. Chem. 265: 1146-1151.
http://www.jbc.org/cgi/reprint/265/2/1146 Yamamoto, F., Clausen, H., White, T., Marken, J., and Hakomori, S. (1990). Molecular genetic basis of histo-blood group ABO system. Nature 345: 229-233.
Yamamoto, F., and Hakomori, S. (1990). Sugar-nucleotide donor specificity of histo-blood group A and B transferases is based on amino acid substitutions. J. Biol. Chem. 265: 19257-19262. http://www.jbc.org/cgi/reprint/265/31/19257 Yamamoto, F., McNeill, PD., and Hakomori, S. (1995). Genomic organization of human histo-blood group ABO genes. Glycobiology 5: 51-58. http://glycob.oxfordjournals.org/cgi/reprint/5/1/51 Saitou, N., and Yamamoto, F. (1997). Evolution of primate ABO blood group genes and their homologous genes. Mol. Biol. Evol. 14: 399-411. http://mbe.oxfordjournals.org/cgi/reprint/14/4/399 Kominato, Y., Tsuchiya, T., Hata, N. Takizawa, H., and Yamamoto, F. (1997). Transcription of the human ABO blood group gene is dependent upon minisatellite sequence which binds the transcription factor CBF/NF-Y. J. Biol. Chem. 272: 25890-25898. http://www.jbc.org/cgi/content/full/272/41/25890 Kominato, Y., Hata, Y., Takizawa, H., Tsuchiya, T., Tsukada, J., and Yamamoto, F. (1999). DNA methylation-dependent expression of human histo-blood group ABO genes. J. Biol. Chem. 274:37240-37250. http://www.jbc.org/cgi/content/full/274/52/37240 Yamamoto, M., Lin, X-H., Kominato, Y., Hata, Y., Noda, R., Saitou, N., and Yamamoto, F. (2001). Murine equivalent of the human histo-blood group ABO gene is a cis-AB gene and encodes a glycosyltransferase with both A and B transferase activity. J. Biol. Chem. 276: 13701-13708.
http://www.jbc.org/cgi/content/full/276/17/13701
Yamamoto, F. and Yamamoto, M. (2001). Molecular genetic basis of porcine histo-blood group AO system. Blood 97: 3308-3310.
http://bloodjournal.hematologylibrary.org/cgi/reprint/97/10/3308 Yamamoto, F. (2001). Cloning and regulation of ABO genes. Transfusion Med. 11: 281-294. http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-3148.2001.00316.x Kominato, Y., Hata, Y., Takizawa, H., Matsumoto, K., Yasui, K., Tsukada, J., and Yamamoto, F. (2002). Alternative promoter identified between an hypermethylated upstream region of repetitive elements and a CpG island in the human ABO histo-blood group genes. J. Biol. Chem. 277: 37936-37948. http://www.jbc.org/cgi/content/full/277/40/37936 Hata, Y., Kominato, Y., Takizawa, H., Tabata, S., Michino, J., Nishino, K., Yasumura, S. and Yamamoto, F. (2003). Transcription starting from an alternative promoter leads to the expression of the human ABO histo-blood group antigen. Transfusion 43: 656-662.
http://www.blackwell-synergy.com/doi/abs/10.1046/j.1537-2995.2003.00382.x
Yamamoto, F. (2004). The ABO Blood Group System: ABH oligosaccharide antigens, anti-A and anti-B antibodies, A and B glycosyltransferases, and ABO genes. Immunohematology 20: 3-22.
http://www.redcross.org/pubs/immuno/ Other interesting information
Blumenfeld, O.O. (2002). Mutation Databases and Other On-Line Sites as a Resource for Transfusion Medicine: History and Attributes. Transfusion Medicine Reviews 16: 103-114. Körmöczi, G.F. and Mayr, W.R. (2005). Milestones in immunology. Transplant Immunology 14, 155-157.
Database Links Ensembl Human Genome Database http://www.ensembl.org/Homo_sapiens/index.html Pub-Med search http://www.ncbi.nlm.nih.gov/sites/entrez The Blood Group Antigen Gene Mutation Database http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/home
Acknowledgment I would like to thank Amy Hathaway and Emili Cid for editing. |
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 Updating... google795d6fd13a9424e8-1.html (0k) Fumiichiro Yamamoto, Jul 17, 2013, 5:37 AM
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