ABO Blood Groups

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Molecular 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.

Grupo Sanguineo ABO (AB0)

Link to the Japanese site is as follows.

ABO血液型の分子遺伝学

Link to the Catalan site is as follows.

Grup sanguini ABO (AB0)

Link to the Italian site is as follows.

Gruppo sanguigno ABO (AB0)

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 in the Context of Blood Transfusion and Beyond

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

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Home

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.