ABO Blood Groups
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.
Link to the Japanese site is as follows.
Link to the Catalan site is as follows.
Link to the Italian site is as follows.
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
"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
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Fumiichiro Yamamoto, Ph.D. Josep Carreras Leukaemia Research Institute (IJC)
Dr. Yamamoto's home page at Josep Carreras Leukaemia Research Institute (IJC)
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.
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.
Yamamoto, F., McNeill, PD., and Hakomori, S. (1995). Genomic organization of human histo-blood group ABO genes. Glycobiology 5: 51-58.
Saitou, N., and Yamamoto, F. (1997). Evolution of primate ABO blood group genes and their homologous genes. Mol. Biol. Evol. 14: 399-411.
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.
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.
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.
Yamamoto, F. and Yamamoto, M. (2001). Molecular genetic basis of porcine histo-blood group AO system. Blood 97: 3308-3310.
Yamamoto, F. (2001). Cloning and regulation of ABO genes. Transfusion Med. 11: 281-294.
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.
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.
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.
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.
Ensembl Human Genome Database
The Blood Group Antigen Gene Mutation Database
I would like to thank Amy Hathaway and Emili Cid for editing.