![]() AT and BT are the same in size with 354 amino acids (353 in alternatively spliced transcripts), but 4 amino acid substitutions differentiate these two enzymes with different sugar specificities. By correlating the sequence differences with the expression of A/B antigens, we were able to demonstrate, what is now called, the Central Dogma of ABO. In 1990, 90 years after the discovery of ABO blood groups, Clausen, Hakomori, and I cloned the A, B, and O allelic cDNAs from stomach and colon cancer cell line cells expressing differential ABO phenotypes, and determined their nucleotide sequences and deduced amino acid sequences ( 1, 2). Consequently, ABO is the subject of research on genetic evolution. Furthermore, the ABO polymorphism is not limited to humans. In fact, the ABO polymorphism was the most widely used evidence to exclude innocent people from possible suspects before DNA typing became popular in the last decade. Biological samples containing A/B antigens can provide crucial evidence in crime scene investigation. A and/or B antigens can also be found in secretion, such as saliva and seminal fluid, as well as hair and skin. Therefore, ABO has become subjects of genetics, biochemistry and enzymology. In the late 1950s, a hypothesis was put forward on the biosynthetic pathways of these antigens: A and B alleles at the ABO genetic locus encode A and B transferases (AT and BT), which catalyze the biosynthesis of A and B antigens by transferring an N-acetyl- D-galactosamine (GalNAc) and a galactose (Gal), respectively, to the same substrates, H substances (Fucα1-2Gal), which are present on the RBCs of individuals of group O. Therefore, they are subjects of glycobiology. The antigens A and B are oligosaccharides, GalNAcα1-3(Fucα1-2)Gal and Galα1-3(Fucα1-2)Gal, respectively. Consequently, ABO compatibility is also essential in cell/tissue/organ transplantation, as well as blood transfusion. Antigens A and B can also be expressed on epithelial cells and endothelial cells, in addition to red blood cells (RBCs), depending on the blood types of the individuals. However, it subsequently expanded into a wide variety of scientific disciplines. ![]() Immunohematology and serology studying erythrocyte antigens and their antibodies, respectively, were the initial fields of ABO research. The dawn of the molecular genetics of the ABO blood group system Received: 10 November 2020 Accepted: 22 February 2021 Published: 30 September 2021. Keywords: Blood group ABO system ABO genes A and B glycosyltransferases A and B oligosaccharide antigens Two examples are presented in this review: the delineation of the ABO gene evolution in a variety of species and the association of single nucleotide variant (SNV) sites in the ABO gene with diseases and biological parameters through genome-wide association studies (GWAS). Now, in this era of genomics, we can harness the vast sequence information to unravel the molecular mechanisms responsible for important biological phenomena associated with the ABO polymorphism. ![]() Because more than 500,000 human genomes have been sequenced and deposited in sequence databases, bioinformaticians can retrieve and analyze this data without generating it. RNA sequencing determines which genes and spliced transcripts are expressed. Genome sequencing has revealed not only the exome but also transcription/translation regulatory elements. However, the situation has changed drastically in the last decade, due to rapid advances in next-generation sequencing (NGS) technology, which has allowed the sequencing of several thousand genes and even the entire genome in individual experiments. Later, other scientists interested in the ABO system characterized many additional ABO alleles. We also identified mutations in several subgroup alleles and also in the cis-AB and B(A) alleles that specify the expression of the A and B antigens by single alleles. We became the first to achieve successful ABO genotyping, discriminating between AA and AO genotypes and between BB and BO, which was impossible using immunohematological/serological methods. We identified four amino acid substitutions between AT and BT and inactivating mutations in the O alleles, clarifying the allelic basis of ABO. ![]() We then demonstrated this central dogma of ABO and opened a new era of molecular genetics. In 1990, my research team cloned human A, B, and O allelic cDNAs. Policy of Dealing with Allegations of Research MisconductĪbstract: The A and B oligosaccharide antigens of the ABO blood group system are produced from the common precursor, H substance, by enzymatic reactions catalyzed by A and B glycosyltransferases (AT and BT) encoded by functional A and B alleles at the ABO genetic locus, respectively.Policy of Screening for Plagiarism Process. ![]()
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