{"title":"Molecular genetics and genomics of the ABO blood group system","authors":"F. Yamamoto","doi":"10.21037/AOB-20-71","DOIUrl":null,"url":null,"abstract":"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. In 1990, my research team cloned human A, B, and O allelic cDNAs. We then demonstrated this central dogma of ABO and opened a new era of molecular genetics. We identified four amino acid substitutions between AT and BT and inactivating mutations in the O alleles, clarifying the allelic basis of ABO. 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 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. Later, other scientists interested in the ABO system characterized many additional ABO alleles. 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. Genome sequencing has revealed not only the exome but also transcription/translation regulatory elements. RNA sequencing determines which genes and spliced transcripts are expressed. 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. 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. 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).Copyright © Annals of Blood. All rights reserved.","PeriodicalId":72211,"journal":{"name":"Annals of blood","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of blood","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21037/AOB-20-71","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 5
ABO血型系统的分子遗传学和基因组学
ABO血型系统的A和B寡糖抗原由常见的前体H物质通过酶促反应产生,酶促反应由ABO基因座上功能性A和B等位基因分别编码的A和B糖基转移酶(AT和BT)催化。1990年,我的研究团队克隆了人类A、B和O等位基因cDNA。然后,我们展示了ABO的核心教条,并开启了分子遗传学的新时代。我们鉴定了AT和BT之间的四个氨基酸取代以及O等位基因的失活突变,阐明了ABO的等位基因基础。我们成为第一个成功进行ABO基因分型的人,区分AA和AO基因型以及BB和BO基因型,这是使用免疫血液学/血清学方法无法实现的。我们还鉴定了几个亚组等位基因以及顺式AB和B(A)等位基因的突变,这些突变通过单个等位基因指定了A和B抗原的表达。后来,其他对ABO系统感兴趣的科学家对许多额外的ABO等位基因进行了表征。然而,在过去十年中,由于下一代测序(NGS)技术的快速发展,情况发生了巨大变化,该技术允许在单个实验中对数千个基因甚至整个基因组进行测序。基因组测序不仅揭示了外显子组,还揭示了转录/翻译调控元件。RNA测序确定哪些基因和剪接转录物被表达。由于超过500000个人类基因组已被测序并存储在序列数据库中,生物信息学家可以在不生成数据的情况下检索和分析这些数据。现在,在这个基因组学时代,我们可以利用大量的序列信息来解开与ABO多态性相关的重要生物现象的分子机制。这篇综述中介绍了两个例子:通过全基因组关联研究(GWAS)描述各种物种的ABO基因进化,以及ABO基因中单核苷酸变异(SNV)位点与疾病和生物学参数的关联。版权所有©血液年鉴。保留所有权利。
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