Molecular genetic analysis of ABO blood group variations reveals 29 novel ABO subgroup alleles
Molecular genetic analysis of ABO blood group variations reveals 29 novel ABO subgroup alleles
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DOI：
10.1111/trf.12168
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发表时间：
2013-11-01
期刊：
影响因子：
2.9
通讯作者：
Xiang, Dong
中科院分区：
文献类型：
--
作者：
Cai, Xiaohong;Jin, Sha;Xiang, Dong
研究背景对ABO基因变异的识别可能揭示ABO血型表型变异的新的生物学机制。我们报告的分子遗传学分析的322个明显无关的ABO亚群个体在估计210万donators.Study设计和MethodsWe进行了表型调查的血清学研究，分析了DNA序列的ABO基因直接测序或测序后克隆，并评估启动子活性的报告assays.ResultsIn 62罕见的ABO等位基因，我们在43个明显无关的亚群个体及其4个可用的家系中鉴定了29个新的ABO亚群等位基因。在这些等位基因中，1个是缺失突变等位基因，4个是杂交等位基因，24个是点突变等位基因。大多数点突变在外显子6至7中检测到，而其他几个也在外显子1至5或剪接区检测到。发现一个ABO启动子突变，-35至-18 del，并证实其降低启动子活性，如双荧光素酶测定所确定。结果发现5-区7 G>T和52 C>T两个突变携带提前的末端密码子E3 X和R18 X，与ABO血型Ael和Bel两个极弱亚型相关。我们提供的第一个证据表明，启动子异常参与形成弱ABO表型。我们还描述了第一个天然存在的ABO等位基因，其5-区末端密码子过早，导致Ael和Bel表型。
BackgroundIdentifying genetic variants of the ABO gene may reveal new biologic mechanisms underlying variant phenotypes of the ABO blood group. We report the molecular genetic analysis of 322 apparently unrelated ABO subgroup individuals in an estimated 2.1 million donors.Study Design and MethodsWe performed phenotype investigations by serology studies, analyzed the DNA sequence of the ABO gene by direct sequencing or sequencing after cloning, and evaluated promoter activity by reporter assays.ResultsIn 62 rare ABO alleles, we identified 29 novel ABO subgroup alleles in 43 apparently unrelated subgroup individuals and their four available pedigrees. Of these alleles, one was a deletion-mutation allele, four were hybrid alleles, and 24 were point-mutation alleles. Most of the point mutations were detected in Exons 6 to 7, while several others were also detected in Exons 1 to 5 or splicing regions. One ABO promoter mutation, -35 to -18 del, was found and verified to reduce promoter activity, as determined by dual luciferase assays. Two mutations, 7G>T and 52C>T, carrying the premature terminal codons E3X and R18X in the 5-region, were found to be associated with the very weak ABO subgroups Ael and Bel.ConclusionTwenty-nine ABO subgroup alleles were newly linked to different kinds of ABO variations. We provide the first evidence that promoter abnormality is involved in the formation of weak ABO phenotypes. We also described the first naturally occurring ABO alleles with premature terminal codons in the 5-region that led to Ael and Bel phenotypes.