Sequence variation at the human ABO locus
Sequence variation at the human ABO locus
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DOI：
10.1017/s0003480001008995
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发表时间：
2002-01-01
影响因子：
1.9
通讯作者：
Yip, SP
中科院分区：
文献类型：
--
作者：
Yip, SP
ABO血型是输血医学中最重要的血型系统。自从ABO基因被克隆和三个主要等位基因的分子基础在大约10年前被描绘出来以来，人们越来越多地通过各种基于DNA的基因分型方法来研究该基因，并通过DNA测序来详细分析该基因。这些研究得出了一些一致的观察结果。首先，当与其他等位基因正确组合时，产生正常血型A、B、AB和O的主要ABO等位基因存在广泛的序列异质性。其次，产生ABO亚群(如A（2)、A(x)和B-3）的各种等位基因的分子基础也存在广泛的异质性。目前报道的ABO等位基因超过70个，这些等位基因突出了基因编码区广泛的序列变异。提出了一个统一的命名系统来命名这些等位基因。第三，在该基因的非编码区也发现了广泛的序列变异，包括5‘非翻译区（UTR）的小卫星重复序列变异，内含子6的21个单核苷酸多态性（SNP）和3’ UTR的1个SNP。这些变异的单倍型揭示了与ABO主要等位基因的特定关系。第四，排除公共等位基因，剩余的等位基因中约有一半是由于新的突变，另一半可以更好地解释为公共等位基因之间的基因内重组（交叉和基因转换）。特别是，通过对内含子6的单倍型分析，可以相当精确地确定杂交等位基因的重组位点。这表明，在产生ABO基因座的遗传多样性方面，重组与点突变同样重要。最后，大量的ABO基因分型方法是基于限制性内切分析、等位基因特异性扩增、基因组合突变筛选等技术。
The ABO blood group is the most important blood group system in transfusion medicine. Since the ABO gene was cloned and the molecular basis of the three major alleles delineated about 10 years ago, the gene has increasingly been examined by a variety of DNA-based genotyping methods and analysed hi detail by DNA sequencing. A few coherent observations emerge from these studies. First, there is extensive sequence heterogeneity underlying the major ABO alleles that produce normal blood groups A, B, AB and O when in correct combination with other alleles. Second, there is also extensive heterogeneity underlying the molecular basis of various alleles producing ABO subgroups such as A(2), A(x) and B-3. There are over 70 ABO alleles reported to date and these alleles highlight the extensive sequence variation in the coding region of the gene. A unifying system of nomenclature is proposed to name these alleles. Third, extensive sequence variation is also found in the non-coding region of the gene, including variation in minisatellite repeats in the 5' untranslated region (UTR), 21 single nucleotide polymorphisms (SNPs) in intron 6 and one SNP in the 3' UTR. The haplotypes of these variations reveal a specific relationship with the major ABO alleles. Fourth, excluding the common alleles, about half of the remaining alleles are due to new mutations and the other half can better be explained by intragenic recombination (both crossover and gene conversion) between common allele's. In particular, the recombination sites in hybrid alleles can be quite precisely defined through haplotype analysis of the SNPs in intron 6. This indicates that recombination is equally as important as point mutations in generating the genetic diversity of the ABO locus. Finally, a large number of ABO genotyping methods are available and are based on restriction analysis, allele specific amplification, mutation screening techniques of their combinations.