Mutational spectrum in the recent human genome inferred by single nucleotide polymorphisms
Mutational spectrum in the recent human genome inferred by single nucleotide polymorphisms
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DOI：
10.1016/j.ygeno.2006.06.003
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发表时间：
2006-11-01
期刊：
影响因子：
4.4
通讯作者：
Zhao, Zhongming
中科院分区：
文献类型：
--
作者：
Jiang, Cizhong;Zhao, Zhongming
到目前为止，还没有全基因组范围内对人类突变谱的估计。在这项研究中，我们系统地检测了人类基因组中点突变的方向性和GC含量的维持，使用了类似于180万个高质量的人类单核苷酸多态及其在黑猩猩中的祖先序列。在所有突变类型中，C>；T(G->；A)改变的频率最高，每种类型转换的频率大约是每种颠换类型的四倍。在基因间隔区，随着GC含量的增加，从G或C变化的频率增加。在外显子中，G：C->；A：T的频率是基因组类别中最高的，主要由CpG位点的频繁突变所致。相反，CpG位点的突变，或CpG->；TPG/CPA突变，相对于具有相似GC含量的基因间区，在CpG岛上发生的频率较低。我们的结果表明，人类基因组中的GC含量总体上是不平衡的，有一种趋势，即人类基因组中AT含量丰富，并且某个区域的GC含量向基因组平均值靠拢。我们的结果不同于以前基于有限基因座或啮齿动物谱系的估计，在最近的人类基因组和分类的基因组区域中提供了第一个具有代表性和可靠的突变谱。(C)2006 Elsevier Inc.保留所有权利。
So far, there is no genome-wide estimation of the mutational spectrum in humans. In this study, we systematically examined the directionality of the point mutations and maintenance of GC content in the human genome using similar to 1.8 million high-quality human single nucleotide polymorphisms and their ancestral sequences in chimpanzees. The frequency of C -> T (G -> A) changes was the highest among all mutation types and the frequency of each type of transition was approximately fourfold that of each type of transversion. In intergenic regions, when the GC content increased, the frequency of changes from G or C increased. In exons, the frequency of G:C -> A:T was the highest among the genomic categories and contributed mainly by the frequent mutations at the CpG sites. In contrast, mutations at the CpG sites, or CpG -> TpG/CpA mutations, occurred less frequently in the CpG islands relative to intergenic regions with similar GC content. Our results suggest that the GC content is overall not in equilibrium in the human genome, with a trend toward shifting the human genome to be AT rich and shifting the GC content of a region to approach the genome average. Our results, which differ from previous estimates based on limited loci or on the rodent lineage, provide the first representative and reliable mutational spectrum in the recent human genome and categorized genomic regions. (c) 2006 Elsevier Inc. All rights reserved.