Mutational and selective effects on copy-number variants in the human genome
Mutational and selective effects on copy-number variants in the human genome
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DOI：
10.1038/ng2054
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发表时间：
2007-07-01
期刊：
影响因子：
30.8
通讯作者：
Eichler, Evan E.
中科院分区：
文献类型：
--
作者：
Cooper, Gregory M.;Nickerson, Deborah A.;Eichler, Evan E.
最近对人类基因组中的大插入/缺失或片段重复多态性（SD）进行了全面的描述。这些注释统称为结构或拷贝数变异 (CNV)，包括数千个离散的基因组区域并跨越数亿个核苷酸。在这里，我们回顾了 CNV 的基因组分布，它与基因、重复和片段重复内容密切相关。考虑到人类多态性的可用数据以及区分人类与其他物种的固定变化，我们探索了产生这种非随机分布的进化机制。突变偏差、选择性效应以及这些力量之间的相互作用很可能都对人类拷贝数变异的范围产生了重大影响。尽管以核苷酸水平的精度定义这些变异仍然是一个尚未满足但至关重要的挑战，但我们对其潜在医学影响和进化重要性的理解正在迅速显现。
Comprehensive descriptions of large insertion/deletion or segmental duplication polymorphisms (SDs) in the human genome have recently been generated. These annotations, known collectively as structural or copy-number variants (CNVs), include thousands of discrete genomic regions and span hundreds of millions of nucleotides. Here we review the genomic distribution of CNVs, which is strongly correlated with gene, repeat and segmental duplication content. We explore the evolutionary mechanisms giving rise to this nonrandom distribution, considering the available data on both human polymorphisms and the fixed changes that differentiate humans from other species. It is likely that mutational biases, selective effects and interactions between these forces all contribute substantially to the spectrum of human copy-number variation. Although defining these variants with nucleotide-level precision remains a largely unmet but critical challenge, our understanding of their potential medical impact and evolutionary importance is rapidly emerging.