Cooper Gregory M, Nickerson Deborah A, Eichler Evan E
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Nat Genet. 2007 Jul;39(7 Suppl):S22-9. doi: 10.1038/ng2054.
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.
最近已经生成了人类基因组中大型插入/缺失或片段重复多态性（SDs）的全面描述。这些注释统称为结构或拷贝数变异（CNVs），包括数千个离散的基因组区域，跨越数亿个核苷酸。在这里，我们回顾了CNVs的基因组分布，其与基因、重复序列和片段重复含量密切相关。我们考虑了关于人类多态性以及区分人类与其他物种的固定变化的现有数据，探讨了导致这种非随机分布的进化机制。突变偏差、选择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谱有重大贡献。尽管以核苷酸水平的精度定义这些变异在很大程度上仍是一项未完成但至关重要的挑战，但我们对其潜在医学影响和进化重要性的理解正在迅速形成。
