来自八个人类基因组的结构变异的图谱绘制与测序

Mapping and sequencing of structural variation from eight human genomes.

作者信息

Kidd Jeffrey M, Cooper Gregory M, Donahue William F, Hayden Hillary S, Sampas Nick, Graves Tina, Hansen Nancy, Teague Brian, Alkan Can, Antonacci Francesca, Haugen Eric, Zerr Troy, Yamada N Alice, Tsang Peter, Newman Tera L, Tüzün Eray, Cheng Ze, Ebling Heather M, Tusneem Nadeem, David Robert, Gillett Will, Phelps Karen A, Weaver Molly, Saranga David, Brand Adrianne, Tao Wei, Gustafson Erik, McKernan Kevin, Chen Lin, Malig Maika, Smith Joshua D, Korn Joshua M, McCarroll Steven A, Altshuler David A, Peiffer Daniel A, Dorschner Michael, Stamatoyannopoulos John, Schwartz David, Nickerson Deborah A, Mullikin James C, Wilson Richard K, Bruhn Laurakay, Olson Maynard V, Kaul Rajinder, Smith Douglas R, Eichler Evan E

机构信息

Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.

出版信息

Nature. 2008 May 1;453(7191):56-64. doi: 10.1038/nature06862.

Abstract

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

摘要

人类个体之间的遗传变异发生在许多不同的尺度上,从人类核型的重大改变到单核苷酸变化。在这里,我们探索中等尺度上的变异——特别是影响几千到几百万碱基对的插入、缺失和倒位。我们采用基于克隆的方法来研究来自不同地理血统的8个人的这种中等结构变异。我们的分析全面概述了这些基因组中存在的结构变异的正常模式,细化了1695个结构变异的位置。我们发现50%的变异在不止一个个体中出现,并且近一半位于以前被描述为结构变异的基因组区域之外。我们发现了525个在人类参考基因组中不存在的新插入序列,并表明其中许多在个体之间的拷贝数是可变的。对261个结构变异的完整测序揭示了相当大的位点复杂性,并为塑造人类基因组的不同突变过程提供了见解。这些数据提供了人类结构变异的首张高分辨率序列图谱——这是基因分型平台的标准,也是未来个体基因组测序项目的前奏。

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