美国华盛顿大学医学院Ira M. Hall研究组绘制和表征了17795个人类基因组中的结构变异（SV）。 2020年5月27日,《自然》杂志发表了这一成果。
他们使用了可扩展的管线22来绘制和表征17,795个深度测序的人类基因组中的SV。他们公开发布点频率数据，以创建迄今为止最大的基于全基因组测序（WGS）的SV资源。平均而言，个体携带2.9个稀有SV，这些SV会改变编码区，影响4.2个基因的剂量或结构，占稀有高影响力编码等位基因的4.0-11.2％。
根据计算模型，他们估计SVs占全基因组罕见等位基因的17.2％，其预测的有害影响与功能丧失编码的等位基因相当。大约90％的此类SV是非编码缺失（每个基因组平均19.1）。他们报告了158,991个超稀有SV，并显示大约2％的人携带超稀有的兆碱基规模SV，其中近一半是平衡或复杂的重排。
最后，他们推断基因和非编码元件的剂量敏感性，揭示与元件类别和保守性有关的趋势。这项工作将有助于指导WGS时代的SV分析和注释。
据悉，用于人类遗传学研究的WGS的主要目标是询问所有形式的变异，包括单核苷酸变异（SNV），小插入/缺失（indel）变异和SV。但是，用于SV研究的工具和资源落后于较小变异的工具和资源。
附：英文原文
Title: Mapping and characterization of structural variation in 17,795 human genomes
Author: Haley J. Abel, David E. Larson, Allison A. Regier, Colby Chiang, Indraniel Das, Krishna L. Kanchi, Ryan M. Layer, Benjamin M. Neale, William J. Salerno, Catherine Reeves, Steven Buyske, Tara C. Matise, Donna M. Muzny, Michael C. Zody, Eric S. Lander, Susan K. Dutcher, Nathan O. Stitziel, Ira M. Hall
Issue&Volume: 2020-05-27
Abstract: A key goal of whole-genome sequencing (WGS) for human genetics studies is to interrogate all forms of variation, including single nucleotide variants (SNV), small insertion/deletion (indel) variants and structural variants (SV). However, tools and resources for the study of SV have lagged behind those for smaller variants. Here, we used a scalable pipeline22 to map and characterize SV in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest WGS-based SV resource to date. On average, individuals carry 2.9 rare SVs that alter coding regions, affecting the dosage or structure of 4.2 genes and accounting for 4.0-11.2% of rare high-impact coding alleles. Based on a computational model, we estimate that SVs account for 17.2% of rare alleles genome-wide with predicted deleterious effects equivalent to loss-of-function coding alleles; approximately 90% of such SVs are non-coding deletions (mean 19.1 per genome). We report 158,991 ultra-rare SVs and show that around 2% of individuals carry ultra-rare megabase-scale SVs, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and non-coding elements, revealing trends related to element class and conservation. This work will help guide SV analysis and interpretation in the era of WGS.
DOI: 10.1038/s41586-020-2371-0
Source: https://www.nature.com/articles/s41586-020-2371-0
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
