• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Mapping and characterization of structural variation in 17,795 human genomes
【24h】

Mapping and characterization of structural variation in 17,795 human genomes

机译：17,795人基因组结构变异的映射和表征

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Structural variants in more than 17,000 human genomes are mapped and characterized using whole-genome sequencing, showing how this type of variation contributes to rare deleterious coding and noncoding alleles.A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline(1)to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0-11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing.
机译：使用全基因组测序映射并表征了17,000多种人类基因组的结构变体，表明这种类型的变异是有助于稀有有害的编码和非分量等位基因。全基因组测序用于研究人类遗传学的关键目标是询问所有变异形式，包括单核苷酸变体，小插入或缺失（吲哚）变体和结构变体。然而，用于研究结构变体的工具和资源已经落后于那些较小的变体。在这里，我们使用可伸缩的管道（1）来映射并表征17,795中的结构变体深度测序的人类基因组。我们公开发布网站频率数据以创建最大，以了解我们的知识，到目前为止，全基因组排序的结构变体资源。平均而言，个人携带2.9稀有结构变体，改变编码区;这些变体影响4.2基因的剂量或结构，占罕见高冲击编码等位基因的4.0-11.2％。使用计算模型，我们估计结构变体占稀有等位基因的17.2％ - 范围内，预测的有害效果相当于函数丧失编码等位基因;大约90％的这种结构变体是非编码缺失（平均每种基因组19.1）。我们报告了158,991个超稀有的结构变体，表明2％的个体携带超稀有的兆级结构变体，其中近一半是平衡或复杂的重排。最后，我们推断基因和非编码元素的剂量敏感性，并揭示了与元素类和保护有关的趋势。这项工作将有助于指导全基因组测序时代结构变体的分析和解释。

著录项

  • 来源
    《Nature》 |2020年第7814期|83-89|共7页
  • 作者

    Abel Haley J.; Larson David E.; Regier Allison A.; Chiang Colby; Das Indraniel; Kanchi Krishna L.; Layer Ryan M.; Neale Benjamin M.; Salerno William J.; Reeves Catherine; Buyske Steven; Matise Tara C.; Muzny Donna M.; Zody Michael C.; Lander Eric S.; Dutcher Susan K.; Stitziel Nathan O.; Hall Ira M.;

  • 作者单位

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Genet St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Genet St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Med St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA;

    Univ Colorado BioFrontiers Inst Boulder CO 80309 USA|Univ Colorado Dept Comp Sci Boulder CO 80309 USA;

    Broad Inst MIT & Harvard Cambridge MA 02142 USA|Broad Inst MIT & Harvard Stanley Ctr Psychiat Res Cambridge MA 02142 USA|Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA;

    Baylor Coll Med Human Genome Sequencing Ctr Houston TX 77030 USA;

    New York Genome Ctr New York NY USA;

    Rutgers State Univ Dept Stat Piscataway NJ USA;

    Rutgers State Univ Dept Genet Piscataway NJ USA;

    Baylor Coll Med Human Genome Sequencing Ctr Houston TX 77030 USA;

    New York Genome Ctr New York NY USA;

    Broad Inst MIT & Harvard Cambridge MA 02142 USA|MIT Dept Biol Cambridge MA USA|Harvard Med Sch Dept Syst Biol Boston MA 02115 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Genet St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Genet St Louis MO 63110 USA|Washington Univ Sch Med Dept Med St Louis MO 63110 USA;

    Washington Univ Sch Med McDonnell Genome Inst St Louis MO 63110 USA|Washington Univ Sch Med Dept Genet St Louis MO 63110 USA|Washington Univ Sch Med Dept Med St Louis MO 63110 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号