美国华盛顿大学医学院Evan E. Eichler、杰克逊基因组医学实验室Jan O. Korbel、德国杜塞尔多夫海因里希·海涅大学Tobias Marschall和欧洲分子生物学实验室Charles Lee研究小组合作的最新研究，揭示了单倍体解析的各种人类基因组和结构变异的整合分析。相关论文于2021年2月25日发表于国际学术期刊《科学》。

研究人员分析了32个不同人基因组的64个重组单倍体。这些高度连续的重组单倍体（平均重叠群N50：26 Mbp）整合了所有形式的遗传变异，甚至跨越了复杂的基因座。研究人员鉴定出107,590个结构变异（SV），其中68％未通过短读测序发现，还有278个SV热点（跨越基因丰富序列的巨型碱基）。

研究表征了130个最活跃的移动元素源，发现63％的SV是由同源重组介导的机制产生。该资源可通过多达50,340个SV短读实现可靠的基因分型，从而鉴定出1,526个表达定量性状的基因座以及可在人群中进行自适应选择的SV候选基因。

据介绍，长读和特定链测序技术共同促进了高质量单倍体解析人类基因组的从头组装，而无需亲子三人组数据。

附：英文原文

Title: Haplotype-resolved diverse human genomes and integrated analysis of structural variation

Author: Peter Ebert, Peter A. Audano, Qihui Zhu, Bernardo Rodriguez-Martin, David Porubsky, Marc Jan Bonder, Arvis Sulovari, Jana Ebler, Weichen Zhou, Rebecca Serra Mari, Feyza Yilmaz, Xuefang Zhao, PingHsun Hsieh, Joyce Lee, Sushant Kumar, Jiadong Lin, Tobias Rausch, Yu Chen, Jingwen Ren, Martin Santamarina, Wolfram Hps, Hufsah Ashraf, Nelson T. Chuang, Xiaofei Yang, Katherine M. Munson, Alexandra P. Lewis, Susan Fairley, Luke J. Tallon, Wayne E. Clarke, Anna O. Basile, Marta Byrska-Bishop, André Corvelo, Uday S. Evani, Tsung-Yu Lu, Mark J.P. Chaisson, Junjie Chen, Chong Li, Harrison Brand, Aaron M. Wenger, Maryam Ghareghani, William T. Harvey, Benjamin Raeder, Patrick Hasenfeld, Allison A. Regier, Haley J. Abel, Ira M. Hall, Paul Flicek, Oliver Stegle, Mark B. Gerstein, Jose M.C. Tubio, Zepeng Mu, Yang I. Li

Issue&Volume: 2021/02/25

Abstract: Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent–child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic variation even across complex loci. We identify 107,590 structural variants (SVs), of which 68% are not discovered by short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterize 130 of the most active mobile element source elements and find that 63% of all SVs arise by homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1,526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.

DOI: 10.1126/science.abf7117

Source: https://science.sciencemag.org/content/early/2021/02/24/science.abf7117