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

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, Ping Hsun Hsieh, Joyce Lee, Sushant Kumar, Jiadong Lin, Tobias Rausch, Yu Chen, Jingwen Ren, Martin SantamarinaWolfram Höps, 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, Xinghua Shi, Alex R. Hastie, Kai Ye, Zechen Chong, Ashley D. Sanders, Michael C. Zody, Michael E. Talkowski, Ryan E. Mills, Scott E. Devine, Charles Lee, Jan O. Korbel, Tobias Marschall, Evan E. Eichler

Research output: Contribution to journalArticlepeer-review

243 Scopus citations


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 minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic variation, even across complex loci. We identified 107,590 structural variants (SVs), of which 68% were not discovered with short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterized 130 of the most active mobile element source elements and found that 63% of all SVs arise through homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.

Original languageEnglish
Article number48
Issue number6537
StatePublished - Apr 2 2021


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