Portal de Periódicos da CAPES

Multi-platform discovery of haplotype-resolved structural variation in human genomes

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-08148-z

2041-1723

Mark Chaisson, Ashley D. Sanders, Xuefang Zhao, Ankit Malhotra, David Porubský, Tobias Rausch, Eugene J. Gardner, Oscar L. Rodriguez, Li Guo, Ryan L. Collins, Xian Fan, Jia Wen, Robert E. Handsaker, Susan Fairley, Zev Kronenberg, Xiangmeng Kong, Fereydoun Hormozdiari, Dillon Lee, Aaron M. Wenger, Alex Hastie, Danny Antaki, Thomas Anantharaman, Peter A. Audano, Harrison Brand, Stuart Cantsilieris, Han Cao, Eliza Cerveira, Chong Chen, Xintong Chen, Chen-Shan Chin, Zechen Chong, Nelson T. Chuang, Christine Lambert, Deanna M. Church, Laura Clarke, Andrew Farrell, Joey Flores, Timur R. Galeev, David U. Gorkin, Madhusudan Gujral, Victor Guryev, Haynes Heaton, Jonas Korlach, Sushant Kumar, Jee Young Kwon, Ernest T. Lam, Jong Eun Lee, Joyce Lee, Wan-Ping Lee, Sau Peng Lee, Shantao Li, Patrick Marks, Karine A. Viaud‐Martinez, Sascha Meiers, Katherine M. Munson, Fábio C. P. Navarro, Bradley J. Nelson, Conor Nodzak, Amina Noor, Sofia Kyriazopoulou-Panagiotopoulou, Andy Wing Chun Pang, Yunjiang Qiu, Gabriel Rosanio, Xian Mallory, Adrian M. Stütz, Diana C.J. Spierings, Alistair Ward, AnneMarie E. Welch, Ming Xiao, Wei Xu, Chengsheng Zhang, Qihui Zhu, Xiangqun Zheng-Bradley, Ernesto Lowy, Sergei Yakneen, Steven A. McCarroll, Goo Jun, Li Ding, Chong‐Lek Koh, Bing Ren, Paul Flicek, Ken Chen, Mark Gerstein, Pui‐Yan Kwok, Peter M. Lansdorp, Gábor Marth, Jonathan Sebat, Xinghua Shi, Ali Bashir, Kai Ye, Scott E. Devine, Michael E. Talkowski, Ryan E. Mills, Tobias Marschall, Jan O. Korbel, Evan E. Eichler, Charles Lee,

Genomics and Rare Diseases

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.