Document Type
Article
Publication Date
4-16-2019
Keywords
JGM
JAX Source
Nat Commun 2019 Apr 16; 10(1):1784
Volume
10
Issue
1
First Page
1784
Last Page
1784
ISSN
2041-1723
PMID
30992455
DOI
https://doi.org/10.1038/s41467-018-08148-z
Grant
HG007497,CA034196
Abstract
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 (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.
Recommended Citation
Chaisson M,
Sanders A,
Zhao X,
Malhotra A,
Porubsky D,
Rausch T,
Gardner E,
Rodriguez O,
Guo L,
Collins R,
Fan X,
Wen J,
Handsaker R,
Fairley S,
Kronenberg Z,
Kong X,
Hormozdiari F,
Lee D,
Wenger A,
Hastie A,
Antaki D,
Anantharaman T,
Audano P,
Brand H,
Cantsilieris S,
Cao H,
Cerveira E,
Chen C,
Chen X,
Chin C,
Chong Z,
Chuang N,
Lambert C,
Church D,
Clarke L,
Farrell A,
Flores J,
Galeev T,
Gorkin D,
Gujral M,
Guryev V,
Heaton W,
Korlach J,
Kumar S,
Kwon J,
Lam E,
Lee J,
Lee J,
Lee W,
Lee S,
Li S,
Marks P,
Viaud-Martinez K,
Meiers S,
Munson K,
Navarro F,
Nelson B,
Nodzak C,
Noor A,
Kyriazopoulou-Panagiotopoulou S,
Pang A,
Qiu Y,
Rosanio G,
Ryan M,
Stütz A,
Spierings D,
Ward A,
Welch A,
Xiao M,
Xu W,
Zhang C,
Zhu Q,
Zheng-Bradley X,
Lowy E,
Yakneen S,
McCarroll S,
Jun G,
Ding L,
Koh C,
Ren B,
Flicek P,
Chen K,
Gerstein M,
Kwok P,
Lansdorp P,
Marth G,
Sebat J,
Shi X,
Bashir A,
Ye K,
Devine S,
Talkowski M,
Mills R,
Marschall T,
Korbel J,
Eichler E,
Lee C.
Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat Commun 2019 Apr 16; 10(1):1784
Comments
Open access under Creative Commons Attribution 4.0 International License