High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios

Marta Byrska-Bishop; Uday S Evani; Xuefang Zhao; Anna O Basile; Haley J Abel; Allison A Regier; André Corvelo; Wayne E Clarke; Rajeeva Musunuri; Kshithija Nagulapalli; Susan Fairley; Alexi Runnels; Lara Winterkorn; Ernesto Lowy; Human Genome Structural Variation Consortium; Paul Flicek; Soren Germer; Harrison Brand; Ira M Hall; Michael E Talkowski; Giuseppe Narzisi; Michael C Zody

doi:10.1016/j.cell.2022.08.004

High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios

Cell. 2022 Sep 1;185(18):3426-3440.e19. doi: 10.1016/j.cell.2022.08.004.

Authors

Marta Byrska-Bishop¹, Uday S Evani², Xuefang Zhao³, Anna O Basile², Haley J Abel⁴, Allison A Regier⁴, André Corvelo², Wayne E Clarke⁵, Rajeeva Musunuri², Kshithija Nagulapalli², Susan Fairley⁶, Alexi Runnels², Lara Winterkorn², Ernesto Lowy⁶; Human Genome Structural Variation Consortium; Paul Flicek⁶, Soren Germer², Harrison Brand⁷, Ira M Hall⁸, Michael E Talkowski⁷, Giuseppe Narzisi², Michael C Zody⁹

Collaborators

Human Genome Structural Variation Consortium:
Evan E Eichler, Jan O Korbel, Charles Lee, Tobias Marschall, Scott E Devine, William T Harvey, Weichen Zhou, Ryan E Mills, Tobias Rausch, Sushant Kumar, Can Alkan, Fereydoun Hormozdiari, Zechen Chong, Yu Chen, Xiaofei Yang, Jiadong Lin, Mark B Gerstein, Ye Kai, Qihui Zhu, Feyza Yilmaz, Chunlin Xiao

Affiliations

¹ New York Genome Center, New York, NY 10013, USA. Electronic address: mbyrska-bishop@nygenome.org.
² New York Genome Center, New York, NY 10013, USA.
³ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁴ McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵ New York Genome Center, New York, NY 10013, USA; Outlier Informatics Inc., Saskatoon, SK S7H 1L4, Canada.
⁶ European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
⁷ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Genomic Health, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
⁹ New York Genome Center, New York, NY 10013, USA. Electronic address: mczody@nygenome.org.

Abstract

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina. We performed single-nucleotide variant (SNV) and short insertion and deletion (INDEL) discovery and generated a comprehensive set of structural variants (SVs) by integrating multiple analytic methods through a machine learning model. We show gains in sensitivity and precision of variant calls compared to phase 3, especially among rare SNVs as well as INDELs and SVs spanning frequency spectrum. We also generated an improved reference imputation panel, making variants discovered here accessible for association studies.

Keywords: 1000 Genomes Project; INDEL; SNV; population genetics; reference imputation panel; structural variation; trio sequencing; whole-genome sequencing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Female
Genome, Human*
High-Throughput Nucleotide Sequencing / methods
Humans
INDEL Mutation
Male
Polymorphism, Single Nucleotide
Whole Genome Sequencing*

Abstract

Publication types

MeSH terms

Grants and funding