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

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.

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


Other Contributors

Marta Byrska-Bishop 1, Uday S Evani 2, Xuefang Zhao 3, Anna O Basile 2, Haley J Abel 4, Allison A Regier 4, André Corvelo 2, Wayne E Clarke 5, Rajeeva Musunuri 2, Kshithija Nagulapalli 2, Susan Fairley 6, Alexi Runnels 2, Lara Winterkorn 2, Ernesto Lowy 6, Human Genome Structural Variation Consortium; Paul Flicek 6, Soren Germer 2, Harrison Brand 7, Ira M Hall 8, Michael E Talkowski 7, Giuseppe Narzisi 2, Michael C Zody 9