Mapping and characterization of structural variation in 17,795 human genomes

Haley J. Abel, David E. Larson, Allison A. Regier, Colby Chiang, Indraniel Das, Krishna L. Kanchi, Ryan M. Layer, Benjamin M. Neale, William J. Salerno, Catherine Reeves, Steven Buyske, Tara C. Matise, Donna M. Muzny, Michael C. Zody, Eric S. Lander, Susan K. Dutcher, Nathan O. Stitziel and Ira M. Hall ()
Additional contact information
Haley J. Abel: Washington University School of Medicine
David E. Larson: Washington University School of Medicine
Allison A. Regier: Washington University School of Medicine
Colby Chiang: Washington University School of Medicine
Indraniel Das: Washington University School of Medicine
Krishna L. Kanchi: Washington University School of Medicine
Ryan M. Layer: University of Colorado
Benjamin M. Neale: Broad Institute of MIT and Harvard
William J. Salerno: Baylor College of Medicine
Catherine Reeves: New York Genome Center
Steven Buyske: Rutgers University
Tara C. Matise: Rutgers University
Donna M. Muzny: Baylor College of Medicine
Michael C. Zody: New York Genome Center
Eric S. Lander: Broad Institute of MIT and Harvard
Susan K. Dutcher: Washington University School of Medicine
Nathan O. Stitziel: Washington University School of Medicine
Ira M. Hall: Washington University School of Medicine

Nature, 2020, vol. 583, issue 7814, 83-89

Abstract: Abstract A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline1 to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0–11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2371-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7814:d:10.1038_s41586-020-2371-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2371-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().