Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

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Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

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Title: Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects
Author: Zou, James; Valiant, Gregory; Valiant, Paul; Karczewski, Konrad; Chan, Siu On; Samocha, Kaitlin; Lek, Monkol; Sunyaev, Shamil; Daly, Mark; MacArthur, Daniel G.

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Citation: Zou, James, Gregory Valiant, Paul Valiant, Konrad Karczewski, Siu On Chan, Kaitlin Samocha, Monkol Lek, Shamil Sunyaev, Mark Daly, and Daniel G. MacArthur. 2016. “Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects.” Nature Communications 7 (1): 13293. doi:10.1038/ncomms13293. http://dx.doi.org/10.1038/ncomms13293.
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Abstract: As new proposals aim to sequence ever larger collection of humans, it is critical to have a quantitative framework to evaluate the statistical power of these projects. We developed a new algorithm, UnseenEst, and applied it to the exomes of 60,706 individuals to estimate the frequency distribution of all protein-coding variants, including rare variants that have not been observed yet in the current cohorts. Our results quantified the number of new variants that we expect to identify as sequencing cohorts reach hundreds of thousands of individuals. With 500K individuals, we find that we expect to capture 7.5% of all possible loss-of-function variants and 12% of all possible missense variants. We also estimate that 2,900 genes have loss-of-function frequency of <0.00001 in healthy humans, consistent with very strong intolerance to gene inactivation.
Published Version: doi:10.1038/ncomms13293
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095512/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626126
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