Cited by 1,613Genomics and Rare DiseasesGenetic Associations and EpidemiologyEvolution and Genetic Dynamics

Evolution and functional impact of rare coding variation from deep sequencing of human exomes

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Tennessen, Jacob A., Bigham, Abigail W., O’Connor, Timothy D., Fu, Wenqing, Kenny, Eimear E., Gravel, Simon, McGee, Sean, Do, Ron +18 more·2012·Science

Abstract

A Deep Look Into Our Genes: Recent debates have focused on the degree of genetic variation and its impact upon health at the genomic level in humans (see the Perspective by Casals and Bertranpetit ). Tennessen et al. (p. 64 , published online 17 May), looking at all of the protein-coding genes in the human genome, and Nelson et al. (p. 100 , published online 17 May), looking at genes that encode drug targets, address this question through deep sequencing efforts on samples from multiple individuals. The findings suggest that most human variation is rare, not shared between populations, and that rare variants are likely to play a role in human health.

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  1. [5]Frazer KA Nature 449 851 2007 17943122 PMC2689609
  2. [10]O'Roak BJ Nat Genet 43 585 2011 21572417 PMC3115696

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Authors
Tennessen, J. A., Bigham, A. W., O’Connor, T. D., Fu, W., Kenny, E. E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G., Kang, H. M., Jordan, D., Leal, S. M., Gabriel, S., Rieder, M. J., Abecasis, G., Altshuler, D., Nickerson, D. A., Boerwinkle, E., Sunyaev, S., Bustamante, C. D., Bamshad, M. J., Akey, J. M., Broad, G. O., Seattle, G. O., & on behalf of the NHLBI Exome Sequencing Project
Affiliations
  • University of Washington (US)
  • Stanford University (US)
  • Broad Institute (US)
  • The University of Texas Health Science Center at Houston (US)
  • University of Michigan (US)
  • Brigham and Women's Hospital (US)
  • Baylor College of Medicine (US)
  • Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Corresponding author
  • Tennessen, Jacob A.
  • Bigham, Abigail W.
  • O’Connor, Timothy D.
  • Bamshad, Michael J.
  • Akey, Joshua M.
Venue
Science
Published
2012-07-06
Volume
337
Issue
6090
Pages
64-69
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1987754412
Cited by
1,613
References
46
Citations by year
2026: 22 · 2025: 44 · 2024: 43 · 2023: 43 · 2022: 57 · 2021: 83 · 2020: 72 · 2019: 106 · 2018: 105 · 2017: 123 · 2016: 175 · 2015: 202 · 2014: 222 · 2013: 240 · 2012: 71
FWCI
139.36
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1rc2hl103010-01)
  • National Heart, Lung, and Blood Institute (RC2HL102925, RC2HL102926, RC2HL102923, RC2HL-103010, RC2HL102924)
  • National Human Genome Research Institute (R01HG003229, U01HG006513)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
rare coding variants, single nucleotide variants, functional impact of variants, population-specific variants, purifying selection, population growth, European ancestry, African ancestry, variant discovery
MeSH terms
Black or African American, Disease, Female, Gene Frequency, Humans, Male, Population Growth, Selection, Genetic, Genetic Variation, Genome, Human, Evolution, Molecular, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Genetic Association Studies, High-Throughput Nucleotide Sequencing, Exome

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