The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This allele is common in African populations [40].”
From Integrated Model of De Novo and Inherited Genetic Variants Yields Greater Power to Identify Risk Genes (2013) · cites this paper as [40]
In the citing paper
“we used the transition:transversion mutation ratio as a figure of merit, and compared this figure to a value of 2.3, which is the ratio for missense mutations observed in large-scale genomic analyses [34,35].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194
Self-citationA framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
Self-citationFinding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877
Self-citationKumar, P., Henikoff, S., & Ng, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.86 · Cited by 6,521
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858
A second generation human haplotype map of over 3.1 million SNPs
The International HapMap Consortium (2007) · Nature · doi:10.1038/nature06258 · Cited by 4,438
Evolutionary Rate at the Molecular Level
KIMURA, M. (1968) · Nature · doi:10.1038/217624a0 · Cited by 3,747
Robust relationship inference in genome-wide association studies
Manichaikul, A., Mychaleckyj, J. C., Rich, S. S., Daly, K., Sale, M., & Chen, W.-M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq559 · Cited by 3,541
Adaptive protein evolution at the Adh locus in Drosophila
McDonald, J. H., & Kreitman, M. (1991) · Nature · doi:10.1038/351652a0 · Cited by 3,313
MutationTaster evaluates disease-causing potential of sequence alterations
Schwarz, J. M., Rödelsperger, C., Schuelke, M., & Seelow, D. (2010) · Nature Methods · doi:10.1038/nmeth0810-575 · Cited by 2,975
Mapping short DNA sequencing reads and calling variants using mapping quality scores
Li, H., Ruan, J., & Durbin, R. (2008) · Genome Research · doi:10.1101/gr.078212.108 · Cited by 2,638
Targeted capture and massively parallel sequencing of 12 human exomes
Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E. E., et al. (2009) · Nature · doi:10.1038/nature08250 · Cited by 2,030
Self-citationExome sequencing identifies the cause of a mendelian disorder
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., Huff, C. D., Shannon, P. T., Jabs, E. W., Nickerson, D. A., et al. (2010) · Nature Genetics · doi:10.1038/ng.499 · Cited by 1,957
Self-citationWorldwide Human Relationships Inferred from Genome-Wide Patterns of Variation
Li, J. Z., Absher, D. M., Tang, H., Southwick, A. M., Casto, A. M., Ramachandran, S., Cann, H. M., Barsh, G. S., Feldman, M. W., Cavalli-Sforza, L. L., et al. (2008) · Science · doi:10.1126/science.1153717 · Cited by 1,915
Gutenkunst, R. N., Hernandez, R. D., Williamson, S. H., & Bustamante, C. D. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000695 · Cited by 1,906
Self-citationExome sequencing as a tool for Mendelian disease gene discovery
Bamshad, M. J., Ng, S. B. H., Bigham, A. W., Tabor, H. K., Emond, M. J., Nickerson, D. A., & Shendure, J. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3031 · Cited by 1,744
Self-citationSequencing of 50 Human Exomes Reveals Adaptation to High Altitude
Yi, X., Liang, Y., Huerta-Sanchez, E., Jin, X., Cuo, Z. X. P., Pool, J. E., Xu, X., Jiang, H., Vinckenbosch, N., Korneliussen, T. S., et al. (2010) · Science · doi:10.1126/science.1190371 · Cited by 1,611
Self-citationDistribution and intensity of constraint in mammalian genomic sequence
Cooper, G. M., Stone, E. A., Asimenos, G., Green, E. D., Batzoglou, S., & Sidow, A. (2005) · Genome Research · doi:10.1101/gr.3577405 · Cited by 1,359
Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome
Ng, S. B. H., Bigham, A. W., Buckingham, K. J., Hannibal, M., McMillin, M. J., Gildersleeve, H. I. S., Beck, A. E., Tabor, H. K., Cooper, G. M., Mefford, H. C., et al. (2010) · Nature Genetics · doi:10.1038/ng.646 · Cited by 1,349
Self-citationRare and common variants: twenty arguments
Gibson, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3118 · Cited by 1,278
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203
Self-citationIdentification of deleterious mutations within three human genomes
Chun, S., & Fay, J. C. (2009) · Genome Research · doi:10.1101/gr.092619.109 · Cited by 1,049
Genetic Heterogeneity in Human Disease
McClellan, J., & King, M.-C. (2010) · Cell · doi:10.1016/j.cell.2010.03.032 · Cited by 981
Statistical Properties of Segregating Sites
Fu, Y. X. (1995) · Theoretical Population Biology · doi:10.1006/tpbi.1995.1025 · Cited by 946
Solving the riddle of codon usage preferences: a test for translational selection
dos Reis, M. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh834 · Cited by 745
Fisher, S., Barry, A. J., Abreu, J., Minie, B., Nolan, J., Delorey, T. M., Young, G., Fennell, T. J., Allen, A., Ambrogio, L., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-1-r1 · Cited by 676
Self-citationDemographic history and rare allele sharing among human populations
Gravel, S., Henn, B. M., Gutenkunst, R. N., Indap, A. R., Marth, G., Clark, A. G., Yu, F., Gibbs, R. A., The 1000 Genomes Project, Bustamante, C. D., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019276108 · Cited by 611
Self-citationPopulation History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes
Akey, J. M., Eberle, M. A., Rieder, M. J., Carlson, C. S., Shriver, M. D., Nickerson, D. A., & Kruglyak, L. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020286 · Cited by 498
Self-citationConstructing genomic maps of positive selection in humans: Where do we go from here?Preprint
Akey, J. M. (2009) · Genome Research · doi:10.1101/gr.086652.108 · Cited by 433
Self-citationProportionally more deleterious genetic variation in European than in African populations
Lohmueller, K. E., Indap, A. R., Schmidt, S., Boyko, A. R., Hernandez, R. D., Hubisz, M. J., Sninsky, J. J., White, T. J., Sunyaev, S. R., Nielsen, R., et al. (2008) · Nature · doi:10.1038/nature06611 · Cited by 372
Self-citationLow-coverage sequencing: Implications for design of complex trait association studiesPreprint
Li, Y., Sidore, C., Kang, H. M., Boehnke, M., & Abecasis, G. R. (2011) · Genome Research · doi:10.1101/gr.117259.110 · Cited by 313
Self-citationRare Variant Association Analysis Methods for Complex Traits
Asimit, J. L., & Zeggini, E. (2010) · Annual Review of Genetics · doi:10.1146/annurev-genet-102209-163421 · Cited by 281
Accurate and comprehensive sequencing of personal genomes.Preprint
Ajay, S., Parker, S., Abaan, H., Fuentes-Fajardo, K., & Margulies, E. (2011) · Genome Research · doi:10.1101/gr.123638.111 · Cited by 233
Deep resequencing reveals excess rare recent variants consistent with explosive population growth
Coventry, A., Bull–Otterson, L., Liu, X., Clark, A. G., Maxwell, T. J., Crosby, J. R., Hixson, J. E., Rea, T. J., Muzny, D. M., Lewis, L. R., et al. (2010) · Nature Communications · doi:10.1038/ncomms1130 · Cited by 229
Self-citationSobreira, N. L. D. M., Cirulli, E. T., Avramopoulos, D., Wohler, E., Oswald, G. L., Stevens, E. L., Ge, D., Shianna, K. V., Smith, J. P., Maia, J. M., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000991 · Cited by 210
The functional spectrum of low-frequency coding variation
Marth, G., Yu, F., Indap, A. R., Garimella, K. V., Gravel, S., Leong, W. F., Tyler‐Smith, C., Bainbridge, M. N., Blackwell, T. W., Zheng-Bradley, X., et al. (2011) · Genome biology · doi:10.1186/gb-2011-12-9-r84 · Cited by 193
Self-citationSingle-nucleotide evolutionary constraint scores highlight disease-causing mutations
Cooper, G. M., Goode, D. L., Ng, S. B. H., Sidow, A., Bamshad, M. J., Shendure, J., & Nickerson, D. A. (2010) · Nature Methods · doi:10.1038/nmeth0410-250 · Cited by 170
Self-citationPower of deep, all-exon resequencing for discovery of human trait genes
Kryukov, G. V., Shpunt, A., Stamatoyannopoulos, J. A., & Sunyaev, S. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812824106 · Cited by 157
Self-citationPatterns of genetic variation in Mendelian and complex traits.
Zwick, M., Cutler, D., & Chakravarti, A. (2000) · Annual review of genomics and human genetics (Print) · doi:10.1146/annurev.genom.1.1.387 · Cited by 98
Waldman, Y. Y., Tuller, T., Shlomi, T., Sharan, R., & Ruppin, E. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq009 · Cited by 78
Ramírez-Soriano, A., & Nielsen, R. (2008) · Genetics · doi:10.1534/genetics.108.094060 · Cited by 35
Signatures of positive selection apparent in a small sample of human exomesPreprint
Tennessen, J. A., Madeoy, J. J., & Akey, J. M. (2010) · Genome Research · doi:10.1101/gr.106161.110 · Cited by 23
Self-citationAutomated High-Throughput Sex-Typing Assay
Yu, L., Martínez, F. D., & Klimecki, W. T. (2004) · BioTechniques · doi:10.2144/04374dd01 · Cited by 8
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- 10.1073/pnas.1019276108 · DOI
Cited by
Sorted by citations
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587
Self-citationAn integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711
Self-citationA general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183
Predicting Functional Effect of Human Missense Mutations Using PolyPhen‐2
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0720s76 · Cited by 3,705
Self-citationREVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants
Ioannidis, N. M., Rothstein, J. H., Pejaver, V., Middha, S., McDonnell, S. K., Baheti, S., Musolf, A., Li, Q., Holzinger, E., Karyadi, D., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.08.016 · Cited by 2,908
Self-citation
Metadata
- 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.
- ORCID
- Tennessen, Jacob A.
- Bigham, Abigail W.
- O’Connor, Timothy D.
- Kenny, Eimear E.
- Gravel, Simon
- McGee, Sean
- Do, Ron
- Liu, Xiaoming
- Jun, Goo
- Kang, Hyun Min
- Jordan, Daniel
- Leal, Suzanne M.
- Gabriel, Stacey
- Rieder, Mark J.
- Altshuler, David
- Nickerson, Deborah A.
- Boerwinkle, Eric
- Sunyaev, Shamil
- Bustamante, Carlos 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
- PMC
- PMC3708544
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
