The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index.
High-throughput discovery of novel developmental phenotypes
Open accessAbstract
Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.
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“Their recent analysis of 1,751 unique gene knockouts found that human disease genes are enriched for essential genes38”
From Unexplored therapeutic opportunities in the human genome (2018) · cites this paper as [38]
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“Growing resources of well-characterized gene knockouts in mouse58 and other model organisms will further help to discover novel gene losses that are potential causes or consequences of phenotypic evolution.”
From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [58]
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“ZNF692 knock-out mice do not exhibit a teratogenic phenotype (International Mouse Phenotyping Consortium et al., 2016)”
From Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome (2018) · cites this paper as International Mouse Phenotyping Consortium et al., 2016
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“The newly added data includes mouse and rat proteins from UniProt (5), with their associated phenotype data extracted from the International Mouse Phenotyping Consortium (6) and the Rat Genome Database (7), respectively.”
From TCRD and pharos 2021: mining the human proteome for disease biology (2021) · cites this paper as [6]
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Citations
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
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-citationThresholding of statistical maps in functional neuroimaging using the false discovery rate
Genovese, C. R., Lazar, N. A., & Nichols, T. (2002) · NeuroImage · doi:10.1006/nimg.2001.1037 · Cited by 4,923
A reproducible evaluation of ANTs similarity metric performance in brain image registration
Avants, B. B., Tustison, N. J., Song, G., Cook, P. A., Klein, A., & Gee, J. C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.025 · Cited by 4,796
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders
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Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space
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“All registrations were performed using a combination of the mni_autoreg tools 9 and ANTS 10 .”
InfluentialThe NHGRI GWAS Catalog, a curated resource of SNP-trait associations
Welter, D., MacArthur, J., Morales, J., Burdett, T., Hall, P., Junkins, H., Klemm, A., Flicek, P., Manolio, T., Hindorff, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1229 · Cited by 2,707
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Prinz, F., Schlange, T., & Asadullah, K. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3439-c1 · Cited by 1,888
Human Gene Mutation Database (HGMD®): 2003 update
Stenson, P., Ball, E. V., Mort, M., Phillips, A. D., Shiel, J. A., Thomas, N., Abeysinghe, S. S., Krawczak, M., & Cooper, D. (2003) · Human Mutation · doi:10.1002/humu.10212 · Cited by 1,887
A conditional knockout resource for the genome-wide study of mouse gene function
Skarnes, W. C., Rosen, B., West, A. P., Koutsourakis, M., Bushell, W., Iyer, V., Mujica, A. O., Thomas, M., Harrow, J., Cox, T., et al. (2011) · Nature · doi:10.1038/nature10163 · Cited by 1,708
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Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
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Variant interpretation using population databases: Lessons from gnomAD
Gudmundsson, S., Singer‐Berk, M., Watts, N. A., Phu, W., Goodrich, J. K., Solomonson, M., Rehm, H. L., MacArthur, D. G., & O’Donnell‐Luria, A. (2021) · Human Mutation · doi:10.1002/humu.24309 · Cited by 714
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Metadata
- Authors
- The International Mouse Phenotyping Consortium, Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., Brown, J. M., Caddle, L. B., Chiani, F., Clary, D., Cleak, J., Daly, M. J., Denegre, J. M., Doe, B., Dolan, M. E., Edie, S. M., Fuchs, H., Gailus-Durner, V., Galli, A., Gambadoro, A., Gallegos, J., Guo, S., Horner, N. R., Hsu, C.-W., Johnson, S. J., Kalaga, S., Keith, L. C., Lanoue, L., Lawson, T. N., Lek, M., Mark, M., Marschall, S., Mason, J., McElwee, M. L., Newbigging, S., Nutter, L. M. J., Peterson, K. A., Ramirez-Solis, R., Rowland, D. J., Ryder, E., Samocha, K. E., Seavitt, J. R., Selloum, M., Szoke-Kovacs, Z., Tamura, M., Trainor, A. G., Tudose, I., Wakana, S., Warren, J., Wendling, O., West, D. B., Wong, L., Yoshiki, A., Wurst, W., MacArthur, D. G., Tocchini-Valentini, G. P., Gao, X., Flicek, P., Bradley, A., Skarnes, W. C., Justice, M. J., Parkinson, H. E., Moore, M., Wells, S., Braun, R. E., Svenson, K. L., de Angelis, M. H., Herault, Y., Mohun, T., Mallon, A.-M., Henkelman, R. M., Brown, S. D. M., Adams, D. J., Lloyd, K. C. K., McKerlie, C., Beaudet, A. L., Bućan, M., & Murray, S. A.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Pennsylvania (US)
- Mary Lyon Centre at MRC Harwell (GB)
- Hospital for Sick Children (CA)
- Wellcome Sanger Institute (GB)
- European Bioinformatics Institute (GB)
- Medical University of Vienna (AT)
- Jackson Laboratory (US)
- University of California, Davis (US)
- National Research Council (IT)
- Broad Institute (US)
- Helmholtz Munich (DE)
- Baylor College of Medicine (US)
- Model Animal Research Center (CN)
- Centre National de la Recherche Scientifique (FR)
- RIKEN BioResource Research Center (JP)
- German Center for Neurodegenerative Diseases (DE)
- National Institute for Medical Research (GB)
- Corresponding author
- Murray, Stephen A.
- ORCID
- Dickinson, Mary E.
- Flenniken, Ann M.
- Ji, Xiao
- Teboul, Lydia
- White, Jacqueline K.
- Meehan, Terrence F.
- Weninger, Wolfgang J.
- Westerberg, Henrik
- Adissu, Hibret
- Baker, Candice N.
- Brown, James M.
- Chiani, Francesco
- Clary, Dave
- Daly, Mark J.
- Denegre, James M.
- Dolan, Mary E.
- Edie, Sarah M.
- Fuchs, Helmut
- Gambadoro, Alessia
- Gallegos, Juan
- Horner, Neil R.
- Hsu, Chih-Wei
- Johnson, Sara J.
- Lanoue, Louise
- Lawson, Thomas N.
- Lek, Monkol
- Mark, Manuel
- Marschall, Susan
- Mason, Jeremy
- Nutter, Lauryl M. J.
- Peterson, Kevin A.
- Rowland, Douglas J.
- Samocha, Kaitlin E.
- Selloum, Mohammed
- Szoke-Kovacs, Zsombor
- Tudose, Ilinca
- Wakana, Shigeharu
- Warren, Jonathan
- Yoshiki, Atsushi
- Wurst, Wolfgang
- MacArthur, Daniel G.
- Gao, Xiang
- Flicek, Paul
- Bradley, Allan
- Parkinson, Helen E.
- Moore, Mark
- Wells, Sara
- Braun, Robert E.
- Svenson, Karen L.
- Mallon, Ann-Marie
- Henkelman, R. Mark
- Brown, Steve D. M.
- Adams, David J.
- Lloyd, K. C. Kent
- McKerlie, Colin
- Beaudet, Arthur L.
- Bućan, Maja
- Murray, Stephen A.
- Venue
- Nature
- Published
- 2016-09-14
- Volume
- 537
- Issue
- 7621
- Pages
- 508-514
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5295821
- OpenAlex
- W2518901523
- Cited by
- 1,196
- References
- 64
- Citations by year
- 2026: 76 · 2025: 86 · 2024: 115 · 2023: 148 · 2022: 145 · 2021: 186 · 2020: 147 · 2019: 124 · 2018: 90 · 2017: 64 · 2016: 10
- FWCI
- 78.01
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-11-08)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Lincoln Repository (University of Lincoln) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Genome Canada (OGI- 051)
- Wellcome Trust
- Ontario Genomics (OGI-051)
- INFRAFRONTIER (01KX1012)
- Government of Canada
- Cancer Research UK (13031)
- Agence Nationale de la Recherche (ANR-10-INBS-07 PHENOMIN., ANR-10-INBS-07, ANR-10-IDEX-0002, ANR-10-IDEX, ANR-10-IDEX0002-02, ANR-10, ANR-10-INBS-0007)
- Institut National de la Santé et de la Recherche Médicale (ANR 10 IDEX 0002, ANR-10-INBS-07 PHENOMIN, ANR-10-IDEX-0002-02, ANR-10-INBS-07)
- Bundesministerium für Bildung und Forschung (01KX1012)
- Université de Strasbourg (ANR-10-IDEX- 0002, ANR-10-IDEX-0002-02)
- Centre National de la Recherche Scientifique (ANR-10-IDEX-0002-02, ANR-10-IDEX-0002)
- PHENOMIN (ANR-10-INBS-07)
- National Institutes of Health (U42OD011185, U42OD011175, U42OD011174, U54‐HG006348, HG006348, UM1OD023222, UM1OD023221, U42OD012210)
- Medical Research Council
- Japan Society for the Promotion of Science (15K06815, 26250024)
- National Human Genome Research Institute (U54HG006348, U54HG006370, U54HG006364, U54HG006332, UM1HG006348, UM1HG006370)
- National Eye Institute (P30EY002520)
- National Cancer Institute (P30CA093373, P30CA034196)
- National Institute of Diabetes and Digestive and Kidney Diseases (U2CDK092993)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- lethal genes, embryonic lethality, International Mouse Phenotyping Consortium, developmental phenotypes, incomplete penetrance, variable expressivity, essential genes, human disease genes, purifying selection, orthologs, congenital disorders
- MeSH terms
- Animals, Disease, Embryo, Mammalian, Genes, Lethal, Humans, Mice, Inbred C57BL, Mutation, Phenotype, Conserved Sequence, Sequence Homology, Mice, Knockout, Penetrance, Genes, Essential, Polymorphism, Single Nucleotide, Imaging, Three-Dimensional, Mice, Genome-Wide Association Study, High-Throughput Screening Assays
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