High-throughput discovery of novel developmental phenotypes.
Identifieur interne : 000086 ( PubMed/Corpus ); précédent : 000085; suivant : 000087High-throughput discovery of novel developmental phenotypes.
Auteurs : Mary E. Dickinson ; Ann M. Flenniken ; Xiao Ji ; Lydia Teboul ; Michael D. Wong ; Jacqueline K. White ; Terrence F. Meehan ; Wolfgang J. Weninger ; Henrik Westerberg ; Hibret Adissu ; Candice N. Baker ; Lynette Bower ; James M. Brown ; L Brianna Caddle ; Francesco Chiani ; Dave Clary ; James Cleak ; Mark J. Daly ; James M. Denegre ; Brendan Doe ; Mary E. Dolan ; Sarah M. Edie ; Helmut Fuchs ; Valerie Gailus-Durner ; Antonella Galli ; Alessia Gambadoro ; Juan Gallegos ; Shiying Guo ; Neil R. Horner ; Chih-Wei Hsu ; Sara J. Johnson ; Sowmya Kalaga ; Lance C. Keith ; Louise Lanoue ; Thomas N. Lawson ; Monkol Lek ; Manuel Mark ; Susan Marschall ; Jeremy Mason ; Melissa L. Mcelwee ; Susan Newbigging ; Lauryl M J. Nutter ; Kevin A. Peterson ; Ramiro Ramirez-Solis ; Douglas J. Rowland ; Edward Ryder ; Kaitlin E. Samocha ; John R. Seavitt ; Mohammed Selloum ; Zsombor Szoke-Kovacs ; Masaru Tamura ; Amanda G. Trainor ; Ilinca Tudose ; Shigeharu Wakana ; Jonathan Warren ; Olivia Wendling ; David B. West ; Leeyean Wong ; Atsushi Yoshiki ; Daniel G. Macarthur ; Glauco P. Tocchini-Valentini ; Xiang Gao ; Paul Flicek ; Allan Bradley ; William C. Skarnes ; Monica J. Justice ; Helen E. Parkinson ; Mark Moore ; Sara Wells ; Robert E. Braun ; Karen L. Svenson ; Martin Hrabe De Angelis ; Yann Herault ; Tim Mohun ; Ann-Marie Mallon ; R Mark Henkelman ; Steve D M. Brown ; David J. Adams ; K C Kent Lloyd ; Colin Mckerlie ; Arthur L. Beaudet ; Maja Bu An ; Stephen A. MurraySource :
- Nature [ 1476-4687 ] ; 2016.
Abstract
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.
DOI: 10.1038/nature19356
PubMed: 27626380
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">High-throughput discovery of novel developmental phenotypes.</title><author><name sortKey="Dickinson, Mary E" sort="Dickinson, Mary E" uniqKey="Dickinson M" first="Mary E" last="Dickinson">Mary E. Dickinson</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Flenniken, Ann M" sort="Flenniken, Ann M" uniqKey="Flenniken A" first="Ann M" last="Flenniken">Ann M. Flenniken</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Xiao" sort="Ji, Xiao" uniqKey="Ji X" first="Xiao" last="Ji">Xiao Ji</name><affiliation><nlm:affiliation>Genomics and Computational Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Teboul, Lydia" sort="Teboul, Lydia" uniqKey="Teboul L" first="Lydia" last="Teboul">Lydia Teboul</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wong, Michael D" sort="Wong, Michael D" uniqKey="Wong M" first="Michael D" last="Wong">Michael D. Wong</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="White, Jacqueline K" sort="White, Jacqueline K" uniqKey="White J" first="Jacqueline K" last="White">Jacqueline K. White</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Meehan, Terrence F" sort="Meehan, Terrence F" uniqKey="Meehan T" first="Terrence F" last="Meehan">Terrence F. Meehan</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Weninger, Wolfgang J" sort="Weninger, Wolfgang J" uniqKey="Weninger W" first="Wolfgang J" last="Weninger">Wolfgang J. Weninger</name><affiliation><nlm:affiliation>Centre for Anatomy and Cell Biology, Medical University of Vienna, Vienna A-1090, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Westerberg, Henrik" sort="Westerberg, Henrik" uniqKey="Westerberg H" first="Henrik" last="Westerberg">Henrik Westerberg</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Adissu, Hibret" sort="Adissu, Hibret" uniqKey="Adissu H" first="Hibret" last="Adissu">Hibret Adissu</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Baker, Candice N" sort="Baker, Candice N" uniqKey="Baker C" first="Candice N" last="Baker">Candice N. Baker</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bower, Lynette" sort="Bower, Lynette" uniqKey="Bower L" first="Lynette" last="Bower">Lynette Bower</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, James M" sort="Brown, James M" uniqKey="Brown J" first="James M" last="Brown">James M. Brown</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Caddle, L Brianna" sort="Caddle, L Brianna" uniqKey="Caddle L" first="L Brianna" last="Caddle">L Brianna Caddle</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Chiani, Francesco" sort="Chiani, Francesco" uniqKey="Chiani F" first="Francesco" last="Chiani">Francesco Chiani</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Clary, Dave" sort="Clary, Dave" uniqKey="Clary D" first="Dave" last="Clary">Dave Clary</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cleak, James" sort="Cleak, James" uniqKey="Cleak J" first="James" last="Cleak">James Cleak</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Daly, Mark J" sort="Daly, Mark J" uniqKey="Daly M" first="Mark J" last="Daly">Mark J. Daly</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Denegre, James M" sort="Denegre, James M" uniqKey="Denegre J" first="James M" last="Denegre">James M. Denegre</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Doe, Brendan" sort="Doe, Brendan" uniqKey="Doe B" first="Brendan" last="Doe">Brendan Doe</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Dolan, Mary E" sort="Dolan, Mary E" uniqKey="Dolan M" first="Mary E" last="Dolan">Mary E. Dolan</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Edie, Sarah M" sort="Edie, Sarah M" uniqKey="Edie S" first="Sarah M" last="Edie">Sarah M. Edie</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Fuchs, Helmut" sort="Fuchs, Helmut" uniqKey="Fuchs H" first="Helmut" last="Fuchs">Helmut Fuchs</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Gailus Durner, Valerie" sort="Gailus Durner, Valerie" uniqKey="Gailus Durner V" first="Valerie" last="Gailus-Durner">Valerie Gailus-Durner</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Galli, Antonella" sort="Galli, Antonella" uniqKey="Galli A" first="Antonella" last="Galli">Antonella Galli</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gambadoro, Alessia" sort="Gambadoro, Alessia" uniqKey="Gambadoro A" first="Alessia" last="Gambadoro">Alessia Gambadoro</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gallegos, Juan" sort="Gallegos, Juan" uniqKey="Gallegos J" first="Juan" last="Gallegos">Juan Gallegos</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Shiying" sort="Guo, Shiying" uniqKey="Guo S" first="Shiying" last="Guo">Shiying Guo</name><affiliation><nlm:affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</nlm:affiliation></affiliation></author><author><name sortKey="Horner, Neil R" sort="Horner, Neil R" uniqKey="Horner N" first="Neil R" last="Horner">Neil R. Horner</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Chih Wei" sort="Hsu, Chih Wei" uniqKey="Hsu C" first="Chih-Wei" last="Hsu">Chih-Wei Hsu</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Johnson, Sara J" sort="Johnson, Sara J" uniqKey="Johnson S" first="Sara J" last="Johnson">Sara J. Johnson</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Kalaga, Sowmya" sort="Kalaga, Sowmya" uniqKey="Kalaga S" first="Sowmya" last="Kalaga">Sowmya Kalaga</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Keith, Lance C" sort="Keith, Lance C" uniqKey="Keith L" first="Lance C" last="Keith">Lance C. Keith</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lanoue, Louise" sort="Lanoue, Louise" uniqKey="Lanoue L" first="Louise" last="Lanoue">Louise Lanoue</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lawson, Thomas N" sort="Lawson, Thomas N" uniqKey="Lawson T" first="Thomas N" last="Lawson">Thomas N. Lawson</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lek, Monkol" sort="Lek, Monkol" uniqKey="Lek M" first="Monkol" last="Lek">Monkol Lek</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mark, Manuel" sort="Mark, Manuel" uniqKey="Mark M" first="Manuel" last="Mark">Manuel Mark</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Marschall, Susan" sort="Marschall, Susan" uniqKey="Marschall S" first="Susan" last="Marschall">Susan Marschall</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Mason, Jeremy" sort="Mason, Jeremy" uniqKey="Mason J" first="Jeremy" last="Mason">Jeremy Mason</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mcelwee, Melissa L" sort="Mcelwee, Melissa L" uniqKey="Mcelwee M" first="Melissa L" last="Mcelwee">Melissa L. Mcelwee</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Newbigging, Susan" sort="Newbigging, Susan" uniqKey="Newbigging S" first="Susan" last="Newbigging">Susan Newbigging</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Nutter, Lauryl M J" sort="Nutter, Lauryl M J" uniqKey="Nutter L" first="Lauryl M J" last="Nutter">Lauryl M J. Nutter</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Peterson, Kevin A" sort="Peterson, Kevin A" uniqKey="Peterson K" first="Kevin A" last="Peterson">Kevin A. Peterson</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ramirez Solis, Ramiro" sort="Ramirez Solis, Ramiro" uniqKey="Ramirez Solis R" first="Ramiro" last="Ramirez-Solis">Ramiro Ramirez-Solis</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Rowland, Douglas J" sort="Rowland, Douglas J" uniqKey="Rowland D" first="Douglas J" last="Rowland">Douglas J. Rowland</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ryder, Edward" sort="Ryder, Edward" uniqKey="Ryder E" first="Edward" last="Ryder">Edward Ryder</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Samocha, Kaitlin E" sort="Samocha, Kaitlin E" uniqKey="Samocha K" first="Kaitlin E" last="Samocha">Kaitlin E. Samocha</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Seavitt, John R" sort="Seavitt, John R" uniqKey="Seavitt J" first="John R" last="Seavitt">John R. Seavitt</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Selloum, Mohammed" sort="Selloum, Mohammed" uniqKey="Selloum M" first="Mohammed" last="Selloum">Mohammed Selloum</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Szoke Kovacs, Zsombor" sort="Szoke Kovacs, Zsombor" uniqKey="Szoke Kovacs Z" first="Zsombor" last="Szoke-Kovacs">Zsombor Szoke-Kovacs</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Tamura, Masaru" sort="Tamura, Masaru" uniqKey="Tamura M" first="Masaru" last="Tamura">Masaru Tamura</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Trainor, Amanda G" sort="Trainor, Amanda G" uniqKey="Trainor A" first="Amanda G" last="Trainor">Amanda G. Trainor</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tudose, Ilinca" sort="Tudose, Ilinca" uniqKey="Tudose I" first="Ilinca" last="Tudose">Ilinca Tudose</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wakana, Shigeharu" sort="Wakana, Shigeharu" uniqKey="Wakana S" first="Shigeharu" last="Wakana">Shigeharu Wakana</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Warren, Jonathan" sort="Warren, Jonathan" uniqKey="Warren J" first="Jonathan" last="Warren">Jonathan Warren</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wendling, Olivia" sort="Wendling, Olivia" uniqKey="Wendling O" first="Olivia" last="Wendling">Olivia Wendling</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="West, David B" sort="West, David B" uniqKey="West D" first="David B" last="West">David B. West</name><affiliation><nlm:affiliation>Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Wong, Leeyean" sort="Wong, Leeyean" uniqKey="Wong L" first="Leeyean" last="Wong">Leeyean Wong</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Yoshiki, Atsushi" sort="Yoshiki, Atsushi" uniqKey="Yoshiki A" first="Atsushi" last="Yoshiki">Atsushi Yoshiki</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Macarthur, Daniel G" sort="Macarthur, Daniel G" uniqKey="Macarthur D" first="Daniel G" last="Macarthur">Daniel G. Macarthur</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tocchini Valentini, Glauco P" sort="Tocchini Valentini, Glauco P" uniqKey="Tocchini Valentini G" first="Glauco P" last="Tocchini-Valentini">Glauco P. Tocchini-Valentini</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, Xiang" sort="Gao, Xiang" uniqKey="Gao X" first="Xiang" last="Gao">Xiang Gao</name><affiliation><nlm:affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</nlm:affiliation></affiliation></author><author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Bradley, Allan" sort="Bradley, Allan" uniqKey="Bradley A" first="Allan" last="Bradley">Allan Bradley</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Skarnes, William C" sort="Skarnes, William C" uniqKey="Skarnes W" first="William C" last="Skarnes">William C. Skarnes</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Justice, Monica J" sort="Justice, Monica J" uniqKey="Justice M" first="Monica J" last="Justice">Monica J. Justice</name><affiliation><nlm:affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Parkinson, Helen E" sort="Parkinson, Helen E" uniqKey="Parkinson H" first="Helen E" last="Parkinson">Helen E. Parkinson</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Moore, Mark" sort="Moore, Mark" uniqKey="Moore M" first="Mark" last="Moore">Mark Moore</name><affiliation><nlm:affiliation>IMPC, San Anselmo, California 94960, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Wells, Sara" sort="Wells, Sara" uniqKey="Wells S" first="Sara" last="Wells">Sara Wells</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Braun, Robert E" sort="Braun, Robert E" uniqKey="Braun R" first="Robert E" last="Braun">Robert E. Braun</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Svenson, Karen L" sort="Svenson, Karen L" uniqKey="Svenson K" first="Karen L" last="Svenson">Karen L. Svenson</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="De Angelis, Martin Hrabe" sort="De Angelis, Martin Hrabe" uniqKey="De Angelis M" first="Martin Hrabe" last="De Angelis">Martin Hrabe De Angelis</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Herault, Yann" sort="Herault, Yann" uniqKey="Herault Y" first="Yann" last="Herault">Yann Herault</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mohun, Tim" sort="Mohun, Tim" uniqKey="Mohun T" first="Tim" last="Mohun">Tim Mohun</name><affiliation><nlm:affiliation>The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW1 1AT, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mallon, Ann Marie" sort="Mallon, Ann Marie" uniqKey="Mallon A" first="Ann-Marie" last="Mallon">Ann-Marie Mallon</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Henkelman, R Mark" sort="Henkelman, R Mark" uniqKey="Henkelman R" first="R Mark" last="Henkelman">R Mark Henkelman</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, Steve D M" sort="Brown, Steve D M" uniqKey="Brown S" first="Steve D M" last="Brown">Steve D M. Brown</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Adams, David J" sort="Adams, David J" uniqKey="Adams D" first="David J" last="Adams">David J. Adams</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lloyd, K C Kent" sort="Lloyd, K C Kent" uniqKey="Lloyd K" first="K C Kent" last="Lloyd">K C Kent Lloyd</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mckerlie, Colin" sort="Mckerlie, Colin" uniqKey="Mckerlie C" first="Colin" last="Mckerlie">Colin Mckerlie</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Beaudet, Arthur L" sort="Beaudet, Arthur L" uniqKey="Beaudet A" first="Arthur L" last="Beaudet">Arthur L. Beaudet</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bu An, Maja" sort="Bu An, Maja" uniqKey="Bu An M" first="Maja" last="Bu An">Maja Bu An</name><affiliation><nlm:affiliation>Departments of Genetics and Psychiatry, Perlman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Murray, Stephen A" sort="Murray, Stephen A" uniqKey="Murray S" first="Stephen A" last="Murray">Stephen A. Murray</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27626380</idno><idno type="pmid">27626380</idno><idno type="doi">10.1038/nature19356</idno><idno type="wicri:Area/PubMed/Corpus">000086</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000086</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">High-throughput discovery of novel developmental phenotypes.</title><author><name sortKey="Dickinson, Mary E" sort="Dickinson, Mary E" uniqKey="Dickinson M" first="Mary E" last="Dickinson">Mary E. Dickinson</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Flenniken, Ann M" sort="Flenniken, Ann M" uniqKey="Flenniken A" first="Ann M" last="Flenniken">Ann M. Flenniken</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Xiao" sort="Ji, Xiao" uniqKey="Ji X" first="Xiao" last="Ji">Xiao Ji</name><affiliation><nlm:affiliation>Genomics and Computational Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Teboul, Lydia" sort="Teboul, Lydia" uniqKey="Teboul L" first="Lydia" last="Teboul">Lydia Teboul</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wong, Michael D" sort="Wong, Michael D" uniqKey="Wong M" first="Michael D" last="Wong">Michael D. Wong</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="White, Jacqueline K" sort="White, Jacqueline K" uniqKey="White J" first="Jacqueline K" last="White">Jacqueline K. White</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Meehan, Terrence F" sort="Meehan, Terrence F" uniqKey="Meehan T" first="Terrence F" last="Meehan">Terrence F. Meehan</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Weninger, Wolfgang J" sort="Weninger, Wolfgang J" uniqKey="Weninger W" first="Wolfgang J" last="Weninger">Wolfgang J. Weninger</name><affiliation><nlm:affiliation>Centre for Anatomy and Cell Biology, Medical University of Vienna, Vienna A-1090, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Westerberg, Henrik" sort="Westerberg, Henrik" uniqKey="Westerberg H" first="Henrik" last="Westerberg">Henrik Westerberg</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Adissu, Hibret" sort="Adissu, Hibret" uniqKey="Adissu H" first="Hibret" last="Adissu">Hibret Adissu</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Baker, Candice N" sort="Baker, Candice N" uniqKey="Baker C" first="Candice N" last="Baker">Candice N. Baker</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bower, Lynette" sort="Bower, Lynette" uniqKey="Bower L" first="Lynette" last="Bower">Lynette Bower</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, James M" sort="Brown, James M" uniqKey="Brown J" first="James M" last="Brown">James M. Brown</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Caddle, L Brianna" sort="Caddle, L Brianna" uniqKey="Caddle L" first="L Brianna" last="Caddle">L Brianna Caddle</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Chiani, Francesco" sort="Chiani, Francesco" uniqKey="Chiani F" first="Francesco" last="Chiani">Francesco Chiani</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Clary, Dave" sort="Clary, Dave" uniqKey="Clary D" first="Dave" last="Clary">Dave Clary</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Cleak, James" sort="Cleak, James" uniqKey="Cleak J" first="James" last="Cleak">James Cleak</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Daly, Mark J" sort="Daly, Mark J" uniqKey="Daly M" first="Mark J" last="Daly">Mark J. Daly</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Denegre, James M" sort="Denegre, James M" uniqKey="Denegre J" first="James M" last="Denegre">James M. Denegre</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Doe, Brendan" sort="Doe, Brendan" uniqKey="Doe B" first="Brendan" last="Doe">Brendan Doe</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Dolan, Mary E" sort="Dolan, Mary E" uniqKey="Dolan M" first="Mary E" last="Dolan">Mary E. Dolan</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Edie, Sarah M" sort="Edie, Sarah M" uniqKey="Edie S" first="Sarah M" last="Edie">Sarah M. Edie</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Fuchs, Helmut" sort="Fuchs, Helmut" uniqKey="Fuchs H" first="Helmut" last="Fuchs">Helmut Fuchs</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Gailus Durner, Valerie" sort="Gailus Durner, Valerie" uniqKey="Gailus Durner V" first="Valerie" last="Gailus-Durner">Valerie Gailus-Durner</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Galli, Antonella" sort="Galli, Antonella" uniqKey="Galli A" first="Antonella" last="Galli">Antonella Galli</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gambadoro, Alessia" sort="Gambadoro, Alessia" uniqKey="Gambadoro A" first="Alessia" last="Gambadoro">Alessia Gambadoro</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gallegos, Juan" sort="Gallegos, Juan" uniqKey="Gallegos J" first="Juan" last="Gallegos">Juan Gallegos</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Guo, Shiying" sort="Guo, Shiying" uniqKey="Guo S" first="Shiying" last="Guo">Shiying Guo</name><affiliation><nlm:affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</nlm:affiliation></affiliation></author><author><name sortKey="Horner, Neil R" sort="Horner, Neil R" uniqKey="Horner N" first="Neil R" last="Horner">Neil R. Horner</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Chih Wei" sort="Hsu, Chih Wei" uniqKey="Hsu C" first="Chih-Wei" last="Hsu">Chih-Wei Hsu</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Johnson, Sara J" sort="Johnson, Sara J" uniqKey="Johnson S" first="Sara J" last="Johnson">Sara J. Johnson</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Kalaga, Sowmya" sort="Kalaga, Sowmya" uniqKey="Kalaga S" first="Sowmya" last="Kalaga">Sowmya Kalaga</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Keith, Lance C" sort="Keith, Lance C" uniqKey="Keith L" first="Lance C" last="Keith">Lance C. Keith</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lanoue, Louise" sort="Lanoue, Louise" uniqKey="Lanoue L" first="Louise" last="Lanoue">Louise Lanoue</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lawson, Thomas N" sort="Lawson, Thomas N" uniqKey="Lawson T" first="Thomas N" last="Lawson">Thomas N. Lawson</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lek, Monkol" sort="Lek, Monkol" uniqKey="Lek M" first="Monkol" last="Lek">Monkol Lek</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mark, Manuel" sort="Mark, Manuel" uniqKey="Mark M" first="Manuel" last="Mark">Manuel Mark</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Marschall, Susan" sort="Marschall, Susan" uniqKey="Marschall S" first="Susan" last="Marschall">Susan Marschall</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Mason, Jeremy" sort="Mason, Jeremy" uniqKey="Mason J" first="Jeremy" last="Mason">Jeremy Mason</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mcelwee, Melissa L" sort="Mcelwee, Melissa L" uniqKey="Mcelwee M" first="Melissa L" last="Mcelwee">Melissa L. Mcelwee</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Newbigging, Susan" sort="Newbigging, Susan" uniqKey="Newbigging S" first="Susan" last="Newbigging">Susan Newbigging</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Nutter, Lauryl M J" sort="Nutter, Lauryl M J" uniqKey="Nutter L" first="Lauryl M J" last="Nutter">Lauryl M J. Nutter</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Peterson, Kevin A" sort="Peterson, Kevin A" uniqKey="Peterson K" first="Kevin A" last="Peterson">Kevin A. Peterson</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ramirez Solis, Ramiro" sort="Ramirez Solis, Ramiro" uniqKey="Ramirez Solis R" first="Ramiro" last="Ramirez-Solis">Ramiro Ramirez-Solis</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Rowland, Douglas J" sort="Rowland, Douglas J" uniqKey="Rowland D" first="Douglas J" last="Rowland">Douglas J. Rowland</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ryder, Edward" sort="Ryder, Edward" uniqKey="Ryder E" first="Edward" last="Ryder">Edward Ryder</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Samocha, Kaitlin E" sort="Samocha, Kaitlin E" uniqKey="Samocha K" first="Kaitlin E" last="Samocha">Kaitlin E. Samocha</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Seavitt, John R" sort="Seavitt, John R" uniqKey="Seavitt J" first="John R" last="Seavitt">John R. Seavitt</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Selloum, Mohammed" sort="Selloum, Mohammed" uniqKey="Selloum M" first="Mohammed" last="Selloum">Mohammed Selloum</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Szoke Kovacs, Zsombor" sort="Szoke Kovacs, Zsombor" uniqKey="Szoke Kovacs Z" first="Zsombor" last="Szoke-Kovacs">Zsombor Szoke-Kovacs</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Tamura, Masaru" sort="Tamura, Masaru" uniqKey="Tamura M" first="Masaru" last="Tamura">Masaru Tamura</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Trainor, Amanda G" sort="Trainor, Amanda G" uniqKey="Trainor A" first="Amanda G" last="Trainor">Amanda G. Trainor</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tudose, Ilinca" sort="Tudose, Ilinca" uniqKey="Tudose I" first="Ilinca" last="Tudose">Ilinca Tudose</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wakana, Shigeharu" sort="Wakana, Shigeharu" uniqKey="Wakana S" first="Shigeharu" last="Wakana">Shigeharu Wakana</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Warren, Jonathan" sort="Warren, Jonathan" uniqKey="Warren J" first="Jonathan" last="Warren">Jonathan Warren</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Wendling, Olivia" sort="Wendling, Olivia" uniqKey="Wendling O" first="Olivia" last="Wendling">Olivia Wendling</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="West, David B" sort="West, David B" uniqKey="West D" first="David B" last="West">David B. West</name><affiliation><nlm:affiliation>Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Wong, Leeyean" sort="Wong, Leeyean" uniqKey="Wong L" first="Leeyean" last="Wong">Leeyean Wong</name><affiliation><nlm:affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Yoshiki, Atsushi" sort="Yoshiki, Atsushi" uniqKey="Yoshiki A" first="Atsushi" last="Yoshiki">Atsushi Yoshiki</name><affiliation><nlm:affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Macarthur, Daniel G" sort="Macarthur, Daniel G" uniqKey="Macarthur D" first="Daniel G" last="Macarthur">Daniel G. Macarthur</name><affiliation><nlm:affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Tocchini Valentini, Glauco P" sort="Tocchini Valentini, Glauco P" uniqKey="Tocchini Valentini G" first="Glauco P" last="Tocchini-Valentini">Glauco P. Tocchini-Valentini</name><affiliation><nlm:affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, Xiang" sort="Gao, Xiang" uniqKey="Gao X" first="Xiang" last="Gao">Xiang Gao</name><affiliation><nlm:affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</nlm:affiliation></affiliation></author><author><name sortKey="Flicek, Paul" sort="Flicek, Paul" uniqKey="Flicek P" first="Paul" last="Flicek">Paul Flicek</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Bradley, Allan" sort="Bradley, Allan" uniqKey="Bradley A" first="Allan" last="Bradley">Allan Bradley</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Skarnes, William C" sort="Skarnes, William C" uniqKey="Skarnes W" first="William C" last="Skarnes">William C. Skarnes</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Justice, Monica J" sort="Justice, Monica J" uniqKey="Justice M" first="Monica J" last="Justice">Monica J. Justice</name><affiliation><nlm:affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Parkinson, Helen E" sort="Parkinson, Helen E" uniqKey="Parkinson H" first="Helen E" last="Parkinson">Helen E. Parkinson</name><affiliation><nlm:affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Moore, Mark" sort="Moore, Mark" uniqKey="Moore M" first="Mark" last="Moore">Mark Moore</name><affiliation><nlm:affiliation>IMPC, San Anselmo, California 94960, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Wells, Sara" sort="Wells, Sara" uniqKey="Wells S" first="Sara" last="Wells">Sara Wells</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Braun, Robert E" sort="Braun, Robert E" uniqKey="Braun R" first="Robert E" last="Braun">Robert E. Braun</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Svenson, Karen L" sort="Svenson, Karen L" uniqKey="Svenson K" first="Karen L" last="Svenson">Karen L. Svenson</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author><author><name sortKey="De Angelis, Martin Hrabe" sort="De Angelis, Martin Hrabe" uniqKey="De Angelis M" first="Martin Hrabe" last="De Angelis">Martin Hrabe De Angelis</name><affiliation><nlm:affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Herault, Yann" sort="Herault, Yann" uniqKey="Herault Y" first="Yann" last="Herault">Yann Herault</name><affiliation><nlm:affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mohun, Tim" sort="Mohun, Tim" uniqKey="Mohun T" first="Tim" last="Mohun">Tim Mohun</name><affiliation><nlm:affiliation>The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW1 1AT, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mallon, Ann Marie" sort="Mallon, Ann Marie" uniqKey="Mallon A" first="Ann-Marie" last="Mallon">Ann-Marie Mallon</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Henkelman, R Mark" sort="Henkelman, R Mark" uniqKey="Henkelman R" first="R Mark" last="Henkelman">R Mark Henkelman</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Brown, Steve D M" sort="Brown, Steve D M" uniqKey="Brown S" first="Steve D M" last="Brown">Steve D M. Brown</name><affiliation><nlm:affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Adams, David J" sort="Adams, David J" uniqKey="Adams D" first="David J" last="Adams">David J. Adams</name><affiliation><nlm:affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Lloyd, K C Kent" sort="Lloyd, K C Kent" uniqKey="Lloyd K" first="K C Kent" last="Lloyd">K C Kent Lloyd</name><affiliation><nlm:affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mckerlie, Colin" sort="Mckerlie, Colin" uniqKey="Mckerlie C" first="Colin" last="Mckerlie">Colin Mckerlie</name><affiliation><nlm:affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Beaudet, Arthur L" sort="Beaudet, Arthur L" uniqKey="Beaudet A" first="Arthur L" last="Beaudet">Arthur L. Beaudet</name><affiliation><nlm:affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bu An, Maja" sort="Bu An, Maja" uniqKey="Bu An M" first="Maja" last="Bu An">Maja Bu An</name><affiliation><nlm:affiliation>Departments of Genetics and Psychiatry, Perlman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania 19104, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Murray, Stephen A" sort="Murray, Stephen A" uniqKey="Murray S" first="Stephen A" last="Murray">Stephen A. Murray</name><affiliation><nlm:affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">27626380</PMID><DateCreated><Year>2016</Year><Month>09</Month><Day>22</Day></DateCreated><DateRevised><Year>2017</Year><Month>02</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN><JournalIssue CitedMedium="Internet"><Volume>537</Volume><Issue>7621</Issue><PubDate><Year>2016</Year><Month>Sep</Month><Day>22</Day></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>High-throughput discovery of novel developmental phenotypes.</ArticleTitle><Pagination><MedlinePgn>508-514</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nature19356</ELocationID><Abstract><AbstractText NlmCategory="UNASSIGNED">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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dickinson</LastName><ForeName>Mary E</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flenniken</LastName><ForeName>Ann M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ji</LastName><ForeName>Xiao</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Genomics and Computational Biology Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teboul</LastName><ForeName>Lydia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Michael D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>White</LastName><ForeName>Jacqueline K</ForeName><Initials>JK</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meehan</LastName><ForeName>Terrence F</ForeName><Initials>TF</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weninger</LastName><ForeName>Wolfgang J</ForeName><Initials>WJ</Initials><AffiliationInfo><Affiliation>Centre for Anatomy and Cell Biology, Medical University of Vienna, Vienna A-1090, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Westerberg</LastName><ForeName>Henrik</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adissu</LastName><ForeName>Hibret</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baker</LastName><ForeName>Candice N</ForeName><Initials>CN</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bower</LastName><ForeName>Lynette</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brown</LastName><ForeName>James M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Caddle</LastName><ForeName>L Brianna</ForeName><Initials>LB</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chiani</LastName><ForeName>Francesco</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Clary</LastName><ForeName>Dave</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cleak</LastName><ForeName>James</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Daly</LastName><ForeName>Mark J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Program in Medical and Population Genetics, Broad Institute MIT and Harvard, Cambridge, Massachusetts 02142, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Denegre</LastName><ForeName>James M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Doe</LastName><ForeName>Brendan</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dolan</LastName><ForeName>Mary E</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Edie</LastName><ForeName>Sarah M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fuchs</LastName><ForeName>Helmut</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gailus-Durner</LastName><ForeName>Valerie</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Galli</LastName><ForeName>Antonella</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gambadoro</LastName><ForeName>Alessia</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallegos</LastName><ForeName>Juan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guo</LastName><ForeName>Shiying</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horner</LastName><ForeName>Neil R</ForeName><Initials>NR</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>Chih-Wei</ForeName><Initials>CW</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Sara J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kalaga</LastName><ForeName>Sowmya</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Keith</LastName><ForeName>Lance C</ForeName><Initials>LC</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lanoue</LastName><ForeName>Louise</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lawson</LastName><ForeName>Thomas N</ForeName><Initials>TN</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lek</LastName><ForeName>Monkol</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Program in Medical and Population Genetics, Broad Institute MIT and Harvard, Cambridge, Massachusetts 02142, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mark</LastName><ForeName>Manuel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marschall</LastName><ForeName>Susan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg 85764, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mason</LastName><ForeName>Jeremy</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McElwee</LastName><ForeName>Melissa L</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Newbigging</LastName><ForeName>Susan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nutter</LastName><ForeName>Lauryl M J</ForeName><Initials>LM</Initials><AffiliationInfo><Affiliation>The Toronto Centre for Phenogenomics, Toronto, Ontario M5T 3H7, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peterson</LastName><ForeName>Kevin A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>The Jackson Laboratory, Bar Harbor, Maine 04609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramirez-Solis</LastName><ForeName>Ramiro</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rowland</LastName><ForeName>Douglas J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ryder</LastName><ForeName>Edward</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Samocha</LastName><ForeName>Kaitlin E</ForeName><Initials>KE</Initials><AffiliationInfo><Affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Program in Medical and Population Genetics, Broad Institute MIT and Harvard, Cambridge, Massachusetts 02142, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seavitt</LastName><ForeName>John R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Selloum</LastName><ForeName>Mohammed</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szoke-Kovacs</LastName><ForeName>Zsombor</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tamura</LastName><ForeName>Masaru</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trainor</LastName><ForeName>Amanda G</ForeName><Initials>AG</Initials><AffiliationInfo><Affiliation>Mouse Biology Program, University of California, Davis, California 95618, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tudose</LastName><ForeName>Ilinca</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wakana</LastName><ForeName>Shigeharu</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Warren</LastName><ForeName>Jonathan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wendling</LastName><ForeName>Olivia</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>West</LastName><ForeName>David B</ForeName><Initials>DB</Initials><AffiliationInfo><Affiliation>Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Leeyean</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yoshiki</LastName><ForeName>Atsushi</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>International Mouse Phenotyping Consortium</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Jackson Laboratory</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS)</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Charles River Laboratories</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>MRC Harwell</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Toronto Centre for Phenogenomics</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>Wellcome Trust Sanger Institute</CollectiveName></Author><Author ValidYN="Y"><CollectiveName>RIKEN BioResource Center</CollectiveName></Author><Author ValidYN="Y"><LastName>MacArthur</LastName><ForeName>Daniel G</ForeName><Initials>DG</Initials><AffiliationInfo><Affiliation>Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Program in Medical and Population Genetics, Broad Institute MIT and Harvard, Cambridge, Massachusetts 02142, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tocchini-Valentini</LastName><ForeName>Glauco P</ForeName><Initials>GP</Initials><AffiliationInfo><Affiliation>Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo I-00015, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Xiang</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flicek</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bradley</LastName><ForeName>Allan</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Skarnes</LastName><ForeName>William C</ForeName><Initials>WC</Initials><AffiliationInfo><Affiliation>The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Justice</LastName><ForeName>Monica J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Parkinson</LastName><ForeName>Helen E</ForeName><Initials>HE</Initials><AffiliationInfo><Affiliation>European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moore</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>IMPC, San Anselmo, California 94960, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wells</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Braun</LastName><ForeName>Robert 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Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Herault</LastName><ForeName>Yann</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS), et Institut de Génétique Biologie Moléculaire et Cellulaire (IGBMC) CNRS, INSERM, University of Strasbourg, Illkirch-Graffenstaden 67404, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohun</LastName><ForeName>Tim</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>The Francis Crick Institute Mill Hill Laboratory, The Ridgeway, Mill Hill, London NW1 1AT, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mallon</LastName><ForeName>Ann-Marie</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire OX11 0RD, UK.</Affiliation></AffiliationInfo></Author><Author 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