Identification of genes required for eye development by high-throughput screening of mouse knockouts

Communications Biology - Tập 1 Số 1
Bret A. Moore1, Brian C. Leonard2, Lionel Sebbag1, Sydney Edwards1, Ann Cooper1, Denise M. Imai3, Ewan Straiton4, Luís Santos4, Christopher M. Reilly3, Stephen M. Griffey3, Lynette Bower5, Dave Clary5, Jeremy Mason6, Michelle Simon7, Hamid Méziane7, Yann Hérault7, Anna Swan4, Ruairidh King4, Piia Keskivali-Bond4, Lois Kelsey8, Igor Vukobradovic8, Dawei Qu8, Ruolin Guo8, Elisa Tran8, Lily Morikawa8, Milan Ganguly8, Napoleon Law8, Xueyuan Shang8, Patricia Feugas8, Yanchun Wang8, Yingchun Zhu8, Kyle Duffin8, Ayexa Ramirez8, Patricia Penton8, Valerie Laurin8, Shannon Clarke8, Qing Lan8, Gillian Sleep8, Amie Creighton8, Elsa Jacob8, Heather Cater8, Joanna Joeng8, Marina Gertsenstein8, Monica Pereira8, Sue MacMaster8, Sandra Tondat8, Thomas J. Carroll8, Jorge Cabezas8, Je Kyung Seong8, Jane Hunter8, Gregory B. Clark8, Mohammed Bubshait8, D. Craig Miller8, Khondoker Sohel8, Alexandr Bezginov8, Matthew McKay9, Kevin Peterson9, Leslie Goodwin9, Rachel Urban9, Susan Kales9, Robin Hallett9, Dong Nguyen-Bresinsky9, Timothy Leach9, Audrie Seluke9, Sara Perkins9, Ann‐Marie Mallon9, Rick Bedigian9, Leah Rae Donahue9, Robert A. Taft9, James M. Denegre9, Zachery Seavey9, Amelia Willett9, Lindsay Bates9, Leslie Haynes9, Julie Creed9, Catherine Witmeyer9, Willson Roper9, James Clark9, Pamela Stanley9, Samantha Burrill9, Jennifer Ryan9, Yuichi Obata10, Masaru Tamura10, Hideki Kaneda10, Tamio Furuse10, Kimio Kobayashi10, Ikuo Miura10, Ikuko Yamada10, Hiroshi Masuya10, Nobuhiko Tanaka10, Shin‐ichi Ayabe10, Atsushi Yoshiki10, Valerie E. Vancollie11, Francesco Chiani12, Paul Dent12, Gianfranco Di Segni12, Olga Ermakova12, Fabrizio Ferrara12, Paolo Fruscoloni12, Alessia Gambadoro12, Serena Gastaldi12, Elisabetta Golini12, Gina La Sala12, Silvia Mandillo12, Daniela Marazziti12, Marzia Massimi12, Rafaele Matteoni12, Tiziana Orsini12, Miriam Pasquini12, Marcello Raspa12, Aline Rauch12, G. F. Rossi12, Nicoletta Rossi12, Sabrina Putti12, Ferdinando Scavizzi12, Glauco P. Tocchini‐Valentini12, Colin McKerlie13, Ann M. Flenniken14, Goo Taeg Oh13, Zorana Berberovic14, Celeste Owen14, Hibret A. Adissu14, Mohammed Eskandarian14, Chih‐Wei Hsu15, Sowmya Kalaga15, Uchechukwu Udensi15, Chinwe Asomugha15, Ritu Bohat9, Juan Gallegos9, John R. Seavitt9, Jason D. Heaney9, Arthur L. Beaudet9, Mary E. Dickinson9, Vivek M. Philip16, Vivek Kumar16, Karen L. Svenson16, Robert E. Braun16, Sara Wells4, Michelle Stewart4, Russell Joynson4, Xiang Gao17, Tomohiro Suzuki10, Shigeharu Wakana10, Damian Smedley18, Mark W. Moore19, Colin Fletcher20, Natasha A. Karp11, Ramiro Ramírez‐Solis11, Jacqueline K. White11, Martin Hrabě de Angelis21, Wolfgang Wurst21, Sara M. Thomasy22, Paul Flicek6, Helen Parkinson6, S.D.M. Brown4, Terrence F. Meehan6, Patsy M. Nishina16, Stephen A. Murray16, Mark P. Krebs16, K. C. Kent Lloyd5, Christopher J. Murphy22, Ala Moshiri22
1William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, 95616, CA, USA
2Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA
3Comparative Pathology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA
4Medical Research Council Harwell Institute (Mammalian Genetis Unit and Mary Lyon Center, Harwell, Oxfordshire, OX11 0RD, UK
5Mouse Biology Program, and Department of Surgery, School of Medicine, University of California-Davis, Davis, CA, 95618, USA
6European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1 SD, UK
7Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France
8The Centre for Phenogenomics, Toronto, ON, M5T 3H7, Canada
9Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
10RIKEN BioResource Center, Tsukuba, Ibaraki, 305-0074, Japan
11The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
12Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Adriano Buzzati-Traverso Campus, Via Ramarini, I-00015, Monterotondo Scalo, Italy
13The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada
14Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
15Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
16The Jackson Laboratory, Bar Harbor, ME 04609, USA
17SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, 210061, China
18Clinical Pharmacology, Charterhouse Square, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
19International Mouse Phenotyping Consortium, San Anselmo, CA, 94960, USA
20National Institutes of Health, Bethesda, MD, 20205 USA
21German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany
22Department of Ophthalmology & Vision Science, School of Medicine, U.C. Davis, Sacramento, CA, 95817, USA

Tóm tắt

AbstractDespite advances in next generation sequencing technologies, determining the genetic basis of ocular disease remains a major challenge due to the limited access and prohibitive cost of human forward genetics. Thus, less than 4,000 genes currently have available phenotype information for any organ system. Here we report the ophthalmic findings from the International Mouse Phenotyping Consortium, a large-scale functional genetic screen with the goal of generating and phenotyping a null mutant for every mouse gene. Of 4364 genes evaluated, 347 were identified to influence ocular phenotypes, 75% of which are entirely novel in ocular pathology. This discovery greatly increases the current number of genes known to contribute to ophthalmic disease, and it is likely that many of the genes will subsequently prove to be important in human ocular development and disease.

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