Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes

作者：Jacqueline K. White, Anna-Karin Gerdin, Natasha A. Karp, Edward J. Ryder, Marija Buljan, James Bussell, Jennifer Salisbury, Simon Clare, Neil J. Ingham, Christine Podrini, Richard C. Houghton, Jeanne Estabel, Joanna R. BOTTOMLEY, David G. Melvin, David Sunter, Niels C. Adams, David Tannahill, Darren William Logan, Daniel G. MacArthur, Jonathan Flint, Vinit B. Mahajan, Stephen H. Tsang, Ian Smyth, Fiona M. Watt, William C. Skarnes, Gordon Dougan, David J. Adams, Ramiro Ramírez‐Solis, Allan Bradley, Karen P. Steel, Lauren A. Baker, Caroline Barnes, Ryan M. Beveridge, Emma L. Cambridge, Damian M. Carragher, Prabhjoat S. Chana, Kay Clarke, Yvette E. Hooks, Natalia Igosheva, Ozama Ismail, Hannah J. Jackson, Leanne Kane, Rosalind Lacey, David Lafont, Mark Lucas, Simon Maguire, Katherine McGill, Rebecca E. McIntyre, Sophie Messager, Lynda Mottram, Lee Mulderrig, Selina A. Pearson, Hayley Protheroe, Laura-Anne Roberson, Grace Salsbury, Mark F. Sanderson, Daniel Sanger, Carl Shannon, Paul C. Thompson, Elizabeth J. Tuck, Valerie E. Vancollie, Lisa Brackenbury, Wendy Bushell, Ross Cook, Priya S. Dalvi, Diane Gleeson, Bishoy Habib, Matt Hardy, Kifayathullah Liakath‐Ali, Evelina Miklejewska, Stacey Price, Debarati Sethi, Elizabeth Trenchard, Dominique Von Schiller, Sapna Vyas, Anthony P. West, John Robert Woodward, Elizabeth H. Wynn, Arthur Evans, David Gannon, Mark N. D. Griffiths, Simon A. Holroyd, Vivek Iyer, Christian Kipp, Morag A. Lewis, Wei Li, Darren Oakley, David Richardson, Damian P. Smedley, Chukwuma A. Agu, Jackie Bryant, Liz Delaney, Nadia I. Gueorguieva, Helen Tharagonnet, Anne J. Townsend, Daniel Biggs, Ellen D Brown, Adam Collinson, Charles-Étienne Dumeau, Evelyn Grau, Sarah J. Harrison, Jamie Harrison, Catherine Ingle, Helen Kundi, Alla Madich, Danielle Mayhew, Tom Metcalf, Stuart Newman, Johanna C. Pass, Laila Pearson, Helen Reynolds, Caroline Sinclair, Hannah Wardle‐Jones, Michael E. Woods, Liam Alexander, Terry Brown, Francesca Flack, Carole Frost, Nicola Griggs, Silvia Hrnciarova, Andrea Kirton, Jordan McDermott, Claire Rogerson, Gemma V. White, Pawel Zielezinski, Tia DiTommaso, Andrew Edwards, Emma Heath, Mary Ann Mahajan, Binnaz Yalcin · 发表于：Cell · 年份：2013 · DOI：10.1016/j.cell.2013.06.022 · 被引用次数：549 · 研究领域：CRISPR and Genetic Engineering、Bioinformatics and Genomic Networks、Receptor Mechanisms and Signaling

Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP: