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

2013; Cell Press; Volume: 154; Issue: 2 Linguagem: Inglês

10.1016/j.cell.2013.06.022

1097-4172

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 Houghton, Jeanne Estabel, Joanna Bottomley, David Melvin, David Sunter, Niels C. Adams, David Tannahill, Darren W. 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 Baker, Caroline Barnes, Ryan M. Beveridge, Emma L. Cambridge, Damian M. Carragher, Prabhjoat Chana, Kay Clarke, Yvette Hooks, Natalia Igosheva, Ozama Ismail, Hannah Jackson, Leanne Kane, R. W. Lacey, David Lafont, Mark Lucas, Simon Maguire, Katherine McGill, Rebecca E. McIntyre, Sophie Messager, Lynda Mottram, Lee Mulderrig, Selina Pearson, Hayley Protheroe, Laura-Anne Roberson, Grace Salsbury, Mark Sanderson, Daniel Sanger, Carl Shannon, Peter Thompson, Elizabeth Tuck, Valerie E. Vancollie, Lisa Brackenbury, Wendy Bushell, Ross Cook, Priya 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 R. Woodward, Elizabeth Wynn, Arthur Evans, David Gannon, Mark Griffiths, S. Holroyd, Vivek Iyer, Christian Kipp, Morag A. Lewis, Wei Li, Darren Oakley, David Richardson, Damian Smedley, Chukwuma A. Agu, Jackie Bryant, Liz Delaney, Nadia I. Gueorguieva, Helen Tharagonnet, Alan J. Townsend, Daniel Biggs, Ellen Brown, Adam Collinson, Charles-Étienne Dumeau, Evelyn Grau, Sarah Harrison, James Harrison, Catherine Ingle, Harun Kundi, Alla Madich, Danielle Mayhew, Tom Metcalf, Stuart Newman, Johanna Pass, Laila Pearson, Helen Reynolds, Caroline Sinclair, Hannah Wardle‐Jones, Michael Woods, Liam Alexander, Terry Brown, Francesca Flack, Carole Frost, Nicola Griggs, Silvia Hrnciarova, Andrea Kirton, J. Mcdermott, Christian M. Rogerson, Gemma V. White, Pawel Zielezinski, Tia DiTommaso, Andrew Edwards, Emma Heath, Mayank Mahajan, Binnaz Yalcin,

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/cms/asset/e2870fc0-4980-42ad-905d-f0f0edb74a34/mmc9.mp3Loading ...(mp3, 3.09 MB) Download audio