This article is part of a special issue on exome sequencing.

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Mutation discovery in mice by whole exome sequencing

Heather Fairfield1, Griffith J Gilbert1, Mary Barter1, Rebecca R Corrigan2, Michelle Curtain1, Yueming Ding3, Mark D'Ascenzo4, Daniel J Gerhardt4, Chao He5, Wenhui Huang6, Todd Richmond4, Lucy Rowe1, Frank J Probst2, David E Bergstrom1, Stephen A Murray1, Carol Bult1, Joel Richardson1, Benjamin T Kile7, Ivo Gut8, Jorg Hager8, Snaevar Sigurdsson9, Evan Mauceli9, Federica Di Palma9, Kerstin Lindblad-Toh9, Michael L Cunningham10, Timothy C Cox10, Monica J Justice2, Mona S Spector5, Scott W Lowe5, Thomas Albert4, Leah Rae Donahue1, Jeffrey Jeddeloh4, Jay Shendure10 and Laura G Reinholdt1*

Author Affiliations

1 The Jackson Laboratory, 600 Main St, Bar Harbor, ME 04609, USA

2 Baylor College of Medicine, Department of Molecular and Human Genetics, One Baylor Plaza R804, Houston, Texas 77030, USA

3 Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA

4 Roche NimbleGen, Inc. Madison, WI 53719, USA

5 National Center for Genome Analysis (CNAG), Parc Científic de Barcelona, Torre I, Baldiri Reixac, 408028 Barcelona, Spain

6 Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052, Australia

7 University of Washington, Department of Pediatrics, Division of Craniofacial Medicine and Seattle Children's Craniofacial Center, 4800 Sand Point Way NE, Seattle, WA 98105, USA

8 Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA

9 Broad Institute of Massachusetts Institute of Technology and Harvard, 5 Cambridge Center, Cambridge, MA 02142, USA

10 University of Washington, Department of Genome Sciences, Foege Building S-250, Box 355065, 3720 15th Ave NE, Seattle, WA 98195-5065, USA

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Genome Biology 2011, 12:R86  doi:10.1186/gb-2011-12-9-r86

Published: 14 September 2011


We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis.