Mutation discovery in mice by whole exome sequencing

• Published in: Genome Biology Vol. 12; no. 9; p. R86
• Main Authors: Fairfield, Heather, Gilbert, Griffith J, Barter, Mary, Corrigan, Rebecca R, Curtain, Michelle, Ding, Yueming, D'Ascenzo, Mark, Gerhardt, Daniel J, He, Chao, Huang, Wenhui, Richmond, Todd, Rowe, Lucy, Probst, Frank J, Bergstrom, David E, Murray, Stephen A, Bult, Carol, Richardson, Joel, Kile, Benjamin T, Gut, Ivo, Hager, Jorg, Sigurdsson, Snaevar, Mauceli, Evan, Di Palma, Federica, Lindblad-Toh, Kerstin, Cunningham, Michael L, Cox, Timothy C, Justice, Monica J, Spector, Mona S, Lowe, Scott W, Albert, Thomas, Donahue, Leah Rae, Jeddeloh, Jeffrey, Shendure, Jay, Reinholdt, Laura G
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.09.2011; BioMed Central
• Subjects: Animals; Chromosome Mapping; Chromosomes, Mammalian - genetics; Collagen Type II - genetics; DNA Mutational Analysis - methods; Exome; Exons; Gene Frequency; Genomics - methods; Genotype; INDEL Mutation; Indicators and Reagents - standards; MAP Kinase Kinase Kinases - genetics; Method; Mice; Mice, Inbred Strains; Mitogen-Activated Protein Kinase Kinase Kinase 11; Mutation; Phenotype
• ISSN: 1474-760X; 1465-6906; 1474-760X; 1465-6914
• DOI: 10.1186/gb-2011-12-9-r86

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.