RT Journal
A1 Fairfield, Heather
A1 Srivastava, Anuj
A1 Ananda, Guruprasad
A1 Liu, Rangjiao
A1 Kircher, Martin
A1 Lakshminarayana, Anuradha
A1 Harris, Belinda S.
A1 Karst, Son Yong
A1 Dionne, Louise A.
A1 Kane, Coleen C.
A1 Curtain, Michelle
A1 Berry, Melissa L.
A1 Ward-Bailey, Patricia F.
A1 Greenstein, Ian
A1 Byers, Candice
A1 Czechanski, Anne
A1 Sharp, Jocelyn
A1 Palmer, Kristina
A1 Gudis, Polyxeni
A1 Martin, Whitney
A1 Tadenev, Abby
A1 Bogdanik, Laurent
A1 Pratt, C. Herbert
A1 Chang, Bo
A1 Schroeder, David G.
A1 Cox, Gregory A.
A1 Cliften, Paul
A1 Milbrandt, Jeffrey
A1 Murray, Stephen
A1 Burgess, Robert
A1 Bergstrom, David E.
A1 Donahue, Leah Rae
A1 Hamamy, Hanan
A1 Masri, Amira
A1 Santoni, Federico A.
A1 Makrythanasis, Periklis
A1 Antonarakis, Stylianos E.
A1 Shendure, Jay
A1 Reinholdt, Laura G.
T1 Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders
JF Genome Research 
JO Genome Research 
YR 2015 
FD July 01 
VO 25 
IS 7 
SP 948 
OP 957 
DO 10.1101/gr.186882.114 
UL http://genome.cshlp.org/content/25/7/948.abstract 
AB Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics pipeline that is optimized for mouse exome data and a variation database that allows for reproducible, user-defined data mining as well as nomination of mutation candidates through knowledge-based integration of sample and variant data. Using these new tools, putative pathogenic mutations were identified for 91 (53%) of the strains in our study. Despite the increased power offered by potentially unlimited pedigrees and controlled breeding, about half of our exome cases remained unsolved. Using a combination of manual analyses of exome alignments and whole-genome sequencing, we provide evidence that a large fraction of unsolved exome cases have underlying structural mutations. This result directly informs efforts to investigate the similar proportion of apparently Mendelian human phenotypes that are recalcitrant to exome sequencing.