Mouse Mutant Resequencing

Mouse Mutant Re-sequencing Project

The Mouse Mutant Re-sequencing project is an NHGRI-funded effort with the goal of identifying mouse mutations using high-throughput sequencing technology and to expedite the recovery of biological information from existing collections of genetically mapped ethylnitrosurea-(ENU) and spontaneous mutants. There are hundreds of well-characterized mouse mutant models, with defects in processes such as neurological function, behavior, and reproduction as well as cancer models. As many of these mutants are models for human disease, associating their phenotype to a causal genetic mutation will directly aid the understanding of the genetic mechanisms underlying human health and disease.

Mutation discovery is carried out via high-throughput sequencing of the candidate regions; sequence data will be analyzed through a customized computational pipeline to identify variants in both the mutant and associated background strain. There are two strategies currently available for the sequencing: whole-exome sequencing using a mouse array comprising the full coding and splice-junction sequence of the mouse genome (mm9) gathered from the Mouse Genome Informatics’ unified gene list; alternately, targeted sequencing of the appropriate genomic locus using a pooling strategy to increase efficiency. The appropriate sequencing strategy is based on the particular mouse mutant model and will be determined by the Broad Institute accordingly.

Data will be analyzed using an internal computational pipeline based heavily on the Genome Analysis Toolkit (McKenna et al., 2010) for identification of SNPs and small insertions and deletions. Where appropriate, copy-number variants and structural rearrangements will also be identified. When the sequencing and analysis is completed, all sequencing data, lists of candidate mutations, and extensive quality-control data will be made available to the proposing investigators.

The Coordinating Committee
The Coordinating Committee will review incoming proposals, insure that the scientific criteria for each proposals are met, organize sample procurement according to Broad Institute requirements, ensure data are returned to the investigators. Projects entering the pipeline will be selected by the Coordinating Committee based on the requirement criteria below.

Members of the Coordinating Committee

  • David Beier, M.D. Ph.D., Harvard Medical School
  • Jennifer Moran, Ph.D., Broad Institute
  • John Schimenti, Ph.D., Cornell University
  • Miriam Meisler, Ph.D., University of Michigan
  • Federica Di Palma, Ph.D., Broad Institute

GATK reference
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010 Sep;20(9):1297-303. Epub 2010 Jul 19.

GATK website

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