Project D: Using Diversity Outbred mice to study metabolic traits;Karen L. Svenson (Jackson) This project will use Diversity Outbred (DO) mice to identify genes involved in complex biological pathways related to metabolic syndrome using a high fat diet perturbation. Mixed genomes in experimental models have historically imposed enormous hurdles to sorting out relevant functional components of fundamental biological processes. With current technologies for high-density genotyping, genetically heterogeneous population is now a welcome resource for interrogating nuances of multiple biological systems that support and maintain life. Adding an environmental perturbation, high fat diet, will help to recapitulate a specific challenge to humans that is increasingly recognized as a significant driver of overall health. This research plan provides an opportunity to integrate with other Center projects to build a gene-environment interaction of complex metabolic processes by generating comprehensive resources to be utilized in studies of epigenetics (Project A), genotype-phenotype networks (Projects E and G), RNA processing (Project F), gene expression (Project G), and metabolites (Project H) under perturbed environmental conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM076468-09
Application #
8691876
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P et al. (2016) Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection. G3 (Bethesda) 6:3893-3902
Korstanje, Ron; Deutsch, Konstantin; Bolanos-Palmieri, Patricia et al. (2016) Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria. J Am Soc Nephrol 27:3271-3277
Morgan, Andrew P; Holt, J Matthew; McMullan, Rachel C et al. (2016) The Evolutionary Fates of a Large Segmental Duplication in Mouse. Genetics 204:267-85
Chick, Joel M; Munger, Steven C; Simecek, Petr et al. (2016) Defining the consequences of genetic variation on a proteome-wide scale. Nature 534:500-5
Gu, Tongjun; Gatti, Daniel M; Srivastava, Anuj et al. (2016) Genetic Architectures of Quantitative Variation in RNA Editing Pathways. Genetics 202:787-98
Morgan, Andrew P; Didion, John P; Doran, Anthony G et al. (2016) Whole Genome Sequence of Two Wild-Derived Mus musculus domesticus Inbred Strains, LEWES/EiJ and ZALENDE/EiJ, with Different Diploid Numbers. G3 (Bethesda) 6:4211-4216
Tyler, Anna L; Donahue, Leah Rae; Churchill, Gary A et al. (2016) Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross. PLoS Genet 12:e1005805
Parvanov, Emil D; Tian, Hui; Billings, Timothy et al. (2016) PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis. Mol Biol Cell :
Walker, Michael; Billings, Timothy; Baker, Christopher L et al. (2015) Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage. Epigenetics Chromatin 8:31
Bogue, Molly A; Churchill, Gary A; Chesler, Elissa J (2015) Collaborative Cross and Diversity Outbred data resources in the Mouse Phenome Database. Mamm Genome 26:511-20

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