Project E: Data Driven Systems Genetics Workflow for New Experimental Platforms;Elissa J. Chesler, Matthew A. Hibbs (Jackson) Systems genetics experiments typically involve separate acquisition of genotype, gene expression and phenotypic data in a genetically diverse population (Fig. 7 left). Conventional QTL and co-expression methods are applied to these data to construct genotype and phenotype networks. Application of this approach is reliant on existing resources, including a well-established reference genome, a dense genetic marker map often derived relative to the reference genome, and microarrays that are biased toward specific transcript structures and alleles. We will develop an approach that avoids these intrinsic biases through the development and application of high throughput RNA sequencing technology (HTPS) as the sole source of transcription and polymorphism data for an expression QTL experiment (Fig. 7 right). These new methods will minimize initial knowledge requirements. We will create software for our data-driven systems genetics approach, called SEQQTL, for use with highly diverse mouse populations, newly sequenced organisms, or in populations without an established genetic map. We will develop and validate these techniques in the DO mouse population.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM076468-08
Application #
8531963
Study Section
Special Emphasis Panel (ZGM1-CBCB-2)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
8
Fiscal Year
2013
Total Cost
$95,220
Indirect Cost
$41,960
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
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

Showing the most recent 10 out of 116 publications