The objectives of this project are to develop and apply statistical methods for the analysis of data collected across multiple phenotypic domains from collaborative cross (CC) strains and their derivatives. These include a diallel cross among the eight founder strains of the CC and a recombinant inbred intercross (RIX) population consisting of the F1 progeny of CC strains. The use of genetically reproducible but outbred RIX animals will enable the integration of data across multiple phenotypic domains in animals with natural levels of heterozygosity. Analysis of this novel cross design will require new methodology development. We will implement analysis tools in the general statistical software package R. Performanceof new methodology will be assessed and validated using simulations and in applications to the experimental data. Integrated analysis of genetic, environmental and physiological variables will provide new insights into the role of stressors on whole organism biology.
Specific Aim 1 : We will develop and apply statistical methods for genetic mapping analysis of the collaborative cross recombinant inbred strains and their derivatives. The objective of these analyses will be to identify genetic factors that interact with experimentally defined stressors in their effects on mean and covariance of measuredphenotypes.
Specific Aim 2 : We will develop and apply statistical methods to conduct an integrated analysis of collaborative cross data across multiple phenotypic domains. We will focus on the application of graphical models that capture interactions among these phenotypes using intuitive visual representations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA017590-04
Application #
8102053
Study Section
Special Emphasis Panel (ZRR1-SRC (99))
Program Officer
Grandison, Lindsey
Project Start
2008-07-20
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$220,588
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Lu, Hong; Lu, Lu; Williams, Robert W et al. (2016) Iris transillumination defect and its gene modulators do not correlate with intraocular pressure in the BXD family of mice. Mol Vis 22:224-33
Ye, R; Carneiro, A M D; Airey, D et al. (2014) Evaluation of heritable determinants of blood and brain serotonin homeostasis using recombinant inbred mice. Genes Brain Behav 13:247-60
Swaminathan, Shankar; Lu, Hong; Williams, Robert W et al. (2013) Genetic modulation of the iris transillumination defect: a systems genetics analysis using the expanded family of BXD glaucoma strains. Pigment Cell Melanoma Res 26:487-98
Andreux, Pénélope A; Williams, Evan G; Koutnikova, Hana et al. (2012) Systems genetics of metabolism: the use of the BXD murine reference panel for multiscalar integration of traits. Cell 150:1287-99
Williams, Robert W; Mulligan, Megan K (2012) Genetic and molecular network analysis of behavior. Int Rev Neurobiol 104:135-57
Ziebarth, Jesse D; Cook, Melloni N; Wang, Xusheng et al. (2012) Treatment- and population-dependent activity patterns of behavioral and expression QTLs. PLoS One 7:e31805
Wolen, Aaron R; Phillips, Charles A; Langston, Michael A et al. (2012) Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications. PLoS One 7:e33575
Boughter Jr, John D; Mulligan, Megan K; St John, Steven J et al. (2012) Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2. PLoS One 7:e38169
Wang, X; Mozhui, K; Li, Z et al. (2012) A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. Transl Psychiatry 2:e73
Reinius, Björn; Johansson, Martin M; Radomska, Katarzyna J et al. (2012) Abundance of female-biased and paucity of male-biased somatically expressed genes on the mouse X-chromosome. BMC Genomics 13:607

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