Dr. Cheverud's group proposes to develop a fine-scale genetic map of chromosomal regions known to carry previously identified QTLs affecting adult body weight and obesity in a cross of LG/J and SM/J mouse strains and to measure interactions among these genes in their effects on body weight and its components fatness and skeletal length. QTLs are loci displaying relatively small quantitative effects (1-2g) on body weight and its components. Quantitative genetic variations such as these are responsible for much of the variation in health in the general population including such conditions as hypertension, heart disease, diabetes and obesity. QTL which affect the same character often act as part of a common complex genetic network so that we should expect that the effect of a quantitative genetic variant will depend critically on its genetic context, the genes present at other, interacting loci. In this project the group will identify these gene interactions as a start in unraveling the genetic networks involved in controlling adult body weight and obesity. They will also generate a fine-scale genetic map of the QTL preparatory to future identification and positional cloning. The goals will be accomplished through three experiments. 1) Advanced Intercross (AI) lines from the F2 intercross of LG and SM strains will be maintained by random mating to the tenth generation at which time local chromosomal regions containing previously detected QTLs will be fine-mapped with microsatellite markers in 1500 mice. Gene interactions will also be measured in this 10th generation. 2) Microsatellite markers closely linked to QTLs will be scored on 225 3rd generation full-sib families and the interaction of the QTLs with each other and with family genetic background measured. 3) Females from 50 recombinant lines inbred from the 2nd generation intercross population will be mated to males from test inbred strains in the 13th generation to determine which loci are responsible for variability in the effect of tester males across recombinant lines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK052514-01
Application #
2018025
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1997-05-15
Project End
2000-04-30
Budget Start
1997-05-15
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Tarakanova, Vera L; Leung-Pineda, Van; Hwang, Seungmin et al. (2007) Gamma-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication. Cell Host Microbe 1:275-86
Kenney-Hunt, Jane P; Vaughn, Ty T; Pletscher, L Susan et al. (2006) Quantitative trait loci for body size components in mice. Mamm Genome 17:526-37
Kardia, Sharon L R; Bielak, Lawrence F; Lange, Leslie A et al. (2006) Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification. Med Sci Monit 12:CR150-8
Ehrich, Thomas H; Hrbek, Tomas; Kenney-Hunt, Jane P et al. (2005) Fine-mapping gene-by-diet interactions on chromosome 13 in a LG/J x SM/J murine model of obesity. Diabetes 54:1863-72
Leamy, L J; Workman, M S; Routman, E J et al. (2005) An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice. Heredity 94:316-25
Zhao, Wei; Chen, Ying Q; Casella, George et al. (2005) A non-stationary model for functional mapping of complex traits. Bioinformatics 21:2469-77
Wu, Rongling; Ma, Chang-Xing; Hou, Wei et al. (2005) Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice. Genetics 171:239-49
Jarvis, Joseph P; Kenney-Hunt, Jane; Ehrich, Thomas H et al. (2005) Maternal genotype affects adult offspring lipid, obesity, and diabetes phenotypes in LGXSM recombinant inbred strains. J Lipid Res 46:1692-702
Ehrich, Thomas H; Kenney-Hunt, Jane P; Pletscher, L Susan et al. (2005) Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines. Genet Res 85:211-22
Wolf, Jason B; Leamy, Larry J; Routman, Eric J et al. (2005) Epistatic pleiotropy and the genetic architecture of covariation within early and late-developing skull trait complexes in mice. Genetics 171:683-94

Showing the most recent 10 out of 26 publications