GENE INTERACTION FOR BODY WEIGHT COMPONENTS IN MICE

Summary

Principal Investigator: James Cheverud
Abstract: DESCRIPTION (Adapted from investigator's abstract): The investigator proposes to fine-map and positionally clone quantitative trait loci (QTLs) responsible for variation in body size and obesity in the cross of LG/J by SM/J inbred mouse strains. The use of animal models for mapping obesity-related genes has several advantages relative to working in human populations. Principally, powerful, replicable experimental designs are available for gene mapping and validation. Under previous support, 11 QTLs for body size in a replicate F2 intercross population have been confirmed and it has been determined which of these QTLs affects adiposity levels. The investigator is narrowing QTL support intervals in the F10 generation of an Advanced Intercross (AI) line from 20 cM to less than 5 cM. Under the present proposal, the QTL support intervals will be further limited to approximately 1 cM by saturation mapping in the F7 and F10 AI line generations, by performing Recombinant Inbred Segregation Tests and forming congenic strains. In addition, previously cloned candidate genes will be sequenced to determine whether they show molecular polymorphism between the LG/J and SM/J strains. Once support intervals reach the 1 cM level, positional cloning will be performed using bacterial artificial chromosomes (BACs). When a compelling candidate gene is identified by database searches or positional cloning, it will be tested using the quantitative hybrid complementation test. In addition to positional cloning of the QTLs, congenic strains will be formed for each QTL and will be tested, along with the LGxSM recombinant inbred strains for a variety of obesity-related traits.
Funding Period: 1997-05-15 - 2004-04-30
more information: NIH RePORT

Top Publications

  1. ncbi An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice
    L J Leamy
    Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
    Heredity (Edinb) 94:316-25. 2005
  2. ncbi Quantitative trait loci for body size components in mice
    Jane P Kenney-Hunt
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Mamm Genome 17:526-37. 2006
  3. ncbi Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification
    Sharon L R Kardia
    Department of Epidemiology, University of Michigan, Ann Arbor, MI 48104 3028, USA
    Med Sci Monit 12:CR150-8. 2006
  4. ncbi Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines
    Thomas H Ehrich
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Genet Res 85:211-22. 2005
  5. pmc Epistatic pleiotropy and the genetic architecture of covariation within early and late-developing skull trait complexes in mice
    Jason B Wolf
    Faculty of Life Sciences, University of Manchester, UK
    Genetics 171:683-94. 2005
  6. pmc Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice
    Rongling Wu
    Department of Statistics, University of Florida, Gainesville 32611, USA
    Genetics 171:239-49. 2005
  7. ncbi Fine-mapping gene-by-diet interactions on chromosome 13 in a LG/J x SM/J murine model of obesity
    Thomas H Ehrich
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    Diabetes 54:1863-72. 2005
  8. ncbi Maternal genotype affects adult offspring lipid, obesity, and diabetes phenotypes in LGXSM recombinant inbred strains
    Joseph P Jarvis
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Lipid Res 46:1692-702. 2005
  9. ncbi A non-stationary model for functional mapping of complex traits
    Wei Zhao
    Department of Statistics, University of Florida, Gainesville, FL 32611, USA
    Bioinformatics 21:2469-77. 2005
  10. pmc Gamma-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication
    Vera L Tarakanova
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Host Microbe 1:275-86. 2007

Scientific Experts

  • R Wu
  • Larry J Leamy
  • Sharon L Kardia
  • Joseph P Jarvis
  • James M Cheverud
  • Jane P Kenney-Hunt
  • Thomas H Ehrich
  • L Susan Pletscher
  • Vera L Tarakanova
  • Jason B Wolf
  • Wei Zhao
  • Katie Matatall
  • Mickael Basson
  • Helen Piwnica-Worms
  • Seungmin Hwang
  • Ren Sun
  • Barry P Sleckman
  • Herbert W Virgin
  • Chiao Wen Yang
  • Van Leung-Pineda
  • Elizabeth Norgard
  • Andrea Peripato
  • David Durand
  • Eric Routman
  • Kilinyaa Cothran
  • Christy Perel
  • Ty T Vaughn
  • Eric J Routman
  • Bing Wang
  • George Casella
  • Clay F Semenkovich
  • Tomas Hrbek
  • Ying Q Chen

Detail Information

Publications10

  1. ncbi An epistatic genetic basis for fluctuating asymmetry of tooth size and shape in mice
    L J Leamy
    Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA
    Heredity (Edinb) 94:316-25. 2005
    ....
  2. ncbi Quantitative trait loci for body size components in mice
    Jane P Kenney-Hunt
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Mamm Genome 17:526-37. 2006
    ..Antagonistic pleiotropy, in which a locus has opposite effects on different characteristics, is uncommon...
  3. ncbi Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification
    Sharon L R Kardia
    Department of Epidemiology, University of Michigan, Ann Arbor, MI 48104 3028, USA
    Med Sci Monit 12:CR150-8. 2006
    ..Since elevated blood pressure (BP) is an important predictor of CAC, genetic polymorphisms in the renin-angiotensin system and their interaction may play a role in explaining CAC quantity variation...
  4. ncbi Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines
    Thomas H Ehrich
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Genet Res 85:211-22. 2005
    ..Therefore, genetic effects for these traits are different depending on the environment an animal is exposed to...
  5. pmc Epistatic pleiotropy and the genetic architecture of covariation within early and late-developing skull trait complexes in mice
    Jason B Wolf
    Faculty of Life Sciences, University of Manchester, UK
    Genetics 171:683-94. 2005
    ..Nearly all single-locus and epistatic pleiotropic effects contributed positive components to covariances between traits, suggesting that genetic integration in the skull is achieved by a complex combination of pleiotropic effects...
  6. pmc Functional mapping of quantitative trait loci that interact with the hg mutation to regulate growth trajectories in mice
    Rongling Wu
    Department of Statistics, University of Florida, Gainesville 32611, USA
    Genetics 171:239-49. 2005
    ..Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals...
  7. ncbi Fine-mapping gene-by-diet interactions on chromosome 13 in a LG/J x SM/J murine model of obesity
    Thomas H Ehrich
    Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    Diabetes 54:1863-72. 2005
    ..The phosphofructokinase (PFK) C (Pfkp) and the pitrilysin metalloprotease 1 (Pitrm1) genes are compelling positional candidate genes in this region that show coding sequence differences between the parental strains in functional domains...
  8. ncbi Maternal genotype affects adult offspring lipid, obesity, and diabetes phenotypes in LGXSM recombinant inbred strains
    Joseph P Jarvis
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Lipid Res 46:1692-702. 2005
    ..We also found an interaction affecting adult phenotype between the effects of maternal care between RI strain mothers and C57BL/6J mothers and a later environmental factor (dietary fat intake) for some age-specific weights...
  9. ncbi A non-stationary model for functional mapping of complex traits
    Wei Zhao
    Department of Statistics, University of Florida, Gainesville, FL 32611, USA
    Bioinformatics 21:2469-77. 2005
    ..Based on results from computer simulation studies, we suggest that these two models are alternative to one another and should be used simultaneously for the same dataset...
  10. pmc Gamma-herpesvirus kinase actively initiates a DNA damage response by inducing phosphorylation of H2AX to foster viral replication
    Vera L Tarakanova
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Host Microbe 1:275-86. 2007
    ..Thus, activation of proximal components of the DNA damage signaling response is an active viral kinase-driven strategy required for efficient gamma-herpesvirus replication...