Abstract

Obesity is reaching epidemic proportions in the U.S. with over 60% of Americans being either obese or overweight. Obesity has a strong genetic component, however, relatively little is known regarding the specific identity of genes with common alleles influencing obesity. To characterize natural genetic variation influencing obesity I propose to study the BCQ-hg/hg congenic strain. BC9-hg/hg mice are congenic for CAST/EiJ chromosome 9 alleles on a C57B /6J-hg/hg background. BC9-hg/hg females are 57% and males are 30% more obese than control mice, hg is a deletion on mouse chromosome 10 leading to a 30-50% increase in body size and evidence suggests that hg is required for obesity in BCQ-hg/hg mice. To better understand the nature of BCQ-hg/hg obesity I have outlined three specific aims.
Aim 1 measures the effect o age and diet on BCQ-hg/hg obesity and will determine if obesity is dependent on the presence of hg.
Aim 2 uses a congenic-derived F2 population to narrow the genomic interval harboring the obesity QTL. Lastly, aim 3 uses a genetical genomics approach to map eQTL for genes within the congenic interval. Data from these aims will enhance our understanding of the genetics and physiology of obesity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK074317-03
Application #
7341762
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Podskalny, Judith M,
Project Start
2006-02-14
Project End
2008-08-31
Budget Start
2008-02-14
Budget End
2008-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$26,009
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Sabik, Olivia L; Medrano, Juan F; Farber, Charles R (2017) Genetic Dissection of a QTL Affecting Bone Geometry. G3 (Bethesda) 7:865-870
Ghazalpour, Anatole; Rau, Christoph D; Farber, Charles R et al. (2012) Hybrid mouse diversity panel: a panel of inbred mouse strains suitable for analysis of complex genetic traits. Mamm Genome 23:680-92
Orozco, Luz D; Bennett, Brian J; Farber, Charles R et al. (2012) Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages. Cell 151:658-70
Ghazalpour, Anatole; Bennett, Brian; Petyuk, Vladislav A et al. (2011) Comparative analysis of proteome and transcriptome variation in mouse. PLoS Genet 7:e1001393
Suwanwela, Jaijam; Farber, Charles R; Haung, Bau-Lin et al. (2011) Systems genetics analysis of mouse chondrocyte differentiation. J Bone Miner Res 26:747-60
Park, Christopher C; Gale, Greg D; de Jong, Simone et al. (2011) Gene networks associated with conditional fear in mice identified using a systems genetics approach. BMC Syst Biol 5:43
Farber, Charles R; Bennett, Brian J; Orozco, Luz et al. (2011) Mouse genome-wide association and systems genetics identify Asxl2 as a regulator of bone mineral density and osteoclastogenesis. PLoS Genet 7:e1002038
Bennett, Brian J; Farber, Charles R; Orozco, Luz et al. (2010) A high-resolution association mapping panel for the dissection of complex traits in mice. Genome Res 20:281-90
Farber, Charles R; Aten, Jason E; Farber, Emily A et al. (2009) Genetic dissection of a major mouse obesity QTL (Carfhg2): integration of gene expression and causality modeling. Physiol Genomics 37:294-302
Farber, Charles R; van Nas, Atila; Ghazalpour, Anatole et al. (2009) An integrative genetics approach to identify candidate genes regulating BMD: combining linkage, gene expression, and association. J Bone Miner Res 24:105-16