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 of 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 #
1F32DK074317-01
Application #
7054580
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Podskalny, Judith M,
Project Start
2006-02-14
Project End
2009-02-13
Budget Start
2006-02-14
Budget End
2007-02-13
Support Year
1
Fiscal Year
2006
Total Cost
$43,996
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