The goal of Project 3 is to identify genes that influence quantitative phenotypes related to dyslipidemia, oxidative damage and hypertension in the baboon model. Methods: We will use two approaches to identify these genes. First, we will use chromosomal region specific gene expression profiling, positional cloning and statistical genomic analysis to identify genes encoding dyslipidemia, oxidative damage and hypertension quantitative trait loci (QTLs). These studies will be conducted for previously identified QTLs and for two new QTLs identified in the pedigreed, genotyped, phenotyped baboons at the SNPRC using biopsied tissues collected after basal and high-cholesterol, high-fat (HCHF) diets. Second, we will use whole genome expression profiling on biopsied tissue RNA from the pedigreed baboons to identify candidate genes and gene networks that regulate quantitative phenotypes related to dyslipidemia, oxidative damage and hypertension. The following Specific Aims will be completed to achieve this goal: 1) To identify and prioritize candidate genes encoding dyslipidemia, oxidative damage and hypertension QTLs. 2) To identify candidate genes and candidate gene networks relevant to dyslipidemia by performing whole genome expression profiling for pedigreed baboons fed the HCHF diet long-term. 3) To determine which of the top priority candidate genes identified in Aims 1 and 2 actually influence measures of dyslipidemia, oxidative damage and hypertension by conducting statistical genomic analyses. 4) To confirm by in vitro functional assays the roles of sequence variants in the regulation of phenotypic variation for five high priority candidate genes identified in Aim 3. 5) For each baboon gene analyzed in Aim 4, to identify statistical functional variants in the human homologue for the same class of polymorphisms. Expected outcomes from these studies include: 1) Identification of genes that regulate five dyslipidemia, oxidative damage and/or hypertension quantitative traits in defined chromosomal regions; 2) Identification of the relationships between these genes that are relevant to cardiovascular disease phenotypic variation; and 3) Identification of polymorphisms that encode the observed phenotypic variation in these genes. Significance: Results from this study will define genetic mechanisms of cardiovascular disease and provide targets for interventions to prevent cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL028972-30
Application #
8376209
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
30
Fiscal Year
2012
Total Cost
$512,913
Indirect Cost
$222,962
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Tiyasatkulkovit, Wacharaporn; Malaivijitnond, Suchinda; Charoenphandhu, Narattaphol et al. (2014) Pueraria mirifica extract and puerarin enhance proliferation and expression of alkaline phosphatase and type I collagen in primary baboon osteoblasts. Phytomedicine 21:1498-503
Chen, Shuyuan; Bastarrachea, Raul A; Roberts, Brad J et al. (2014) Successful ? cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1. Cell Cycle 13:1145-51
Higgins, Paul B; Rodriguez, Perla J; Voruganti, V Saroja et al. (2014) Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism. Am J Phys Anthropol 153:9-14
Karere, Genesio M; Glenn, Jeremy P; Birnbaum, Shifra et al. (2013) Identification of candidate genes encoding an LDL-C QTL in baboons. J Lipid Res 54:1776-85
Shi, Qiang; Hodara, Vida; Simerly, Calvin R et al. (2013) Ex vivo reconstitution of arterial endothelium by embryonic stem cell-derived endothelial progenitor cells in baboons. Stem Cells Dev 22:631-42
Shi, Qiang; Schatten, Gerald; Hodara, Vida et al. (2013) Endothelial reconstitution by CD34+ progenitors derived from baboon embryonic stem cells. J Cell Mol Med 17:242-51
Rodríguez-Sánchez, I P; Garza-Rodríguez, M L; Mohamed-Noriega, K et al. (2013) Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea, and retina. J Med Primatol 42:105-11
Fabbrini, Elisa; Higgins, Paul B; Magkos, Faidon et al. (2013) Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model. Am J Physiol Endocrinol Metab 304:E444-51
Spradling, Kimberly D; Glenn, Jeremy P; Garcia, Roy et al. (2013) The baboon kidney transcriptome: analysis of transcript sequence, splice variants, and abundance. PLoS One 8:e57563
Shi, Qiang; Hornsby, Peter J; Meng, Qinghe et al. (2013) Longitudinal analysis of short-term high-fat diet on endothelial senescence in baboons. Am J Cardiovasc Dis 3:107-19

Showing the most recent 10 out of 287 publications