Publications

Physiogenomic resources for rat models of heart, lung and blood disorders

Malek RL, Wang HY, Kwitek AE, Greene AS, Bhagabati N, Borchardt G, Cahill L, Currier T, Frank B, Fu X, Hasinoff M, Howe E, Letwin N, Luu TV, Saeed A, Sajadi H, Salzberg SL, Sultana R, Thiagarajan M, Tsai J, Veratti K, White J, Quackenbush J, Jacob HJ, Lee NH

PMID: 16415889

Abstract

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.