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FULL-GENOME ANALYSIS OF ALTERNATIVE SPLICING IN MOUSE LIVER AFTER HEPATOTOXICANT EXPOSURE
Citation:
VALLANAT, B., J. S. LEE, W. O. WARD, H. REN, M. B. ROSEN, S. D. HESTER, S. NESNOW, C. S. LAU, D. A. DELKER, AND C. CORTON. FULL-GENOME ANALYSIS OF ALTERNATIVE SPLICING IN MOUSE LIVER AFTER HEPATOTOXICANT EXPOSURE. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
We will use information about changes in alternative splicing to predict comprehensive changes in the structure of the proteome after chemical exposure, to identify new biomarkers of exposure, and to understand chemical mode of action.
Description:
Alternative splicing plays a role in determining gene function and protein diversity. We have employed whole genome exon profiling using Affymetrix Mouse Exon 1.0 ST arrays to understand the significance of alternative splicing on a genome-wide scale in response to multiple toxicants. Mice were exposed to three hepatotoxicants including PFOA (perfluorooctanoic acid), propiconazole (conazole-triazole), and phenobarbital. Alternative splicing and gene expression were evaluated from the RNA isolated from the livers of treated and control animals. Preliminary analysis of transcript changes after PFOA exposure using a mixed model, nested analysis of variance (p-val < 0.001) and a FDR at 0.001 with Biotique's X-Ray software, suggested alternative exon usage for 600 transcript cluster ID's. Ontological categorization of these genes indicated G-protein coupled receptor protein signaling pathway, cell surface receptor linked signal transduction, cellular lipid metabolism, generation of precursor metabolites and energy, lipid metabolism, carboxylic acid metabolism, organic acid metabolism, electron transport and fatty acid metabolism to be significantly altered. These categories of genes were also those that exhibited consistent gene expression changes in our historical data. We will use information about changes in alternative splicing to predict comprehensive changes in the structure of the proteome after chemical exposure, to identify new biomarkers of exposure, and to understand chemical mode of action.