Genomic Systems approaches to dissecting Cardiovascular and Metabolic Risk Factors
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Prof. Dr. Norbert Huebner
87: Timoféeff-Ressovsky-House (Genomcentrum)
Room: 0.09
Tel. 9406-2530
The rat genome sequence together with other genomic resources, including genetic and structural variation maps, provide an exceptional opportunities for identifying genes and pathways underlying disease phenotypes.
Our collaborators and we have devised a general approach for dissecting genetic networks systematically across the biological scale, from molecular to physiological, using segregating rat populations. We combined linkage analyses with genome-wide expression profiling and identified independent genes contributing to heart failure susceptibility, increased left ventricular mass, and hypertension in spontaneously hypertensive rats (SHR) and SHR derived substrains. While hypertension and cardiac hypertrophy are strong risk factors for heart failure our studies demonstrate that genetic variation contributes to each of these traits independently. Due to the complex sequel of genetic and clinical risk factors these studies suggest that rodent genetics will likely continue to contribute to provide important insights into molecular pathways underlying human diseases in the era of human whole genome association / re-sequencing studies.
The datasets on genome wide expression data collected in a reference population of recombinant inbred (RI) strains provide extraordinary opportunities for systems approaches for analysis of cardiovascular and metabolic phenotypes. We study the genetic regulation of gene expression in a range of insulin sensitive tissues including fat, kidney, adrenal, heart, skeletal muscle, the vasculature, and liver in rat RI strains. Using data collected across multiple tissues we will investigate the genotype dependent co-expression of gene networks and analyse their possible biological implications for common cardiovascular disorders.
link to the research group of Prof. Dr. Norbert Huebner