German Network for Systems Genetics (GeNeSys), WP7: Obesity and activation of the immune system

<p>Our project is part of the established virtual institute German Network for Systems Genetics (GeNeSys) for the identification of complex genotype-phenotype relationships that contribute to the predisposition and manifestation of infectious diseases in humans. These studies will form the basis for deeper mechanistic understanding and for the design of novel therapeutics to prevent and treat infectious diseases and diseases caused by or related to infections. The GeNeSys consortium will launch a concerted action for the phenotypic analysis of infection susceptibility, obesity, liver fibrogenesis, adult neurogenesis, and associated whole genome transcript analysis.</p>

<p>The best genetic resource of mouse strains for these studies are recombinant inbred lines (RI strains). A RI set should model a diverse human population, and it is fair to ask if fully inbred strains can be a good model for heterozygous human populations. The uniqueness of the proposed GeNeSys network is that all its partners will use the same RI strain set as a common Genetic Reference Population (GRP) for their phenotype analyses allowing us to correlate many different phenotypes and genotypes. The partner laboratories of the GeNeSys will perform whole-genome expression analysis in their individual biological systems, first with the parental strains to determine the best parameters for comparative analysis and, in the extension phase of the project, of the entire BXD RI strain collection.</p>

<p>Since all the consortium partners are analysing the same GRP, a comparison of many phenotypes will be possible. A systematic systems genetic study will be performed to assess the relationships between many gene variants, many environmental variants, and many phenotypes. The systems genetics approach allows to compare data on infection susceptibility with other biological characteristics that are relevant for human disease, e.g. blood pressure, obesity, allergy, etc. Therefore, in the long-term, the approach outlined here has enormous implications for the understanding of diseases in humans that are caused by complex genetic interactions and to test hypotheses generated from epidemiological studies in humans.</p>

<p>In our project, we will phenotype mice of the GRP for growth related traits in dependence of high fat diet. Our study is aimed at mapping of genetic traits for diet-induced obesity, for factors involved in the activation of the immune system, and factors responsible for differential gene expression. Body weight and obesity as well as immune response are influenced by many genes. The studies proposed here will contribute to recognize early inflammation processes as result of obesity and to develop new strategies to suppress these inflammation processes in order to prevent later diseases.</p>

<p>The GeNeSys consortium includes groups from the Helmholtz-Association, Leibniz-Association and universities. We have integrated the expert groups in Germany working on complex trait genetics, with a focus on infection research. The German consortium is complemented by international experts in the field as associated partners. A start-up funding from the Helmholtz-Association will allow to establish a network on systems genetics in Germany and permit the network partners to strengthen their interactions in Europe.</p>