Syntenic regions for atherosclerosis in mice and humans

Coordinator:		PD Dr. Daniel Teupser
Institution:		Universität Leipzig
Homepage:		http://www.uniklinikum-leipzig.de

The overall aim of this proposal is to identify novel modulators of atherosclerosis susceptibility using comparative genetics in humans and mice. The rationale for our approach is based on the observation that disease-susceptibility genes are shared between species. Comparison of disease loci will thus have a filtering function for atherosclerosis candidate genes from genome-wide association (GWA) studies in humans.
To this end, we will focus on two significant loci of atherosclerosis susceptibility, identified in our previous work by quantitative trait locus mapping on mouse chromosomes 3 and 12. We will test the corresponding syntenic regions in humans for genetic variants with significant associations to MI in a 500K study performed by the Lübeck and Regensburg group funded by the EU-project Cardiogenics (Hengstenberg/Erdmann/Schunkert). Genetic variants will be confirmed and the identified genes and their mouse orthologs will be tested functionally. The novel use of comparative genetics will speed up identification of human atherosclerosis susceptibility genes, thus strengthen the overall aim of the IG to develop novel diagnostic tools and therapeutic targets for individualized prevention of atherosclerotic vascular disease.