Identification of natural genetic variation linked to high fatness in selected mouse lines

The subproject is aimed at the identification of candidate genes affecting obesity and related physiological factors in mice. The focus on natural genetic variation for obesity in mice is based on the fact that many human obesity genes were originally identified in mutant mice. As model we use the unique high fatness-selected Berlin fat mouse line as a novel model for polygenic obesity. The Berlin fat mouse line has been selected for high fatness at 10 weeks for over 40 generations and is partially inbred. A spontaneous mutation increased the initial fat percentage of 25% to 40-45% under standard diet (5% fat). Candidate genes will be selected from a joined data analysis of genetic linkage mapping in a cross-bred population, differential gene expression profiling, and comparative DNA sequencing of differentially expressed positional candidate genes. Fine mapping of chromosomal segments and changes of frequency distribution of alleles in candidate genes as result of selection will be analyzed. Functional analyses of identified candidate genes harboring genetic variants will be performed and bioinformatically analyzed. The identified murine candidate genes will be provided for further analyses in human populations.