In humans, individuals vary in their response to dietary fat. Some individuals gain substantial amounts of weight and fat while other individuals gain little on a high fat diet. There is some evidence that variability in response to a high fat diet may have a genetic basis in humans. The main goal of the proposed project is to map and measure the effect of genes on the response to a high fat diet in a new multigenic obesity model, strains derived from the intercross between SM/J and LG/J inbred mouse strains. The SM/J and LG/J strains show substantial differences in body size and fatness. They also differ dramatically in their response to a high fat diet. Dietary responses vary with age. A series of 40 recombinant (RI) strains derived from the SM/J by LG/J cross will be brought to effectively inbred status (F greater than 0.98). These strains will then be used to map genes for dietary obesity by measuring variability in the response of each RI strain to a high fat diet. Sixteen animals from each strain will be fed the high and low fat diets. Interval mapping will be used to localize quantitative trait locus effects on dietary obesity to a 10-20 cM interval. A single Advanced Intercross (AI) line will be maintained and used to fine-map QTLs discovered in the RI strain analysis to a 1-2 cM interval. This project will be the first to detect and map genes specifically affecting response to a high fat diet.
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