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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Yanovski, Susan Z
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Washington University
Anatomy/Cell Biology
Schools of Medicine
Saint Louis
United States
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Partridge, Charlyn G; Fawcett, Gloria L; Wang, Bing et al. (2014) The effect of dietary fat intake on hepatic gene expression in LG/J AND SM/J mice. BMC Genomics 15:99
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Minkina, Olga; Cheverud, James M; Fawcett, Gloria et al. (2012) Quantitative trait loci affecting liver fat content in mice. G3 (Bethesda) 2:1019-25
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Lawson, Heather A; Lee, Arthur; Fawcett, Gloria L et al. (2011) The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J × SM/J murine model. Mamm Genome 22:197-208
Cheverud, James M; Lawson, Heather A; Fawcett, Gloria L et al. (2011) Diet-dependent genetic and genomic imprinting effects on obesity in mice. Obesity (Silver Spring) 19:160-70
Pavlicev, Mihaela; Cheverud, James M; Wagner, Günter P (2011) Evolution of adaptive phenotypic variation patterns by direct selection for evolvability. Proc Biol Sci 278:1903-12
Jarvis, Joseph P; Cheverud, James M (2011) Mapping the epistatic network underlying murine reproductive fatpad variation. Genetics 187:597-610

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