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Fine-mapping of quantitative trait loci with large effects on growth and fatness on mouse chromosome 2
Mouse models undergoing long-term selection have been useful to characterize the complex genetic basis of growth and fatness. The M16 line of mice, result from selection for 3–6 wk weight gain, is a unique model for studying these traits. A congenic strain was developed to characterize and fine-map a previously identified region of distal mouse chromosome 2 (MMU2) harboring QTLs with large effects on growth and fatness. The congenic line (MC) was created using the M16 line as the recipient for a ∼38 cM region on MMU2 from the inbred line C57BL/6J. Phenotypic characterization of MC for a variety of relevant phenotypes at three ages (6, 15, 24 wk) and on two diets (low, high fat) was conducted. The absence of the M16 allele in MC resulted in a significant decrease in size and adiposity, confirming the presence of at least one relevant QTL in this region. A large F2 cohort (1,200 mice) originating from a cross between MC and M16i was developed. Furthermore, 40 F2 males with recombinations within the relevant QTL region were used to produce 700 progeny. Linkage analysis of the F2 population detected a single QTL affecting body weight, body fat, lean and bone mineral density located at the same marker interval. In addition, three other QTLs were identified for fat-related traits. One QTL for liver weight mapped to a different position than the rest. The confidence intervals of the QTLs were narrowed to regions of 1.5 to 4.5 cM. Recombinant progeny testing confirmed the existence of the QTL. Finally, several potential candidate genes were identified using the Celera Discovery System, based on the map positions of these genes relative to the QTLs and the known association of these genes with growth and fat metabolism. These efforts toward fine mapping reduced the estimated region harboring QTLs from 38 to 12 cM and better characterized phenotypic effects of the QTL; decreasing the number of candidate genes influencing in growth and body composition. Identification of genes underlying these traits may help to develop drugs or gene therapy approaches to treat obesity and other related diseases, and it could allow manipulation of body composition (i.e., fat content) through marker-assisted selection or by pharmacologic strategies in livestock. ^
Jerez, Nancy Coromoto, "Fine-mapping of quantitative trait loci with large effects on growth and fatness on mouse chromosome 2" (2003). ETD collection for University of Nebraska - Lincoln. AAI3085738.