Dr. Cheverud's group proposes to develop a fine-scale genetic map of chromosomal regions known to carry previously identified QTLs affecting adult body weight and obesity in a cross of LG/J and SM/J mouse strains and to measure interactions among these genes in their effects on body weight and its components fatness and skeletal length. QTLs are loci displaying relatively small quantitative effects (1-2g) on body weight and its components. Quantitative genetic variations such as these are responsible for much of the variation in health in the general population including such conditions as hypertension, heart disease, diabetes and obesity. QTL which affect the same character often act as part of a common complex genetic network so that we should expect that the effect of a quantitative genetic variant will depend critically on its genetic context, the genes present at other, interacting loci. In this project the group will identify these gene interactions as a start in unraveling the genetic networks involved in controlling adult body weight and obesity. They will also generate a fine-scale genetic map of the QTL preparatory to future identification and positional cloning. The goals will be accomplished through three experiments. 1) Advanced Intercross (AI) lines from the F2 intercross of LG and SM strains will be maintained by random mating to the tenth generation at which time local chromosomal regions containing previously detected QTLs will be fine-mapped with microsatellite markers in 1500 mice. Gene interactions will also be measured in this 10th generation. 2) Microsatellite markers closely linked to QTLs will be scored on 225 3rd generation full-sib families and the interaction of the QTLs with each other and with family genetic background measured. 3) Females from 50 recombinant lines inbred from the 2nd generation intercross population will be mated to males from test inbred strains in the 13th generation to determine which loci are responsible for variability in the effect of tester males across recombinant lines.
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