Genomic mapping of direct and correlated responses to long-term selection for rapid growth rate in mice

Understanding the genetic architecture of traits such as growth, body composition, and energy balance has become a primary focus for biomedical and agricultural research. The objective of this study was to map QTL in a large F-2 (n = 1181) population resulting from an intercross between the M16 and ICR lines of mice. The M16 line, developed by long-term selection for 3- to 6-week weight gain, is larger, heavier, fatter, hyperphagic, and diabetic relative to its randomly selected control line of ICR origin. The F-2 population was phenotyped for growth and energy intake at weekly intervals from 4 to 8 weeks of age and for body composition and plasma levels of insulin, leptin, TNF alpha, IL6, and glucose at 8 weeks and was genotyped for 80 microsatellite markers. Since the F-2 was a cross between a selection line and its unselected control, the QTL identified likely represent genes that contributed to direct and correlated responses to long-term selection for rapid growth rate. Across all traits measured, 95 QTL were identified, likely representing 19 unique regions on 13 chromosomes. Four chromosomes (2, 6, 11, and 17) harbored loci contributing disproportionately to selection response. Several QTL demonstrating differential regulation of regional adipose deposition and age-dependent regulation of growth and energy consumption were identified.