Candidate genes for obesity revealed from a C57BL/6J x 129S1/SvImJ intercross.

To identify the genes controlling body fat, we carried out a quantitative trait locus (QTL) analysis using C57BL/6J (B6) and 129S1/SvImJ (129) mice, which differ in obesity susceptibility after consuming an atherogenic diet. Mice were fed chow until 8 weeks and an atherogenic diet from 8 to 16 weeks; body fatness was measured by X-ray absorptiometry in 528 (B6 x 129) F(2) at 8 and 16 weeks. A high-density genome scan was performed using 508 polymorphic markers. After identifying the genetic loci, we narrowed the QTL using comparative genomics and bioinformatics. The percentage of body fat was significantly linked to loci on chromosomes (Chr) 1 (22, 68 and 173 Mb), 4 (74 Mb), 5 (73 Mb), 7 (88 Mb), 8 (43 and 80 Mb), 9 (55 Mb), 11 (115 Mb) and 12 (32 Mb); three suggestive loci on Chrs 6 (76 Mb), 9 (30 Mb) and 16 (26 Mb) and two pairs of interacting loci (Chr 2 at 99.8 Mb with Chr 7; Chr 1 at 68 Mb with Chr 11). Comparative genomics narrowed the QTL intervals by 20-57% depending on the chromosome; in most cases, haplotype analysis further narrowed them by about 90%. Our analysis identified 15 QTL for percentage of body fat. We narrowed the QTL using comparative genomics and haplotype analysis and suggest several candidate genes: Apcs on Chr 1, Ppargc1a on Chr 5, Ucp1 on Chr 8, Angptl6 on Chr 9 and Lpin1 on Chr 12.