Original Article
International Journal of Obesity advance online publication 15 April 2008; doi: 10.1038/ijo.2008.56
Candidate genes for obesity revealed from a C57BL/6J 
129S1/SvImJ intercross
Z Su1, R Korstanje1, S-W Tsaih1 and B Paigen1
1The Jackson Laboratory, Bar Harbor, ME, USA
Correspondence: Dr B Paigen, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. E-mail: bev.paigen@jax.org
Received 26 November 2007; Revised 23 January 2008; Accepted 14 March 2008; Published online 15 April 2008.
Abstract
Objective:
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.
Methods:
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 129) F2 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.
Results:
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%.
Conclusions:
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.
Keywords:
quantitative trait loci, comparative genomics, haplotype, SNP, fat mass
