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

• Published in: International Journal of Obesity 2008-07, Vol.32 (7), p.1180-1189
• Main Authors: SU, Z, KORSTANJE, R, TSAIH, S.-W, PAIGEN, B
• Format: Article
• Language: English
• Subjects: Adipose tissues; Biological and medical sciences; Genetic aspects; Genetic research; Medical sciences; Metabolic diseases; Obesity; Properties; Risk factors
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2008.56

Objective: To identify the genes controlling body fat, we carried out a quantitative trait locus (QTL) analysis using C57BL/6] (B6) and 129S1/SvlmJ (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 x 129) F sub(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. 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.