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

Z Su, R Korstanje, SW Tsaih, B Paigen - International journal of obesity, 2008 - nature.com
Z Su, R Korstanje, SW Tsaih, B Paigen
International journal of obesity, 2008nature.com
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) 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 …
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) 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.
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.
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