Experiment
Dietary obsesity genes were studied using C57BL/6ByJ mice, the more susceptible to dietary obesity, and 129P3/J mice, the more resistant. C57BL/6ByJ female mice were mated with males from the congenic strain, 129P3/J.C57BL/6ByJTas1r3, to produce 213 F2mice. Percent body fat was assessed after a low energy diet and again after a high energy diet.
Since male mice are typically fatter than female mice LOD scores were compared when sex was included as an additive covariate with scores when sex was included as both an additive and an interactive covariate. The differences in scores were then used to determine whether a locus was sex dependent. All analyses included age and litter size as covariates.
Linkage analysis identified four main effect QTL associated with dietary obesity on Chrs 7, 9, 12 and 17, all of which were diet dependent.
The Chr 7 QTL, labeled Pbft4, was associated with higher LOD scores when mice were fed the low energy diet; LOD=3.42, peaking at 3cM with D7Mit21. It was also determinedto be sex dependent with female mice homozygous for the allele derived from the 129P3/J strain having higher body fat than the heterozygous and homozygous mice with the C57BL/6ByJ allele.
The remaing three QTL on Chr 9, 12 and 17 were all linked to percent body fat after being fed the higher energy diet.
The Chr 9 QTL, LOD=3.88, peaking at 28 cM with marker D9Mit2 was equated with Obq5.
02.24.2015 Curator Note: Since the Chr 9 QTL cited here was mapped using a cross between C57BL/6ByJ and 129P3/J which differs from the crosses used in both cited studies as Obq5 [Table 4: C57BL/6J x 129S1/SvImJ, J:151286 (2008) and KK/H1Lt x C57BL/6J in J:57787 (1999)] we consider this a separate map study and have named the QTL Pbft5.
Pbft5 did not display sex dependence; the plus allele was described as overdominant,the phenotype of heterozygotes differed from the phenotpyes of both homozygotes.
The Chr 12 QTL, LOD=3.88, peaking at 34 cM with SNP rs3724069 was equated with Obq34.
02.24.2015 Curator Note: Again,since Obq34 was originally mapped using (C57BL/6J x 129S1/SvImJ)F2 mice in J:151286 (2008) which differs from the cross used here we consider this a separate map study and have named this QTL Pbft6.
Pbft6 was determined to be a sex dependent QTL. There was an additive effect in female mice, with the 129P3/J allele increasing body fat.
The Chr 17 QTL has been named Pbft7; LOD=4.56, peaking at 10 cM with SNP rs4231344. It was not sex dependent. The C57BL/6ByJ allele was the plus allele, increasing percentbody fat.
A combination of filtering methods, genotype association mapping, differential gene expression, and genome comparison between parental strains highlighted seven candidate genes within the various QTL boundaries. Crx and Dmpk within the Chr 7 Pbft4 QTL(0-26Mb); Ahr within the Chr 12 Pbft6 QTL (35-88Mb) and genes Mrpl28, Glo1, Tubb5 and Mut within the Chr 17 Pbft7 QTL (8-48Mb).
Analysis Tools