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Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways

¹ Department of Gene Expression, Roslin Institute, Edinburgh, Scotland
² Medical Research Council Mammalian Genetics Unit, Harwell, England
³ Animal Breeding and Development, Sustainable Livestock Systems, Scottish Agricultural College, Bush Estate, Penicuik, Scotland
⁴ School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom
⁵ University of Ljubljana, Biotechnical Faculty, Zootechnical Department, Domzale, Slovenia

Obesity-related diseases are poised to become the primary cause of death in developed nations. While a number of monogenic causes of obesity have recently been identified, these are responsible for only a small proportion of human cases of obesity. Quantitative trait locus (QTL) studies using animal models have revealed hundreds of potential loci that affect obesity; however, few have been further analyzed beyond the original QTL scan. We previously mapped four QTL in an F₂ between divergently selected Fat (F) and Lean (L) lines. A QTL of large effect on chromosome 15 (Fob3) was subsequently mapped to a higher resolution into two smaller-effect QTL (Fob3a and Fob3b) using crosses between the F-line and a congenic line containing L-line alleles at the Fob3 QTL region. Here we report the gene expression characterization of Fob3b. Microarray expression analysis using the NIA-NIH 15K cDNA array set containing 14,938 mouse ESTs was employed to identify candidate genes and pathways that are differentially expressed between the F-line and a congenic line containing only the Fob3b QTL (Fob3b-line). Our study suggests squalene epoxidase (Sqle), a cholesterol biosynthesis enzyme, as a strong positional candidate gene for Fob3b. Several other cholesterol biosynthesis pathway genes unlinked to Fob3b were found to be differentially expressed, suggesting that a perturbation of this pathway could be in part responsible for the phenotypic difference between the F-line and Fob3b-line mice.

Depdc6; congenic

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