title: Microarray gene expression analysis of the Fob3b obesity QTL identifies positional candidate gene Sqle and perturbed cholesterol and glycolysis pathways.
abstract: 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 F(2) 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.
authors.affiliation: Department of Gene Expression, Roslin Institute, Edinburgh, Scotland. jstylian@jax.org
authors.forename: Ioannis M
authors.initials: IM
authors.lastname: Stylianou
authors.forename: Michael
authors.initials: M
authors.lastname: Clinton
authors.forename: Peter D
authors.initials: PD
authors.lastname: Keightley
authors.forename: Clare
authors.initials: C
authors.lastname: Pritchard
authors.forename: Zuzzana
authors.initials: Z
authors.lastname: Tymowska-Lalanne
authors.forename: Lutz
authors.initials: L
authors.lastname: Bünger
authors.forename: Simon
authors.initials: S
authors.lastname: Horvat
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D020224:Expressed Sequence Tags; D006019:Glycolysis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D050603:Squalene Monooxygenase / Q000235:genetics*
chemical_list: D012313:RNA; D002784:Cholesterol; D050603:Squalene Monooxygenase