Uncovering Pathways Associated with Obesity
Uncovering Pathways Associated with Obesity
A review of Genomic analysis of metabolic pathway gene expression in mice.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Ghazalpour and colleagues (2005) integrate genetic and gene expression data to identify obesity-associated pathways. The group took advantage of Agilent’s custom microarray design services, creating an array of 23,574 60-mer oligonucleotide probes to profile obesity-related traits and liver gene expression in (C57BL/6JxDBA/2J)F2 intercross mice. Combining global gene expression microarray data with phenotypic and genetic segregation analyses, the group was able to identify 13 obesity-related metabolic pathways, specific regulatory controlling regions, and novel genes associated with these pathways — offering a truly integrated perspective and functional analysis.
Figure 1. Significantly differentially regulated pathways identified by gene set enrichment analysis (GSEA).
The histogram represents the frequency distribution of maximum enrichment scores (ES) obtained with gene set enrichment analysis (GSEA) after 1,000 random permutations of class assignment (obese or lean. The location of the gray arrow corresponds to p = 0.05 (ES = 114.0). Pathways with scores greater than this are indicated by black arrows.
Figure 2. Relationship of the 13 differentially regulated pathways identified by GSEA.
Nine pathways are related via the tricarboxylic acid (TCA) cycle and three other pathways are linked through cholesterol metabolism. The aggregate gene set from all 13 pathways contains a total of 170 genes, some of which are present in multiple pathways. 150 of these genes were represented on the arrays.
Title: Genomic analysis of metabolic pathway gene expression in mice
Authors: Ghazalpour A, Doss S, Sheth SS, Ingram-Drake LA, Schadt EE, Lusis AJ, Drake TA.
Journal: Genome Biol. 2005; 6(7): R59.
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