Pathway analysis of expression QTL data in fat identifies a role for cyclin H in oxidative phosphorylation

  • Chunlei Wu (Contributor)
  • Nico Mitro (Contributor)
  • Jeff Janes (Contributor)
  • Phillip McClurg (Contributor)
  • Serge Batalov (Contributor)
  • Jie Zhang (Contributor)
  • Kazuhiro Shimomura (Contributor)
  • Akira Kohsaka (Contributor)
  • Joseph Bass (Contributor)
  • Enrique Saez (Contributor)
  • Tim Wiltshire (Contributor)



Genome-wide gene expression profiling has been extensively used to generate biological hypotheses based on differential expression. Recently, many studies have used microarrays to measure gene expression levels across genetic mapping populations. These gene expression phenotypes have been used for genome-wide association analyses, an analysis referred to as expression QTL (eQTL) mapping. Here, eQTL analysis was performed in fat issue from 28 inbred strains of mice. We focused our analysis on “trans-eQTL bands”, defined as instances in which the expression patterns of many genes were all associated to a common genetic locus. Genes comprising trans-eQTL bands were screened for enrichments in functional gene sets representing known biological pathways, while genes located at associated trans-eQTL band loci were considered candidate transcriptional modulators. We demonstrate that these patterns reflect previously characterized relationships between known upstream transcriptional regulators and their downstream target genes. Moreover, we used this strategy to identify both novel regulators and novel members of known pathways. Finally, based on putative regulatory relationship identified in our analysis, we validated in vitro a previously uncharacterized role for cyclin H in the regulation of oxidative phosphorylation. Keywords: strain comparison tissues were taken from different mouse strains under identical baseline conditions
Date made available2008

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