Abstract
BackgroundWe performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis.ResultsWe were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus.ConclusionsThe brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.
Highlights
We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J
We identified large coexpression modules that are significantly associated with differences between mouse strains and brain regions
In order to better understand the high frequency of sequence variation in probe regions of the Magenta module genes, we investigated whether the target genes of the probes in the Magenta module with and without a Single Nucleotide Polymorphism (SNP) were cis- or trans-regulated genes
Summary
We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. We hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. Genome-wide gene expression profiling has been used to aid in the discovery of genes involved in human diseases and to discriminate between disease subtypes. This approach has already been successfully applied in cancer and obesity research [1,2], but similar approaches have not yet been widely applied to human neuropsychiatric traits. Regional gene expression in the brain has been shown to be conserved between non-human primates, rodents and man, making it possible to study mice in relation to human neurobiology [8,9]
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