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Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background.

de Jong S, Fuller TF, Janson E, Strengman E, Horvath S, Kas MJ, Ophoff RA - BMC Genomics (2010)

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

ABSTRACT

Background: We 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.

Results: We 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.

Conclusions: The 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.

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Related in: MedlinePlus

Module eigengene values can separate samples based on mouse strain or brain region. The module eigengene is a single representative expression profile for each sample, based on the first principal component of that module. The box plots show that the Magenta eigengene values separate samples perfectly into an A/J and C57BL/6J group (b) but not brain region (a). The Red module eigengenes creates groups of amygdala and hippocampus samples (c), but does not separate between strains (d). The Pink module eigengene differentiates between brain regions as well, but to a lesser extent (e and f).
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Figure 2: Module eigengene values can separate samples based on mouse strain or brain region. The module eigengene is a single representative expression profile for each sample, based on the first principal component of that module. The box plots show that the Magenta eigengene values separate samples perfectly into an A/J and C57BL/6J group (b) but not brain region (a). The Red module eigengenes creates groups of amygdala and hippocampus samples (c), but does not separate between strains (d). The Pink module eigengene differentiates between brain regions as well, but to a lesser extent (e and f).

Mentions: Figure 2a-f and Additional File 1 show the eigengene expression values of the Magenta, Red and Pink modules. The eigengene comparison showed that the Magenta module completely separates the inbred mouse strains, while the Pink and Red modules distinguish the amygdala and hippocampus independent of strain origin. The Red module is most informative in distinguishing the brain regions amygdala and hippocampus.


Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background.

de Jong S, Fuller TF, Janson E, Strengman E, Horvath S, Kas MJ, Ophoff RA - BMC Genomics (2010)

Module eigengene values can separate samples based on mouse strain or brain region. The module eigengene is a single representative expression profile for each sample, based on the first principal component of that module. The box plots show that the Magenta eigengene values separate samples perfectly into an A/J and C57BL/6J group (b) but not brain region (a). The Red module eigengenes creates groups of amygdala and hippocampus samples (c), but does not separate between strains (d). The Pink module eigengene differentiates between brain regions as well, but to a lesser extent (e and f).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2823687&req=5

Figure 2: Module eigengene values can separate samples based on mouse strain or brain region. The module eigengene is a single representative expression profile for each sample, based on the first principal component of that module. The box plots show that the Magenta eigengene values separate samples perfectly into an A/J and C57BL/6J group (b) but not brain region (a). The Red module eigengenes creates groups of amygdala and hippocampus samples (c), but does not separate between strains (d). The Pink module eigengene differentiates between brain regions as well, but to a lesser extent (e and f).
Mentions: Figure 2a-f and Additional File 1 show the eigengene expression values of the Magenta, Red and Pink modules. The eigengene comparison showed that the Magenta module completely separates the inbred mouse strains, while the Pink and Red modules distinguish the amygdala and hippocampus independent of strain origin. The Red module is most informative in distinguishing the brain regions amygdala and hippocampus.

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

ABSTRACT

Background: We 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.

Results: We 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.

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus