Limits...
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.

Show MeSH

Related in: MedlinePlus

Network construction identifies distinct modules of co-expressed genes using hippocampus and amygdala samples of A/J and C57BL/6J mice (n = 35). The dendrogram was produced by average linkage hierarchical clustering of genes using topological overlap. Modules of co-expressed genes were assigned colors corresponding to the branches indicated by the horizontal bar beneath the dendrogram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2823687&req=5

Figure 1: Network construction identifies distinct modules of co-expressed genes using hippocampus and amygdala samples of A/J and C57BL/6J mice (n = 35). The dendrogram was produced by average linkage hierarchical clustering of genes using topological overlap. Modules of co-expressed genes were assigned colors corresponding to the branches indicated by the horizontal bar beneath the dendrogram.

Mentions: For branch cutting (module detection) we used the dynamic branch-cutting algorithm implemented in the dynamicTreeCut and WGCNA (weighted gene co-expression network analysis) R library [26,34]. Each module (or branch) is assigned a unique color label which is visualized in the color band underneath the cluster tree (see Figure 1). We found 10 modules, each of which contained at least 50 probes. Our module detection method followed the standard WGCNA approach that has been successfully used in multiple applications [8,25,26,29,35]. Since our modules are large and distinct, we expect them to be found by many alternative detection methods. Average gene expression levels of all modules range from 8.52 to 9.51.


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)

Network construction identifies distinct modules of co-expressed genes using hippocampus and amygdala samples of A/J and C57BL/6J mice (n = 35). The dendrogram was produced by average linkage hierarchical clustering of genes using topological overlap. Modules of co-expressed genes were assigned colors corresponding to the branches indicated by the horizontal bar beneath the dendrogram.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Network construction identifies distinct modules of co-expressed genes using hippocampus and amygdala samples of A/J and C57BL/6J mice (n = 35). The dendrogram was produced by average linkage hierarchical clustering of genes using topological overlap. Modules of co-expressed genes were assigned colors corresponding to the branches indicated by the horizontal bar beneath the dendrogram.
Mentions: For branch cutting (module detection) we used the dynamic branch-cutting algorithm implemented in the dynamicTreeCut and WGCNA (weighted gene co-expression network analysis) R library [26,34]. Each module (or branch) is assigned a unique color label which is visualized in the color band underneath the cluster tree (see Figure 1). We found 10 modules, each of which contained at least 50 probes. Our module detection method followed the standard WGCNA approach that has been successfully used in multiple applications [8,25,26,29,35]. Since our modules are large and distinct, we expect them to be found by many alternative detection methods. Average gene expression levels of all modules range from 8.52 to 9.51.

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