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PLoS One. 2013;8(3):e58951. doi: 10.1371/journal.pone.0058951. Epub 2013 Mar 21.

Differential network analysis reveals genetic effects on catalepsy modules.

Author information

  • 1Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. iancuo@ohsu.edu

Abstract

We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.

PMID:
23555609
[PubMed - indexed for MEDLINE]
PMCID:
PMC3605410
Free PMC Article
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