Differential Network Analysis Reveals Genetic Effects on Catalepsy Modules

Ovidiu Iancu, Denesa Oberbeck, Priscila Darakjian, Sunita Kawane, Jason Erk, Shannon McWeeney, Robert Hitzemann

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere58951
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 21 2013

Fingerprint

Catalepsy
Haloperidol
Electric network analysis
haloperidol
genetic techniques and protocols
selection methods
genetic background
Genetic Structures
Genetic Polymorphisms
Polymorphism
Gene Expression
Gene expression
Genes
genetic polymorphism
Population
gene expression
mice
Selective Breeding
Genetic Background
genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Differential Network Analysis Reveals Genetic Effects on Catalepsy Modules. / Iancu, Ovidiu; Oberbeck, Denesa; Darakjian, Priscila; Kawane, Sunita; Erk, Jason; McWeeney, Shannon; Hitzemann, Robert.

In: PLoS One, Vol. 8, No. 3, e58951, 21.03.2013.

Research output: Contribution to journalArticle

Iancu, Ovidiu ; Oberbeck, Denesa ; Darakjian, Priscila ; Kawane, Sunita ; Erk, Jason ; McWeeney, Shannon ; Hitzemann, Robert. / Differential Network Analysis Reveals Genetic Effects on Catalepsy Modules. In: PLoS One. 2013 ; Vol. 8, No. 3.
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