title: Gene networks associated with conditional fear in mice identified using a systems genetics approach.
abstract: BACKGROUND
  Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP) with high mapping resolution.
  
  
  RESULTS
  A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes.
  
  
  CONCLUSIONS
  Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Park
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gale
authors.forename: Simone
authors.initials: S
authors.lastname: de Jong
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
authors.forename: Charles R
authors.initials: CR
authors.lastname: Farber
authors.forename: Peter
authors.initials: P
authors.lastname: Langfelder
authors.forename: Andy
authors.initials: A
authors.lastname: Lin
authors.forename: Arshad H
authors.initials: AH
authors.lastname: Khan
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D040641:Quantitative Trait Loci; D049490:Systems Biology / Q000379:methods*; D054875:Ubiquitination
chemical_list: D005819:Genetic Markers