Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse Line

Clarissa C Parker; Greta Sokoloff; Riyan Cheng; Abraham A Palmer

doi:10.1007/s10519-011-9524-8

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Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse Line

Journal article

Open access

Peer reviewed

Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse Line

Clarissa C Parker, Greta Sokoloff, Riyan Cheng and Abraham A Palmer

Behavior genetics, Vol.42(3), pp.437-448

01/12/2012

DOI: 10.1007/s10519-011-9524-8

PMCID: PMC3351497

PMID: 22237917

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https://www.ncbi.nlm.nih.gov/pmc/articles/3351497View

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Abstract

Fear conditioning (FC) may provide a useful model for some components of post-traumatic stress disorder (PTSD). We used a C57BL/6J × DBA/2J F 2 intercross (n = 620) and a C57BL/6J × DBA/2J F 8 advanced inter-cross line (n = 567) to fine-map quantitative trait loci (QTL) associated with FC. We conducted an integrated genome-wide association analysis in QTLRel and identified five highly significant QTL affecting freezing to context as well as four highly significant QTL associated with freezing to cue. The average percent decrease in QTL width between the F 2 and the integrated analysis was 59.2%. Next, we exploited bioinformatic sequence and expression data to identify candidate genes based on the existence of non-synonymous coding polymorphisms and/or expression QTLs. We identified numerous candidate genes that have been previously implicated in either fear learning in animal models ( Bcl2 , Btg2 , Dbi , Gabr1b , Lypd1 , Pam and Rgs14 ) or PTSD in humans ( Gabra2 , Oprm1 and Trkb ); other identified genes may represent novel findings. The integration of F 2 and AIL data maintains the advantages of studying FC in model organisms while significantly improving resolution over previous approaches.

Advanced intercross lines

Fear conditioning

Fear learning

Genome-wide association

Post-traumatic stress disorder

Quantitative trait loci

Details

Title: Subtitle: Genome-Wide Association for Fear Conditioning in an Advanced Intercross Mouse Line
Creators: Clarissa C Parker - University of Chicago
Greta Sokoloff - University of Chicago
Riyan Cheng - University of Chicago
Abraham A Palmer - University of Chicago
Resource Type: Journal article
Publication Details: Behavior genetics, Vol.42(3), pp.437-448
DOI: 10.1007/s10519-011-9524-8
PMID: 22237917
PMCID: PMC3351497
NLM abbreviation: Behav Genet
ISSN: 0001-8244
eISSN: 1573-3297
Grant note: R01 GM097737-02 || GM / National Institute of General Medical Sciences : NIGMS R01 DA021336-03S1 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-04S1 || DA / National Institute on Drug Abuse : NIDA R21 DA024845-02 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-05 || DA / National Institute on Drug Abuse : NIDA R01 MH079103-03S1 || MH / National Institute of Mental Health : NIMH R01 MH079103-04 || MH / National Institute of Mental Health : NIMH R01 GM097737-01A1 || GM / National Institute of General Medical Sciences : NIGMS R01 MH079103-02 || MH / National Institute of Mental Health : NIMH R01 DA021336-07 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-01 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-03 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-04S2 || DA / National Institute on Drug Abuse : NIDA R21 DA024845-01 || DA / National Institute on Drug Abuse : NIDA R01 MH079103-01 || MH / National Institute of Mental Health : NIMH R01 MH079103-05 || MH / National Institute of Mental Health : NIMH R01 DA021336-02 || DA / National Institute on Drug Abuse : NIDA R01 DA021336-06 || DA / National Institute on Drug Abuse : NIDA R01 MH079103-03 || MH / National Institute of Mental Health : NIMH R01 DA021336-04 || DA / National Institute on Drug Abuse : NIDA
Language: English
Date published: 01/12/2012
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9984256934802771

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