Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line

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

doi:10.1111/j.1601-183X.2011.00747.x

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Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line

Journal article

Peer reviewed

Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line

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

Genes, brain and behavior, Vol.11(1), pp.52-61

11/23/2011

DOI: 10.1111/j.1601-183X.2011.00747.x

PMCID: PMC3368015

PMID: 22032291

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https://www.ncbi.nlm.nih.gov/pmc/articles/3368015View

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Abstract

Sensitivity to the locomotor stimulant effects of methamphetamine is a heritable trait that utilizes neurocircuitry also associated with the rewarding effects of drugs. We used the power of a C57BL/6J x DBA/2J F 2 intercross (n = 676) and the precision of a C57BL/6J x DBA/2J F 8 advanced intercross line (Aap: B6, D2 – G8; or F 8 AIL; n = 552) to identify and narrow quantitative trait loci (QTL) associated with sensitivity to the locomotor stimulant effects of methamphetamine. We used the program QTLRel to simultaneously map QTL in the F 2 and F 8 AIL mice. We identified six genome-wide significant QTLs associated with locomotor activity at baseline and seven genome-wide significant QTLs associated with methamphetamine induced locomotor activation. The average percent decrease in QTL width between the F 2 and the integrated analysis was 65%. Additionally, these QTLs showed a distinct temporal specificity within each session that allowed us to further refine their locations, and identify one QTL with a 1.8-LOD support interval = 1.47 Mb. Next, we utilized publicly available bioinformatics resources to exploit strain-specific sequence data and strain- and region-specific expression data to identify candidate genes. These results illustrate the power of AILs in conjunction with sequence and gene expression data to investigate the genetic underpinnings of behavioral and other traits.

activity

addiction

amphetamine

drug abuse

genetic

GWAS

psychostimulant

quantitative trait loci

Details

Title: Subtitle: Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line
Creators: Clarissa C Parker - University of Chicago
Riyan Cheng - University of Chicago
Greta Sokoloff - University of Chicago
Abraham A Palmer - University of Chicago
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.11(1), pp.52-61
DOI: 10.1111/j.1601-183X.2011.00747.x
PMID: 22032291
PMCID: PMC3368015
NLM abbreviation: Genes Brain Behav
ISSN: 1601-1848
eISSN: 1601-183X
Language: English
Date published: 11/23/2011
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9984256933302771

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