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Congenic dissection of a major QTL for methamphetamine sensitivity implicates epistasis
C D Bryant1, L A Kole, M A Guido
1Department of Human Genetics, University of Chicago, IL 60637, USA.
Genes, Brain, and Behavior
|April 11, 2012
Summary
Researchers identified a gene region on mouse chromosome 11 influencing methamphetamine (MA) activity. Fine mapping revealed complex interactions, suggesting epistasis, which complicated pinpointing the exact gene responsible for MA-induced locomotor activity.
Area of Science:
- Neurogenetics
- Behavioral Pharmacology
- Quantitative Genetics
Background:
- Methamphetamine (MA) induced locomotor activity is influenced by genetic factors.
- Previous studies identified a major quantitative trait locus (QTL) on mouse chromosome 11 affecting MA response.
Purpose of the Study:
- To fine-map the QTL influencing MA-induced locomotor activity on mouse chromosome 11.
- To investigate potential epistatic interactions affecting MA sensitivity.
- To identify candidate genes within the QTL region using gene expression data.
Main Methods:
- Creation of congenic and subcongenic mouse lines to narrow the QTL interval.
- Behavioral testing including locomotor activity and conditioned place preference (CPP) assays.
- Gene expression analysis using Affymetrix GeneChip Mouse Gene 1.0ST Array.
Main Results:
- A 12-Mb region on chromosome 11 was identified that recapitulated the QTL for MA locomotor activity.
- Subcongenic lines spanning this region abolished the MA sensitivity difference, indicating epistasis.
- Genotype did not affect MA-CPP, supporting the QTL's specificity for locomotor activity.
Conclusions:
- Fine mapping of QTLs using congenic lines can be challenging due to epistatic interactions.
- Epistasis can obscure the identification of specific genes underlying complex behavioral traits.
- This study provides a refined genetic interval and highlights the complexity of MA response genetics.
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