Abstract
Drosophila melanogaster appears to be well suited as a model organism for quantitative pharmacogenetic analysis. A genome-wide deficiency screen for haploinsufficient effects on prepupal heart rate identified nine regions of the genome that significantly reduce (five deficiencies) or increase (four deficiencies) heart rate across a range of genetic backgrounds. Candidate genes include several neurotransmitter receptor loci, particularly monoamine receptors, consistent with results of prior pharmacological manipulations of heart rate, as well as genes associated with paralytic phenotypes. Significant genetic variation is also shown to exist for a suite of four autonomic behaviors that are exhibited spontaneously upon decapitation, namely, grooming, grasping, righting, and quivering. Overall activity levels are increased by application of particular concentrations of the drugs octopamine and nicotine, but due to high environmental variance both within and among replicate vials, the significance of genetic variation among wild-type lines for response to the drugs is difficult to establish. An interval mapping design was also used to map two or three QTL for each behavioral trait in a set of recombinant inbred lines derived from the laboratory stocks Oregon-R and 2b.
