title: Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster.
abstract: Although most genetic association studies are performed with the intention of detecting nucleotide polymorphisms that are correlated with a complex trait, transcript abundance should also be expected to associate with diseases or phenotypes. We performed a scan for such quantitative trait transcripts in adult female heads of the fruit fly (Drosophila melanogaster) that might explain variation for nicotine resistance. The strongest association was seen for abundance of ornithine aminotransferase transcripts, implicating detoxification and neurotransmitter biosynthesis as mediators of the quantitative response to the drug. Subsequently, genetic analysis and metabolite profiling confirmed a complex role for ornithine and GABA levels in modification of survival time upon chronic nicotine exposure. Differences between populations from North Carolina and California suggest that the resistance mechanism may be an evolved response to environmental exposure.
authors.affiliation: Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
authors.forename: Gisele
authors.initials: G
authors.lastname: Passador-Gurgel
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Hsieh
authors.forename: Priscilla
authors.initials: P
authors.lastname: Hunt
authors.forename: Nigel
authors.initials: N
authors.lastname: Deighton
authors.forename: Greg
authors.initials: G
authors.lastname: Gibson
mesh_terms: D000818:Animals; D002140:California; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D004351:Drug Resistance; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008136:Longevity; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D009657:North Carolina; D009953:Ornithine-Oxo-Acid Transaminase / Q000378:metabolism; D040641:Quantitative Trait Loci; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D009953:Ornithine-Oxo-Acid Transaminase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1