Data from: Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster
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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.
尽管绝大多数遗传关联研究均旨在检测与复杂性状相关的核苷酸多态性(nucleotide polymorphisms),但转录本丰度(transcript abundance)同样有望与疾病或表型存在关联。本研究对黑腹果蝇(Drosophila melanogaster)成年雌性头部组织中的数量性状转录本(quantitative trait transcripts)开展了扫描分析,以期解释尼古丁抗性的变异机制。其中,鸟氨酸转氨酶(ornithine aminotransferase)转录本的丰度与尼古丁抗性的关联最为显著,提示解毒作用与神经递质生物合成可能是介导该药物数量性状响应的核心途径。后续的遗传分析与代谢物谱分析(metabolite profiling)证实,鸟氨酸与γ-氨基丁酸(GABA)的水平在慢性尼古丁暴露下的存活时间调控中发挥着复杂作用。北卡罗来纳州与加利福尼亚州的种群间存在的差异表明,该抗性机制可能是对环境暴露的演化适应性响应。



