Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster
Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster
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DOI：
10.1186/gb-2007-8-10-r231
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发表时间：
2007-01-01
期刊：
影响因子：
12.3
通讯作者：
Mackay, Trudy Fc
中科院分区：
文献类型：
--
作者：
Morozova, Tatiana V.;Anholt, Robert R. H.;Mackay, Trudy Fc
背景：酒精中毒是一种复杂的疾病，由遗传和环境危险因素相互作用决定。果蝇代表了一个强大的模型系统来剖析酒精敏感性的遗传结构，因为大量的果蝇可以很容易地在特定的遗传背景和受控的环境条件下饲养。此外，暴露在乙醇中的果蝇会经历类似于人类酒精中毒的生理和行为变化，包括失去姿势控制、镇静和耐受性的形成。结果：我们进行了35代酒精敏感性的人工选择，并创建了对酒精暴露高度敏感或抵抗的重复选择系和未选择的对照系。我们使用全基因组表达分析来鉴定1,678个不同品系之间表达水平不同的探针集，这些探针集跨重复汇集在一起，错误发现率为Q<；0.001。我们通过测量35个候选基因中37个同基因P元件插入突变的酒精敏感性，评估了转录调控改变的基因可能在多大程度上与酒精敏感性有关，并发现其中32个突变对酒精暴露的敏感性与其同基因对照不同。结论：将全基因组表达谱分析与遗传分化系选择相结合，是识别影响酒精敏感性等复杂性状的候选基因的有效方法。由于功能的进化保守，很可能是影响果蝇酒精敏感性的基因的人类同源基因可能有助于人类的酒精相关表型。
Background: Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance.Results: We performed artificial selection for alcohol sensitivity for 35 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues.Conclusion: Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans.