@article{hsieh_passador-gurgel_stone_gibson_2007, title={Mixture modeling of transcript abundance classes in natural populations}, volume={8}, ISSN={["1474-760X"]}, DOI={10.1186/gb-2007-8-6-r98}, abstractNote={Populations diverge in genotype and phenotype under the influence of such evolutionary processes as genetic drift, mutation accumulation, and natural selection. Because genotype maps onto phenotype by way of transcription, it is of interest to evaluate how these evolutionary factors influence the structure of variation at the level of transcription. Here, we explore the distributions of cis-acting and trans-acting factors and their relative contributions to expression of transcripts that exhibit two or more classes of abundance among individuals within populations.Expression profiling using cDNA microarrays was conducted in Drosophila melanogaster adult female heads for 58 nearly isogenic lines from a North Carolina population and 50 from a California population. Using a mixture modeling approach, transcripts were identified that exhibit more than one mode of transcript abundance across the samples. Power studies indicate that sample sizes of 50 individuals will generally be sufficient to detect divergent transcript abundance classes. The distribution of transcript abundance classes is skewed toward low frequency minor classes, which is reminiscent of the typical skew in genotype frequencies. Similar results are observed in reported data on gene expression in human lymphoblast cell lines, in which analysis of association with linked polymorphisms implies that cis-acting single nucleotide polymorphisms make only a modest contribution to bimodal distributions of transcript abundance.Population surveys of gene expression may complement genetical genomics as a general approach to quantifying sources of transcriptional variation. Differential expression of transcripts among individuals is due to a complex interplay of cis-acting and trans-acting factors.}, number={6}, journal={GENOME BIOLOGY}, author={Hsieh, Wen-Ping and Passador-Gurgel, Gisele and Stone, Eric A. and Gibson, Greg}, year={2007} }
 @article{passador-gurgel_hsieh_hunt_deighton_gibson_2007, title={Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster}, volume={39}, ISSN={["1061-4036"]}, DOI={10.1038/ng1944}, abstractNote={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.}, number={2}, journal={NATURE GENETICS}, author={Passador-Gurgel, Gisele and Hsieh, Wen-Ping and Hunt, Priscilla and Deighton, Nigel and Gibson, Greg}, year={2007}, month={Feb}, pages={264–268} }