@article{ayroles_carbone_stone_jordan_lyman_magwire_rollmann_duncan_lawrence_anholt_et al._2009, title={Systems genetics of complex traits in Drosophila melanogaster}, volume={41}, ISSN={["1546-1718"]}, DOI={10.1038/ng.332}, abstractNote={Trudy Mackay and colleagues present a resource of 40 Drosophila melanogaster wild-derived inbred lines. The authors quantify genome-wide variation in transcript abundance for six ecologically relevant traits, characterize the transcriptome and identify transcriptional modules. Determining the genetic architecture of complex traits is challenging because phenotypic variation arises from interactions between multiple, environmentally sensitive alleles. We quantified genome-wide transcript abundance and phenotypes for six ecologically relevant traits in D. melanogaster wild-derived inbred lines. We observed 10,096 genetically variable transcripts and high heritabilities for all organismal phenotypes. The transcriptome is highly genetically intercorrelated, forming 241 transcriptional modules. Modules are enriched for transcripts in common pathways, gene ontology categories, tissue-specific expression and transcription factor binding sites. The high degree of transcriptional connectivity allows us to infer genetic networks and the function of predicted genes from annotations of other genes in the network. Regressions of organismal phenotypes on transcript abundance implicate several hundred candidate genes that form modules of biologically meaningful correlated transcripts affecting each phenotype. Overlapping transcripts in modules associated with different traits provide insight into the molecular basis of pleiotropy between complex traits.}, number={3}, journal={NATURE GENETICS}, author={Ayroles, Julien F. and Carbone, Mary Anna and Stone, Eric A. and Jordan, Katherine W. and Lyman, Richard F. and Magwire, Michael M. and Rollmann, Stephanie M. and Duncan, Laura H. and Lawrence, Faye and Anholt, Robert R. H. and et al.}, year={2009}, month={Mar}, pages={299–307} } @article{mackay_lyman_lawrence_2005, title={Polygenic mutation in Drosophila melanogaster: Mapping spontaneous mutations affecting sensory bristle number}, volume={170}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.032581}, abstractNote={Abstract Our ability to predict long-term responses to artificial and natural selection, and understand the mechanisms by which naturally occurring variation for quantitative traits is maintained, depends on detailed knowledge of the properties of spontaneous polygenic mutations, including the quantitative trait loci (QTL) at which mutations occur, mutation rates, and mutational effects. These parameters can be estimated by mapping QTL that cause divergence between mutation-accumulation lines that have been established from an inbred base population and selected for high and low trait values. Here, we have utilized quantitative complementation to deficiencies to map QTL at which spontaneous mutations affecting Drosophila abdominal and sternopleural bristle number have occurred in 11 replicate lines during 206 generations of divergent selection. Estimates of the numbers of mutations were consistent with diploid per-character mutation rates for bristle traits of 0.03. The ratio of the per-character mutation rate to total mutation rate (0.023) implies that >2% of the genome could affect just one bristle trait and that there must be extensive pleiotropy for quantitative phenotypes. The estimated mutational effects were not, however, additive and exhibited dependency on genetic background consistent with diminishing epistasis. However, these inferences must be tempered by the potential for epistatic interactions between spontaneous mutations and QTL affecting bristle number on the deficiency-bearing chromosomes, which could lead to overestimates in numbers of QTL and inaccurate inference of gene action.}, number={4}, journal={GENETICS}, author={Mackay, TFC and Lyman, RF and Lawrence, F}, year={2005}, month={Aug}, pages={1723–1735} } @article{huang_richards_carbone_zhu_anholt_ayroles_duncan_jordan_lawrence_magwire_et al., title={Epistasis dominates the genetic architecture of Drosophila quantitative traits}, volume={109}, number={39}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Huang, W. and Richards, S. and Carbone, M. A. and Zhu, D. H. and Anholt, R. R. H. and Ayroles, J. F. and Duncan, L. and Jordan, K. W. and Lawrence, F. and Magwire, M. M. and et al.}, pages={15553–15559} } @article{dembeck_huang_magwire_lawrence_lyman_mackay, title={Genetic architecture of abdominal pigmentation in Drosophila melanogaster}, volume={11}, number={5}, journal={PLoS Genetics}, author={Dembeck, L. M. and Huang, W. and Magwire, M. M. and Lawrence, F. and Lyman, R. F. and Mackay, T. F. C.} } @article{mackay_richards_stone_barbadilla_ayroles_zhu_casillas_han_magwire_cridland_et al., title={The Drosophila melanogaster genetic reference panel}, volume={482}, number={7384}, journal={Nature}, author={Mackay, T. F. C. and Richards, S. and Stone, E. A. and Barbadilla, A. and Ayroles, J. F. and Zhu, D. H. and Casillas, S. and Han, Y. and Magwire, M. M. and Cridland, J. M. and et al.}, pages={173–178} }