@article{dworkin_anderson_idaghdour_parker_stone_gibson_2011, title={The Effects of Weak Genetic Perturbations on the Transcriptome of the Wing Imaginal Disc and Its Association With Wing Shape in Drosophila melanogaster}, volume={187}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.110.125922}, abstractNote={Abstract
               A major objective of genomics is to elucidate the mapping between genotypic and phenotypic space as a step toward understanding how small changes in gene function can lead to elaborate phenotypic changes. One approach that has been utilized is to examine overall patterns of covariation between phenotypic variables of interest, such as morphology, physiology, and behavior, and underlying aspects of gene activity, in particular transcript abundance on a genome-wide scale. Numerous studies have demonstrated that such patterns of covariation occur, although these are often between samples with large numbers of unknown genetic differences (different strains or even species) or perturbations of large effect (sexual dimorphism or strong loss-of-function mutations) that may represent physiological changes outside of the normal experiences of the organism. We used weak mutational perturbations in genes affecting wing development in Drosophila melanogaster that influence wing shape relative to a co-isogenic wild type. We profiled transcription of 1150 genes expressed during wing development in 27 heterozygous mutants, as well as their co-isogenic wild type and one additional wild-type strain. Despite finding clear evidence of expression differences between mutants and wild type, transcriptional profiles did not covary strongly with shape, suggesting that information from transcriptional profiling may not generally be predictive of final phenotype. We discuss these results in the light of possible attractor states of gene expression and how this would affect interpretation of covariation between transcriptional profiles and other phenotypes.}, number={4}, journal={GENETICS}, author={Dworkin, Ian and Anderson, Julie A. and Idaghdour, Youssef and Parker, Erin Kennerly and Stone, Eric A. and Gibson, Greg}, year={2011}, month={Apr}, pages={1171–U314} }
 @article{dworkin_kennerly_tack_hutchinson_brown_mahaffey_gibson_2009, title={Genomic Consequences of Background Effects on scalloped Mutant Expressivity in the Wing of Drosophila melanogaster}, volume={181}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.108.096453}, abstractNote={AbstractGenetic background effects contribute to the phenotypic consequences of mutations and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scallopedE3 (sdE3) mutation of Drosophila melanogaster is background dependent and is the result of at least one major modifier segregating between two standard lab wild-type strains. We provide evidence that at least one of the modifiers is linked to the vestigial region and demonstrate that the background effects modify the spatial distribution of known sd target genes in a genotype-dependent manner. In addition, microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large as or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sdE3 and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis and studies of epistasis and cryptic genetic variation segregating in natural populations.}, number={3}, journal={GENETICS}, author={Dworkin, Ian and Kennerly, Erin and Tack, David and Hutchinson, Jennifer and Brown, Julie and Mahaffey, James and Gibson, Greg}, year={2009}, month={Mar}, pages={1065–1076} }
 @article{hall_dworkin_ungerer_purugganan_2007, title={Genetics of microenvironmental canalization in Arabidopsis thaliana}, volume={104}, number={34}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Hall, M. C. and Dworkin, I. and Ungerer, M. C. and Purugganan, M.}, year={2007}, pages={13717–13722} }
 @article{dworkin_gibson_2006, title={Epidermal growth factor receptor and transforming growth factor-beta signaling contributes to variation for wing shape in Drosophila melanogaster}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.053868}, abstractNote={Abstract
               Wing development in Drosophila is a common model system for the dissection of genetic networks and their roles during development. In particular, the RTK and TGF-β regulatory networks appear to be involved with numerous aspects of wing development, including patterning, cell determination, growth, proliferation, and survival in the developing imaginal wing disc. However, little is known as to how subtle changes in the function of these genes may contribute to quantitative variation for wing shape, per se. In this study 50 insertional mutations, representing 43 loci in the RTK, Hedgehog, TGF-β pathways, and their genetically interacting factors were used to study the role of these networks on wing shape. To concurrently examine how genetic background modulates the effects of the mutation, each insertion was introgressed into two wild-type genetic backgrounds. Using geometric morphometric methods, it is shown that the majority of these mutations have profound effects on shape but not size of the wing when measured as heterozygotes. To examine the relationships between how each mutation affects wing shape hierarchical clustering was used. Unlike previous observations of environmental canalization, these mutations did not generally increase within-line variation relative to their wild-type counterparts. These results provide an entry point into the genetics of wing shape and are discussed within the framework of the dissection of complex phenotypes.}, number={3}, journal={GENETICS}, author={Dworkin, Ian and Gibson, Greg}, year={2006}, month={Jul}, pages={1417–1431} }
 @misc{emlen_szafran_corley_dworkin_2006, title={Insulin signaling and limb-patterning: candidate pathways for the origin and evolutionary diversification of beetle 'horns'}, volume={97}, number={3}, journal={Heredity}, author={Emlen, D. J. and Szafran, Q. and Corley, L. S. and Dworkin, I.}, year={2006}, pages={179–191} }
 @article{dworkin_2005, title={A  study of canalization and developmental stability in the sternopleural bristle system of Drosophila melanogaster}, volume={59}, number={7}, journal={Evolution}, author={Dworkin, I.}, year={2005}, pages={1500–1509} }
 @article{dworkin_2005, title={Evidence for canalization of Distal-less function in the leg of Drosophila melanogaster}, volume={7}, ISSN={["1520-541X"]}, DOI={10.1111/j.1525-142X.2005.05010.x}, abstractNote={Summary
					 A considerable body of theory pertaining to the evolution of canalization has emerged recently, yet there have been few empirical investigations of their predictions. To address this, patterns of canalization and trait correlation were investigated under the individual and joint effects of the introgression of a loss‐of‐function allele of the Distal‐less gene and high‐temperature stress on a panel of iso‐female lines. Variation was examined for number of sex comb teeth and the length of the basi‐tarsus on the pro‐thoracic leg of male Drosophila melanogaster. I demonstrate that whereas there is evidence for trait canalization, there is no evidence to support the hypothesis of the evolution of genetic canalization as a response to microenvironmental canalization. Furthermore, I demonstrate that although there are genetic correlations between these traits, there is no association between their measures of canalization. I discuss the prospects of the evolutionary lability of the Distal‐less gene within the context of changes in genetic variation and covariation.}, number={2}, journal={EVOLUTION & DEVELOPMENT}, author={Dworkin, I}, year={2005}, pages={89–100} }
 @article{dworkin_palsson_gibson_2005, title={Replication of an egfr-wing shape association in a wild-caught cohort of Drosaphila melanogaster}, volume={169}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.035766}, abstractNote={Abstract
               Linkage disequilibrium mapping has been used extensively in medical and evolutionary genetics to map causal polymorphisms within genes associated with disease status or phenotypic variation for a trait. However, the initial findings of most nonhuman studies have not been replicated in subsequent studies, due in part to false positives, as well as additional factors that can render true positives unreplicable. These factors may be more severe when the initial study is performed using an experimental population of organisms reared under controlled lab conditions. We demonstrate that despite considerable phenotypic differences for wing shape between a lab-reared experimental population and a wild-caught cohort of Drosophila melanogaster, an association between a putative regulatory polymorphism in Egfr and wing shape can be replicated. These results are discussed both within the framework of future association-mapping studies and within the context of the evolutionary dynamics of alleles in populations.}, number={4}, journal={GENETICS}, author={Dworkin, I and Palsson, A and Gibson, G}, year={2005}, month={Apr}, pages={2115–2125} }
 @article{palsson_dodgson_dworkin_gibson_2005, title={Tests for the replication of an association between Egfr and natural variation in Drosophila melanogaster wing morphology}, volume={6}, journal={BMC Genetics}, author={Palsson, A. and Dodgson, J. and Dworkin, I. and Gibson, G.}, year={2005} }
 @article{dworkin_2005, title={Towards a genetic architecture of cryptic genetic variation and genetic assimilation: The contribution of K.G. Bateman}, volume={84}, ISSN={["0022-1333"]}, DOI={10.1007/BF02715794}, number={3}, journal={JOURNAL OF GENETICS}, author={Dworkin, I}, year={2005}, month={Dec}, pages={223–226} }
 @article{palsson_rouse_riley-berger_dworkin_gibson_2004, title={Nucleotide variation in the Egfr locus of Drosophila melanogaster}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.104.026252}, abstractNote={Abstract
               The Epidermal growth factor receptor is an essential gene with diverse pleiotropic roles in development throughout the animal kingdom. Analysis of sequence diversity in 10.9 kb covering the complete coding region and 6.4 kb of potential regulatory regions in a sample of 250 alleles from three populations of Drosophila melanogaster suggests that the intensity of different population genetic forces varies along the locus. A total of 238 independent common SNPs and 20 indel polymorphisms were detected, with just six common replacements affecting >1475 amino acids, four of which are in the short alternate first exon. Sequence diversity is lowest in a 2-kb portion of intron 2, which is also highly conserved in comparison with D. simulans and D. pseudoobscura. Linkage disequilibrium decays to background levels within 500 bp of most sites, so haplotypes are generally restricted to up to 5 polymorphisms. The two North American samples from North Carolina and California have diverged in allele frequency at a handful of individual SNPs, but a Kenyan sample is both more divergent and more polymorphic. The effect of sample size on inference of the roles of population structure, uneven recombination, and weak selection in patterning nucleotide variation in the locus is discussed.}, number={3}, journal={GENETICS}, author={Palsson, A and Rouse, A and Riley-Berger, R and Dworkin, I and Gibson, G}, year={2004}, month={Jul}, pages={1199–1212} }
 @misc{gibson_dworkin_2004, title={Uncovering cryptic genetic variation}, volume={5}, ISSN={["1471-0064"]}, DOI={10.1038/nrg1426}, abstractNote={Cryptic genetic variation is the dark matter of biology: it is variation that is not normally seen, but that might be an essential source of physiological and evolutionary potential. It is uncovered by environmental or genetic perturbations, and is thought to modify the penetrance of common diseases, the response of livestock and crops to artificial selection and the capacity of populations to respond to the emergence of a potentially advantageous macro-mutation. We argue in this review that cryptic genetic variation is pervasive but under-appreciated, we highlight recent progress in determining the nature and identity of genes that underlie cryptic genetic effects and we outline future research directions.}, number={9}, journal={NATURE REVIEWS GENETICS}, author={Gibson, G and Dworkin, I}, year={2004}, month={Sep}, pages={681–U11} }
 @article{dworkin_palsson_birdsall_gibson_2003, title={Evidence that Egfr contributes to cryptic genetic variation for photoreceptor determination in natural populations of Drosophila melanogaster}, volume={13}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2003.10.001}, abstractNote={One objective of quantitative genetics is to identify the nucleotide variants within genes that contribute to phenotypic variation and susceptibility [1Stern D.L. Perspective evolutionary developmental biology and the problem of variation.Evolution. 2000; 54: 1079-1091PubMed Google Scholar]. In an evolutionary context, this means characterizing the molecular polymorphisms that modify the penetrance and expressivity of perturbed traits. A survey of association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the degree of eye roughening due to a gain-of-function EgfrE1 allele crossed into 210 isogenic wild-type lines provides evidence that a handful of synonymous substitutions supply cryptic variation for photoreceptor determination. Ten sites exceed Bonferroni threshold for association in two sets of crosses to different EgfrE1 backgrounds including a particularly significant cluster of sites in tight linkage disequilibrium toward the 3′ end of the coding region. Epistatic interaction of this cluster with one other site enhances the expressivity of this haplotype. Replication of the strongest associations with an independent sample of 302 phenotypically extreme individuals derived from 1000 crosses of EgfrE1 to freshly trapped males was achieved using modified case-control and transmission-disequilibrium tests. A tendency for the rarer alleles to have more disrupted eye development suggests that mutation-selection balance is a possible mechanism contributing to maintaining cryptic variation for Egfr.}, number={21}, journal={CURRENT BIOLOGY}, author={Dworkin, I and Palsson, A and Birdsall, K and Gibson, G}, year={2003}, month={Oct}, pages={1888–1893} }