@article{ozsoy_yilmaz_patlar_emecen_durmaz_magwire_zhou_huang_anholt_mackay_2021, title={Epistasis for head morphology in Drosophila melanogaster}, volume={11}, ISSN={["2160-1836"]}, DOI={10.1093/g3journal/jkab285}, abstractNote={Epistasis-gene-gene interaction-is common for mutations with large phenotypic effects in humans and model organisms. Epistasis impacts quantitative genetic models of speciation, response to natural and artificial selection, genetic mapping, and personalized medicine. However, the existence and magnitude of epistasis between alleles with small quantitative phenotypic effects are controversial and difficult to assess. Here, we use the Drosophila melanogaster Genetic Reference Panel of sequenced inbred lines to evaluate the magnitude of naturally occurring epistasis modifying the effects of mutations in jing and inv, two transcription factors that have subtle quantitative effects on head morphology as homozygotes. We find significant epistasis for both mutations and performed single marker genome-wide association analyses to map candidate modifier variants and loci affecting head morphology. A subset of these loci was significantly enriched for a known genetic interaction network, and mutations of the candidate epistatic modifier loci also affect head morphology.}, number={10}, journal={G3-GENES GENOMES GENETICS}, author={Ozsoy, Ergi D. and Yilmaz, Murat and Patlar, Bahar and Emecen, Guzin and Durmaz, Esra and Magwire, Michael M. and Zhou, Shanshan and Huang, Wen and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2021}, month={Oct} }
 @article{johnstun_shankar_mokashi_sunkara_ihearahu_lyman_mackay_anholt_2021, title={Functional Diversification, Redundancy, and Epistasis among Paralogs of the Drosophila melanogaster Obp50a-d Gene Cluster}, volume={38}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msab004}, abstractNote={Abstract Large multigene families, such as the insect odorant-binding proteins (OBPs), are thought to arise through functional diversification after repeated gene duplications. Whereas many OBPs function in chemoreception, members of this family are also expressed in tissues outside chemosensory organs. Paralogs of the Obp50 gene cluster are expressed in metabolic and male reproductive tissues, but their functions and interrelationships remain unknown. Here, we report the genetic dissection of four members of the Obp50 cluster, which are in close physical proximity without intervening genes. We used CRISPR technology to excise the entire cluster while introducing a PhiC31 reintegration site to reinsert constructs in which different combinations of the constituent Obp genes were either intact or rendered inactive. We performed whole transcriptome sequencing and assessed sexually dimorphic changes in transcript abundances (transcriptional niches) associated with each gene-edited genotype. Using this approach, we were able to estimate redundancy, additivity, diversification, and epistasis among Obp50 paralogs. We analyzed the effects of gene editing of this cluster on organismal phenotypes and found a significant skewing of sex ratios attributable to Obp50a, and sex-specific effects on starvation stress resistance attributable to Obp50d. Thus, there is functional diversification within the Obp50 cluster with Obp50a contributing to development and Obp50d to stress resistance. The deletion–reinsertion approach we applied to the Obp50 cluster provides a general paradigm for the genetic dissection of paralogs of multigene families.}, number={5}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Johnstun, Joel A. and Shankar, Vijay and Mokashi, Sneha S. and Sunkara, Lakshmi T. and Ihearahu, Ugonna E. and Lyman, Roberta L. and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2021}, month={May}, pages={2030–2044} }
 @article{baker_carbone_huang_anholt_mackay_2021, title={Genetic basis of variation in cocaine and methamphetamine consumption in outbred populations of Drosophila melanogaster}, volume={118}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.2104131118}, abstractNote={Significance The use of cocaine and methamphetamine presents significant socioeconomic problems. However, identifying the genetic underpinnings that determine susceptibility to substance use is challenging in human populations. The fruit fly, Drosophila melanogaster , presents a powerful genetic model since we can control the genetic background and environment, 75% of disease-causing genes in humans have a fly counterpart, and flies—like humans—exhibit adverse effects upon cocaine and methamphetamine exposure. We showed that the genetic architecture underlying variation in voluntary cocaine and methamphetamine consumption differs between sexes and is dominated by variants in genes associated with connectivity and function of the nervous system. Results obtained from the Drosophila gene discovery model can guide studies on substance abuse susceptibility in human populations.}, number={23}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Baker, Brandon M. and Carbone, Mary Anna and Huang, Wen and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2021}, month={Jun} }
 @article{tallo_duncan_yamamoto_slaydon_arya_turlapati_mackay_carbone_2021, title={Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy}, volume={11}, ISSN={["2160-1836"]}, DOI={10.1093/g3journal/jkaa014}, abstractNote={Abstract In cats, mutations in myosin binding protein C (encoded by the MYBPC3 gene) have been associated with hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms linking these mutations to HCM remain unknown. Here, we establish Drosophila melanogaster as a model to understand this connection by generating flies harboring MYBPC3 missense mutations (A31P and R820W) associated with feline HCM. The A31P and R820W flies displayed cardiovascular defects in their heart rates and exercise endurance. We used RNA-seq to determine which processes are misregulated in the presence of mutant MYBPC3 alleles. Transcriptome analysis revealed significant downregulation of genes encoding small nucleolar RNA (snoRNAs) in exercised female flies harboring the mutant alleles compared to flies that harbor the wild-type allele. Other processes that were affected included the unfolded protein response and immune/defense responses. These data show that mutant MYBPC3 proteins have widespread effects on the transcriptome of co-regulated genes. Transcriptionally differentially expressed genes are also candidate genes for future evaluation as genetic modifiers of HCM as well as candidate genes for genotype by exercise environment interaction effects on the manifestation of HCM; in cats as well as humans.}, number={1}, journal={G3-GENES GENOMES GENETICS}, author={Tallo, Christian A. and Duncan, Laura H. and Yamamoto, Akihiko H. and Slaydon, Joshua D. and Arya, Gunjan H. and Turlapati, Lavanya and Mackay, Trudy F. C. and Carbone, Mary A.}, year={2021}, month={Jan} }
 @article{huang_campbell_carbone_jones_unselt_anholt_mackay_2020, title={Context-dependent genetic architecture of Drosophila life span}, volume={18}, ISSN={["1545-7885"]}, DOI={10.1371/journal.pbio.3000645}, abstractNote={Understanding the genetic basis of variation in life span is a major challenge that is difficult to address in human populations. Evolutionary theory predicts that alleles affecting natural variation in life span will have properties that enable them to persist in populations at intermediate frequencies, such as late-life–specific deleterious effects, antagonistic pleiotropic effects on early and late-age fitness components, and/or sex- and environment-specific or antagonistic effects. Here, we quantified variation in life span in males and females reared in 3 thermal environments for the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and an advanced intercross outbred population derived from a subset of DGRP lines. Quantitative genetic analyses of life span and the micro-environmental variance of life span in the DGRP revealed significant genetic variance for both traits within each sex and environment, as well as significant genotype-by-sex interaction (GSI) and genotype-by-environment interaction (GEI). Genome-wide association (GWA) mapping in both populations implicates over 2,000 candidate genes with sex- and environment-specific or antagonistic pleiotropic allelic effects. Over 1,000 of these genes are associated with variation in life span in other D. melanogaster populations. We functionally assessed the effects of 15 candidate genes using RNA interference (RNAi): all affected life span and/or micro-environmental variance of life span in at least one sex and environment and exhibited sex-and environment-specific effects. Our results implicate novel candidate genes affecting life span and suggest that variation for life span may be maintained by variable allelic effects in heterogeneous environments.}, number={3}, journal={PLOS BIOLOGY}, author={Huang, Wen and Campbell, Terry and Carbone, Mary Anna and Jones, W. Elizabeth and Unselt, Desiree and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2020}, month={Mar} }
 @article{everett_huang_zhou_carbone_lyman_arya_geisz_ma_morgante_st armour_et al._2020, title={Gene expression networks in the Drosophila Genetic Reference Panel}, volume={30}, ISSN={["1549-5469"]}, DOI={10.1101/gr.257592.119}, abstractNote={A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here, we performed deep RNA sequencing of 200 Drosophila Genetic Reference Panel inbred lines with complete genome sequences and for which phenotypes of many quantitative traits have been evaluated. We mapped expression quantitative trait loci for annotated genes, novel transcribed regions, transposable elements, and microbial species. We identified host variants that affect expression of transposable elements, independent of their copy number, as well as microbiome composition. We constructed sex-specific expression quantitative trait locus regulatory networks. These networks are enriched for novel transcribed regions and target genes in heterochromatin and euchromatic regions of reduced recombination, as well as genes regulating transposable element expression. This study provides new insights regarding the role of natural genetic variation in regulating gene expression and generates testable hypotheses for future functional analyses.}, number={3}, journal={GENOME RESEARCH}, author={Everett, Logan J. and Huang, Wen and Zhou, Shanshan and Carbone, Mary Anna and Lyman, Richard F. and Arya, Gunjan H. and Geisz, Matthew S. and Ma, Junwu and Morgante, Fabio and St Armour, Genevieve and et al.}, year={2020}, month={Mar}, pages={485–496} }
 @article{parker_kohn_spirina_mcmillen_huang_mackay_2020, title={Genetic Basis of Increased Lifespan and Postponed Senescence in Drosophila melanogaster}, volume={10}, ISSN={["2160-1836"]}, DOI={10.1534/g3.120.401041}, abstractNote={Abstract Limited lifespan and senescence are near-universal phenomena. These quantitative traits exhibit variation in natural populations due to the segregation of many interacting loci and from environmental effects. Due to the complexity of the genetic control of lifespan and senescence, our understanding of the genetic basis of variation in these traits is incomplete. Here, we analyzed the pattern of genetic divergence between long-lived (O) Drosophila melanogaster lines selected for postponed reproductive senescence and unselected control (B) lines. We quantified the productivity of the O and B lines and found that reproductive senescence is maternally controlled. We therefore chose 57 candidate genes that are expressed in ovaries, 49 of which have human orthologs, and assessed the effects of RNA interference in ovaries and accessary glands on lifespan and reproduction. All but one candidate gene affected at least one life history trait in one sex or productivity week. In addition, 23 genes had antagonistic pleiotropic effects on lifespan and productivity. Identifying evolutionarily conserved genes affecting increased lifespan and delayed reproductive senescence is the first step toward understanding the evolutionary forces that maintain segregating variation at these loci in nature and may provide potential targets for therapeutic intervention to delay senescence while increasing lifespan.}, number={3}, journal={G3-GENES GENOMES GENETICS}, author={Parker, Grace A. and Kohn, Nathan and Spirina, Ally and McMillen, Anna and Huang, Wen and Mackay, Trudy F. C.}, year={2020}, month={Mar}, pages={1087–1098} }
 @article{yanagawa_huang_yamamoto_wada-katsumata_schal_mackay_2020, title={Genetic Basis of Natural Variation in Spontaneous Grooming in Drosophila melanogaster}, volume={10}, ISSN={["2160-1836"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85090276700&partnerID=MN8TOARS}, DOI={10.1534/g3.120.401360}, abstractNote={Abstract Spontaneous grooming behavior is a component of insect fitness. We quantified spontaneous grooming behavior in 201 sequenced lines of the Drosophila melanogaster Genetic Reference Panel and observed significant genetic variation in spontaneous grooming, with broad-sense heritabilities of 0.25 and 0.24 in females and males, respectively. Although grooming behavior is highly correlated between males and females, we observed significant sex by genotype interactions, indicating that the genetic basis of spontaneous grooming is partially distinct in the two sexes. We performed genome-wide association analyses of grooming behavior, and mapped 107 molecular polymorphisms associated with spontaneous grooming behavior, of which 73 were in or near 70 genes and 34 were over 1 kilobase from the nearest gene. The candidate genes were associated with a wide variety of gene ontology terms, and several of the candidate genes were significantly enriched in a genetic interaction network. We performed functional assessments of 29 candidate genes using RNA interference, and found that 11 affected spontaneous grooming behavior. The genes associated with natural variation in Drosophila grooming are involved with glutamate metabolism (Gdh) and transport (Eaat); interact genetically with (CCKLR-17D1) or are in the same gene family as (PGRP-LA) genes previously implicated in grooming behavior; are involved in the development of the nervous system and other tissues; or regulate the Notch and Epidermal growth factor receptor signaling pathways. Several DGRP lines exhibited extreme grooming behavior. Excessive grooming behavior can serve as a model for repetitive behaviors diagnostic of several human neuropsychiatric diseases.}, number={9}, journal={G3-GENES GENOMES GENETICS}, author={Yanagawa, Aya and Huang, Wen and Yamamoto, Akihiko and Wada-Katsumata, Ayako and Schal, Coby and Mackay, Trudy F. C.}, year={2020}, month={Sep}, pages={3453–3460} }
 @article{huang_carbone_lyman_anholt_mackay_2020, title={Genotype by environment interaction for gene expression in Drosophila melanogaster}, volume={11}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-020-19131-y}, abstractNote={Abstract The genetics of phenotypic responses to changing environments remains elusive. Using whole-genome quantitative gene expression as a model, here we study how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed in different environments (25 °C and 18 °C). We find a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increases at 18 °C relative to 25 °C for most genes that have a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments are shared and have similar effects, analysis of the environment-specific eQTLs reveals enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks are highly conserved across environments. Genes with higher network connectivity are under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Huang, Wen and Carbone, Mary Anna and Lyman, Richard F. and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2020}, month={Oct} }
 @article{morgante_huang_sorensen_maltecca_mackay_2020, title={Leveraging Multiple Layers of Data To Predict Drosophila Complex Traits}, volume={10}, ISSN={["2160-1836"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85097210372&partnerID=MN8TOARS}, DOI={10.1534/g3.120.401847}, abstractNote={Abstract The ability to accurately predict complex trait phenotypes from genetic and genomic data are critical for the implementation of personalized medicine and precision agriculture; however, prediction accuracy for most complex traits is currently low. Here, we used data on whole genome sequences, deep RNA sequencing, and high quality phenotypes for three quantitative traits in the ∼200 inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to compare the prediction accuracies of gene expression and genotypes for three complex traits. We found that expression levels (r = 0.28 and 0.38, for females and males, respectively) provided higher prediction accuracy than genotypes (r = 0.07 and 0.15, for females and males, respectively) for starvation resistance, similar prediction accuracy for chill coma recovery (null for both models and sexes), and lower prediction accuracy for startle response (r = 0.15 and 0.14 for female and male genotypes, respectively; and r = 0.12 and 0.11, for females and male transcripts, respectively). Models including both genotype and expression levels did not outperform the best single component model. However, accuracy increased considerably for all the three traits when we included gene ontology (GO) category as an additional layer of information for both genomic variants and transcripts. We found strongly predictive GO terms for each of the three traits, some of which had a clear plausible biological interpretation. For example, for starvation resistance in females, GO:0033500 (r = 0.39 for transcripts) and GO:0032870 (r = 0.40 for transcripts), have been implicated in carbohydrate homeostasis and cellular response to hormone stimulus (including the insulin receptor signaling pathway), respectively. In summary, this study shows that integrating different sources of information improved prediction accuracy and helped elucidate the genetic architecture of three Drosophila complex phenotypes.}, number={12}, journal={G3-GENES GENOMES GENETICS}, author={Morgante, Fabio and Huang, Wen and Sorensen, Peter and Maltecca, Christian and Mackay, Trudy F. C.}, year={2020}, month={Dec}, pages={4599–4613} }
 @article{matute_comeault_earley_serrato-capuchina_peede_monroy-eklund_huang_jones_mackay_coyne_2020, title={Rapid and Predictable Evolution of Admixed Populations Between Two Drosophila Species Pairs}, volume={214}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.119.302685}, abstractNote={Abstract In this article, Matute et al. report an experiment in which they generated eight interspecific admixed populations using two species pairs of Drosophila. They found that in both species pairs, and across all experimental replicates... The consequences of hybridization are varied, ranging from the origin of new lineages, introgression of some genes between species, to the extinction of one of the hybridizing species. We generated replicate admixed populations between two pairs of sister species of Drosophila: D. simulans and D. mauritiana; and D. yakuba and D. santomea. Each pair consisted of a continental species and an island endemic. The admixed populations were maintained by random mating in discrete generations for over 20 generations. We assessed morphological, behavioral, and fitness-related traits from each replicate population periodically, and sequenced genomic DNA from the populations at generation 20. For both pairs of species, species-specific traits and their genomes regressed to those of the continental species. A few alleles from the island species persisted, but they tended to be proportionally rare among all sites in the genome and were rarely fixed within the populations. This paucity of alleles from the island species was particularly pronounced on the X-chromosome. These results indicate that nearly all foreign genes were quickly eliminated after hybridization and that selection against the minor species genome might be similar across experimental replicates.}, number={1}, journal={GENETICS}, author={Matute, Daniel R. and Comeault, Aaron A. and Earley, Eric and Serrato-Capuchina, Antonio and Peede, David and Monroy-Eklund, Anais and Huang, Wen and Jones, Corbin D. and Mackay, Trudy F. C. and Coyne, Jerry A.}, year={2020}, month={Jan}, pages={211–230} }
 @article{zhou_morgante_geisz_ma_anholt_mackay_2020, title={Systems genetics of the Drosophila metabolome}, volume={30}, ISSN={["1549-5469"]}, DOI={10.1101/gr.243030.118}, abstractNote={How effects of DNA sequence variants are transmitted through intermediate endophenotypes to modulate organismal traits remains a central question in quantitative genetics. This problem can be addressed through a systems approach in a population in which genetic polymorphisms, gene expression traits, metabolites, and complex phenotypes can be evaluated on the same genotypes. Here, we focused on the metabolome, which represents the most proximal link between genetic variation and organismal phenotype, and quantified metabolite levels in 40 lines of the Drosophila melanogaster Genetic Reference Panel. We identified sex-specific modules of genetically correlated metabolites and constructed networks that integrate DNA sequence variation and variation in gene expression with variation in metabolites and organismal traits, including starvation stress resistance and male aggression. Finally, we asked to what extent SNPs and metabolites can predict trait phenotypes and generated trait- and sex-specific prediction models that provide novel insights about the metabolomic underpinnings of complex phenotypes.}, number={3}, journal={GENOME RESEARCH}, author={Zhou, Shanshan and Morgante, Fabio and Geisz, Matthew S. and Ma, Junwu and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2020}, month={Mar}, pages={392–405} }
 @article{highfill_baker_stevens_anholt_mackay_2019, title={Genetics of cocaine and methamphetamine consumption and preference in Drosophila melanogaster}, volume={15}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1007834}, abstractNote={Illicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. Whereas neural mechanisms that mediate the effects of these drugs are well-characterized, genetic factors that account for individual variation in susceptibility to substance abuse and addiction remain largely unknown. Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to these compounds elicits effects similar to those observed in people, suggesting conserved evolutionary mechanisms underlying drug responses. Here, we used the D. melanogaster Genetic Reference Panel to investigate the genetic basis for variation in psychostimulant drug consumption, to determine whether similar or distinct genetic networks underlie variation in consumption of cocaine and methamphetamine, and to assess the extent of sexual dimorphism and effect of genetic context on variation in voluntary drug consumption. Quantification of natural genetic variation in voluntary consumption, preference, and change in consumption and preference over time for cocaine and methamphetamine uncovered significant genetic variation for all traits, including sex-, exposure- and drug-specific genetic variation. Genome wide association analyses identified both shared and drug-specific candidate genes, which could be integrated in genetic interaction networks. We assessed the effects of ubiquitous RNA interference (RNAi) on consumption behaviors for 34 candidate genes: all affected at least one behavior. Finally, we utilized RNAi knockdown in the nervous system to implicate dopaminergic neurons and the mushroom bodies as part of the neural circuitry underlying experience-dependent development of drug preference.}, number={5}, journal={PLOS GENETICS}, author={Highfill, Chad A. and Baker, Brandon M. and Stevens, Stephenie D. and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2019}, month={May} }
 @article{harbison_kumar_huang_mccoy_smith_mackay_2019, title={Genome-Wide Association Study of Circadian Behavior in Drosophila melanogaster}, volume={49}, ISSN={["1573-3297"]}, DOI={10.1007/s10519-018-9932-0}, abstractNote={Circadian rhythms influence physiological processes from sleep–wake cycles to body temperature and are controlled by highly conserved cycling molecules. Although the mechanistic basis of the circadian clock has been known for decades, the extent to which circadian rhythms vary in nature and the underlying genetic basis for that variation is not well understood. We measured circadian period (Ʈ) and rhythmicity index in the Drosophila Genetic Reference Panel (DGRP) and observed extensive genetic variation in both. Seven DGRP lines had sexually dimorphic arrhythmicity and one line had an exceptionally long Ʈ. Genome-wide analyses identified 584 polymorphisms in 268 genes. We observed differences among transcripts for nine genes predicted to interact among themselves and canonical clock genes in the long period line and a control. Mutations/RNAi knockdown targeting these genes also affected circadian behavior. Our observations reveal that complex genetic interactions influence high levels of variation in circadian phenotypes.}, number={1}, journal={BEHAVIOR GENETICS}, author={Harbison, Susan T. and Kumar, Shailesh and Huang, Wen and McCoy, Lenovia J. and Smith, Kirklin R. and Mackay, Trudy F. C.}, year={2019}, month={Jan}, pages={60–82} }
 @article{gabrawy_campbell_carbone_morozova_arya_turlapati_walston_starz-gaiano_everett_mackay_et al._2019, title={Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster}, volume={74}, ISSN={["1758-535X"]}, DOI={10.1093/gerona/glz152}, abstractNote={Abstract Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear. Here, we tested the effects of the ACE-inhibitor Lisinopril on life span, and age-specific speed, endurance, and strength using three genotypes of the Drosophila melanogaster Genetic Reference Panel. We show that age-related decline in physical performance and survivorship varies with genetic background. Lisinopril treatment increased mean life span in all Drosophila Genetic Reference Panel lines, but its effects on life span, speed, endurance, and strength depended on genotype. We show that genotypes with increased physical performance on Lisinopril treatment experienced reduced age-related protein aggregation in muscle. Knockdown of skeletal muscle-specific Ance, the Drosophila ortholog of ACE, abolished the effects of Lisinopril on life span, implying a role for skeletal muscle Ance in survivorship. Using transcriptome profiling, we identified genes involved in stress response that showed expression changes associated with genotype and age-dependent responsiveness to Lisinopril. Our results demonstrate that Ance is involved in physical decline and demonstrate genetic variation in phenotypic responses to an ACE inhibitor.}, number={12}, journal={JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES}, author={Gabrawy, Mariann M. and Campbell, Sarah and Carbone, Mary Anna and Morozova, Tatiana V and Arya, Gunjan H. and Turlapati, Lavanya B. and Walston, Jeremy D. and Starz-Gaiano, Michelle and Everett, Logan and Mackay, Trudy F. C. and et al.}, year={2019}, month={Dec}, pages={1844–1852} }
 @article{morgante_huang_maltecca_mackay_2018, title={Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals}, volume={120}, ISSN={["1365-2540"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85041836520&partnerID=MN8TOARS}, DOI={10.1038/s41437-017-0043-0}, abstractNote={Predicting complex phenotypes from genomic data is a fundamental aim of animal and plant breeding, where we wish to predict genetic merits of selection candidates; and of human genetics, where we wish to predict disease risk. While genomic prediction models work well with populations of related individuals and high linkage disequilibrium (LD) (e.g., livestock), comparable models perform poorly for populations of unrelated individuals and low LD (e.g., humans). We hypothesized that low prediction accuracies in the latter situation may occur when the genetics architecture of the trait departs from the infinitesimal and additive architecture assumed by most prediction models. We used simulated data for 10,000 lines based on sequence data from a population of unrelated, inbred Drosophila melanogaster lines to evaluate this hypothesis. We show that, even in very simplified scenarios meant as a stress test of the commonly used Genomic Best Linear Unbiased Predictor (G-BLUP) method, using all common variants yields low prediction accuracy regardless of the trait genetic architecture. However, prediction accuracy increases when predictions are informed by the genetic architecture inferred from mapping the top variants affecting main effects and interactions in the training data, provided there is sufficient power for mapping. When the true genetic architecture is largely or partially due to epistatic interactions, the additive model may not perform well, while models that account explicitly for interactions generally increase prediction accuracy. Our results indicate that accounting for genetic architecture can improve prediction accuracy for quantitative traits.}, number={6}, journal={HEREDITY}, author={Morgante, Fabio and Huang, Wen and Maltecca, Christian and Mackay, Trudy F. C.}, year={2018}, month={Jun}, pages={500–514} }
 @article{lstiburek_bittner_hodge_picek_mackay_2018, title={Estimating Realized Heritability in Panmictic Populations}, volume={208}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.117.300508}, abstractNote={Abstract Narrow sense heritability (h2) is a key concept in quantitative genetics, as it expresses the proportion of the observed phenotypic variation that is transmissible from parents to offspring. h2 determines the resemblance among relatives, and the rate of response to artificial and natural selection. Classical methods for estimating h2 use random samples of individuals with known relatedness, as well as response to artificial selection, when it is called realized heritability. Here, we present a method for estimating realized h2 based on a simple assessment of a random-mating population with no artificial manipulation of the population structure, and derive SE of the estimates. This method can be applied to arbitrary phenotypic segments of the population (for example, the top-ranking p parents and offspring), rather than random samples. It can thus be applied to nonpedigreed random mating populations, where relatedness is determined from molecular markers in the p selected parents and offspring, thus substantially saving on genotyping costs. Further, we assessed the method by stochastic simulations, and, as expected from the mathematical derivation, it provides unbiased estimates of h2. We compared our approach to the regression and maximum-likelihood approaches utilizing Galton’s dataset on human heights, and all three methods provided identical results.}, number={1}, journal={GENETICS}, author={Lstiburek, Milan and Bittner, Vaclav and Hodge, Gary R. and Picek, Jan and Mackay, Trudy F. C.}, year={2018}, month={Jan}, pages={89–95} }
 @article{meurs_friedenberg_williams_keene_atkins_adin_aona_defrancesco_tou_mackay_et al._2018, title={Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration}, volume={232}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2017.12.002}, abstractNote={Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here.}, journal={VETERINARY JOURNAL}, author={Meurs, Kathryn and Friedenberg, S. G. and Williams, B. and Keene, B. W. and Atkins, C. E. and Adin, D. and Aona, B. and DeFrancesco, Teresa and Tou, S. and Mackay, T. and et al.}, year={2018}, month={Feb}, pages={16–19} }
 @article{dumont_williams_ng_horncastle_chambers_mcgraw_adams_mackay_breen_2018, title={Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles}, volume={210}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.118.301182}, abstractNote={Abstract On the heterogametic sex chromosomes, the homology-driven processes of pairing, recombination, and segregation are restricted to a short region of X/Y homology known as the pseudoautosomal region (PAR). Although failure of X/Y associations in most mammals... In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles (Microtus) to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (Microtus montanus), never (Microtus mogollonensis), and occasionally synapse (Microtus ochrogaster) at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, M. montanus. Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles.}, number={1}, journal={GENETICS}, author={Dumont, Beth L. and Williams, Christina L. and Ng, Bee Ling and Horncastle, Valerie and Chambers, Carol L. and McGraw, Lisa A. and Adams, David and Mackay, Trudy F. C. and Breen, Matthew}, year={2018}, month={Sep}, pages={83–97} }
 @article{gerken_mackay_morgan_2016, title={Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection}, volume={59}, ISSN={["1879-0992"]}, DOI={10.1016/j.jtherbio.2016.04.004}, abstractNote={Artificial selection can be used to create populations with extreme phenotypic responses to environmental stressors. When artificial selection is applied to a single component of a stress response, this selection may result in correlated responses in other stress responses, a phenomenon called cross-tolerance, which is ultimately controlled by the genetic correlations among traits. We selected for extreme responses to cold tolerance by selecting for chill-coma recovery time from a single temperate population of Drosophila melanogaster. Chill-coma recovery time is a common metric of low, but non-lethal, cold temperature tolerance. Replicated divergent artificial selection was applied to a genetically variable base population for 31 generations, resulting in two cold resistant, two cold susceptible, and two unselected control lines. To quantify the relationship between selection on chill-coma recovery and other metrics of thermal performance, we also measured survivorship after acute cold exposure, survivorship after chronic cold exposure, survivorship after cold exposure following a pre-treatment period (rapid cold hardening), starvation tolerance, and heat tolerance. We find that chill-coma recovery time is heritable within this population and that there is an asymmetric response to increased and decreased chill-coma recovery time. Surprisingly, we found no cross-tolerances between selection on chill-coma recovery time and the other environmental stress response traits. These results suggest that although artificial selection has dramatically altered chill-coma recovery time, the correlated response to selection on other stress response phenotypes has been negligible. The lack of a correlated response suggests that chill-coma recovery time in these selection lines is likely genetically independent from measures of cold survivorship tested here.}, journal={JOURNAL OF THERMAL BIOLOGY}, author={Gerken, Alison R. and Mackay, Trudy F. C. and Morgan, Theodore J.}, year={2016}, month={Jul}, pages={77–85} }
 @article{riedl_oster_busto_mackay_sokolowski_2016, title={Natural variability in Drosophila larval and pupal NaCl tolerance}, volume={88}, ISSN={["1879-1611"]}, DOI={10.1016/j.jinsphys.2016.02.007}, abstractNote={The regulation of NaCl is essential for the maintenance of cellular tonicity and functionality, and excessive salt exposure has many adverse effects. The fruit fly, Drosophila melanogaster, is a good osmoregulator and some strains can survive on media with very low or high NaCl content. Previous analyses of mutant alleles have implicated various stress signaling cascades in NaCl sensitivity or tolerance; however, the genes influencing natural variability of NaCl tolerance remain for the most part unknown. Here, we use two approaches to investigate natural variation in D. melanogaster NaCl tolerance. We describe four D. melanogaster lines that were selected for different degrees of NaCl tolerance, and present data on their survival, development, and pupation position when raised on varying NaCl concentrations. After finding evidence for natural variation in salt tolerance, we present the results of Quantitative Trait Loci (QTL) mapping of natural variation in larval and pupal NaCl tolerance, and identify different genomic regions associated with NaCl tolerance during larval and pupal development.}, journal={JOURNAL OF INSECT PHYSIOLOGY}, author={Riedl, Craig A. L. and Oster, Sara and Busto, Macarena and Mackay, Trudy F. C. and Sokolowski, Marla B.}, year={2016}, month={May}, pages={15–23} }
 @article{morgante_sorensen_sorensen_maltecca_mackay_2015, title={Genetic Architecture of Micro-Environmental Plasticity in Drosophila melanogaster}, volume={5}, ISSN={["2045-2322"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84928974596&partnerID=MN8TOARS}, DOI={10.1038/srep09785}, abstractNote={Individuals of the same genotype do not have the same phenotype for quantitative traits when reared under common macro-environmental conditions, a phenomenon called micro-environmental plasticity. Genetic variation in micro-environmental plasticity is assumed in models of the evolution of phenotypic variance, and is important in applied breeding and personalized medicine. Here, we quantified genetic variation for micro-environmental plasticity for three quantitative traits in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel. We found substantial genetic variation for micro-environmental plasticity for all traits, with broad sense heritabilities of the same magnitude or greater than those of trait means. Micro-environmental plasticity is not correlated with residual segregating variation, is trait-specific, and has genetic correlations with trait means ranging from zero to near unity. We identified several candidate genes associated with micro-environmental plasticity of startle response, including Drosophila Hsp90, setting the stage for future genetic dissection of this phenomenon.}, journal={SCIENTIFIC REPORTS}, author={Morgante, Fabio and Sorensen, Peter and Sorensen, Daniel A. and Maltecca, Christian and Mackay, Trudy F. C.}, year={2015}, month={May} }
 @article{huang_massouras_inoue_peiffer_ramia_tarone_turlapati_zichner_zhu_lyman_et al._2014, title={Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines}, volume={24}, number={7}, journal={Genome Research}, author={Huang, W. and Massouras, A. and Inoue, Y. and Peiffer, J. and Ramia, M. and Tarone, A. M. and Turlapati, L. and Zichner, T. and Zhu, D. H. and Lyman, R. F. and et al.}, year={2014}, pages={1193–1208} }
 @article{morozova_ayroles_jordan_duncan_carbone_lyman_stone_govindaraju_ellison_mackay_et al._2009, title={Alcohol Sensitivity in Drosophila: Translational Potential of Systems Genetics}, volume={183}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.109.107490}, abstractNote={Identification of risk alleles for human behavioral disorders through genomewide association studies (GWAS) has been hampered by a daunting multiple testing problem. This problem can be circumvented for some phenotypes by combining genomewide studies in model organisms with subsequent candidate gene association analyses in human populations. Here, we characterized genetic networks that underlie the response to ethanol exposure in Drosophila melanogaster by measuring ethanol knockdown time in 40 wild-derived inbred Drosophila lines. We associated phenotypic variation in ethanol responses with genomewide variation in gene expression and identified modules of correlated transcripts associated with a first and second exposure to ethanol vapors as well as the induction of tolerance. We validated the computational networks and assessed their robustness by transposon-mediated disruption of focal genes within modules in a laboratory inbred strain, followed by measurements of transcript abundance of connected genes within the module. Many genes within the modules have human orthologs, which provides a stepping stone for the identification of candidate genes associated with alcohol drinking behavior in human populations. We demonstrated the potential of this translational approach by identifying seven intronic single nucleotide polymorphisms of the Malic Enzyme 1 (ME1) gene that are associated with cocktail drinking in 1687 individuals of the Framingham Offspring cohort, implicating that variation in levels of cytoplasmic malic enzyme may contribute to variation in alcohol consumption.}, number={2}, journal={GENETICS}, author={Morozova, Tatiana V. and Ayroles, Julien F. and Jordan, Katherine W. and Duncan, Laura H. and Carbone, Mary Anna and Lyman, Richard E. and Stone, Eric A. and Govindaraju, Diddahally R. and Ellison, R. Curtis and Mackay, Trudy F. C. and et al.}, year={2009}, month={Oct}, pages={733–745} }
 @article{harbison_carbone_ayroles_stone_lyman_mackay_2009, title={Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep}, volume={41}, ISSN={["1546-1718"]}, DOI={10.1038/ng.330}, abstractNote={Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes. Studies in Drosophila have revealed molecular pathways and neural tissues regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we characterized sleep in 40 wild-derived Drosophila lines and observed abundant genetic variation in sleep architecture. We associated sleep with genome-wide variation in gene expression to identify candidate genes. We independently confirmed that molecular polymorphisms in Catsup (Catecholamines up) are associated with variation in sleep and that P-element mutations in four candidate genes affect sleep and gene expression. Transcripts associated with sleep grouped into biologically plausible genetically correlated transcriptional modules. We confirmed co-regulated gene expression using P-element mutants. Quantitative genetic analysis of natural phenotypic variation is an efficient method for revealing candidate genes and pathways.}, number={3}, journal={NATURE GENETICS}, author={Harbison, Susan T. and Carbone, Mary Anna and Ayroles, Julien F. and Stone, Eric A. and Lyman, Richard F. and Mackay, Trudy F. C.}, year={2009}, month={Mar}, pages={371–375} }
 @article{edwards_mackay_2009, title={Quantitative Trait Loci for Aggressive Behavior in Drosophila melanogaster}, volume={182}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.109.101691}, abstractNote={Abstract Aggressive behavior is observed across animal taxa and is likely to be evolutionarily conserved. Although potentially advantageous, aggression can have social and health consequences in humans, and is a component of a number of psychiatric disorders. As a complex genetic trait, it is modulated by numerous quantitative trait loci (QTL) with allelic effects that can vary in direction and magnitude and that are sensitive to environmental perturbations. Assays to quantify aggressive behavior in Drosophila melanogaster have been developed, making this an ideal model system in which to dissect the genomic architecture underlying manifestation of and variation in aggressive behavior. Here, we map QTL affecting variation in aggression between two wild-type Drosophila strains. We identified a minimum of five QTL in a genomewide scan: two on chromosome 2 and three on chromosome 3. At least three and possibly all five of these QTL interact epistatically. We used deficiency complementation mapping to subdivide two linked, epistatically interacting QTL of large effect on chromosome 3 into at least six QTL, and complementation tests to mutations identified four candidate quantitative trait genes. Extensive epistasis poses a serious challenge for understanding the genetic basis of complex traits.}, number={3}, journal={GENETICS}, author={Edwards, Alexis C. and Mackay, Trudy F. C.}, year={2009}, month={Jul}, pages={889–897} }
 @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={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{yamamoto_zwarts_callaerts_norga_mackay_anholt_2008, title={Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster}, volume={105}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0804889105}, abstractNote={Understanding how the genome empowers the nervous system to express behaviors remains a critical challenge in behavioral genetics. The startle response is an attractive behavioral model for studies on the relationship between genes, brain, and behavior, as the ability to respond rapidly to harmful changes in the environment is a universal survival trait. Drosophila melanogaster provides a powerful system in which genetic studies on individuals with controlled genetic backgrounds and reared under controlled environmental conditions can be combined with neuroanatomical studies to analyze behaviors. In a screen of 720 lines of D. melanogaster , carrying single P[GT1] transposon insertions, we found 267 lines that showed significant changes in startle-induced locomotor behavior. Excision of the transposon reversed this effect in five lines out of six tested. We infer that most of the 267 lines show mutant effects on startle-induced locomotion that are caused by the transposon insertions. We selected a subset of 15 insertions in the same genetic background in autosomal genes with strong mutant effects and crossed them to generate all 105 possible nonreciprocal double heterozygotes. These hybrids revealed an extensive network of epistatic interactions on the behavioral trait. In addition, we observed changes in neuroanatomy that were caused by these 15 mutations, individually and in their double heterozygotes. We find that behavioral and neuroanatomical phenotypes are determined by a common set of genes that are organized as partially overlapping genetic networks.}, number={34}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Yamamoto, Akihiko and Zwarts, Liesbeth and Callaerts, Patrick and Norga, Koenraad and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2008}, month={Aug}, pages={12393–12398} }
 @article{sambandan_carbone_anholt_mackay_2008, title={Phenotypic plasticity and genotype by environment interaction for olfactory behavior in Drosophila melanogaster}, volume={179}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.108.086769}, abstractNote={Abstract Genotype by environment interactions (GEI) play a major part in shaping the genetic architecture of quantitative traits and are confounding factors in genetic studies, for example, in attempts to associate genetic variation with disease susceptibility. It is generally not known what proportion of phenotypic variation is due to GEI and how many and which genes contribute to GEI. Behaviors are complex traits that mediate interactions with the environment and, thus, are ideally suited for studies of GEI. Olfactory behavior in Drosophila melanogaster presents an opportunity to systematically dissect GEI, since large numbers of genetically identical individuals can be reared under defined environmental conditions and the olfactory system of Drosophila and its behavioral response to odorants have been well characterized. We assessed variation in olfactory behavior in a population of 41 wild-derived inbred lines and asked to what extent different larval-rearing environments would influence adult olfactory behavior and whether GEI is a minor or major contributing source of phenotypic variation. We found that ∼50% of phenotypic variation in adult olfactory behavior is attributable to GEI. In contrast, transcriptional analysis revealed that only 20 genes show GEI at the level of gene expression [false discovery rate (FDR) < 0.05], some of which are associated with physiological responses to environmental chemicals. Quantitative complementation tests with piggyBac-tagged mutants for 2 of these genes (CG9664 and Transferrin 1) demonstrate that genes that show transcriptional GEI are candidate genes for olfactory behavior and that GEI at the level of gene expression is correlated with GEI at the level of phenotype.}, number={2}, journal={GENETICS}, author={Sambandan, Deepa and Carbone, Mary Anna and Anholt, Robert R. H. and Mackay, Trudy E. C.}, year={2008}, month={Jun}, pages={1079–1088} }
 @article{rollmann_zwarts_edwards_yamamoto_callaerts_norga_mackay_anholt_2008, title={Pleiotropic effects of Drosophila neuralized on complex behaviors and brain structure}, volume={179}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.108.088435}, abstractNote={Abstract Understanding how genotypic variation influences variation in brain structures and behavioral phenotypes represents a central challenge in behavioral genetics. In Drosophila melanogaster, the neuralized (neur) gene plays a key role in development of the nervous system. Different P-element insertional mutations of neur allow the development of viable and fertile adults with profoundly altered behavioral phenotypes that depend on the exact location of the inserted P element. The neur mutants exhibit reduced responsiveness to noxious olfactory and mechanosensory stimulation and increased aggression when limited food is presented after a period of food deprivation. These behavioral phenotypes are correlated with distinct structural changes in integrative centers in the brain, the mushroom bodies, and the ellipsoid body of the central complex. Transcriptional profiling of neur mutants revealed considerable overlap among ensembles of coregulated genes in the different mutants, but also distinct allele-specific differences. The diverse phenotypic effects arising from nearby P-element insertions in neur provide a new appreciation of the concept of allelic effects on phenotype, in which the wild type and null mutant are at the extreme ends of a continuum of pleiotropic allelic effects.}, number={3}, journal={GENETICS}, author={Rollmann, Stephanie A. and Zwarts, Liesbeth and Edwards, Alexis C. and Yamamoto, Akihiko and Callaerts, Patrick and Norga, Koenraad and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2008}, month={Jul}, pages={1327–1336} }
 @article{mackay_anholt_2007, title={Ain't misbehavin? Genotype-environment interactions and the genetics of behavior}, volume={23}, ISSN={["1362-4555"]}, DOI={10.1016/j.tig.2007.03.013}, abstractNote={Although the multiple interacting genes affecting complex traits can readily be dissected, how much genotype-environment interactions contribute to variation in complex traits remains elusive. A recent study that quantified several behavioral phenotypes on the same mouse strains in different laboratories decades apart, shows that some behavioral differences between laboratories remain greatly replicable, whereas others are less robust over time. This report, together with studies from Drosophila, stresses the importance of understanding genotype-environment interactions.}, number={7}, journal={TRENDS IN GENETICS}, author={Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2007}, month={Jul}, pages={311–314} }
 @article{wang_lyman_shabalina_mackay_anholt_2007, title={Association of polymorphisms in odorant-binding protein genes with variation in olfactory response to benzaldehyde in Drosophila}, volume={177}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.107.079731}, abstractNote={Adaptive evolution of animals depends on behaviors that are essential for their survival and reproduction. The olfactory system of Drosophila melanogaster has emerged as one of the best characterized olfactory systems, which in addition to a family of odorant receptors, contains an approximately equal number of odorant-binding proteins (OBPs), encoded by a multigene family of 51 genes. Despite their abundant expression, little is known about their role in chemosensation, largely due to the lack of available mutations in these genes. We capitalized on naturally occurring mutations (polymorphisms) to gain insights into their functions. We analyzed the sequences of 13 Obp genes in two chromosomal clusters in a population of wild-derived inbred lines, and asked whether polymorphisms in these genes are associated with variation in olfactory responsiveness. Four polymorphisms in 3 Obp genes exceeded the statistical permutation threshold for association with responsiveness to benzaldehyde, suggesting redundancy and/or combinatorial recognition by these OBPs of this odorant. Model predictions of alternative pre-mRNA secondary structures associated with polymorphic sites suggest that alterations in Obp mRNA structure could contribute to phenotypic variation in olfactory behavior.}, number={3}, journal={GENETICS}, author={Wang, Ping and Lyman, Richard F. and Shabalina, Svetlana A. and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2007}, month={Nov}, pages={1655–1665} }
 @article{lai_parnell_lyman_ordovas_mackay_2007, title={Candidate genes affecting Drosophila life span identified by integrating microarray gene expression analysis and QTL mapping}, volume={128}, ISSN={["1872-6216"]}, DOI={10.1016/j.mad.2006.12.003}, abstractNote={The current increase in life expectancy observed in industrialized societies underscores the need to achieve a better understanding of the aging process that could help the development of effective strategies to achieve healthy aging. This will require not only identifying genes involved in the aging process, but also understanding how their effects are modulated by environmental factors, such as dietary intake and life style. Although the human genome has been sequenced, it may be impractical to study humans or other long-lived organisms to gain a mechanistic understanding about the aging process. Thus, short-lived animal models are essential to identifying the mechanisms and genes that affect the rate and quality of aging as a first step towards identifying genetic variants in humans. In this study, we investigated gene expression changes between two strains of Drosophila (Oregon and 2b) for which quantitative trait loci (QTLs) affecting life span were identified previously. We collected males and females from both strains at young and old ages, and assessed whole genome variation in transcript abundance using Affymetrix GeneChips. We observed 8217 probe sets with detectable transcripts. A total of 2371 probe sets, representing 2220 genes, exhibited significant changes in transcript abundance with age; and 839 probe sets were differentially expressed between Oregon and 2b. We focused on the 359 probe sets (representing 354 genes) that exhibited significant changes in gene expression both with age and between strains. We used these genes to integrate the analysis of microarray gene expression data, bioinformatics, and the results of genetic mapping studies reported previously, to identify 49 candidate genes and four pathways that could potentially be responsible for regulating life span and involved in the process of aging in Drosophila and humans.}, number={3}, journal={MECHANISMS OF AGEING AND DEVELOPMENT}, author={Lai, Chao-Qiang and Parnell, Laurence D. and Lyman, Richard F. and Ordovas, Jose A. and Mackay, Trudy F. C.}, year={2007}, month={Mar}, pages={237–249} }
 @article{riedl_riedl_mackay_sokolowski_2007, title={Genetic and behavioral analysis of natural variation in Drosophila melanogaster pupation position}, volume={1}, ISSN={["1933-6942"]}, DOI={10.4161/fly.3830}, abstractNote={Drosophila melanogaster pupae are exposed to many biotic and abiotic dangers while immobilized during several days of metamorphosis. As a passive defense mechanism, appropriate pupation site selection represents an important mitigation of these threats. Pupation site selection is sensitive to genetic and environmental influences, but the specific mechanisms of the behavior are largely unknown. Using a set of 76 recombinant inbred strains we identify a single quantitative trait locus, at polytene position 56A01-C11, associated with pupation site variation. We furthermore present a detailed investigation into the wandering behaviors of two strains expressing different pupation position tendencies, and identify behavioral differences. Larvae from a strain that tends to pupate relatively far from the food also tend to travel significantly farther from the media during wandering. We did not observe consistent differences in either the number or duration of wandering forays made by near or far pupating strains. The ability of larvae to integrate several internal and external environmental cues while choosing a contextually appropriate pupation site, and specifically, the variation in this ability, presents a very interesting behavioral phenotype in this highly tractable genetic model organism.}, number={1}, journal={FLY}, author={Riedl, Craig A. L. and Riedl, Marit and Mackay, Trudy F. C. and Sokolowski, Marla B.}, year={2007}, pages={23–32} }
 @article{lai_leips_zou_roberts_wollenberg_parnell_zeng_ordovas_mackay_2007, title={Speed-mapping quantitative trait loci using microarrays}, volume={4}, ISSN={["1548-7105"]}, DOI={10.1038/NMETH1084}, number={10}, journal={NATURE METHODS}, author={Lai, Chao-Qiang and Leips, Jeff and Zou, Wei and Roberts, Jessica F. and Wollenberg, Kurt R. and Parnell, Laurence D. and Zeng, Zhao-Bang and Ordovas, Jose M. and Mackay, Trudy F. C.}, year={2007}, month={Oct}, pages={839–841} }
 @article{rollmann_yamamoto_goossens_zwarts_callaerts-vegh_callaerts_norga_mackay_anholt_2007, title={The early developmental gene Semaphorin 5c contributes to olfactory behavior in adult Drosophila}, volume={176}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.106.069781}, abstractNote={Abstract Behaviors are complex traits influenced by multiple pleiotropic genes. Understanding the mechanisms that give rise to complex behaviors requires an understanding of how variation in transcriptional regulation shapes nervous system development and how variation in brain structure influences an organism's ability to respond to its environment. To begin to address this problem, we used olfactory behavior in Drosophila melanogaster as a model and showed that a hypomorphic transposon-mediated mutation of the early developmental gene Semaphorin-5c (Sema-5c) results in aberrant behavioral responses to the repellant odorant benzaldehyde. We fine mapped this effect to the Sema-5c locus using deficiency mapping, phenotypic reversion through P-element excision, and transgenic rescue. Morphometric analysis of this Sema-5c allele reveals subtle neuroanatomical changes in the brain with a reduction in the size of the ellipsoid body. High-density oligonucleotide expression microarrays identified 50 probe sets with altered transcriptional regulation in the Sema-5c background and quantitative complementation tests identified epistatic interactions between nine of these coregulated genes and the transposon-disrupted Sema-5c gene. Our results demonstrate how hypomorphic mutation of an early developmental gene results in genomewide transcriptional consequences and alterations in brain structure accompanied by profound impairment of adult behavior.}, number={2}, journal={GENETICS}, author={Rollmann, Stephanie M. and Yamamoto, Akihiko and Goossens, Tim and Zwarts, Liesbeth and Callaerts-Vegh, Zsuzsanna and Callaerts, Patrick and Norga, Koenraad and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2007}, month={Jun}, pages={947–956} }
 @article{sambandan_yamamoto_fanara_mackay_anholt_2006, title={Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster}, volume={174}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.106.060574}, abstractNote={Abstract Understanding the genetic architecture of complex traits requires identification of the underlying genes and characterization of gene-by-gene and genotype-by-environment interactions. Behaviors that mediate interactions between organisms and their environment are complex traits expected to be especially sensitive to environmental conditions. Previous studies on the olfactory avoidance response of Drosophila melanogaster showed that the genetic architecture of this model behavior depends on epistatic networks of pleiotropic genes. We performed a screen of 1339 co-isogenic p[GT1]-element insertion lines to identify novel genes that contribute to odor-guided behavior and identified 55 candidate genes with known p[GT1]-element insertion sites. Characterization of the expression profiles of 10 p[GT1]-element insertion lines showed that the effects of the transposon insertions are often dependent on developmental stage and that hypomorphic mutations in developmental genes can elicit profound adult behavioral deficits. We assessed epistasis among these genes by constructing all possible double heterozygotes and measuring avoidance responses under two stimulus conditions. We observed enhancer and suppressor effects among subsets of these P-element-tagged genes, and surprisingly, epistatic interactions shifted with changes in the concentration of the olfactory stimulus. Our results show that the manifestation of epistatic networks dynamically changes with alterations in the environment.}, number={3}, journal={GENETICS}, author={Sambandan, Deepa and Yamamoto, Akihiko and Fanara, Juan-Jose and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2006}, month={Nov}, pages={1349–1363} }
 @article{wilson_morgan_mackay_2006, title={High-resolution mapping of quantitative trait loci affecting increased life span in Drosophila melanogaster}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.055111}, abstractNote={Limited life span and senescence are near-universal characteristics of eukaryotic organisms, controlled by many interacting quantitative trait loci (QTL) with individually small effects, whose expression is sensitive to the environment. Analyses of mutations in model organisms have shown that genes affecting stress resistance and metabolism affect life span across diverse taxa. However, there is considerable segregating variation for life span in nature, and relatively little is known about the genetic basis of this variation. Replicated lines of Drosophila that have evolved increased longevity as a correlated response to selection for postponed senescence are valuable resources for identifying QTL affecting naturally occurring variation in life span. Here, we used deficiency complementation mapping to identify at least 11 QTL on chromosome 3 that affect variation in life span between five old (O) lines selected for postponed senescence and their five base (B) population control lines. Most QTL were sex specific, and all but one affected multiple O lines. The latter observation is consistent with alleles at intermediate frequency in the base population contributing to the response to selection for postponed senescence. The QTL were mapped with high resolution and contained from 12 to 170 positional candidate genes.}, number={3}, journal={GENETICS}, author={Wilson, Rhonda H. and Morgan, Theodore J. and Mackay, Trudy F. C.}, year={2006}, month={Jul}, pages={1455–1463} }
 @article{carbone_jordan_lyman_harbison_leips_morgan_deluca_awadalla_mackay_2006, title={Phenotypic variation and natural selection at Catsup, a pleiotropic quantitative trait gene in Drosphila}, volume={16}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2006.03.051}, abstractNote={Quantitative traits are shaped by networks of pleiotropic genes . To understand the mechanisms that maintain genetic variation for quantitative traits in natural populations and to predict responses to artificial and natural selection, we must evaluate pleiotropic effects of underlying quantitative trait genes and define functional allelic variation at the level of quantitative trait nucleotides (QTNs). Catecholamines up (Catsup), which encodes a negative regulator of tyrosine hydroxylase , the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster. We used association mapping to determine whether the same or different QTNs at Catsup are associated with naturally occurring variation in multiple quantitative traits. We sequenced 169 Catsup alleles from a single population and detected 33 polymorphisms with little linkage disequilibrium (LD). Different molecular polymorphisms in Catsup are independently associated with variation in longevity, locomotor behavior, and sensory bristle number. Most of these polymorphisms are potentially functional variants in protein coding regions, have large effects, and are not common. Thus, Catsup is a pleiotropic quantitative trait gene, but individual QTNs do not have pleiotropic effects. Molecular population genetic analyses of Catsup sequences are consistent with balancing selection maintaining multiple functional polymorphisms.}, number={9}, journal={CURRENT BIOLOGY}, author={Carbone, Mary Anna and Jordan, Katherine W. and Lyman, Richard F. and Harbison, Susan T. and Leips, Jeff and Morgan, Theodore J. and DeLuca, Maria and Awadalla, Philip and Mackay, Trudy F. C.}, year={2006}, month={May}, pages={912–919} }
 @article{rollmann_magwire_morgan_ozsoy_yamamoto_mackay_anholt_2006, title={Pleiotropic fitness effects of the Tre1-Gr5a region in Drosophila melanogaster}, volume={38}, ISSN={["1546-1718"]}, DOI={10.1038/ng1823}, number={7}, journal={NATURE GENETICS}, author={Rollmann, Stephanie M. and Magwire, Michael M. and Morgan, Theodore J. and Ozsoy, Ergi D. and Yamamoto, Akihiko and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2006}, month={Jul}, pages={824–829} }
 @article{edwards_rollmann_morgan_mackay_2006, title={Quantitative genomics of aggressive behavior in Drosophila melanogaster}, volume={2}, ISSN={["1553-7390"]}, DOI={10.1371/journal.pgen.0020154}, abstractNote={Aggressive behavior is important for animal survival and reproduction, and excessive aggression is an enormous social and economic burden for human society. Although the role of biogenic amines in modulating aggressive behavior is well characterized, other genetic mechanisms affecting this complex behavior remain elusive. Here, we developed an assay to rapidly quantify aggressive behavior in Drosophila melanogaster, and generated replicate selection lines with divergent levels of aggression. The realized heritability of aggressive behavior was approximately 0.10, and the phenotypic response to selection specifically affected aggression. We used whole-genome expression analysis to identify 1,539 probe sets with different expression levels between the selection lines when pooled across replicates, at a false discovery rate of 0.001. We quantified the aggressive behavior of 19 mutations in candidate genes that were generated in a common co-isogenic background, and identified 15 novel genes affecting aggressive behavior. Expression profiling of genetically divergent lines is an effective strategy for identifying genes affecting complex traits.}, number={9}, journal={PLOS GENETICS}, author={Edwards, Alexis C. and Rollmann, Stephanie M. and Morgan, Theodore J. and Mackay, Trudy F. C.}, year={2006}, month={Sep}, pages={1386–1395} }
 @article{jordan_morgan_mackay_2006, title={Quantitative trait loci for locomotor behavior in Drosophila melanogaster}, volume={174}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.106.058099}, abstractNote={Abstract Locomotion is an integral component of most animal behaviors and many human diseases and disorders are associated with locomotor deficits, but little is known about the genetic basis of natural variation in locomotor behavior. Locomotion is a complex trait, with variation attributable to the joint segregation of multiple interacting quantitative trait loci (QTL), with effects that are sensitive to the environment. We assessed variation in a component of locomotor behavior (locomotor reactivity) in a population of 98 recombinant inbred lines of Drosophila melanogaster and mapped four QTL affecting locomotor reactivity by linkage to polymorphic roo transposable element insertion sites. We used complementation tests of deficiencies to fine map these QTL to 12 chromosomal regions and complementation tests of mutations to identify 13 positional candidate genes affecting locomotor reactivity, including Dopa decarboxylase (Ddc), which catalyzes the final step in the synthesis of serotonin and dopamine. Linkage disequilibrium mapping in a population of 164 second chromosome substitution lines derived from a single natural population showed that polymorphisms at Ddc were associated with naturally occurring genetic variation in locomotor behavior. These data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in locomotor reactivity.}, number={1}, journal={GENETICS}, author={Jordan, Katherine W. and Morgan, Theodore J. and Mackay, Trudy F. C.}, year={2006}, month={Sep}, pages={271–284} }
 @article{morgan_mackay_2006, title={Quantitative trait loci for thermotolerance phenotypes in Drosophila melanogaster}, volume={96}, ISSN={["1365-2540"]}, DOI={10.1038/sj.hdy.6800786}, abstractNote={For insects, temperature is a major environmental variable that can influence an individual's behavioral activities and fitness. Drosophila melanogaster is a cosmopolitan species that has had great success in adapting to and colonizing diverse thermal niches. This adaptation and colonization has resulted in complex patterns of genetic variation in thermotolerance phenotypes in nature. Although extensive work has been conducted documenting patterns of genetic variation, substantially less is known about the genomic regions or genes that underlie this ecologically and evolutionarily important genetic variation. To begin to understand and identify the genes controlling thermotolerance phenotypes, we have used a mapping population of recombinant inbred (RI) lines to map quantitative trait loci (QTL) that affect variation in both heat- and cold-stress resistance. The mapping population was derived from a cross between two lines of D. melanogaster (Oregon-R and 2b) that were not selected for thermotolerance phenotypes, but exhibit significant genetic divergence for both phenotypes. Using a design in which each RI line was backcrossed to both parental lines, we mapped seven QTL affecting thermotolerance on the second and third chromosomes. Three of the QTL influence cold-stress resistance and four affect heat-stress resistance. Most of the QTL were trait or sex specific, suggesting that overlapping but generally unique genetic architectures underlie resistance to low- and high-temperature extremes. Each QTL explained between 5 and 14% of the genetic variance among lines, and degrees of dominance ranged from completely additive to partial dominance. Potential thermotolerance candidate loci contained within our QTL regions are identified and discussed.}, number={3}, journal={HEREDITY}, author={Morgan, TJ and Mackay, TFC}, year={2006}, month={Mar}, pages={232–242} }
 @misc{leips_gilligan_mackay_2006, title={Quantitative trait loci with age-specific effects on fecundity in Drosophila melanogaster}, volume={172}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.048520}, abstractNote={Abstract Life-history theory and evolutionary theories of aging assume the existence of alleles with age-specific effects on fitness. While various studies have documented age-related changes in the genetic contribution to variation in fitness components, we know very little about the underlying genetic architecture of such changes. We used a set of recombinant inbred lines to map and characterize the effects of quantitative trait loci (QTL) affecting fecundity of Drosophila melanogaster females at 1 and 4 weeks of age. We identified one QTL on the second chromosome and one or two QTL affecting fecundity on the third chromosome, but these QTL affected fecundity only at 1 week of age. There was more genetic variation for fecundity at 4 weeks of age than at 1 week of age and there was no genetic correlation between early and late-age fecundity. These results suggest that different loci contribute to the variation in fecundity as the organism ages. Our data provide support for the mutation accumulation theory of aging as applied to reproductive senescence. Comparing the results from this study with our previous work on life-span QTL, we also find evidence that antagonistic pleiotropy may contribute to the genetic basis of senescence in these lines as well.}, number={3}, journal={GENETICS}, author={Leips, J and Gilligan, P and Mackay, TFC}, year={2006}, month={Mar}, pages={1595–1605} }
 @article{moehring_llopart_elwyn_coyne_mackay_2006, title={The genetic basis of postzygotic reproductive isolation between Drosophila santomea and D-yakuba due to hybrid male sterility}, volume={173}, ISSN={["0016-6731"]}, DOI={10.1534/genetics.105.052985}, abstractNote={Abstract A major unresolved challenge of evolutionary biology is to determine the nature of the allelic variants of “speciation genes”: those alleles whose interaction produces inviable or infertile interspecific hybrids but does not reduce fitness in pure species. Here we map quantitative trait loci (QTL) affecting fertility of male hybrids between D. yakuba and its recently discovered sibling species, D. santomea. We mapped three to four X chromosome QTL and two autosomal QTL with large effects on the reduced fertility of D. yakuba and D. santomea backcross males. We observed epistasis between the X-linked QTL and also between the X and autosomal QTL. The X chromosome had a disproportionately large effect on hybrid sterility in both reciprocal backcross hybrids. However, the genetics of hybrid sterility differ between D. yakuba and D. santomea backcross males, both in terms of the magnitude of main effects and in the epistatic interactions. The QTL affecting hybrid fertility did not colocalize with QTL affecting sexual isolation in this species pair, but did colocalize with QTL affecting the marked difference in pigmentation between D. yakuba and D. santomea. These results provide the basis for future high-resolution mapping and ultimately, molecular cloning, of the interacting genes that contribute to hybrid sterility.}, number={1}, journal={GENETICS}, author={Moehring, AJ and Llopart, A and Elwyn, S and Coyne, JA and Mackay, TFC}, year={2006}, month={May}, pages={225–233} }
 @article{moehring_llopart_elwyn_coyne_mackay_2006, title={The genetic basis of prezygotic reproductive isolation between Drosophila santomea and D-yakuba due to mating preference}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.052993}, abstractNote={Abstract Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila santomea and D. yakuba. We mapped at least three QTL affecting discrimination of D. santomea females against D. yakuba males: one X-linked and one autosomal QTL affected the likelihood of copulation, and a second X chromosome QTL affected copulation latency. Three autosomal QTL also affected mating success of D. yakuba males with D. santomea. No epistasis was detected between QTL affecting sexual isolation. The QTL do not overlap between males and females and are not disproportionately concentrated on the X chromosome. There was some overlap in map locations of QTL affecting sexual isolation between D. santomea and D. yakuba with QTL affecting sexual isolation between D. simulans and D. mauritiana and with QTL affecting differences in pigmentation between D. santomea and D. yakuba. Future high-resolution mapping and, ultimately, positional cloning, will reveal whether these traits do indeed have a common genetic basis.}, number={1}, journal={GENETICS}, author={Moehring, Amanda J. and Llopart, Ana and Elwyn, Susannah and Coyne, Jerry A. and Mackay, Trudy F. C.}, year={2006}, month={May}, pages={215–223} }
 @article{mackay_lyman_2005, title={Drosophila bristles and the nature of quantitative genetic variation}, volume={360}, number={1459}, journal={Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, author={Mackay, T. F. C. and Lyman, R. F.}, year={2005}, month={Jul}, pages={1513–1527} }
 @article{mackay_heinsohn_lyman_moehring_morgan_rollmann_2005, title={Genetics and genomics of Drosophila mating behavior}, volume={102}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0501986102}, abstractNote={The first steps of animal speciation are thought to be the development of sexual isolating mechanisms. In contrast to recent progress in understanding the genetic basis of postzygotic isolating mechanisms, little is known about the genetic architecture of sexual isolation. Here, we have subjected Drosophila melanogaster to 29 generations of replicated divergent artificial selection for mating speed. The phenotypic response to selection was highly asymmetrical in the direction of reduced mating speed, with estimates of realized heritability averaging 7%. The selection response was largely attributable to a reduction in female receptivity. We assessed the whole genome transcriptional response to selection for mating speed using Affymetrix GeneChips and a rigorous statistical analysis. Remarkably, >3,700 probe sets (21% of the array elements) exhibited a divergence in message levels between the Fast and Slow replicate lines. Genes with altered transcriptional abundance in response to selection fell into many different biological process and molecular function Gene Ontology categories, indicating substantial pleiotropy for this complex behavior. Future functional studies are necessary to test the extent to which transcript profiling of divergent selection lines accurately predicts genes that directly affect the selected trait.}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Mackay, TFC and Heinsohn, SL and Lyman, RF and Moehring, AJ and Morgan, TJ and Rollmann, SM}, year={2005}, month={May}, pages={6622–6629} }
 @article{wayne_korol_mackay_2005, title={Microclinal variation for ovariole number and body size in Drosophila melanogaster in 'Evolution Canyon'}, volume={123}, ISSN={["1573-6857"]}, DOI={10.1007/s10709-004-5056-y}, number={3}, journal={GENETICA}, author={Wayne, ML and Korol, A and Mackay, TFC}, year={2005}, month={Mar}, pages={263–270} }
 @article{rollmann_mackay_anholt_2005, title={Pinocchio, a novel protein expressed in the antenna, contributes to olfactory behavior in Drosophila melanogaster}, volume={63}, ISSN={["0022-3034"]}, DOI={10.1002/neu.20123}, abstractNote={Most organisms depend on chemoreception for survival and reproduction. In Drosophila melanogaster multigene families of chemosensory receptors and putative odorant binding proteins have been identified. Here, we introduce an additional distinct protein, encoded by the CG4710 gene, that contributes to olfactory behavior. Previously, we identified through P[lArB]-element mutagenesis a smell impaired (smi) mutant, smi21F, with odorant-specific defects in avoidance responses. Here, we show that the smi21F mutant also exhibits reduced attractant responses to some, but not all, of a select group of odorants. Furthermore, electroantennogram amplitudes are increased in smi21F flies. Characterization of flanking sequences of the P[lArB] insertion site, complementation mapping, phenotypic reversion through P-element excision, and expression analysis implicate a predicted gene, CG4710, as the candidate smi gene. CG4710 produces two transcripts that encode proteins that contain conserved cysteines and which are reduced in the smi21F mutant. Furthermore, in situ hybridization reveals CG4710 expression in the third antennal segment. We have named this gene of previously unknown function and its product "Pinocchio (Pino)".}, number={2}, journal={JOURNAL OF NEUROBIOLOGY}, author={Rollmann, SM and Mackay, TFC and Anholt, RRH}, year={2005}, month={May}, pages={146–158} }
 @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{lstiburek_mullin_mackay_huber_li_2005, title={Positive assortative mating with family size as a function of predicted parental breeding values}, volume={171}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.041723}, abstractNote={Abstract While other investigations have described benefits of positive assortative mating (PAM) for forest tree breeding, the allocation of resources among mates in these studies was either equal or varied, using schemes corresponding only to parental rank (i.e., more resources invested in higher-ranking parents). In this simulation study, family sizes were proportional to predicted midparent BLUP values. The distribution of midparent BLUP values was standardized by a constant, which was varied to study the range of distributions of family size. Redistributing progenies from lower- to higher-ranking families to a point where an equal number of progenies were still selected out of each family to the next generation caused minimal change in group coancestry and inbreeding in the breeding population (BP), while the additive genetic response and variance in the BP were both greatly enhanced. This generated additional genetic gains for forest plantations by selecting more superior genotypes from the BP (compared to PAM with equal family sizes) for production of improved regeneration materials. These conclusions were verified for a range of heritability under a polygenic model and under a mixed-inheritance model with a QTL contributing to the trait variation.}, number={3}, journal={GENETICS}, author={Lstiburek, M and Mullin, TJ and Mackay, TFC and Huber, D and Li, B}, year={2005}, month={Nov}, pages={1311–1320} }
 @article{carbone_llopart_deangelis_coyne_mackay_2005, title={Quantitative trait loci affecting the difference in pigmentation between Drosophila yakuba and D. santomea}, volume={171}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.105.044412}, abstractNote={Using quantitative trait locus (QTL) mapping, we studied the genetic basis of the difference in pigmentation between two sister species of Drosophila: Drosophila yakuba, which, like other members of the D. melanogaster subgroup, shows heavy black pigmentation on the abdomen of males and females, and D. santomea, an endemic to the African island of São Tomé, which has virtually no pigmentation. Here we mapped four QTL with large effects on this interspecific difference in pigmentation: two on the X chromosome and one each on the second and third chromosomes. The same four QTL were detected in male hybrids in the backcrosses to both D. santomea and D. yakuba and in the female D. yakuba backcross hybrids. All four QTL exhibited strong epistatic interactions in male backcross hybrids, but only one pair of QTL interacted in females from the backcross to D. yabuka. All QTL from each species affected pigmentation in the same direction, consistent with adaptive evolution driven by directional natural selection. The regions delimited by the QTL included many positional candidate loci in the pigmentation pathway, including genes affecting catecholamine biosynthesis, melanization of the cuticle, and many additional pleiotropic effects.}, number={1}, journal={GENETICS}, author={Carbone, MA and Llopart, A and DeAngelis, M and Coyne, JA and Mackay, TFC}, year={2005}, month={Sep}, pages={211–225} }
 @article{pasyukova_nuzhdin_morozova_mackay_2004, title={Accumulation of transposable elements in the genome of Drosophila melanogaster is associated with a decrease in fitness}, volume={95}, ISSN={["1465-7333"]}, DOI={10.1093/jhered/esh050}, abstractNote={Replicates of the two isogenic laboratory strains of Drosophila melanogaster, 2b and Harwich, contain different average transposable element (TE) copy numbers in the same genetic background. These lines were used to analyze the correlation between TE copy number and fitness. Assuming a weak deleterious effect of each TE insertion, a decrease in fitness is expected with an increase in genomic TE copy number. Higher rates of ectopic exchanges and, consequently, chromosomal rearrangements resulting in early embryonic death are also predicted from an increase in TE copy number. Therefore egg hatchability is expected to decrease as the genomic TE copy number increases. In 2b, where replicate lines have diverged up by 90 TE copies per haploid genome, a negative correlation between the number of TE insertions and both fitness and egg hatchability were found. Neither correlation was significant for the Harwich replicates, which have only diverged by 30 TE copies. The average deleterious effect of a TE insertion on fitness and its components was estimated as 0.004. Both homozygous and heterozygous TE insertions were shown to have deleterious effects on fitness and its components.}, number={4}, journal={JOURNAL OF HEREDITY}, author={Pasyukova, EG and Nuzhdin, SV and Morozova, TV and Mackay, TFC}, year={2004}, month={Jul}, pages={284–290} }
 @article{mackay_2004, title={Complementing complexity}, volume={36}, ISSN={["1546-1718"]}, DOI={10.1038/ng1104-1145}, abstractNote={One challenge in modern biology is to understand the detailed genetic basis of variation for quantitative traits, including complex behaviors. A new study shows that historical recombination in outbred strains combined with functional complementation tests can identify pleiotropic genes with small effects on naturally occurring variation for anxiety-related behaviors in mice.}, number={11}, journal={NATURE GENETICS}, author={Mackay, TFC}, year={2004}, month={Nov}, pages={1145–1147} }
 @article{mackay_2004, title={Douglas Scott Falconer (1913-2004)}, volume={93}, ISSN={["1365-2540"]}, DOI={10.1038/sj.hdy.6800506}, number={2}, journal={HEREDITY}, author={Mackay, TFC}, year={2004}, month={Aug}, pages={119–121} }
 @article{genissel_pastinen_dowell_mackay_long_2004, title={No evidence for an association between common nonsynonymous polymorphisms in Delta and bristle number variation in natural and laboratory populations of Drosophila melanogaster}, volume={166}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.166.1.291}, abstractNote={Abstract We test the hypothesis that naturally occurring nonsynonymous variants in the Delta ligand of the Notch signaling pathway contribute to standing variation in sternopleural and/or abdominal bristle number in Drosophila melanogaster, for both a large cohort of wild-caught flies and previously described laboratory lines. We sequenced the transcribed region of Delta for 16 naturally occurring chromosomes and 65 SNPs, including 7 nonsynonymous SNPs (nsSNPs), were observed. Identified nsSNPs and 6 additional common SNPs, all located in exon 6 and the 3′ UTR, were genotyped in 2060 wild-caught flies using an OLA-based methodology and genotyped in 38 additional natural chromosomes via DNA sequencing. None of the genotyped nsSNPs were significantly associated with natural variation in bristle number as assessed by a permutation test. A 95% upper bound on the additive genetic variance attributable to each genotyped SNP in the large natural cohort is <2% of the total phenotypic variation. Results suggest that two previously detected genotype/phenotype associations between bristle number and variants in the introns of Delta cannot be explained by linkage disequilibrium between these variants and nearby nonsynonymous variants. Unidentified regulatory variants more parsimoniously explain previous observations.}, number={1}, journal={GENETICS}, author={Genissel, A and Pastinen, T and Dowell, A and Mackay, TFC and Long, AD}, year={2004}, month={Jan}, pages={291–306} }
 @misc{anholt_mackay_2004, title={Quantitative genetic analyses of complex behaviours in Drosophila}, volume={5}, ISSN={["1471-0056"]}, DOI={10.1038/nrg1472}, number={11}, journal={NATURE REVIEWS GENETICS}, author={Anholt, RRH and Mackay, TFC}, year={2004}, month={Nov}, pages={838–849} }
 @article{geiger-thornsberry_mackay_2004, title={Quantitative trait loci affecting natural variation in Drosophila longevity}, volume={125}, ISSN={["1872-6216"]}, DOI={10.1016/j.mad.2003.12.008}, abstractNote={Limited life span and senescence are universal phenomena, controlled by genetic and environmental factors whose interactions both limit life span and generate variation in life span between individuals, populations and species. To understand the genetic architecture of longevity it is necessary to know what loci affect variation in life span, what are the allelic effects at these loci and what molecular polymorphisms define quantitative trait locus (QTL) alleles. Here, we used quantitative complementation tests to determine whether genes that regulate longevity also contribute to naturally occurring variation in Drosophila life span. Inbred strains derived from a natural population were crossed to stocks containing null mutations (m) or deficiencies (Df) uncovering the candidate genes, maintained over a Balancer (Bal) chromosome. We measured the life span of the resulting F(1) genotypes, +(i)/m (Df) and +(i)/Bal, where +(i) denotes one of the i natural alleles. Failure of the QTL alleles to complement the candidate gene mutation is indicated by a significant cross (mutant versus wild-type allele of the candidate gene) by inbred line interaction term from analysis of variance of life span. Failure to complement indicates a genetic interaction between the candidate gene allele and the naturally occurring life span QTL, and implicates the candidate gene as potential cause of variation in longevity. Of the 16 candidate regions and genes tested, Df(2L)c17, Df(3L)Ly, Df(3L)AC1 and Df(3R)e-BS2 showed significant failure to complement wild-type alleles in both sexes, and an Alcohol dehydrogenase mutant failed to complement in females. Several genes that regulate life span (e.g., Superoxide dismutase, Catalase, and rosy) complemented the life span effects of wild-derived alleles, suggesting little natural variation affecting longevity at these loci, at least in this sample of alleles. Quantitative complementation tests are therefore useful for identifying QTL contributing to segregating genetic variation in life span in nature.}, number={3}, journal={MECHANISMS OF AGEING AND DEVELOPMENT}, author={Geiger-Thornsberry, GL and Mackay, TFC}, year={2004}, month={Mar}, pages={179–189} }
 @article{harbison_yamamoto_fanara_norga_mackay_2004, title={Quantitative trait loci affecting starvation resistance in Drosophila melanogaster}, volume={166}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.166.4.1807}, abstractNote={The ability to withstand periods of scarce food resources is an important fitness trait. Starvation resistance is a quantitative trait controlled by multiple interacting genes and exhibits considerable genetic variation in natural populations. This genetic variation could be maintained in the face of strong selection due to a trade-off in resource allocation between reproductive activity and individual survival. Knowledge of the genes affecting starvation tolerance and the subset of genes that affect variation in starvation resistance in natural populations would enable us to evaluate this hypothesis from a quantitative genetic perspective. We screened 933 co-isogenic P-element insertion lines to identify candidate genes affecting starvation tolerance. A total of 383 P-element insertions induced highly significant and often sex-specific mutational variance in starvation resistance. We also used deficiency complementation mapping followed by complementation to mutations to identify 12 genes contributing to variation in starvation resistance between two wild-type strains. The genes we identified are involved in oogenesis, metabolism, and feeding behaviors, indicating a possible link to reproduction and survival. However, we also found genes with cell fate specification and cell proliferation phenotypes, which implies that resource allocation during development and at the cellular level may also influence the phenotypic response to starvation.}, number={4}, journal={GENETICS}, author={Harbison, ST and Yamamoto, AH and Fanara, JJ and Norga, KK and Mackay, TFC}, year={2004}, month={Apr}, pages={1807–1823} }
 @article{moehring_li_schug_smith_deangelis_mackay_coyne_2004, title={Quantitative trait loci for sexual isolation between Drosophila simulans and D-mauritiana}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.103.024364}, abstractNote={Abstract Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While recent progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila simulans and D. mauritiana. We mapped at least seven QTL affecting discrimination of D. mauritiana females against D. simulans males, three QTL affecting D. simulans male traits against which D. mauritiana females discriminate, and six QTL affecting D. mauritiana male traits against which D. simulans females discriminate. QTL affecting sexual isolation act additively, are largely different in males and females, and are not disproportionately concentrated on the X chromosome: The QTL of greatest effect are located on chromosome 3. Unlike the genetic components of postzygotic isolation, the loci for prezygotic isolation do not interact epistatically. The observation of a few QTL with moderate to large effects will facilitate positional cloning of genes underlying sexual isolation.}, number={3}, journal={GENETICS}, author={Moehring, AJ and Li, JA and Schug, MD and Smith, SG and deAngelis, M and Mackay, TFC and Coyne, JA}, year={2004}, month={Jul}, pages={1265–1274} }
 @article{pasyukova_roshina_mackay_2004, title={Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan}, volume={3}, ISSN={["1474-9726"]}, DOI={10.1111/j.1474-9728.2004.00114.x}, abstractNote={Variation in longevity in natural populations is attributable to the segregation of multiple interacting loci, whose effects are sensitive to the environment. Although there has been considerable recent progress towards understanding the environmental factors and genetic pathways that regulate lifespan, little is known about the genes causing naturally occurring variation in longevity. Previously, we used deficiency complementation mapping to map two closely linked quantitative trait loci (QTL) causing female-specific variation in longevity between the Oregon (Ore) and 2b strains of Drosophila melanogaster to 35B9-C3 and 35C3 on the second chromosome. The 35B9-C3 QTL encompasses a 50-kb region including four genes, for one of which, shuttle craft (stc), mutations have been generated. The 35C3 QTL localizes to a 200-kb interval with 15 genes, including three genes for which mutations exist (reduced (rd), guftagu (gft) and ms(2)35Ci). Here, we report quantitative complementation tests to mutations at these four positional candidate genes, and show that ms(2)35Ci and stc are novel candidate quantitative trait genes affecting variation in Drosophila longevity. Complementation tests with stc alleles reveal sex- and allele-specific failure to complement, and complementation effects are dependent on the genetic background, indicating considerable epistasis for lifespan. In addition, a homozygous viable stc allele has a sex-specific effect on lifespan. stc encodes an RNA polymerase II transcription factor, and is an attractive candidate gene for the regulation of longevity and variation in longevity, because it is required for motoneuron development and is expressed throughout development. Quantitative genetic analysis of naturally occurring variants with subtle effects on lifespan can identify novel candidate genes and pathways important in the regulation of longevity.}, number={5}, journal={AGING CELL}, author={Pasyukova, EG and Roshina, NV and Mackay, TFC}, year={2004}, month={Oct}, pages={297–307} }
 @misc{mackay_2004, title={The genetic architecture of quantitative traits: lessons from Drosophila}, volume={14}, ISSN={["1879-0380"]}, DOI={10.1016/j.gde.2004.04.003}, abstractNote={Understanding the genetic architecture of quantitative traits begins with identifying the genes regulating these traits, mapping the subset of genetically varying quantitative trait loci (QTLs) in natural populations, and pinpointing the molecular polymorphisms defining QTL alleles. Studies in Drosophila have revealed large numbers of pleiotropic genes that interact epistatically to regulate quantitative traits, and large numbers of QTLs with sex-, environment- and genotype-specific effects. Multiple molecular polymorphisms in regulatory regions of candidate genes are often associated with variation for complex traits. These observations offer valuable lessons for understanding the genetic basis of variation for complex traits in other organisms, including humans.}, number={3}, journal={CURRENT OPINION IN GENETICS & DEVELOPMENT}, author={Mackay, TFC}, year={2004}, month={Jun}, pages={253–257} }
 @article{moehring_mackay_2004, title={The quantitative genetic basis of male mating behavior in Drosophila melanogaster}, volume={167}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.103.024372}, abstractNote={Male mating behavior is an important component of fitness in Drosophila and displays segregating variation in natural populations. However, we know very little about the genes affecting naturally occurring variation in mating behavior, their effects, or their interactions. Here, we have mapped quantitative trait loci (QTL) affecting courtship occurrence, courtship latency, copulation occurrence, and copulation latency that segregate between a D. melanogaster strain selected for reduced male mating propensity (2b) and a standard wild-type strain (Oregon-R). Mating behavior was assessed in a population of 98 recombinant inbred lines derived from these two strains and QTL affecting mating behavior were mapped using composite interval mapping. We found four QTL affecting male mating behavior at cytological locations 1A;3E, 57C;57F, 72A;85F, and 96F;99A. We used deficiency complementation mapping to map the autosomal QTL with much higher resolution to five QTL at 56F5;56F8, 56F9;57A3, 70E1;71F4, 78C5;79A1, and 96F1;97B1. Quantitative complementation tests performed for 45 positional candidate genes within these intervals revealed 7 genes that failed to complement the QTL: eagle, 18 wheeler, Enhancer of split, Polycomb, spermatocyte arrest, l(2)05510, and l(2)k02206. None of these genes have been previously implicated in mating behavior, demonstrating that quantitative analysis of subtle variants can reveal novel pleiotropic effects of key developmental loci on behavior.}, number={3}, journal={GENETICS}, author={Moehring, AJ and Mackay, TFC}, year={2004}, month={Jul}, pages={1249–1263} }
 @article{de luca_roshina_geiger-thornsberry_lyman_pasyukova_mackay_2003, title={Dopa decarboxylase (Ddc) affects variation in Drosophila longevity}, volume={34}, ISSN={["1546-1718"]}, DOI={10.1038/ng1218}, number={4}, journal={NATURE GENETICS}, author={De Luca, M and Roshina, NV and Geiger-Thornsberry, GL and Lyman, RF and Pasyukova, EG and Mackay, TFC}, year={2003}, month={Aug}, pages={429–433} }
 @article{ungerer_halldorsdottir_purugganan_mackay_2003, title={Genotype-environment interactions at quantitative trait loci affecting inflorescence development in Arabidopsis thaliana}, volume={165}, number={1}, journal={Genetics}, author={Ungerer, M. C. and Halldorsdottir, S. S. and Purugganan, M. D. and Mackay, T. F. C.}, year={2003}, month={Sep}, pages={353–365} }
 @article{weinig_dorn_kane_german_hahdorsdottir_ungerer_toyonaga_mackay_purugganan_schmitt_2003, title={Heterogeneous selection at specific loci in natural environments in Arabidopsis thaliana}, volume={165}, number={1}, journal={Genetics}, author={Weinig, C. and Dorn, L. A. and Kane, N. C. and German, Z. M. and Hahdorsdottir, S. S. and Ungerer, M. C. and Toyonaga, Y. and Mackay, T. F. C. and Purugganan, M. D. and Schmitt, J.}, year={2003}, month={Sep}, pages={321–329} }
 @article{norga_gurganus_dilda_yamamoto_lyman_patel_rubin_hoskins_mackay_bellen_2003, title={Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development}, volume={13}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(03)00546-3}, abstractNote={The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation.Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci.Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.}, number={16}, journal={CURRENT BIOLOGY}, author={Norga, KK and Gurganus, MC and Dilda, CL and Yamamoto, A and Lyman, RF and Patel, PH and Rubin, GM and Hoskins, RA and Mackay, TF and Bellen, HJ}, year={2003}, month={Aug}, pages={1388–1397} }
 @article{ganguly_mackay_anholt_2003, title={Scribble is essential for olfactory Behavior in Drosphila melanogaster}, volume={164}, number={4}, journal={Genetics}, author={Ganguly, I. and MacKay, T. F. C. and Anholt, R. R. H.}, year={2003}, month={Aug}, pages={1447–1457} }
 @article{anholt_dilda_chang_fanara_kulkarni_ganguly_rollmann_kamdar_mackay_2003, title={The genetic architecture of odor-guided behavior in Drosophila: epistasis and the transcriptome}, volume={35}, ISSN={["1546-1718"]}, DOI={10.1038/ng1240}, number={2}, journal={NATURE GENETICS}, author={Anholt, RRH and Dilda, CL and Chang, S and Fanara, JJ and Kulkarni, NH and Ganguly, I and Rollmann, SM and Kamdar, KP and Mackay, TFC}, year={2003}, month={Oct}, pages={180–184} }
 @article{borras_morozova_heinsohn_lyman_mackay_anholt_2003, title={Transcription profiling in Drosophila eyes that overexpress the human glaucoma-associated trabecular meshwork-inducible glucocorticoid response protein/myocilin (TIGR/MYOC)}, volume={163}, number={2}, journal={Genetics}, author={Borras, T. and Morozova, T. V. and Heinsohn, S. L. and Lyman, R. F. and Mackay, T. F. C. and Anholt, R. R. H.}, year={2003}, month={Feb}, pages={637–645} }
 @article{geiger-thornsberry_mackay_2002, title={Association of single-nucleotide polymorphisms at the Delta locus with genotype by environment interaction for sensory bristle number in Drosophila melanogaster}, volume={79}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672302005621}, abstractNote={The nature of forces maintaining variation for quantitative traits can only be assessed at the level of individual genes affecting variation in the traits. Identification of single-nucleotide polymorphisms (SNPs) associated with variation in Drosophila sensory bristle number at the Delta (Dl) locus provides us with the opportunity to test a model for the maintenance of variation in bristle number by genotype by environment interaction (GEI). Under this model, genetic variation is maintained at a locus under stabilizing selection if phenotypic values of heterozygotes are more stable than homozygotes across a range of environments, and the mean allelic effect is much smaller than the standard deviation of allelic effects across environments. Homozygotes and heterozygotes for two SNPs at Dl, one affecting sternopleural and the other abdominal bristle number, were reared in five different environments. There was significant GEI for both bristle traits. Neither condition of the model was satisfied for Dl SNPs exhibiting GEI for sternopleural bristle number. Heterozygotes for the abdominal bristle number SNPs were indeed the most stable genotype for two of the three environment pairs exhibiting GEI, but the mean genotypic effect was greater than the standard deviation of effects across environments. Therefore, this mechanism of GEI seems unlikely to be responsible for maintaining the common bristle number polymorphisms at Dl.}, number={3}, journal={GENETICS RESEARCH}, author={Geiger-Thornsberry, GL and Mackay, TFC}, year={2002}, month={Jun}, pages={211–218} }
 @misc{gibson_mackay_2002, title={Enabling population and quantitative genomics}, volume={80}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672302005839}, abstractNote={Dissection of quantitative traits to the nucleotide level requires phenotypic and genotypic analysis of traits on a genome scale. Here we discuss the set of community-wide genetic and molecular resources, including panels of specific types of inbred lines and high density resequencing and SNP detection, that will facilitate such studies.}, number={1}, journal={GENETICS RESEARCH}, author={Gibson, G and Mackay, TFC}, year={2002}, month={Aug}, pages={1–6} }
 @article{weinig_ungerer_dorn_kane_toyonaga_halldorsdottir_mackay_purugganan_schmitt_2002, title={Novel loci control variation in reproductive timing in Arabidopsis thaliana in natural environments}, volume={162}, number={4}, journal={Genetics}, author={Weinig, C. and Ungerer, M. C. and Dorn, L. A. and Kane, N. C. and Toyonaga, Y. and Halldorsdottir, S. S. and Mackay, T. F. C. and Purugganan, M. D. and Schmitt, J.}, year={2002}, month={Dec}, pages={1875–1884} }
 @article{ungerer_halldorsdottir_modliszewski_mackay_purugganan_2002, title={Quantitative trait loci for inflorescence development in Arabidopsis thaliana}, volume={160}, number={3}, journal={Genetics}, author={Ungerer, M. C. and Halldorsdottir, S. S. and Modliszewski, J. L. and Mackay, T. F. C. and Purugganan, M. D.}, year={2002}, month={Mar}, pages={1133–1151} }
 @article{kulkarni_yamamoto_robinson_mackay_anholt_2002, title={The DSC1 channel, encoded by the smi60E locus, contributes to odor-guided behavior in Drosophila melanogaster}, volume={161}, number={4}, journal={Genetics}, author={Kulkarni, N. H. and Yamamoto, A. H. and Robinson, K. O. and Mackay, T. F. C. and Anholt, R. R. H.}, year={2002}, month={Aug}, pages={1507–1516} }
 @article{leips_mackay_2002, title={The complex genetic architecture of Drosophila life span}, volume={28}, ISSN={["1096-4657"]}, DOI={10.1080/03610730290080399}, abstractNote={Continuous phenotypic variation in life span results from segregating genetic variation at multiple loci, the environmental sensitivity of expression of these loci, and the history of environmental variation experienced by the organism throughout its life. We have mapped quantitative trait loci (QTL) that produce variation in the life span of mated Drosophila melanogaster using a panel of recombinant inbred lines (RIL) that were backcrossed to the parental strains from which they were derived. Five QTL were identified that influence mated life span, three were male-specific, one was female-specific, and one affected life span in both sexes. The additive allelic effects and dominance of QTL were highly sex-specific. One pair of QTL also exhibited significant epistatic effects on life span. We summarize all of the QTL mapping data for Drosophila life span, and outline future prospects for disentangling the genetic and environmental influences on this trait.}, number={4}, journal={EXPERIMENTAL AGING RESEARCH}, author={Leips, J and Mackay, TFC}, year={2002}, pages={361–390} }
 @article{dilda_mackay_2002, title={The genetic architecture of drosophila sensory bristle number}, volume={162}, number={4}, journal={Genetics}, author={Dilda, C. L. and Mackay, T. F. C.}, year={2002}, month={Dec}, pages={1655–1674} }
 @article{robin_lyman_long_langley_mackay_2002, title={The hairy: A quantitative trait locus for Drosophila sensory bristle number}, volume={162}, number={1}, journal={Genetics}, author={Robin, C. and Lyman, R. F. and Long, A. D. and Langley, C. H. and Mackay, T. F. C.}, year={2002}, month={Sep}, pages={155–164} }
 @article{mackay_2002, title={The nature of quantitative genetic variation for Drosophila longevity}, volume={123}, DOI={10.1016/S0047-6374(01)00330-X}, abstractNote={Longevity is a typical quantitative trait: the continuous variation in life span observed in natural populations is attributable to genetic variation at multiple quantitative trait loci (QTL), environmental sensitivity of QTL alleles, and truly continuous environmental variation. To begin to understand the genetic architecture of longevity at the level of individual QTL, we have mapped QTL for Drosophila life span that segregate between two inbred strains that were not selected for longevity. A mapping population of 98 recombinant inbred lines (RIL) was derived from these strains, and life span of virgin male and female flies measured under control culture conditions, chronic heat and cold stress, heat shock and starvation stress, and high and low density larval environments. The genotypes of the RIL were determined for polymorphic roo transposable element insertion sites, and life span QTL were mapped using composite interval mapping methods. A minimum of 19 life span QTL were detected by recombination mapping. The life span QTL exhibited strong genotype by sex, genotype by environment, and genotype by genotype (epistatic) interactions. These interactions complicate mapping efforts, but evolutionary theory predicts such properties of segregating QTL alleles. Quantitative deficiency mapping of four longevity QTL detected in the control environment by recombination mapping revealed a minimum of 11 QTL in these regions. Clearly, longevity is a complex quantitative trait. In the future, linkage disequilibrium mapping can be used to determine which candidate genes in a QTL region correspond to the genetic loci affecting variation in life span, and define the QTL alleles at the molecular level.}, number={2-3}, journal={Mechanisms of Ageing and Development}, author={MacKay, T. F. C.}, year={2002}, pages={95–104} }
 @article{fanara_robinson_rollmann_anholt_mackay_2002, title={Vanaso is a candidate quantitative trait gene for Drosophila olfactory behavior}, volume={162}, number={3}, journal={Genetics}, author={Fanara, J. J. and Robinson, K. O. and Rollmann, S. M. and Anholt, R. R. H. and MacKay, T. F. C.}, year={2002}, month={Nov}, pages={1321–1328} }
 @article{lyman_nevo_mackay_2002, title={Variation in Drosophila sensory bristle number at 'Evolution Canyon'}, volume={80}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672302005876}, abstractNote={'Evolution Canyon' on Mount Carmel, Israel, displays highly contrasting physical and biotic environments on a micro-geographic scale, and is a natural laboratory for investigating genetic responses to variable and extreme environments across species. Samples of Drosophila melanogaster and D. simulans were collected from three sites each on the north- and south-facing slopes of the canyon along altitudinal transects, and one site on the valley floor. Numbers of abdominal and sternopleural sensory bristles were recorded for each of these subpopulations in three thermal environments. In D. simulans, sternopleural bristle number exhibited micro-geographic differentiation between the north- and south-facing slopes, while abdominal bristle number was stable across subpopulations. In D. melanogaster, the magnitudes of the difference in mean sternopleural bristle number between the north- and south-facing slopes and of mean abdominal bristle number along the altitudinal gradients were both conditional on rearing temperature. Thus, the pattern of genetic variation between sites was consistent with underlying heterogeneity of genetic mechanisms for response to the same environmental gradients between traits and sibling species. In contrast, the genetic architecture of bristle number at the level of variation within populations was very similar between species for the same bristle trait, although the two traits differed in the relative contribution of genotype by temperature and genotype by sex interaction.}, number={3}, journal={GENETICS RESEARCH}, author={Lyman, RF and Nevo, E and Mackay, TFC}, year={2002}, month={Dec}, pages={215–223} }
 @article{anholt_fanara_fedorowicz_ganguly_kulkarni_mackay_rollmann_2001, title={Functional genomics of odor-guided behavior in Drosophila melanogaster}, volume={26}, ISSN={["0379-864X"]}, DOI={10.1093/chemse/26.2.215}, abstractNote={The avoidance response to repellent odorants in Drosophila melanogaster, a response essential for survival, provides an advantageous model for studies on the genetic architecture of olfactory behavior. Transposon tagging in a highly inbred strain of flies in combination with a rapid and simple statistical behavioral assay enables the identification of not only large phenotypic effects, but also small aberrations from wild-type avoidance behavior. The recent completion of the sequence of the Drosophila genome facilitates the molecular characterization of transposon-tagged genes and correlation between gene expression and behavior in smell-impaired (smi) mutant lines. Quantitative genetic analyses of a collection of smi lines in a co-isogenic background revealed an extensive network of epistatic interactions among genes that shape the olfactory avoidance response. Candidate genes for several of these transposon-tagged smi loci implicate genes that mediate odorant recognition, including a novel odorant binding protein; signal propagation, including a voltage-gated sodium channel; and a protein containing multiple leucine rich repeats and PDZ domains likely to be involved in postsynaptic organization in the olfactory pathway. Several novel genes of unknown function have also been implicated, including a novel tyrosine-regulated protein kinase. The discovery and characterization of novel gene products that have major, hitherto unappreciated effects on olfactory behavior will provide new insights in the generation and regulation of odor-guided behavior. The identification and functional characterization of proteins encoded by smi genes that form part of the olfactory subgenome and correlation of polymorphisms in these genes with variation in odor-guided behavior in natural populations will advance our understanding of the genetic architecture of chemosensory behavior.}, number={2}, journal={CHEMICAL SENSES}, author={Anholt, RRH and Fanara, JJ and Fedorowicz, GM and Ganguly, I and Kulkarni, NH and Mackay, TFC and Rollmann, SM}, year={2001}, month={Feb}, pages={215–221} }
 @misc{mackay_2001, title={Quantitative trait loci in Drosophila}, volume={2}, ISSN={["1471-0064"]}, DOI={10.1038/35047544}, number={1}, journal={NATURE REVIEWS GENETICS}, author={Mackay, TFC}, year={2001}, month={Jan}, pages={11–20} }
 @article{wayne_hackett_dilda_nuzhdin_pasyukova_mackay_2001, title={Quantitative trait locus mapping of fitness-related traits in Drosophila melanogaster}, volume={77}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672300004894}, abstractNote={We examined the genetic architecture of four fitness-related traits (reproductive success, ovariole number, body size and early fecundity) in a panel of 98 Oregon-R × 2b3 recombinant inbred lines (RILs). Highly significant genetic variation was observed in this population for female, but not male, reproductive success. The cross-sex genetic correlation for reproductive success was 0·20, which is not significantly different from zero. There was significant genetic variation segregating in this cross for ovariole number, but not for body size or early fecundity. The RILs were genotyped for cytological insertion sites of roo transposable elements, yielding 76 informative markers with an average spacing of 3·2 cM. Quantitative trait loci (QTL) affecting female reproductive success and ovariole number were mapped using a composite interval mapping procedure. QTL for female reproductive success were located at the tip of the X chromosome between markers at cytological locations 1B and 3E; and on the left arm of chromosome 2 in the 30D–38A cytological region. Ovariole number QTL mapped to cytological intervals 62D–69D and 98A–98E, both on the third chromosome. The regions harbouring QTL for female reproductive success and ovariole number were also identified as QTL for longevity in previous studies with these lines.}, number={1}, journal={GENETICAL RESEARCH}, author={Wayne, ML and Hackett, JB and Dilda, CL and Nuzhdin, SV and Pasyukova, EG and MacKay, TFC}, year={2001}, month={Feb}, pages={107–116} }
 @article{anholt_mackay_2001, title={The genetic architecture of odor-guided behavior in Drosophila melanogaster}, volume={31}, ISSN={["0001-8244"]}, DOI={10.1023/A:1010201723966}, number={1}, journal={BEHAVIOR GENETICS}, author={Anholt, RRH and Mackay, TFC}, year={2001}, month={Jan}, pages={17–27} }
 @misc{mackay_2001, title={The genetic architecture of quantitative traits}, volume={35}, ISSN={["1545-2948"]}, DOI={10.1146/annurev.genet.35.102401.090633}, abstractNote={▪ Abstract Phenotypic variation for quantitative traits results from the segregation of alleles at multiple quantitative trait loci (QTL) with effects that are sensitive to the genetic, sexual, and external environments. Major challenges for biology in the post-genome era are to map the molecular polymorphisms responsible for variation in medically, agriculturally, and evolutionarily important complex traits; and to determine their gene frequencies and their homozygous, heterozygous, epistatic, and pleiotropic effects in multiple environments. The ease with which QTL can be mapped to genomic intervals bounded by molecular markers belies the difficulty in matching the QTL to a genetic locus. The latter requires high-resolution recombination or linkage disequilibrium mapping to nominate putative candidate genes, followed by genetic and/or functional complementation and gene expression analyses. Complete genome sequences and improved technologies for polymorphism detection will greatly advance the genetic dissection of quantitative traits in model organisms, which will open avenues for exploration of homologous QTL in related taxa.}, journal={ANNUAL REVIEW OF GENETICS}, author={Mackay, TFC}, year={2001}, pages={303–339} }
 @article{long_lyman_morgan_langley_mackay_2000, title={Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster}, volume={154}, number={3}, journal={Genetics}, author={Long, A. D. and Lyman, R. F. and Morgan, A. H. and Langley, C. H. and Mackay, T. F. C.}, year={2000}, month={Mar}, pages={1255–1269} }
 @article{pasyukova_vieira_mackay_2000, title={Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster}, volume={156}, number={3}, journal={Genetics}, author={Pasyukova, E. G. and Vieira, C. and Mackay, T. F. C.}, year={2000}, month={Nov}, pages={1129–1146} }
 @article{vieira_pasyukova_zeng_hackett_lyman_mackay_2000, title={Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster}, volume={154}, number={1}, journal={Genetics}, author={Vieira, C. and Pasyukova, E. G. and Zeng, Z. B. and Hackett, J. B. and Lyman, R. F. and Mackay, T. F. C.}, year={2000}, pages={213–227} }
 @article{juenger_purugganan_mackay_2000, title={Quantitative trait loci for floral morphology in Arabidopsis thaliana}, volume={156}, number={3}, journal={Genetics}, author={Juenger, T. and Purugganan, M. and MacKay, T. F. C.}, year={2000}, month={Nov}, pages={1379–1392} }
 @article{leips_mackay_2000, title={Quantitative trait loci for life span in Drosophila melanogaster: Interactions with genetic background and larval density}, volume={155}, number={4}, journal={Genetics}, author={Leips, J. and Mackay, T. F. C.}, year={2000}, month={Aug}, pages={1773–1788} }
 @article{gurganus_nuzhdin_leips_mackay_1999, title={High-resolution mapping of quantitative trait loci for sternopleural bristle number in Drosophila melanogaster}, volume={152}, number={4}, journal={Genetics}, author={Gurganus, M. C. and Nuzhdin, S. V. and Leips, J. W. and Mackay, T. F. C.}, year={1999}, month={Aug}, pages={1585–1604} }
 @article{lyman_lai_mackay_1999, title={Linkage disequilibrium mapping of molecular polymorphisms at the scabrous locus associated with naturally occurring variation in bristle number in Drosophila melanogaster}, volume={74}, ISSN={["1469-5073"]}, DOI={10.1017/S001667239900419X}, abstractNote={We evaluated the hypothesis that the Drosophila melanogaster second chromosome gene scabrous ( sca ), a candidate sensory bristle number quantitative trait locus (QTL), contributes to naturally occurring variation in bristle number. Variation in abdominal and sternopleural bristle number was quantified for wild-derived sca alleles in seven genetic backgrounds: as homozygous second chromosomes (C 2 ) in an isogenic background, homozygous lines in which approximately 20 cM including the sca locus had been introgressed into the isogenic background ( sca BC), as C 2 and sca BC heterozygotes and hemizygotes against a P element insertional sca allele and a P -induced sca deficiency in the same isogenic background, and as sca BC heterozygotes against the wild-type sca allele of isogenic strain. Molecular restriction map variation was determined for a 45 kb region including the sca locus, and single-stranded conformational polymorphism (SSCP) was examined for the third intron and parts of the third and fourth exons. Associations between each of the 27 molecular polymorphisms and bristle number were evaluated within each genotype and on the first principal component score determined from all seven genotypes, separately for each sex and bristle trait. Permutation tests were used to assess the empirical significance thresholds, accounting for multiple, correlated tests, and correlated markers. Three sites in regulatory regions were associated with female-specific variation in abdominal bristle number, one of which was an SSCP site in the region of the gene associated with regulation of sca in embryonic abdominal segments.}, number={3}, journal={GENETICS RESEARCH}, author={Lyman, RF and Lai, CQ and Mackay, TFC}, year={1999}, month={Dec}, pages={303–311} }
 @article{nuzhdin_dilda_mackay_1999, title={The genetic architecture of selection response: Inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster}, volume={153}, number={3}, journal={Genetics}, author={Nuzhdin, S. V. and Dilda, C. L. and Mackay, T. F. C.}, year={1999}, month={Nov}, pages={1317–1331} }
 @article{lyman_mackay_1998, title={Candidate quantitative trait loci and naturally occurring phenotypic variation for bristle number in Drosophila melanogaster: The Delta-Hairless gene region}, volume={149}, number={2}, journal={Genetics}, author={Lyman, R. F. and Mackay, T. F. C.}, year={1998}, month={Jun}, pages={983–998} }
 @article{fedorowicz_fry_anholt_mackay_1998, title={Epistatic interactions between smell-impaired loci in Drosophila melanogaster}, volume={148}, number={4}, journal={Genetics}, author={Fedorowicz, G. M. and Fry, J. D. and Anholt, R. R. H. and MacKay, T. F. C.}, year={1998}, month={Apr}, pages={1885–1891} }
 @article{gurganus_fry_nuzhdin_pasyukova_lyman_mackay_1998, title={Genotype-environment interaction at quantitative trait loci affecting sensory bristle number in Drosophila melanogaster}, volume={149}, number={4}, journal={Genetics}, author={Gurganus, M. C. and Fry, J. D. and Nuzhdin, S. V. and Pasyukova, E. G. and Lyman, R. F. and MacKay, T. F. C.}, year={1998}, month={Aug}, pages={1883–1898} }
 @article{fry_heinsohn_mackay_1998, title={Heterosis for viability, fecundity, and male fertility in Drosophila melanogaster: Comparison of mutational and standing variation}, volume={148}, number={3}, journal={Genetics}, author={Fry, J. D. and Heinsohn, S. L. and MacKay, T. F. C.}, year={1998}, pages={1171–1188} }
 @article{currie_mackay_partridge_1998, title={Pervasive effects of P element mutagenesis on body size in Drosophila melanogaster}, volume={72}, ISSN={["1469-5073"]}, DOI={10.1017/S0016672398003383}, abstractNote={A set of Drosophila melanogaster was generated, all derived from a common isogenic base stock and each with a single new P element insert on the second or third chromosome. The lines were scored for their body size, measured as thorax length. P inserts were associated with highly significant effects on body size, although the genotypes of the construct and of the control prevented deduction of the direction of mutant effects. In addition to mutant effects on the thorax length of both sexes, there were also highly significant sex-specific effects. Pleiotropic effects of inserts affecting body size on viability and bristle number, as ascertained in a separate study of these lines (Lyman et al ., 1996), were weak. Insertional mutagenesis is potentially a powerful tool for investigating the genes involved in size-control in Drosophila , but the technique requires fine tuning for use on polygenic and fitness-related traits.}, number={1}, journal={GENETICS RESEARCH}, author={Currie, DB and Mackay, TFC and Partridge, L}, year={1998}, month={Aug}, pages={19–24} }
 @article{wayne_mackay_1998, title={Quantitative genetics of ovariole number in Drosophila melanogaster. II. Mutational variation and genotype-environment interaction}, volume={148}, number={1}, journal={Genetics}, author={Wayne, M. L. and Mackay, T. F. C.}, year={1998}, pages={201–210} }
 @article{lai_mcmahon_young_mackay_langley_1998, title={Quemao, a Drosophila bristle locus, encodes geranylgeranyl pyrophosphate synthase}, volume={149}, number={2}, journal={Genetics}, author={Lai, C. Q. and McMahon, R. and Young, C. and Mackay, T. F. C. and Langley, C. H.}, year={1998}, month={Jun}, pages={1051–1061} }
 @article{schug_hutter_wetterstrand_gaudette_mackay_aquadro_1998, title={The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster}, volume={15}, ISSN={["1537-1719"]}, DOI={10.1093/oxfordjournals.molbev.a025901}, abstractNote={In a recent study, we reported that the combined average mutation rate of 10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster was 6.3 x 10(-6) mutations per locus per generation, a rate substantially below that of microsatellite repeat units in mammals studied to date (range = 10(-2)-10(-5) per locus per generation). To obtain a more precise estimate of mutation rate for dinucleotide repeat motifs alone, we assayed 39 new dinucleotide repeat microsatellite loci in the mutation accumulation lines from our earlier study. Our estimate of mutation rate for a total of 49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only slightly higher than the estimate from our earlier study. We also estimated the relative difference in microsatellite mutation rate among di-, tri-, and tetranucleotide repeats in the genome of D. melanogaster using a method based on population variation, and we found that tri- and tetranucleotide repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide repeats, respectively. The slower mutation rates of tri- and tetranucleotide repeats appear to be associated with a relatively short repeat unit length of these repeat motifs in the genome of D. melanogaster. A positive correlation between repeat unit length and allelic variation suggests that mutation rate increases as the repeat unit lengths of microsatellites increase.}, number={12}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Schug, MD and Hutter, CM and Wetterstrand, KA and Gaudette, MS and Mackay, TFC and Aquadro, CF}, year={1998}, month={Dec}, pages={1751–1760} }
 @article{long_lyman_langley_mackay_1998, title={Two sites in the Delta gene region contribute to naturally occurring variation in bristle number in Drosophila melanogaster}, volume={149}, number={2}, journal={Genetics}, author={Long, A. D. and Lyman, R. F. and Langley, C. H. and Mackay, T. F. C.}, year={1998}, month={Jun}, pages={999–1017} }
 @article{nuzhdin_pasyukova_mackay_1997, title={Accumulation of transposable elements in laboratory lines of Drosophila melanogaster}, volume={100}, ISSN={["1573-6857"]}, DOI={10.1023/A:1018381512384}, number={1-3}, journal={GENETICA}, author={Nuzhdin, SV and Pasyukova, EG and Mackay, TFC}, year={1997}, pages={167–175} }
 @article{lage_shrimpton_flavell_mackay_brown_1997, title={Genetic and molecular analysis of smooth, a quantitative trait locus affecting bristle number in Drosophila melanogaster}, volume={146}, number={2}, journal={Genetics}, author={Lage, P. Z. and Shrimpton, A. D. and Flavell, A. J. and Mackay, T. F. C. and Brown, A. J. L.}, year={1997}, pages={607–618} }
 @article{schug_mackay_aquadro_1997, title={Low mutation rates of microsatellite loci in Drosophila melanogaster}, volume={15}, ISSN={["1061-4036"]}, DOI={10.1038/ng0197-99}, number={1}, journal={NATURE GENETICS}, author={Schug, MD and Mackay, TFC and Aquadro, CF}, year={1997}, month={Jan}, pages={99–102} }
 @article{wayne_hackett_mackay_1997, title={Quantitative genetics of ovariole number in Drosophila melanogaster. I. Segregating variation and fitness}, volume={51}, DOI={10.2307/2411045}, number={4}, journal={Evolution}, author={Wayne, M. L. and Hackett, J. B. and Mackay, T. F. C.}, year={1997}, pages={1156–1163} }
 @article{nuzhdin_pasyukova_dilda_zeng_mackay_1997, title={Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster}, volume={94}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.94.18.9734}, abstractNote={Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms. Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life. Analyses of Drosophila spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late-age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis. The QTLs had large sex-specific effects on lifespan and age-specific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects. Late age-of-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan.}, number={18}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Nuzhdin, SV and Pasyukova, EG and Dilda, CL and Zeng, ZB and Mackay, TFC}, year={1997}, month={Sep}, pages={9734–9739} }
 @article{fry_heinsohn_mackay_1997, title={The contribution of new mutations to genotype-environment interaction for fitness in Drosophila melanogaster}, volume={50}, DOI={10.2307/2410700}, number={6}, journal={Evolution}, author={Fry, J. D. and Heinsohn, S. L. and MacKay, T. F.C.}, year={1997}, pages={2316–2327} }
 @misc{mackay_1996, title={The nature of quantitative genetic variation revisited: Lessons from Drosophila bristles}, volume={18}, ISSN={["0265-9247"]}, DOI={10.1002/bies.950180207}, abstractNote={Most characters that distinguish one individual from another, like height or weight, vary continuously in populations. Continuous variation of these ‘quantitative’ traits is due to the simultaneous segregation of multiple quantitative trait loci (QTLs) as well as environmental influences. A major challenge in human medicine, animal and plant breeding and evolutionary genetics is to identify QTLs and determine their genetic properties. Studies of the classic quantitative traits, abdominal and sternopleural bristle numbers of Drosophila, have shown that: (1) many loci have small effects on bristle number, but a few have large effects and cause most of the genetic variation; (2) ‘candidate’ loci involved in bristle development often have large quantitative effects on bristle number; and (3) alleles at QTLs affecting bristle number have variable degrees of dominance, interact with each other, and affect other quantitative traits, including fitness. Lessons learned from this model system will be applicable to studies of the genetic basis of quantitative variation in other species.}, number={2}, journal={BIOESSAYS}, author={Mackay, TFC}, year={1996}, month={Feb}, pages={113–121} }
 @article{mackay_1995, title={THE GENETIC-BASIS OF QUANTITATIVE VARIATION - NUMBERS OF SENSORY BRISTLES OF DROSOPHILA-MELANOGASTER AS A MODEL SYSTEM}, volume={11}, ISSN={["0168-9525"]}, DOI={10.1016/S0168-9525(00)89154-4}, abstractNote={The numbers of sensory hairs of Drosophila melanogaster present an ideal model system to elucidate the genetic basis of morphological quantitative variation. Loci affecting bristle number can be identified and their properties studied by accumulating spontaneous mutations, by P element mutagenesis, by mapping factors causing divergence between selection lines and by the association of phenotype variation with molecular variation at candidate neurogenic loci. The consensus emerging from the application of all approaches is that much of the mutational and segregating variation affecting bristle number is attributable to alleles with large phenotype effects at a small number of candidate loci.}, number={12}, journal={TRENDS IN GENETICS}, author={MACKAY, TFC}, year={1995}, month={Dec}, pages={464–470} }
 @article{zhou_luoma_armour_thakkar_mackay_anholt, title={A drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure}, volume={13}, number={7}, journal={PLoS Genetics}, author={Zhou, S. S. and Luoma, S. E. and Armour, G. E. S. and Thakkar, E. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{edwards_ayroles_stone_carbone_lyman_mackay, title={A transcriptional network associated with natural variation in Drosophila aggressive behavior}, volume={10}, number={7}, journal={Genome Biology}, author={Edwards, A. C. and Ayroles, J. F. and Stone, E. A. and Carbone, M. A. and Lyman, R. F. and Mackay, T. F. C.} }
 @article{mackay, title={A-maize-ing diversity}, volume={325}, number={5941}, journal={Science}, author={Mackay, T. F. C.}, pages={688–689} }
 @article{ober_huang_magwire_schlather_simianer_mackay, title={Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait}, volume={10}, number={5}, journal={PLoS One}, author={Ober, U. and Huang, W. and Magwire, M. and Schlather, M. and Simianer, H. and Mackay, T. F. C.} }
 @article{mackay, title={Alan Robertson (1920-1989)}, volume={125}, number={1}, journal={Genetics}, author={Mackay, T. F. C.}, pages={1} }
 @article{swarup_huang_mackay_anholt, title={Analysis of natural variation reveals neurogenetic networks for Drosophila olfactory behavior}, volume={110}, number={3}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Swarup, S. and Huang, W. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={1017–1022} }
 @article{hill_mackay, title={Anecdotal, historical and critical commentaries on genetics}, volume={167}, number={4}, journal={Genetics}, author={Hill, W. G. and Mackay, T. F. C.}, pages={1529–1536} }
 @misc{mackay_huang, title={Charting the genotype-phenotype map: Lessons from the Drosophila melanogaster genetic reference panel}, volume={7}, number={1}, journal={Wiley Interdisciplinary Reviews-Developmental Biology}, author={Mackay, T. F. C. and Huang, W.} }
 @article{zwarts_magwire_carbone_versteven_herteleer_anholt_callaerts_mackay, title={Complex genetic architecture of Drosophila aggressive behavior}, volume={108}, number={41}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Zwarts, L. and Magwire, M. M. and Carbone, M. A. and Versteven, M. and Herteleer, L. and Anholt, R. R. H. and Callaerts, P. and Mackay, T. F. C.}, pages={17070–17075} }
 @misc{mackay, title={Douglas Scott Falconer (1913-2004)}, volume={93}, number={2}, journal={Heredity}, author={MacKay, T. F. C.}, pages={119–121} }
 @misc{mackay, title={Epistasis and quantitative traits: using model organisms to study gene-gene interactions}, volume={15}, number={1}, journal={Nature Reviews. Genetics}, author={Mackay, T. F. C.}, pages={22–33} }
 @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{mackay, title={Epistasis for quantitative traits in Drosophila}, volume={1253}, journal={Epistasis: methods and protocols}, author={Mackay, T. F. C.}, pages={47–70} }
 @article{yamamoto_anholt_mackay, title={Epistatic interactions attenuate mutations affecting startle behaviour in Drosophila melanogaster}, volume={91}, number={6}, journal={Genetical Research}, author={Yamamoto, A. and Anholt, R. R. H. and Mackay, T. F. C.}, pages={373–382} }
 @article{friedenberg_meurs_mackay, title={Evaluation of artificial selection in Standard Poodles using whole-genome sequencing}, volume={27}, number={11-12}, journal={Mammalian Genome}, author={Friedenberg, S. G. and Meurs, K. M. and Mackay, T. F. C.}, pages={599–609} }
 @misc{manolio_collins_cox_goldstein_hindorff_hunter_mccarthy_ramos_cardon_chakravarti_et al., title={Finding the missing heritability of complex diseases}, volume={461}, number={7265}, journal={Nature}, author={Manolio, T. A. and Collins, F. S. and Cox, N. J. and Goldstein, D. B. and Hindorff, L. A. and Hunter, D. J. and McCarthy, M. I. and Ramos, E. M. and Cardon, L. R. and Chakravarti, A. and et al.}, pages={747–753} }
 @article{ayroles_laflamme_stone_wolfner_mackay, title={Functional genome annotation of Drosophila seminal fluid proteins using transcriptional genetic networks}, volume={93}, number={6}, journal={Genetical Research}, author={Ayroles, J. F. and Laflamme, B. A. and Stone, E. A. and Wolfner, M. F. and Mackay, T. F. C.}, pages={387–395} }
 @article{rohde_ostergaard_kristensen_sorensen_loeschcke_mackay_sarup, title={Functional validation of candidate genes detected by genomic feature models}, volume={8}, number={5}, journal={G3-Genes Genomes Genetics}, author={Rohde, P. D. and Ostergaard, S. and Kristensen, T. N. and Sorensen, P. and Loeschcke, V. and Mackay, T. F. C. and Sarup, P.}, pages={1659–1668} }
 @article{rohde_ostergaard_kristensen_sorensen_loeschcke_mackay_sarup, title={Functional validation of candidate genes detected by genomic feature models}, volume={8}, number={5}, journal={G3-Genes Genomes Genetics}, author={Rohde, P. D. and Ostergaard, S. and Kristensen, T. N. and Sorensen, P. and Loeschcke, V. and Mackay, T. F. C. and Sarup, P.}, pages={1659–1668} }
 @article{garlapow_everett_zhou_gearhart_fay_huang_morozova_arya_turlapati_st armour_et al., title={Genetic and genomic response to selection for food consumption in Drosophila melanogaster}, volume={47}, number={2}, journal={Behavior Genetics}, author={Garlapow, M. E. and Everett, L. J. and Zhou, S. S. and Gearhart, A. W. and Fay, K. A. and Huang, W. and Morozova, T. V. and Arya, G. H. and Turlapati, L. and St Armour, G. and et al.}, pages={227–243} }
 @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{shorter_couch_huang_carbone_peiffer_anholt_mackay, title={Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior}, volume={112}, number={27}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Shorter, J. and Couch, C. and Huang, W. and Carbone, M. A. and Peiffer, J. and Anholt, R. R. H. and Mackay, T. F. C.}, pages={E3555–3563} }
 @article{dembeck_boroczky_huang_schal_anholt_mackay, title={Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster}, volume={4}, journal={Elife}, author={Dembeck, L. M. and Boroczky, K. and Huang, W. and Schal, C. and Anholt, R. R. H. and Mackay, T. F. C.} }
 @article{carbone_yamamoto_huang_lyman_meadors_yamamoto_anholt_mackay, title={Genetic architecture of natural variation in visual senescence in Drosophila}, volume={113}, number={43}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Carbone, M. A. and Yamamoto, A. and Huang, W. and Lyman, R. A. and Meadors, T. B. and Yamamoto, R. and Anholt, R. R. H. and Mackay, T. F. C.}, pages={E6620–6629} }
 @misc{flint_mackay, title={Genetic architecture of quantitative traits in mice, flies, and humans}, volume={19}, number={5}, journal={Genome Research}, author={Flint, J. and Mackay, T. F. C.}, pages={723–733} }
 @article{dembeck_huang_carbone_mackay, title={Genetic basis of natural variation in body pigmentation in Drosophila melanogaster}, volume={9}, number={2}, journal={Fly}, author={Dembeck, L. M. and Huang, W. and Carbone, M. A. and Mackay, T. F. C.}, pages={75–81} }
 @article{huang_carbone_magwire_peiffer_lyman_stone_anholt_mackay, title={Genetic basis of transcriptome diversity in Drosophila melanogaster}, volume={112}, number={44}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Huang, W. and Carbone, M. A. and Magwire, M. M. and Peiffer, J. A. and Lyman, R. F. and Stone, E. A. and Anholt, R. R. H. and Mackay, T. F. C.}, pages={E6010–6019} }
 @article{sorensen_campos_morgante_mackay_sorensen, title={Genetic control of environmental variation of two quantitative traits of Drosophila melanogaster revealed by whole-genome sequencing}, volume={201}, number={2}, journal={Genetics}, author={Sorensen, P. and Campos, G. and Morgante, F. and Mackay, T. F. C. and Sorensen, D.}, pages={487-} }
 @article{ramaswami_deng_zhang_carbone_mackay_li, title={Genetic mapping uncovers cis-regulatory landscape of RNA editing}, volume={6}, journal={Nature Communications}, author={Ramaswami, G. and Deng, P. and Zhang, R. and Carbone, M. A. and Mackay, T. F. C. and Li, J. B.} }
 @article{clowers_lyman_mackay_morgan, title={Genetic variation in senescence marker protein-30 is associated with natural variation in cold tolerance in Drosophila}, volume={92}, number={2}, journal={Genetical Research}, author={Clowers, K. J. and Lyman, R. F. and Mackay, T. F. C. and Morgan, T. J.}, pages={103–113} }
 @misc{morozova_mackay_anholt, title={Genetics and genomics of alcohol sensitivity}, volume={289}, number={3}, journal={Molecular Genetics and Genomics}, author={Morozova, T. V. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={253–269} }
 @article{fochler_morozova_davis_gearhart_huang_mackay_anholt, title={Genetics of alcohol consumption in Drosophila melanogaster}, volume={16}, number={7}, journal={Genes Brain and Behavior}, author={Fochler, S. and Morozova, T. V. and Davis, M. R. and Gearhart, A. W. and Huang, W. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={675–685} }
 @article{vonesch_lamparter_mackay_bergmann_hafen, title={Genome-wide analysis reveals novel regulators of growth in Drosophila melanogaster}, volume={12}, number={1}, journal={PLoS Genetics}, author={Vonesch, S. C. and Lamparter, D. and Mackay, T. F. C. and Bergmann, S. and Hafen, E.} }
 @article{weber_khan_magwire_tabor_mackay_anholt, title={Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster}, volume={7}, number={4}, journal={PLoS One}, author={Weber, A. L. and Khan, G. F. and Magwire, M. M. and Tabor, C. L. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{montgomery_vorojeikina_huang_mackay_anholt_rand, title={Genome-wide association analysis of tolerance to methylmercury toxicity in Drosophila implicates myogenic and neuromuscular developmental pathways}, volume={9}, number={10}, journal={PLoS One}, author={Montgomery, S. L. and Vorojeikina, D. and Huang, W. and Mackay, T. F. C. and Anholt, R. R. H. and Rand, M. D.} }
 @article{jordan_craver_magwire_cubilla_mackay_anholt, title={Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster}, volume={7}, number={6}, journal={PLoS One}, author={Jordan, K. W. and Craver, K. L. and Magwire, M. M. and Cubilla, C. E. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{rohde_gaertner_ward_sorensen_mackay, title={Genomic analysis of genotype-by-social environment interaction for Drosophila melanogaster aggressive behavior}, volume={206}, number={4}, journal={Genetics}, author={Rohde, P. D. and Gaertner, B. and Ward, K. and Sorensen, P. and Mackay, T. F. C.}, pages={1969–1984} }
 @article{edwards_sorensen_sarup_mackay_sorensen, title={Genomic prediction for quantitative traits is improved by mapping variants to gene ontology categories in Drosophila melanogaster}, volume={203}, number={4}, journal={Genetics}, author={Edwards, S. M. and Sorensen, I. F. and Sarup, P. and Mackay, T. F. C. and Sorensen, P.}, pages={1871-} }
 @article{wilson_lai_lyman_mackay, title={Genomic response to selection for postponed senescence in Drosophila}, volume={134}, number={3-4}, journal={Mechanisms of Ageing and Development}, author={Wilson, R. H. and Lai, C. Q. and Lyman, R. F. and Mackay, T. F. C.}, pages={79–88} }
 @article{massouras_waszak_albarca-aguilera_hens_holcombe_ayroles_dermitzakis_stone_jensen_mackay_et al., title={Genomic variation and its impact on gene expression in Drosophila melanogaster}, volume={8}, number={11}, journal={PLoS Genetics}, author={Massouras, A. and Waszak, S. M. and Albarca-Aguilera, M. and Hens, K. and Holcombe, W. and Ayroles, J. F. and Dermitzakis, E. T. and Stone, E. A. and Jensen, J. D. and Mackay, T. F. C. and et al.} }
 @article{gaertner_ruedi_mccoy_moore_wolfner_mackay, title={Heritable variation in courtship patterns in Drosophila melanogaster}, volume={5}, number={4}, journal={G3-Genes Genomes Genetics}, author={Gaertner, B. E. and Ruedi, E. A. and McCoy, L. J. and Moore, J. M. and Wolfner, M. F. and Mackay, T. F. C.}, pages={531–539} }
 @article{ellis_huang_quinn_ahuja_alfrejd_gomez_hjelmen_moore_mackay_johnston_et al., title={Intrapopulation genome size variation in D. melanogaster reflects life history variation and plasticity}, volume={10}, number={7}, journal={PLoS Genetics}, author={Ellis, L. L. and Huang, W. and Quinn, A. M. and Ahuja, A. and Alfrejd, B. and Gomez, F. E. and Hjelmen, C. E. and Moore, K. L. and Mackay, T. F. C. and Johnston, J. S. and et al.} }
 @book{falconer_mackay, title={Introduction to quantitative genetics}, ISBN={0582243025}, publisher={Essex, England: Longman}, author={Falconer, D. S. and Mackay, T. F. C.} }
 @article{ivanov_escott-price_ziehm_magwire_mackay_partridge_thomton, title={Longevity GWAS using the Drosophila Genetic Reference Panel}, volume={70}, number={12}, journal={Journals of Gerontology. Series A, Biological Sciences Medical Sciences}, author={Ivanov, D. K. and Escott-Price, V. and Ziehm, M. and Magwire, M. M. and Mackay, T. F. C. and Partridge, L. and Thomton, J. M.}, pages={1470–1478} }
 @misc{mackay, title={Mutations and quantitative genetic variation: Lessons from Drosophila}, volume={365}, number={1544}, journal={Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, author={Mackay, T. F. C.}, pages={1229–1239} }
 @article{wang_lyman_mackay_anholt, title={Natural variation in odorant recognition among odorant-binding proteins in Drosophila melanogaster}, volume={184}, number={3}, journal={Genetics}, author={Wang, P. and Lyman, R. F. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={759–767} }
 @article{arya_weber_wang_magwire_negron_mackay_anholt, title={Natural variation, functional pleiotropy and transcriptional contexts of odorant binding protein genes in Drosophila melanogaster}, volume={186}, number={4}, journal={Genetics}, author={Arya, G. H. and Weber, A. L. and Wang, P. and Magwire, M. M. and Negron, Y. L. S. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={1475–623} }
 @article{jumbo-lucioni_bu_harbison_slaughter_mackay_moellering_de luca, title={Nuclear genomic control of naturally occurring variation in mitochondrial function in Drosophila melanogaster}, volume={13}, journal={BMC Genomics}, author={Jumbo-Lucioni, P. and Bu, S. and Harbison, S. T. and Slaughter, J. C. and Mackay, T. F. C. and Moellering, D. R. and De Luca, M.} }
 @article{shorter_dembeck_everett_morozova_arya_turlapati_st armour_schal_mackay_anholt, title={Obp56h modulates mating behavior in Drosophila melanogaster}, volume={6}, number={10}, journal={G3-Genes Genomes Genetics}, author={Shorter, J. R. and Dembeck, L. M. and Everett, L. J. and Morozova, T. V. and Arya, G. H. and Turlapati, L. and St Armour, G. E. and Schal, C. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={3335–3342} }
 @article{rollmann_wang_date_west_mackay_anholt, title={Odorant receptor polymorphisms and natural variation in olfactory behavior in Drosophila melanogaster}, volume={186}, number={2}, journal={Genetics}, author={Rollmann, S. M. and Wang, P. and Date, P. and West, S. A. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={687–364} }
 @misc{mackay_anholt, title={Of flies and man: Drosophila as a model for human complex traits}, volume={7}, journal={Annual Review of Genomics and Human Genetics}, author={Mackay, T. E. C. and Anholt, R. R. H.}, pages={339–367} }
 @article{carbone_ayroles_yamamoto_morozova_west_magwire_mackay_anholt, title={Overexpression of myocilin in the Drosophila eye activates the unfolded protein response: Implications for glaucoma}, volume={4}, number={1}, journal={PLoS One}, author={Carbone, M. A. and Ayroles, J. F. and Yamamoto, A. and Morozova, T. V. and West, S. A. and Magwire, M. M. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{morozova_anholt_mackay, title={Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster}, volume={8}, number={10}, journal={Genome Biology}, author={Morozova, T. V. and Anholt, R. R. and MacKay, T. F.} }
 @article{zhou_stone_mackay_anholt, title={Plasticity of the chemoreceptor repertoire in Drosophila melanogaster}, volume={5}, number={10}, journal={PLoS Genetics}, author={Zhou, S. S. and Stone, E. A. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{mackay_lyman, title={Polygenic mutation in Drosophila melanogaster: Genotype x environment interaction for spontaneous mutations affecting bristle number}, volume={102-103}, number={1-6}, journal={Genetica}, author={Mackay, T. F. C. and Lyman, R. F.}, pages={199–215} }
 @article{mackay_lyman_hill, title={Polygenic mutation in Drosophila melanogaster: Non-linear divergence among unselected strains}, volume={139}, number={2}, journal={Genetics}, author={Mackay, T. F. C. and Lyman, R. F. and Hill, W. G.}, pages={849} }
 @article{morozova_huang_pray_whitham_anholt_mackay, title={Polymorphisms in early neurodevelopmental genes affect natural variation in alcohol sensitivity in adult drosophila}, volume={16}, journal={BMC Genomics}, author={Morozova, T. V. and Huang, W. and Pray, V. A. and Whitham, T. and Anholt, R. R. H. and Mackay, T. F. C.} }
 @article{mackay, title={Q & A - Trudy Mackay}, volume={16}, number={17}, journal={Current Biology}, author={Mackay, T.}, pages={R659–661} }
 @article{magwire_yamamoto_carbone_roshina_symonenko_pasyukova_morozova_mackay, title={Quantitative and molecular genetic analyses of mutations increasing Drosophila life span}, volume={6}, number={7}, journal={PLoS Genetics}, author={Magwire, M. M. and Yamamoto, A. and Carbone, M. A. and Roshina, N. V. and Symonenko, A. V. and Pasyukova, E. G. and Morozova, T. V. and Mackay, T. F. C.} }
 @article{mackay_hackett_lyman_wayne_anholt, title={Quantitative genetic variation of odor-guided behavior in a natural population of Drosophila melanogaster}, volume={144}, number={2}, journal={Genetics}, author={Mackay, T. F. C. and Hackett, J. B. and Lyman, R. F. and Wayne, M. L. and Anholt, R. R. H.}, pages={727} }
 @article{garlapow_huang_yarboro_peterson_mackay, title={Quantitative genetics of food intake in Drosophila melanogaster}, volume={10}, number={9}, journal={PLoS One}, author={Garlapow, M. E. and Huang, W. and Yarboro, M. T. and Peterson, K. R. and Mackay, T. F. C.} }
 @article{jordan_carbone_yamamoto_morgan_mackay, title={Quantitative genomics of locomotor behavior in Drosophila melanogaster}, volume={8}, number={8}, journal={Genome Biology}, author={Jordan, K. W. and Carbone, M. A. and Yamamoto, A. and Morgan, T. J. and Mackay, T. F.} }
 @article{harbison_chang_kamdar_mackay, title={Quantitative genomics of starvation stress resistance in Drosophila}, volume={6}, number={4}, journal={Genome Biology}, author={Harbison, S. T. and Chang, S. and Kamdar, K. P. and MacKay, T. F. C.} }
 @article{desroches_busto_riedl_mackay_sokolowski, title={Quantitative trait locus mapping of gravitaxis behaviour in Drosophila melanogaster}, volume={92}, number={3}, journal={Genetical Research}, author={Desroches, C. E. and Busto, M. and Riedl, C. A. L. and Mackay, T. F. C. and Sokolowski, M. B.}, pages={167–174} }
 @article{garcia_carbone_mackay_anholt, title={Regulation of Drosophila lifespan by bellwether promoter alleles}, volume={7}, journal={Scientific Reports}, author={Garcia, J. F. and Carbone, M. A. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{ganguly_mackay_anholt, title={Scribble is essential for olfactory behavior in Drosophila melanogaster}, volume={164}, number={4}, journal={Genetics}, author={Ganguly, I. and MacKay, T. F. C. and Anholt, R. R. H.}, pages={1447–1457} }
 @article{huang_lyman_lyman_carbone_harbison_magwire_mackay, title={Spontaneous mutations and the origin and maintenance of quantitative genetic variation}, volume={5}, journal={Elife}, author={Huang, W. and Lyman, R. F. and Lyman, R. A. and Carbone, M. A. and Harbison, S. T. and Magwire, M. M. and Mackay, T. F. C.} }
 @article{jumbo-lucioni_ayroles_chambers_jordan_leips_mackay_de_luca, title={Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster}, volume={11}, journal={BMC Genomics}, author={Jumbo-Lucioni, P. and Ayroles, J. F. and Chambers, M. M. and Jordan, K. W. and Leips, J. and Mackay, T. F. C. and De and Luca, M.} }
 @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} }
 @inproceedings{zielinska_welk_mayhorn_murphy-hill, title={The Persuasive phish: examining the social psychological principles hidden in phishing emails}, booktitle={Symposium and Bootcamp on the Science of Security}, author={Zielinska, O. and Welk, A. and Mayhorn, C. B. and Murphy-Hill, E.}, pages={126–126} }
 @article{shorter_geisz_ozsoy_magwire_carbone_mackay, title={The effects of royal jelly on fitness traits and gene expression in Drosophila melanogaster}, volume={10}, number={7}, journal={PLoS One}, author={Shorter, J. R. and Geisz, M. and Ozsoy, E. and Magwire, M. M. and Carbone, M. A. and Mackay, T. F. C.} }
 @misc{aitman_boone_churchill_hengartner_mackay_stemple, title={The future of model organisms in human disease research}, volume={12}, number={8}, journal={Nature Reviews. Genetics}, author={Aitman, T. J. and Boone, C. and Churchill, G. A. and Hengartner, M. O. and Mackay, T. F. C. and Stemple, D. L.}, pages={575–582} }
 @inproceedings{mackay, title={The genetic architecture of complex behaviors: Lessons from Drosophila}, volume={136}, number={2}, booktitle={Genetica}, author={Mackay, T. F. C.}, pages={295–302} }
 @article{hunter_huang_mackay_singh, title={The genetic architecture of natural variation in recombination rate in Drosophila melanogaster}, volume={12}, number={4}, journal={PLoS Genetics}, author={Hunter, C. M. and Huang, W. and Mackay, T. F. C. and Singh, N. D.} }
 @article{arya_magwire_huang_serrano-negron_mackay_anholt, title={The genetic basis for variation in olfactory behavior in Drosophila melanogaster}, volume={40}, number={4}, journal={Chemical Senses}, author={Arya, G. H. and Magwire, M. M. and Huang, W. and Serrano-Negron, Y. L. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={233–243} }
 @article{zhou_morozova_hussain_luoma_mccoy_yamamoto_mackay_anholt, title={The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster}, volume={124}, number={7}, journal={Environmental Health Perspectives}, author={Zhou, S. S. and Morozova, T. V. and Hussain, Y. N. and Luoma, S. E. and McCoy, L. and Yamamoto, A. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={1062–1070} }
 @misc{morozova_goldman_mackay_anholt, title={The genetic basis of alcoholism: Multiple phenotypes, many genes, complex networks}, volume={13}, number={2}, journal={Genome Biology}, author={Morozova, T. V. and Goldman, D. and Mackay, T. F. C. and Anholt, R. R. H.} }
 @article{zwarts_vanden broeck_cappuyns_ayroles_magwire_vulsteke_clements_mackay_callaerts, title={The genetic basis of natural variation in mushroom body size in Drosophila melanogaster}, volume={6}, journal={Nature Communications}, author={Zwarts, L. and Vanden Broeck, L. and Cappuyns, E. and Ayroles, J. F. and Magwire, M. M. and Vulsteke, V. and Clements, J. and Mackay, T. F. C. and Callaerts, P.} }
 @misc{mackay_stone_ayroles, title={The genetics of quantitative traits: Challenges and prospects}, volume={10}, number={8}, journal={Nature Reviews. Genetics}, author={Mackay, T. F. C. and Stone, E. A. and Ayroles, J. F.}, pages={565–577} }
 @article{carnes_campbell_huang_butler_carbone_duncan_harbajan_king_peterson_weitzel_et al., title={The genomic basis of postponed senescence in Drosophila melanogaster}, volume={10}, number={9}, journal={PLoS One}, author={Carnes, M. U. and Campbell, T. and Huang, W. and Butler, D. G. and Carbone, M. A. and Duncan, L. H. and Harbajan, S. V. and King, E. M. and Peterson, K. R. and Weitzel, A. and et al.} }
 @article{anholt_mackay, title={The road less traveled: from genotype to phenotype in flies and humans}, volume={29}, number={1-2}, journal={Mammalian Genome}, author={Anholt, R. R. H. and Mackay, T. F. C.}, pages={5–23} }
 @article{morozova_mackay_anholt, title={Transcriptional networks for alcohol sensitivity in drosophila melanogaster}, volume={187}, number={4}, journal={Genetics}, author={Morozova, T. V. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={1193–345} }
 @article{morozova_anholt_mackay, title={Transcriptional response to alcohol exposure in Drosophila melanogaster}, volume={7}, number={10}, journal={Genome Biology}, author={Morozova, T. V. and Anholt, R. R. H. and MacKay, T. F. C.} }
 @article{zhou_mackay_anholt, title={Tuning the chemosensory window A fly's perspective}, volume={4}, number={3}, journal={Fly}, author={Zhou, S. S. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={230–235} }
 @misc{harbison_mackay_anholt, title={Understanding the neurogenetics of sleep: Progress from Drosophila}, volume={25}, number={6}, journal={Trends in Genetics}, author={Harbison, S. T. and Mackay, T. F. C. and Anholt, R. R. H.}, pages={262–269} }
 @article{ober_ayroles_stone_richards_zhu_gibbs_stricker_gianola_schlather_mackay_et al., title={Using whole-genome sequence data to predict quantitative trait phenotypes in Drosophila melanogaster}, volume={8}, number={5}, journal={PLoS Genetics}, author={Ober, U. and Ayroles, J. F. and Stone, E. A. and Richards, S. and Zhu, D. H. and Gibbs, R. A. and Stricker, C. and Gianola, D. and Schlather, M. and Mackay, T. F. C. and et al.} }
 @article{mackay_moore, title={Why epistasis is important for tackling complex human disease genetics}, volume={6}, journal={Genome Medicine}, author={Mackay, T. F. C. and Moore, J. H.} }
 @article{mackay_moore, title={Why epistasis is important for tackling complex human disease genetics (vol 6, 124, 2014)}, volume={7}, journal={Genome Medicine}, author={Mackay, T. F. C. and Moore, J. H.} }