@article{yamamoto_huang_anholt_mackay_2024, title={Article The genetic basis of variation in Drosophila melanogaster mating behavior}, volume={27}, ISSN={["2589-0042"]}, DOI={10.1016/j.isci.2024.109837}, abstractNote={Mating behavior is an essential fitness trait. We used the inbred, sequenced lines of the}, number={5}, journal={ISCIENCE}, author={Yamamoto, Akihiko and Huang, Wen and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2024}, month={May} }
@article{lyman_lyman_yamamoto_huang_harbison_zhou_anholt_mackay_2023, title={Natural genetic variation in a dopamine receptor is associated with variation in female fertility in Drosophila melanogaster}, volume={290}, ISSN={["1471-2954"]}, DOI={10.1098/rspb.2023.0375}, abstractNote={
Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50
Drosophila
Genetic Reference Panel inbred lines with whole genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome. Validation of candidate genes by RNAi knockdown confirmed the role of the dopamine 2-like receptor (
Dop2R
) in promoting egg laying. We replicated the
Dop2R
effect in an independently collected productivity dataset and showed that the effect of the
Dop2R
variant was mediated in part by regulatory gene expression variation. This study demonstrates the strong potential of genome-wide association analysis in this diverse panel of inbred strains and subsequent functional analyses for understanding the genetic architecture of fitness traits.
}, number={1996}, journal={PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, author={Lyman, Richard F. and Lyman, Rachel A. and Yamamoto, Akihiko and Huang, Wen and Harbison, Susan T. and Zhou, Shanshan and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2023}, month={Apr} }
@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={Abstract}, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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}, 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_sørensen_sorensen_maltecca_mackay_2015, title={Genetic Architecture of Micro-Environmental Plasticity in Drosophila melanogaster}, volume={5}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/srep09785}, DOI={10.1038/srep09785}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Morgante, Fabio and Sørensen, 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={Abstract}, 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}, 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}, 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}, 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={Abstract}, 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}, abstractNote={We developed a rapid, economical method for high-resolution quantitative trait locus (QTL) mapping using microarrays for selective genotyping of pooled DNA samples. We generated 21,207 F2 flies from two inbred Drosophila melanogaster strains with known QTLs affecting lifespan, and hybridized DNA pools of young and old flies to microarrays. We used changes of gene frequency of 2,326 single-feature polymorphisms (SFPs) to map previously identified and additional QTLs affecting lifespan.}, 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}, 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}, 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={Abstract}, 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}, abstractNote={The abundance of transposable elements and DNA repeat sequences in mammalian genomes raises the question of whether such insertions represent passive evolutionary baggage or may influence the expression of complex traits. We addressed this question in Drosophila melanogaster, in which the effects of single transposable elements on complex traits can be assessed in genetically identical individuals reared in controlled environments. Here we demonstrate that single P-element insertions in the intergenic region between the gustatory receptor 5a (Gr5a, also known as Tre) and trapped in endoderm 1 (Tre1), which encodes an orphan receptor, exert complex pleiotropic effects on fitness traits, including selective nutrient intake, life span, and resistance to starvation and heat stress. Mutations in this region interact epistatically with downstream components of the insulin signaling pathway. Transposon-induced sex-specific and sex-antagonistic effects further accentuate the complex influences that intergenic transposable elements can contribute to quantitative trait phenotypes.}, 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}, 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}, 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}, 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}, 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}, abstractNote={Sites that display strong environmental contrasts in close proximity, such as 'Evolution Canyon' on Mt. Carmel, Israel, are natural theatres for investigating adaptive evolution in action. We reared Drosophila melanogaster from collection sites along altitudinal transects on the north- and south-facing canyon slopes in each of three temperature environments, and assessed genetic variation in ovariole number and body size between and within collection sites, and temperature plasticity. Both traits exhibited significant genetic variation within collection sites and phenotypic plasticity in response to temperature, but not genetic variation for plasticity. Between-site genetic variation in ovariole number was negatively correlated with altitude on both slopes of the canyon, and collections from the north- and south-facing slopes were genetically differentiated for male, but not female, body size. Genetic variation between sites within easy dispersal range is consistent with the action of strong natural selection, although neither the selective agent(s) nor the direct targets of selection are known.}, 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}, 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}, 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={Abstract}, 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}, 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}, abstractNote={Behaviours are exceptionally complex quantitative traits. Sensitivity to environmental variation and genetic background, the presence of sexual dimorphism, and the widespread functional pleiotropy that is inherent in behavioural phenotypes pose daunting challenges for unravelling their underlying genetics. Drosophila melanogaster provides an attractive system for elucidating the unifying principles of the genetic architectures that drive behaviours, as genetically identical individuals can be reared rapidly in controlled environments and extensive publicly accessible genetic resources are available. Recent advances in quantitative genetic and functional genomic approaches now enable the extensive characterization of complex genetic networks that mediate behaviours in this important model organism.}, 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}, 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={Summary}, 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={Abstract}, 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}, abstractNote={Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.}, 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={Abstract
Background: 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. Results: 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. Conclusions: 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}, abstractNote={We combined transcriptional profiling and quantitative genetic analysis to elucidate the genetic architecture of olfactory behavior in Drosophila melanogaster. We applied whole-genome expression analysis to five coisogenic smell-impaired (smi) mutant lines and their control. We used analysis of variance to partition variation in transcript abundance between males and females and between smi genotypes and to determine the genotype-by-sex interaction. A total of 666 genes showed sexual dimorphism in transcript abundance, and 530 genes were coregulated in response to one or more smi mutations, showing considerable epistasis at the level of the transcriptome in response to single mutations. Quantitative complementation tests of mutations at these coregulated genes with the smi mutations showed that in most cases (67%) epistatic interactions for olfactory behavior mirrored epistasis at the level of transcription, thus identifying new candidate genes regulating olfactory behavior.}, 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}, abstractNote={Phenotypic variation for quantitative traits results from the simultaneous segregation of alleles at multiple quantitative trait loci. Understanding the genetic architecture of quantitative traits begins with mapping quantitative trait loci to broad genomic regions and ends with the molecular definition of quantitative trait loci alleles. This has been accomplished for some quantitative trait loci in Drosophila. Drosophila quantitative trait loci have sex-, environment- and genotype-specific effects, and are often associated with molecular polymorphisms in non-coding regions of candidate genes. These observations offer valuable lessons to those seeking to understand quantitative traits in other organisms, including humans.}, 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}, 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 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 coisogenic background revealed an extensive network of epistatic interactions among genes that shape the olfactory avoidance response. 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={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 (C2) 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 C2 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}, abstractNote={Analysis of variation at microsatellite DNA loci is widely used in studies of parentage, linkage and evolutionary history. The utility of microsatellites is primarily due to high levels of allelic diversity, believed to reflect mutation rates orders of magnitude higher than base pair substitutions at single-copy genes. For humans, mice, rats and pigs, microsatellite mutation rates have been estimated at 10(-3)-10(-5). However, a recent study comparing microsatellite variation in humans with non-human primates suggests that microsatellite mutation rates may vary considerably across taxa. We measured mutation rates of 24 microsatellite loci in mutation accumulation lines of Drosophila melanogaster. Surprisingly, only a single mutation was detected after screening 157,680 allele-generations, yielding an estimated average mutation rate per locus of 6.3 x 10(-6), a mutation rate considerably lower than reported for various mammals. We propose that the comparatively low mutation rate is primarily a function of short microsatellite repeat lengths in the D. melanogaster genome.}, 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={Abstract}, 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 phenotypic 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 phenotypic 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.} }