@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{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{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{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{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{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{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{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{rivas_tadevosyan_gorewit_anderson_lyman_gonzalez_2006, title={Relationships between the phagocytic ability of milk macrophages and polymorphonuclear cells and somatic cell counts in uninfected cows}, volume={70}, number={1}, journal={Canadian Journal of Veterinary Research}, author={Rivas, A. L. and Tadevosyan, R. and Gorewit, R. C. and Anderson, K. L. and Lyman, R. and Gonzalez, R. N.}, year={2006}, pages={68–74} } @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{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{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{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={