@article{johnstun_shankar_mokashi_sunkara_ihearahu_lyman_mackay_anholt_2021, title={Functional Diversification, Redundancy, and Epistasis among Paralogs of the Drosophila melanogaster Obp50a-d Gene Cluster}, volume={38}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msab004}, abstractNote={Abstract
               Large multigene families, such as the insect odorant-binding proteins (OBPs), are thought to arise through functional diversification after repeated gene duplications. Whereas many OBPs function in chemoreception, members of this family are also expressed in tissues outside chemosensory organs. Paralogs of the Obp50 gene cluster are expressed in metabolic and male reproductive tissues, but their functions and interrelationships remain unknown. Here, we report the genetic dissection of four members of the Obp50 cluster, which are in close physical proximity without intervening genes. We used CRISPR technology to excise the entire cluster while introducing a PhiC31 reintegration site to reinsert constructs in which different combinations of the constituent Obp genes were either intact or rendered inactive. We performed whole transcriptome sequencing and assessed sexually dimorphic changes in transcript abundances (transcriptional niches) associated with each gene-edited genotype. Using this approach, we were able to estimate redundancy, additivity, diversification, and epistasis among Obp50 paralogs. We analyzed the effects of gene editing of this cluster on organismal phenotypes and found a significant skewing of sex ratios attributable to Obp50a, and sex-specific effects on starvation stress resistance attributable to Obp50d. Thus, there is functional diversification within the Obp50 cluster with Obp50a contributing to development and Obp50d to stress resistance. The deletion–reinsertion approach we applied to the Obp50 cluster provides a general paradigm for the genetic dissection of paralogs of multigene families.}, number={5}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Johnstun, Joel A. and Shankar, Vijay and Mokashi, Sneha S. and Sunkara, Lakshmi T. and Ihearahu, Ugonna E. and Lyman, Roberta L. and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2021}, month={May}, pages={2030–2044} }
 @article{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={AbstractThe genetics of phenotypic responses to changing environments remains elusive. Using whole-genome quantitative gene expression as a model, here we study how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed in different environments (25 °C and 18 °C). We find a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increases at 18 °C relative to 25 °C for most genes that have a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments are shared and have similar effects, analysis of the environment-specific eQTLs reveals enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks are highly conserved across environments. Genes with higher network connectivity are under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Huang, Wen and Carbone, Mary Anna and Lyman, Richard F. and Anholt, Robert R. H. and Mackay, Trudy F. C.}, year={2020}, month={Oct} }
 @article{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={Trudy Mackay and colleagues measure sleep phenotypes in 40 wild-derived Drosophila lines, and report candidate genes and transcriptional networks associated with sleep regulation. Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes1. Studies in Drosophila2,3 have revealed molecular pathways4,5,6,7 and neural tissues8,9,10 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 expression11 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={Trudy Mackay and colleagues present a resource of 40 Drosophila melanogaster wild-derived inbred lines. The authors quantify genome-wide variation in transcript abundance for six ecologically relevant traits, characterize the transcriptome and identify transcriptional modules. Determining the genetic architecture of complex traits is challenging because phenotypic variation arises from interactions between multiple, environmentally sensitive alleles. We quantified genome-wide transcript abundance and phenotypes for six ecologically relevant traits in D. melanogaster wild-derived inbred lines. We observed 10,096 genetically variable transcripts and high heritabilities for all organismal phenotypes. The transcriptome is highly genetically intercorrelated, forming 241 transcriptional modules. Modules are enriched for transcripts in common pathways, gene ontology categories, tissue-specific expression and transcription factor binding sites. The high degree of transcriptional connectivity allows us to infer genetic networks and the function of predicted genes from annotations of other genes in the network. Regressions of organismal phenotypes on transcript abundance implicate several hundred candidate genes that form modules of biologically meaningful correlated transcripts affecting each phenotype. Overlapping transcripts in modules associated with different traits provide insight into the molecular basis of pleiotropy between complex traits.}, number={3}, journal={NATURE GENETICS}, author={Ayroles, Julien F. and Carbone, Mary Anna and Stone, Eric A. and Jordan, Katherine W. and Lyman, Richard F. and Magwire, Michael M. and Rollmann, Stephanie M. and Duncan, Laura H. and Lawrence, Faye and Anholt, Robert R. H. and et al.}, year={2009}, month={Mar}, pages={299–307} }
 @article{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
               Adaptive evolution of animals depends on behaviors that are essential for their survival and reproduction. The olfactory system of Drosophila melanogaster has emerged as one of the best characterized olfactory systems, which in addition to a family of odorant receptors, contains an approximately equal number of odorant-binding proteins (OBPs), encoded by a multigene family of 51 genes. Despite their abundant expression, little is known about their role in chemosensation, largely due to the lack of available mutations in these genes. We capitalized on naturally occurring mutations (polymorphisms) to gain insights into their functions. We analyzed the sequences of 13 Obp genes in two chromosomal clusters in a population of wild-derived inbred lines, and asked whether polymorphisms in these genes are associated with variation in olfactory responsiveness. Four polymorphisms in 3 Obp genes exceeded the statistical permutation threshold for association with responsiveness to benzaldehyde, suggesting redundancy and/or combinatorial recognition by these OBPs of this odorant. Model predictions of alternative pre-mRNA secondary structures associated with polymorphic sites suggest that alterations in Obp mRNA structure could contribute to phenotypic variation in olfactory behavior.}, number={3}, journal={GENETICS}, author={Wang, Ping and Lyman, Richard F. and Shabalina, Svetlana A. and Mackay, Trudy F. C. and Anholt, Robert R. H.}, year={2007}, month={Nov}, pages={1655–1665} }
 @article{lai_parnell_lyman_ordovas_mackay_2007, title={Candidate genes affecting Drosophila life span identified by integrating microarray gene expression analysis and QTL mapping}, volume={128}, ISSN={["1872-6216"]}, DOI={10.1016/j.mad.2006.12.003}, abstractNote={The current increase in life expectancy observed in industrialized societies underscores the need to achieve a better understanding of the aging process that could help the development of effective strategies to achieve healthy aging. This will require not only identifying genes involved in the aging process, but also understanding how their effects are modulated by environmental factors, such as dietary intake and life style. Although the human genome has been sequenced, it may be impractical to study humans or other long-lived organisms to gain a mechanistic understanding about the aging process. Thus, short-lived animal models are essential to identifying the mechanisms and genes that affect the rate and quality of aging as a first step towards identifying genetic variants in humans. In this study, we investigated gene expression changes between two strains of Drosophila (Oregon and 2b) for which quantitative trait loci (QTLs) affecting life span were identified previously. We collected males and females from both strains at young and old ages, and assessed whole genome variation in transcript abundance using Affymetrix GeneChips. We observed 8217 probe sets with detectable transcripts. A total of 2371 probe sets, representing 2220 genes, exhibited significant changes in transcript abundance with age; and 839 probe sets were differentially expressed between Oregon and 2b. We focused on the 359 probe sets (representing 354 genes) that exhibited significant changes in gene expression both with age and between strains. We used these genes to integrate the analysis of microarray gene expression data, bioinformatics, and the results of genetic mapping studies reported previously, to identify 49 candidate genes and four pathways that could potentially be responsible for regulating life span and involved in the process of aging in Drosophila and humans.}, number={3}, journal={MECHANISMS OF AGEING AND DEVELOPMENT}, author={Lai, Chao-Qiang and Parnell, Laurence D. and Lyman, Richard F. and Ordovas, Jose A. and Mackay, Trudy F. C.}, year={2007}, month={Mar}, pages={237–249} }
 @article{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 [1Mackay T.F.C. The genetic architecture of quantitative traits.Annu. Rev. Genet. 2001; 35: 303-339Crossref PubMed Scopus (753) Google Scholar]. 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 [2Stathakis D.G. Burton D.Y. McIvor W.E. Krishnakumar S. Wright T.R. O'Donnell J.M. The Catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.Genetics. 1999; 153: 361-382Crossref PubMed Google Scholar], the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster [2Stathakis D.G. Burton D.Y. McIvor W.E. Krishnakumar S. Wright T.R. O'Donnell J.M. The Catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity.Genetics. 1999; 153: 361-382Crossref PubMed Google Scholar, 3O'Donnell J.M. Wang Z. Chaudhuri A. Effects of perturbation of catecholamine regulation on resistance of Drosophila melanogaster to environmental stress.in: Blau N. Thony B. Pterins, Folates, and Related Biogenic Amines. SPS Publications, Heilbronn2004: 94-100Google Scholar, 4Mackay T.F.C. Roshina N.V. Leips J.W. Pasyukova E.G. Complex genetic architecture of Drosophila longevity.in: Masaro E.J. Austad S.N. Handbook of the Biology of Aging. Sixth Edition. Elsevier Press, Burlington2005: 181-216Crossref Scopus (24) Google Scholar]. 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
               Our ability to predict long-term responses to artificial and natural selection, and understand the mechanisms by which naturally occurring variation for quantitative traits is maintained, depends on detailed knowledge of the properties of spontaneous polygenic mutations, including the quantitative trait loci (QTL) at which mutations occur, mutation rates, and mutational effects. These parameters can be estimated by mapping QTL that cause divergence between mutation-accumulation lines that have been established from an inbred base population and selected for high and low trait values. Here, we have utilized quantitative complementation to deficiencies to map QTL at which spontaneous mutations affecting Drosophila abdominal and sternopleural bristle number have occurred in 11 replicate lines during 206 generations of divergent selection. Estimates of the numbers of mutations were consistent with diploid per-character mutation rates for bristle traits of 0.03. The ratio of the per-character mutation rate to total mutation rate (0.023) implies that >2% of the genome could affect just one bristle trait and that there must be extensive pleiotropy for quantitative phenotypes. The estimated mutational effects were not, however, additive and exhibited dependency on genetic background consistent with diminishing epistasis. However, these inferences must be tempered by the potential for epistatic interactions between spontaneous mutations and QTL affecting bristle number on the deficiency-bearing chromosomes, which could lead to overestimates in numbers of QTL and inaccurate inference of gene action.}, number={4}, journal={GENETICS}, author={Mackay, TFC and Lyman, RF and Lawrence, F}, year={2005}, month={Aug}, pages={1723–1735} }
 @article{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={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{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{luo_cannon_wekesa_lyman_vandenbergh_anholt_2002, title={Impaired olfactory behavior in mice deficient in the a subunit of G(0)}, volume={941}, ISSN={["0006-8993"]}, DOI={10.1016/S0006-8993(02)02566-0}, abstractNote={The ability to respond to chemical signals is essential for the survival and reproduction of most organisms. Olfactory signaling involves odorant receptor-mediated activation of G(olf), a homologue of G(s), on the dendrites of olfactory neurons. Olfactory receptor cells, however, also express Galpha(i2) and Galpha(o) on their axons, with all neurons expressing G(o) and a subset G(i2). Despite their abundance, possible contributions of G(o) and G(i2) to chemoreception remain unexplored. We investigated whether homologous recombinant mice deficient in the alpha subunit of G(o) are able to respond to odorants, whether possible olfactory impairments are dependent on genetic background, and whether formation of glomeruli in their olfactory bulbs is compromised. In an olfactory habituation/dishabituation test, G(o)-/- mice were unresponsive when exposed to odorants. Analysis of variance shows that performance of G(o)+/- mice crossed into the CD-1 background is also diminished in this test compared to their G(o)+/+ counterparts. Following food deprivation, G(o)-/- mice in the 129 Sv-ter/C57BL/6 genetic background were unable to locate a buried food pellet until they were approximately 10 weeks of age after which they performed as well as their litter mate controls. However, CD-1 G(o)-/- mice could locate a buried food pellet even when tested immediately after weaning. Despite their compromised olfactory responsiveness, histological examination did not reveal gross alterations in the olfactory bulbs of G(o)-/- mice. Thus, Galpha(o) is necessary for the expression of olfactory behavior under normal conditions and dependent on genetic background, but is not essential for the formation and maintenance of glomeruli.}, number={1-2}, journal={BRAIN RESEARCH}, author={Luo, AH and Cannon, EH and Wekesa, KS and Lyman, RF and Vandenbergh, JG and Anholt, RRH}, year={2002}, month={Jun}, pages={62–71} }
 @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{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{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{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{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{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}, pages={983–998} }
 @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}, pages={1883–1898} }
 @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}, pages={999–1017} }
 @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{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.} }
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 @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} }
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