Director, Clemson University Center for Human Genetics
Self Family Endowed Chair of Human Genetics
Professor of Genetics and Biochemistry
Email: tmackay@clemson.edu
Phone: 864-889-0522
Biosketch
Dr. Trudy Frances Charlene Mackay
I received my B. Sc. and M.Sc. in Biology from Dalhousie University (Halifax, Canada) and my Ph.D. in Genetics from the University of Edinburgh (Edinburgh, Scotland). I was a lecturer in the Department of Genetics at the University of Edinburgh from 1980-1987. I joined the faculty of North Carolina State University in 1987, where I was a Distinguished University Professor and Goodnight Innovation Distinguished Chair of Biological Sciences until June 2018. I joined Clemson University July 1, 2018 as the Director of the Clemson University Center for Human Genetics and the Self Family Endowed Chair in Human Genetics in the Department of Genetics and Biochemistry.
I have received several honors and awards for my work on the genetic and environmental factors affecting variation for quantitative traits, including the Genetics Society of America Medal; the O. Max Gardner Award from the University of North Carolina; the North Carolina Award for Science; the Alexander Quarles Holladay Medal for Excellence from North Carolina State University; the Alumni Outstanding Research Award from the College of Sciences, North Carolina State University; the Wolf Prize for Agriculture and the Dawson Prize in Genetics from Trinity College, Dublin, Ireland. I am a Fellow of the American Association for the Advancement of Science, the American Academy of Arts and Science, the Royal Society of London and the US National Academy of Sciences.
Research
Most variation between individuals in physiology, behavior, morphology, disease susceptibility and components of reproductive fitness is quantitative, with variation in natural populations attributable to many interacting quantitative trait loci (QTLs) whose expression is sensitive to the environment. Determining the genetic architecture of quantitative traits is important for medicine, food production, and adaptive evolution, but the underlying genetic complexity poses a major challenge to this endeavor. My research goal has been to transform our understanding the genetic basis of quantitative traits from complex statistics to complex genetics, and to identify individual genes and genetic networks affecting quantitative traits, their effects in different environments, and the nature of molecular polymorphisms associated with naturally occurring variation. Working primarily with Drosophila as a model system, I assessed the quantitative effects of single P-element mutations in an isogenic background as an effective tool for identifying genes affecting quantitative traits, and performed diallel crosses among such mutations to determine genetic networks. My group performed the first QTL mapping experiments in Drosophila, using both linkage and association mapping designs. I introduced the quantitative complementation test as a means to narrow QTLs intervals using overlapping deficiencies, and identifying candidate position genes within QTL regions. More recently I spear-headed the generation and sequencing of the Drosophila Genetic Reference Panel (DGRP), a community resource for genome wide association mapping and systems genetics analysis of Drosophila quantitative traits, when all variants are known. Much of this work has been in collaboration with Robert Anholt. My laboratory has identified many novel genes affecting quantitative traits relevant to human biology, including lifespan, aggression, stress resistance, and alcohol and drug sensitivity. This work has demonstrated that the effects of new mutations and natural variants on quantitative traits are highly context-dependent, and are conditional on sex, genetic background and external environment. These observations provide guidelines for analysis of complex traits, and candidate genes for studying homologous traits in other species, including humans.
Publications
Simkhada B, Nazario-Yepiz NO, Freymuth PS, Lyman RA, Shankar V, Wiggins K, Flanagan-Steet H, Basu A, Weiss RJ, Anholt RRH, Mackay TFC. 2025. A Drosophila model of mucopolysaccharidosis IIIB. Genetics 229: iyae219. doi: 10.1093/genetics/iyae219
Ates I, Stuart C, Rathbone T, Barzi M, He G, Major AM, Shankar V, Lyman RA, Angner SS, Mackay TFC, Srinivasan S, Farris AB, Bissig K-D, Cottle RN. 2024. Ex vivo gene editing and cell therapy for hereditary Tyrosinemia Type 1. Hepatology Comm 8: e0424. doi: 10.1097/HC9.0000000000000424
Collins KM, Howansky E, Macon-Foley SC, Adonay ME, Shankar V, Lyman RF, Nazario-Yepiz NO, Brooks JK, Lyman RA, Mackay TFC, Anholt RRH. 2024. Drosophila toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole. Hum Genomics 18: 119. doi: 10.1186/s40246-024-00689-3
Mackay TFC, Anholt RRH. 2024. Pleiotropy, epistasis and the genetic architecture of quantitative traits. Nat Rev Genet 25: 639-657. doi: 10.1038/s41576-024-00711-3
Yamamoto A, Huang W, Anholt RRH, Mackay TFC. 2024. The genetic basis of variation in Drosophila melanogaster mating behavior. iScience 27: 109837. doi: 10.1016/j.isci.2024.109837
Yamamoto A, Huang W, Carbone MA, Anholt RRH, Mackay TFC. 2024. The genetic basis of incipient sexual isolation in Drosophila melanogaster. Proc Roy Soc Lond B 291: 20240672. doi: 10.1098/rspb.2024.0672
Anholt RRH, Mackay TFC. 2023. The genetic architecture of behavioral canalization. Trend Genet 39: 602-608. doi: 10.1016/j.tig.2023.02.007
Lyman RF, Lyman RA, Yamamoto A, Huang W, Harbison ST, Zhou S, Anholt RRH, Mackay TFC. 2023. Natural genetic variation in a dopamine receptor is associated with variation in female fertility in Drosophila melanogaster. Proc Roy Soc B 290: 20230375. doi: 10.1098/rspb.2023.0375
Mackay TFC. 2023. William George Hill. Biog Mem Roy Soc https://doi.org/10.1098/rsbm.2023.0003
MacPherson RA, Shankar V, Anholt RRH, Mackay TFC. 2023. Genetic and genomic analyses of Drosophila melanogaster models of chromatin modification disorders. Genetics 224: iyad061. doi: 10.1093/genetics/iyad061
Mokashi SS, Shankar V, Johnstun JA, Huang W, Mackay TFC, Anholt RRH. 2023. Pleiotropic fitness effects of a Drosophila odorant-binding protein. G3 (Bethesda) 13: jkac307. doi: 10.1093/g3journal/jkac307
Olivares GH, Núñez F, Candia N, Oróstica K, González-Ramírez MC, Vega-Macaya F, Zúñiga N, Molina C, Mackay TFC, Verdugo RA, Olguín P. 2023. Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster. Sleep 46: zsad016. doi: 10.1093/sleep/zsad016
Rand MD, Tennessen JM, Mackay TFC, Anholt RRH. 2023. Perspectives on the Drosophila melanogaster model for advances in toxicological science. Curr Protoc 3: e870. doi: 10.1002/cpz1.870
Riley VA, Shankar V, Holmberg JC, Sokolov AM, Neckles VN, Williams K, Lyman R, Mackay TFC, Feliciano DM. 2023. Tsc2 coordinates neuroprogenitor differentiation. iScience 26: 108442. doi: 10.1016/j.isci.2023.108442
Mackay TFC, Anholt RRH. 2022. Gregor Mendel’s legacy in quantitative genetics. PLoS Biol 20: e3001692. doi: 10.1371/journal.pbio.3001692
MacPherson RA, Shankar V, Sunkara LT, Hannah RC, Campbell MR 3rd, Anholt RRH, Mackay TFC. 2022. Pleiotropic fitness effects of the lncRNA Uhg4 in Drosophila melanogaster. BMC Genomics 23: 781. doi: 10.1186/s12864-022-08972-0
Morozova TV, Shankar V, MacPherson RA, Mackay TFC, Anholt RRH. 2022. Modulation of the Drosophila transcriptome by developmental alcohol exposure. BMC Genomics 23: 347. doi: 10.1186/s12864-022-08559-9
Punzi G, Ursini G, Chen Q, Radulescu E, Tao R, Huuki LA, Di Carlo P, Collado-Torres L, Shin JH, Catanesi R, Jaffe AE, Hyde TM, Kleinman JE, Mackay TFC, Weinberger DR. 2022. Genetics and brain transcriptomics of completed suicide. Am J Psychiatry 179: 226-241. doi: 10.1176/appi.ajp.2021.21030299
Baker BB, Carbone MA, Huang W, Anholt RRH, Mackay TFC. 2021. Genetic basis of variation in cocaine and methamphetamine consumption in outbred populations of Drosophila melanogaster. Proc Natl Acad Sci USA 118: e2104131118. doi: 10.1073/pnas.2104131118
Baker BB, Mokashi SS, Shankar V, Hatfield JS, Hannah RC, Mackay TFC, Anholt RRH. 2021. The Drosophila brain on cocaine at single-cell resolution. Genome Res 31: 1927-1937. doi: 10.1101/gr.268037.120
Huggett SB, Hatfield JS, Walters JD, McGreary JE, Welsh JW, Mackay TFC, Anholt RRH, Palmer RGC. 2021. Ibrutinib as a potential therapeutic for cocaine use disorder. Transl Psychiatry 11: 623. doi: 10.1038/s41398-021-01737-5
Johnstun JA, Shankar V, Mokashi SS, Sunkara LT, Ihearahu UE, Lyman RL, Mackay TFC, Anholt RRH. 2021. Functional diversification, redundancy and epistasis among paralogs of the Drosophila melanogaster Obp50a-d gene cluster. Mol Biol Evol 38: 2030-2044. doi: 10.1093/molbev/msab004
Mokashi SS, Shankar V, MacPherson RA, Hannah RC, Mackay TFC, Anholt RRH. 2021. Developmental alcohol exposure in Drosophila: Effects on adult phenotypes and gene expression in the brain. Front Psych 12: 699033. doi: 10.3389/fpsyt.2021.699033
Nazario-Yepiz NO, Sobaberas JF, Lyman R, Campbell MR, Shankar V, Anholt RRH, Mackay TFC. 2021. A Drosophila model for metabolic syndrome: Physiological and metabolic consequences of reduced expression of the brummer triglyceride lipase. PLoS One 16: e0255198. doi: 10.1371/journal.pone.0255198
Özsoy ED, Yılmaz M, Patlar B, Emecen G, Durmaz E, Magwire MM, Zhou S, Huang W, Anholt RRH, Mackay TFC. 2021. Epistasis for head morphology in Drosophila melanogaster. G3 (Bethesda) 11: jkab285. doi: 10.1093/g3journal/jkab285
Tallo CA, Duncan LH, Yamamoto AH, Slaydon JD, Arya GH, Turlapati L, Mackay TFC, Carbone MA. 2021. Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy. G3 (Bethesda) 11: jkaa014. doi: 10.1093/g3journal/jkaa014
Walters JD, Hatfield J, Baker BB, Anholt RRH, Mackay TFC. 2021. A high throughput microplate feeder assay for quantification of consumption in Drosophila. J Vis Exp 172: 10.3791/62771. doi: 10.3791/62771.
Everett LJ, Zhou S, Carbone MA, Lyman RF, Arya GH, Geisz MS, Huang W, Ma J, Morgante F, St Amour G, Turlapati L, Anholt RRH, Mackay TFC. 2020. Gene expression networks in the Drosophila Genetic Reference Panel. Genome Res 30: 485-496. doi: 10.1101/gr.257592.119
Huang W, Campbell T, Carbone MA, Jones WE, Unselt D, Anholt RRH and Mackay TFC. 2020. Context-dependent genetic architecture of Drosophila lifespan. PLoS Biol 18: e3000645. doi: 10.1371/journal.pbio.3000645.
Huang W, Carbone MA, Lyman RF, Anholt RRH and Mackay TFC. 2020. Genotype by environment interaction for gene expression in Drosophila melanogaster. Nat Commun. 11: 5451. doi: 10.1038/s41467-020-19131-y.
Matute DR, Comeault AA, Earley E, Serrato-Capuchina A, Peede D, Monroy-Eklund A, Huang W, Jones CD, Mackay TFC and Coyne JA. 2020. Rapid and predictable evolution of admixed populations between two Drosophila species pairs. Genetics 214: 211-230. doi: 10.1534/genetics.119.302685.
Morgante F, Huang W, Sørensen P, Maltecca C and Mackay TFC. 2020. Leveraging multiple layers of data to predict Drosophila complex traits. G3 (Bethesda) 10: 4599-4613. doi: 10.1534/g3.120.401847.
Parker GA, Kohn N, Spirina A, McMillen A, Huang W and Mackay TFC. 2020. Genetic basis of increased lifespan and postponed senescence in Drosophila melanogaster. G3 (Bethesda) 10: 1087-1098. doi: 10.1534/g3.120.401041.
Sass TN, MacPherson RA, Mackay TFC and Anholt RRH. 2020. A high-throughput method for measuring alcohol sedation time of individual Drosophila melanogaster. J Vis Exp 158: e61108. doi: 10.3791/61108.
Yanagawa A, Huang W, Yamamoto A, Wada-Katsumata A, Schal C and Mackay TFC. 2020. Genetic basis of natural variation in spontaneous grooming in Drosophila melanogaster. G3 (Bethesda) 10: 3453-3460. doi: 10.1534/g3.120.401360.
Zhou S, Morgante F, Geisz MS, Ma J, Anholt RRH and Mackay TFC. 2020. Systems genetics of the Drosophila metabolome. Genome Res 30: 392-405. doi: 10.1101/gr.243030.118.
Gabrawy MM, Campbell S, Carbone MA, Morozova TV, Arya GH, B Turlapati L, Walston JD, Starz-Gaiano M, Everett L, Mackay TFC, Leips J, Abadir PM. 2019. Lisinopril preserves physical resilience and extends life span in a genotype-specific manner in Drosophila melanogaster. J Gerontol A Biol Sci Med Sci pii: glz152.
Harbison ST, Kumar S, Huang W, McCoy LJ, Mackay TFC. 2019. Genome wide association study of circadian behavior in Drosophila melanogaster. Behav Genet 49: 60-82.
Highfill CA, Baker BM, Stevens SD, Anholt RRH, Mackay TFC. 2019. Genetics of cocaine and methamphetamine consumption and preference in Drosophila melanogaster. PLoS Genet 15: e1007834.
Anholt RRH, Mackay TFC. 2018. The road less traveled: From genotype to phenotype in flies and humans. Mamm Genome 29: 5-23.
Dumont BL, Williams CL, Ng BL, Horncastle V, Chambers CL, McGraw LA, Adams D, Mackay TFC, Breen M. 2018. Relationship between sequence homology, genome architecture, and meiotic behavior of the sex chromosomes in North American voles. Genetics 210: 83-97.
Lstibůrek M, Bittner V, Hodge GR, Picek J, Mackay TFC. 2018. Estimating realized heritability in panmictic populations. Genetics 208: 89-95.
Meurs KM, Friedenberg SG, Williams B, Keene BW, Atkins CE, Adin D, Aona B, DeFrancesco T, Tou S, Mackay TFC. 2018. Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration. Vet J 232: 16-19.
Morgante F, Huang W, Maltecca C, Mackay TFC. 2018. Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals. Heredity 120: 500-514.
Morozova TV, Hussain Y, McCoy LJ, Zhirnov EV, Davis MR, Pray VA, Lyman RA, Duncan LH, McMillen A, Jones A, Mackay TFC, Anholt RRH. 2018. A Cyclin E centered genetic network contributes to alcohol-induced variation in Drosophila development. G3 8: 2643-2653.
Rohde PD, Østergaard S, Kristensen TN, Sørensen P, Loeschcke V, Mackay TFC, Sarup P. 2018. Functional validation of candidate genes detected by genomic feature models. G3 8: 1659-1668.
Fochler S, Morozova TV, Davis M, Gearhart A, Huang W, Mackay TFC, Anholt RRH. 2017. Genetics of alcohol consumption in Drosophila melanogaster. Genes Brain Behav 16: 675-685.
Garcia JF, Carbone MA, Mackay TFC, Anholt RRH. 2017. Regulation of Drosophila lifespan by bellwether promoter alleles. Sci Reports 7: 4109.
Garlapow ME, Everett LJ, Zhou S, Gearhart AW, Fay KA, Huang W, Morozova TV, Arya GH, Turlapati L, St. Armour G, Hussain YN, McAdams SE, Fochler S, Mackay TFC. 2017. Genetic and genomic response to selection for food consumption in Drosophila melanogaster. Behav Genet 42: 227-243.
Mackay TFC, Huang W. 2018. Charting the genotype-phenotype map: Lessons from the Drosophila melanogaster Genetic Reference Panel. Wiley Interdiscip Rev Dev Biol 7(1). doi: 10.1002/wdev.289.
Rohde PD, Gaertner B, Ward K, Sorenson P, Mackay TFC. 2017. Genomic analysis of genotype by social environment interaction for Drosophila aggressive behavior. Genetics 206: 1969-1984.
Zhou S, Luoma SE, St Armour GE, Thakkar E, Mackay TFC, Anholt RRH. 2017. A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure. PLoS Genetics 13: e1006907.
Carbone MA, Yamamoto A, Huang W, Lyman RA, Meadors TB, Yamamoto R, Anholt RRH, Mackay TFC. 2016. Genetic architecture of natural variation in visual senescence in Drosophila. Proc Natl Acad Sci USA 113: E6620-E6629.
Edwards SM, Sørensen IF, Sarup P, Mackay TFC, Sørensen P. 2016. Genomic prediction for quantitative traits is improved by mapping variants to Gene Ontology categories in Drosophila melanogaster. Genetics 203: 1871-1883.
Friedenberg SG, Meurs KM, Mackay TFC. 2016. Evaluation of artificial selection in Standard Poodles using whole genome sequencing. Mamm Genome 27: 599-609.
Gerken AR, Mackay TFC, Morgan TJ. 2016. Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection. J Thermal Biol 59: 77-85.
He X, Zhou S, St Armour GE, Mackay TFC, Anholt RRH. 2016. Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior. Genes Brain Behav 15: 280-290.
Huang W, Lyman RF, Lyman R, Carbone MA, Harbison ST, Magwire MM, Mackay TFC. 2016. Spontaneous mutation and the origin and maintenance of quantitative genetic variation. eLife 5: e14625
Huang W, Mackay TFC. 2016. The genetic architecture of quantitative traits cannot be inferred from variance component analysis. PLoS Genetics 12: e1006421.
Hunter CM, Huang W, Mackay TFC, Singh ND. 2016. The genetic architecture of natural variation in recombination rate in Drosophila melanogaster. PLoS Genetics 12: e1005951.
Reidl C, Oster S, Busto M, Mackay TFC, Sokolowski M. 2016. Natural variability in Drosophila larval and pupal NaCl tolerance. J Insect Physiol 88: 15-23.
Shorter JR, Dembeck LM, Everett LJ, Morozova TV, Arya GH, Turlapati L, St Amour GE, Schal C, Mackay TFC, Anholt RRH. 2016. Obp56h modulates mating behavior in Drosophila melanogaster. G3 6: 3335-3342.
Vonesch SC, Lamparter D, Mackay TFC, Bergmann S, Hafen E. 2016. Genome-wide analysis reveals novel regulators of growth in Drosophila melanogaster. PLoS Genetics 12: e1005616.
Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TFC, Anholt RRH. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124: 1062-1070.
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