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
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
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.
Link to Google Scholar
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