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Genetics and Biochemistry Profiles


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Trudy Mackay

Genetics and Biochemistry

Endowed Chair

Director, Center for Human Genetics
Professor, Department of Genetics and Biochemistry

864-889-0522
Long Hall 106 [Office]
Self Regional Hall (Greenwood Genetics Lab) 110 [Office]

tmackay@clemson.edu
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Educational Background

BSc, Biology, Dalhousie University
MSc, Genetics, Dalhousie University
PhD, Genetics, University of Edinburgh

Profile/About Me

Trudy Mackay received her B.Sc. and M.Sc. from Dalhousie University, Canada and her Ph.D. from the University of Edinburgh. She has been a faculty member at the University of Edinburgh and North Carolina State University. Currently, she is the Director of the Center for Human Genetics, the Self Family Endowed Chair of Human Genetics and Professor of Genetics and Biochemistry at Clemson University. Her laboratory focuses on understanding the genetic and environmental factors affecting variation in quantitative traits, using Drosophila as a translational model system. Her laboratory seeks to identify the genetic loci at which segregating and mutational variation occurs, allelic effects and environmental sensitivities, and the causal molecular variants. She is a Fellow of the American Association for the Advancement of Science, the American Academy of Arts and Sciences and the Royal Society, a member of the US National Academy of Sciences and the American Philosophical Society, the 2016 Wolf Prize Laureate for Agriculture and the 2018 Dawson Prize recipient, Trinity College, Dublin.

Research Interests

My general research goal is to understand the genetic and environmental factors affecting variation in quantitative (or complex) traits. Quantitative trait phenotypes vary continuously in populations, due to the segregation of multiple Quantitative Trait Loci (QTLs) affecting them, as well as effects of environments to which the individuals are exposed. My research seeks to determine the genetic architecture of quantitative traits, which includes knowledge of all QTLs at which segregating and mutational variation occurs; the homozygous, heterozygous and epistatic effects, pleiotropic effects on other characters, environmental sensitivities of QTL alleles; and the molecular genetic basis of quantitative variation in nature. This knowledge is needed in order to predict adaptive evolutionary responses to changing environments, understand and predict human health and disease, and precision breeding of domestic animals and crops.

My research mainly focuses on Drosophila melanogaster, which has a wealth of genetic and genomic resources, and many complex traits related to fitness, human health and disease. We use two complementary approaches to identify QTLs and determine their effects for each of the traits of interest. First, we screen random P transposable element insert lines, derived in an inbred background, to identify candidate genes and pathways affecting quantitative trait phenotypes. Second, we map QTLs causing naturally occurring variation for quantitative traits by linkage or association with molecular markers, respectively, in linkage mapping populations and in samples of alleles from random breeding populations. We have derived a population of 205 inbred lines from the Raleigh, NC natural population with complete sequences, which we are currently expanding to 2,000 lines. These lines constitute the Drosophila Genetic Reference Panel (DGRP), a community resource for whole genome association mapping of quantitative traits. Because DNA polymorphisms do not directly affect variation in quantitative traits, but do so via networks of interacting transcripts, proteins, and metabolites, we are performing whole genome expression analyses on the DGRP lines to derive causal networks of genetically variable transcripts associated with quantitative traits. Since the effects of QTL alleles can be environment-specific, we incorporate ecologically relevant macro-environments in all the above studies. In addition, we are using the DGRP to map modifiers of mutations causing rare human diseases for which there is variable penetrance and/or expressivity.

Selected Publications

Link to full publication list in PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=Mackay+t+f&sort=pubdate&size=100

Publications from 2018

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.

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 doi: 10.1101/gr.268037.120. Online ahead of print.

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.

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, in press.

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 11: 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, in press.

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.

Huang W, Campbell T, Carbone MA, Jones WE, Unselt D, Anholt RRH, Mackay TFC. 2020. Context-dependent genetic architecture of Drosophila life span. PLoS Biol 18: e3000645.

Huang W, Carbone MA, Lyman RF, Anholt RRH, Mackay TFC. 2020. Genotype by environment interaction for gene expression in Drosophila melanogaster. Nat Commun 11: 5451.

Matute DR, Comeault AA, Early E, Serrato-Capuchina A, Peede D, Eckland-Monroy A, Huang W, Jones CD, Mackay TFC, Coyne JA. 2020. Rapid and predictable evolution of admixed populations between two Drosophila species pairs. Genetics 214: 211-230.

Morgante F, Huang W, Sorensen P, Maltecca C, Mackay TFC. 2020. Leveraging multiple layers of data to predict Drosophila complex traits. G3 10: 4599-4613.

Parker GA, Kohn N, Spirina A, McMillen A, Huang W, Mackay TFC. 2020. Genetic basis of increased lifespan and postponed senescence in Drosophila melanogaster. G3 10: 1087-1098.

Sass TN, MacPherson RA, Mackay TFC, Anholt RRH. 2020. High-throughput method for measuring alcohol sedation time of individual Drosophila melanogaster. J Vis Exp 158: doi: 10.3791/61108.

Yanagawa A, Huang W, Yamamoto A, Wada-Katsumata A, Schal C, Mackay TFC. 2020. Genetic basis of natural variation in spontaneous grooming in Drosophila melanogaster. G3 10: 3453-3460.

Zhou S, Morgante F, Anholt RRH, Mackay TFC. 2020. Systems genetics of the Drosophila metabolome. Genome Res 30: 392-405.

Gabrawy MM, Campbell S, Carbone MA, Morozova TV, Arya GHB, 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 74: 1844-1852.

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.

Lstib?rek M, Bittner V, Hodge GR, Picek J, Mackay TFC. 2018. Estimating realized heritability in panmictic populations. Genetics 208: 89-95.

Mackay TFC, Huang W. 2018. Charting the genotype-phenotype map: Lessons from the Drosophila melanogaster Genetic Reference Panel. Wiley Interdiscip Rev Dev Biol 7: doi: 10.1002/wdev.289.

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.

Honors and Awards

Dalhousie University Entrance Scholarship, 1970-1974

BSc awarded with first class honours in Biology, Dalhousie University, 1974

Dalhousie University Medal in Biology, 1974

National Research Council of Canada Graduate Fellowship, Department of Biology, Dalhousie University, 1974-1975

Killam Graduate Scholarship, Department of Biology, Dalhousie University, 1974-1975

MSc Thesis approved with distinction, Dalhousie University, 1976

Royal Commission for the Exhibition of 1851 Overseas Scholarship, Department of Genetics, University of Edinburgh, 1976-1979

McCauley Award, Department of Genetics, University of Edinburgh, 1979

Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship, Department of Biology, Dalhousie University, 1979-1980

Killam Postdoctoral Fellowship, Department of Biology, Dalhousie University (honorary), 1979-1980

Alumni Outstanding Research Award, College of Agriculture and Life Sciences, NC State University, 2000

Fellow, American Association for the Advancement of Science, 2003

Genetics Society of America Medal, 2004

Fellow, American Academy of Arts and Sciences, 2005

Fellow, Royal Society, 2006

Member, New York Academy of Sciences, 2007

O. Max Gardner Award, University of NC, 2007

Fellow, National Academy of Sciences of the USA, 2010

North Carolina Award for Science, 2011

Honoris Causa, University of Buenos Aires, Argentina, 2013

Alexander Quarles Holladay Medal for Excellence, NC State University, 2015

Wolf Prize for Agriculture, 2016

Alumni Outstanding Research Award, College of Sciences, NC State University, 2016

NC State University Research Leadership Academy, 2016-2018

5th International Conference on Quantitative Genetics Award for Outstanding Contributions in Research and Teaching in Quantitative Genetics, 2016

Honorary Professor, Beijing Forestry University, China, 2016

Dawson Prize in Genetics, Trinity College, Dublin, Ireland, 2018

Member, American Philosophical Society, 2021