Trudy F.C. Mackay

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Trudy Mackay’s research focuses on understanding the genetic and environmental factors affecting variation in quantitative traits, using Drosophila as a model system. Understanding of the genetic architecture of quantitative traits requires that we know the genetic loci at which segregating and mutational variation occurs; the homozygous, heterozygous and epistatic allelic effects, pleiotropic effects on other characters, including fitness; environmental sensitivities of QTL alleles; and the molecular genetic basis of quantitative variation in nature. We use several complementary approaches to achieve these goals. We screen P-element insertion mutations to identify candidate genes and pathways. We map QTLs by linkage to polymorphic molecular markers in crosses between genetically divergent strains, followed by complementation tests to deficiencies for high resolution mapping and to mutations to identify candidate genes. We also map QTLs by associating molecular polymorphisms with quantitative phenotypes on a genome wide scale using our Drosophila Genetic Reference Panel of 192 inbred lines, for which complete genome sequence will be available in the near future. Since DNA polymorphisms affect variation in quantitative traits by perturbing transcripts, metabolites and proteins, we are incorporating variation in transcript abundance in these studies, to provide biological context to the QTLs and identify transcriptional and genetic networks affecting complex traits. The effects of QTL alleles can also be environment-specific; therefore, we incorporate ecologically relevant environments in the above studies. We perform these studies on morphological (sensory bristle number); behavioral (olfaction, locomotion, aggression, mating, alcohol sensitivity, sleep) and life history (longevity, resistance to starvation, heat, cold and oxidative stress) traits in D. melanogaster; and on morphological (pigmentation) and behavioral (mating) divergence between closely related species pairs (D. mauritiana/D. simulans and D. yakuba/D. santomea). Understanding the genetic architecture of Drosophila quantitative traits is necessary to understand the evolutionary forces causing variation for quantitative traits within populations and phenotypic divergence between populations and species. General principles are likely to be conserved in other species, including humans. Finally, the same genes and networks affecting complex traits that are orthologous between flies and humans may be conserved–an hypothesis that we are directly testing for several traits.
  

Recent Publications:

Rollmann, S., Edwards, A., Yamamoto, A., Zwarts, L., Callaerts, P., Norga, K., Mackay. T., and Anholt, R. (2008). Pleiotropic effects of Drosohila neuralized on complex behaviors and brain structure. Genetics. 179: 1327–1336. PMCID: PMC2475736.

Sambandan, D., Carbone, M., Anholt, R., and Mackay, T. (2008). Phenotypic plasticity and genotype by environment interaction for olfactory behavior in Drosophila melanogaster. Genetics. 179: 1079–1088. PMCID: PMC2429861.

Yamamoto, Al, Zwarts, L., Callaerts, P., Norga, K., Mackay, T., and Anholt, R. (2008). Neurogenetic networks for startle-induced locomotion in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 105: 1393–12398. PMCID: PMC2527922.

Lai, C. Q., Leips, J., Zou, W., Roberts, J.F., Wollenberg, K.R., Parnell, L.D., Zeng, Z.-B., Ordovas, J.M. & Mackay, T.F.C. (2007). Speed-mapping quantitative trait loci using microarrays. Nat. Methods. 10: 839–841. [pdf file]

Morozova, T.V., Anholt, R.R.H., and Mackay, T.F.C. (2007). Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster. Genome Biology. 8: R231. doi:10.1186/gb-2007-8-10-r231.

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