All this stuff is going to be public
D.Phil , Zoology, University of Oxford
B.A., Biological Sciences , St. John’s College, University of Oxford
Complex phenotypes are influenced by a number of genetic loci and environmental factors. Examples of complex traits include susceptibility to a variety of human diseases, such as heart disease and many forms of mental illness, as well as numerous ecologically- and evolutionarily-relevant traits. Even though complex traits are tremendously important with regard to human health and organismal diversity, they have proven difficult to molecularly characterize. Indeed, we have only limited information on a broad range of key questions:
What types of loci contribute to variation in complex traits? Are they generally structural (protein-coding) or regulatory in nature?
How many loci contribute to genetic variation in complex traits? What are the effects of these causative sites?
Do causative loci interact epistatically with each other?
Do variants show different phenotypic effects in different environments (genotype-by-environment interaction)?
Only by identifying the precise DNA variants that contribute to variation in complex traits can we begin to answer these questions. Such understanding is vital both for human health (Can we assess whether a patient carries alleles at certain genes that may predispose them to develop disease? Is it possible to predict which individuals may have adverse reactions to drug regimes?) and evolutionary biology (How is genetic variation in complex traits maintained in the face of selection which should erode this variation?).
In our lab we use the elite model genetic organism Drosophila melanogaster to answer fundamental questions about the molecular genetics of complex traits. Drosophila is an excellent model system because, (1) complete genome sequences are available for D. melanogaster and several closely-related species, (2) sophisticated genetic tools are available for Drosophila, and (3) flies can be easily/rapidly cultured in the laboratory, allowing us to carry out powerful experiments on a massive scale. We also implement empirical high-throughput technologies to allow us to collect vast genetic polymorphism (SNP - Single Nucleotide Polymorphism) datasets, and use computationally intensive analytical approaches to examine the relationship between phenotype and genotype.
Current projects in the lab include association mapping of Drosophila bristle number (a model quantitative trait), developing novel methodologies for genetic mapping, and QTL (Quantitative Trait Locus) mapping of morphological traits distinguishing Drosophila species.
- Genetics of complex traits
- Genome biology
- Drosophila quantitative genetics
Najarro, M. A, Hackett, J. L, Smith, B. R, Highfill, C. A, King, E. G, Long, A. D, & Macdonald, S. J (2015). Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila. PLoS genetics, 11(11), e1005663. DOI:10.1371/journal.pgen.1005663
Marriage, T. N, King, E. G, Long, A. D, & Macdonald, S. J (2014). Fine-mapping nicotine resistance Loci in Drosophila using a multiparent advanced generation inter-cross population. Genetics, 198(1), 45-57. DOI:10.1534/genetics.114.162107
Long, A. D, Macdonald, S. J, & King, E. G (2014). Dissecting complex traits using the Drosophila Synthetic Population Resource. Trends in genetics : TIG. DOI:10.1016/j.tig.2014.07.009
King, E. G, Sanderson, B. J, McNeil, C. L, Long, A. D, & Macdonald, S. J (2014). Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity. PLoS genetics, 10(5), e1004322. DOI:10.1371/journal.pgen.1004322
- Hackett JL, X Wang, BR Smith, and SJ Macdonald, 2016 Mapping QTL contributing to variation in posterior lobe morphology between strains of Drosophila melanogaster. PLoS ONE 11: e0162573.
- Highfill CA, GA Reeves, and SJ Macdonald, 2016 Genetic analysis of variation in lifespan using a multiparental advanced intercross Drosophila mapping population. BMC Genetics 17: 113.
- Najarro MA, JL Hackett, BR Smith, CA Highfill, EG King, AD Long, and SJ Macdonald, 2015 Identifying loci contributing to natural variation in xenobiotic resistance in Drosophila. PLoS Genetics 11: e1005663.
- Marriage TN, EG King, AD Long, and SJ Macdonald, 2014 Fine-mapping nicotine resistance loci in Drosophila using a multiparent advanced generation intercross population. Genetics 198: 45–57.
- King EG, BJ Sanderson, CL McNeil, AD Long, and SJ Macdonald, 2014 Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity. PLoS Genetics 10: e1004322.
- King EG, CM Merkes, CL McNeil, SR Hoofer, S Sen, KW Broman, AD Long, and SJ Macdonald, 2012 Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource. Genome Research 22: 1558–1566.
- McNeil CL, CL Bain, and SJ Macdonald, 2011 Multiple quantitative trait loci influence the shape of a male-specific genital structure in Drosophila melanogaster. G3: Genes, Genomes, Genetics 1: 343–351.
- Macdonald SJ, Long AD. Joint estimates of quantitative trait locus effect and frequency using synthetic recombinant populations of Drosophila melanogaster. Genetics 2007; 176(2):1261–81.
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