Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource

Elizabeth G. King, Chris M. Merkes, Casey L. McNeil, Steven R. Hoofer, Saunak Sen, Karl W. Broman, Anthony D. Long, Stuart J. Macdonald

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Genetic dissection of complex, polygenic trait variation is a key goal of medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, and an inability to identify variants that cumulatively explain the bulk of standing genetic variation in genome-wide association studies (GWAS). Thus, much of the heritability remains unexplained for most complex traits. Here we describe a novel, freely available resource for the Drosophila community consisting of two sets of recombinant inbred lines (RILs), each derived from an advanced generation cross between a different set of eight highly inbred, completely resequenced founders. The Drosophila Synthetic Population Resource (DSPR) has been designed to combine the high mapping resolution offered by multiple generations of recombination, with the high statistical power afforded by a linkage-based design. Here, we detail the properties of the mapping panel of >1600 genotyped RILs, and provide an empirical demonstration of the utility of the approach by genetically dissecting alcohol dehydrogenase (ADH) enzyme activity. We confirm that a large fraction of the variation in this classic quantitative trait is due to allelic variation at the Adh locus, and additionally identify several previously unknown modest-effect trans-acting QTL (quantitative trait loci). Using a unique property of multiparental linkage mapping designs, for each QTL we highlight a relatively small set of candidate causative variants for follow-up work. The DSPR represents an important step toward the ultimate goal of a complete understanding of the genetics of complex traits in the Drosophila model system.

Original languageEnglish (US)
Pages (from-to)1558-1566
Number of pages9
JournalGenome Research
Volume22
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Drosophila
Dissection
Quantitative Trait Loci
Population
Multifactorial Inheritance
Alcohol Dehydrogenase
Chromosome Mapping
Genome-Wide Association Study
Medical Genetics
Genetic Recombination
Enzymes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

King, E. G., Merkes, C. M., McNeil, C. L., Hoofer, S. R., Sen, S., Broman, K. W., ... Macdonald, S. J. (2012). Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource. Genome Research, 22(8), 1558-1566. https://doi.org/10.1101/gr.134031.111

Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource. / King, Elizabeth G.; Merkes, Chris M.; McNeil, Casey L.; Hoofer, Steven R.; Sen, Saunak; Broman, Karl W.; Long, Anthony D.; Macdonald, Stuart J.

In: Genome Research, Vol. 22, No. 8, 08.2012, p. 1558-1566.

Research output: Contribution to journalArticle

King, EG, Merkes, CM, McNeil, CL, Hoofer, SR, Sen, S, Broman, KW, Long, AD & Macdonald, SJ 2012, 'Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource', Genome Research, vol. 22, no. 8, pp. 1558-1566. https://doi.org/10.1101/gr.134031.111
King, Elizabeth G. ; Merkes, Chris M. ; McNeil, Casey L. ; Hoofer, Steven R. ; Sen, Saunak ; Broman, Karl W. ; Long, Anthony D. ; Macdonald, Stuart J. / Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource. In: Genome Research. 2012 ; Vol. 22, No. 8. pp. 1558-1566.
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