Abstract
Identifying the genetic variation underlying quantitative trait loci remains problematic. Consequently, our molecular understanding of genetically complex, quantitative traits is limited. To address this issue directly, we mapped three quantitative trait loci that control yeast sporulation efficiency to single-nucleotide resolution in a noncoding regulatory region (RME1) and to two missense mutations (TAO3 and MKT1). For each quantitative trait locus, the responsible polymorphism is rare among a diverse set of 13 yeast strains, suggestive of genetic heterogeneity in the control of yeast sporulation. Additionally, under optimal conditions, we reconstituted ∼92% of the sporulation efficiency difference between the two genetically distinct parents by engineering three nucleotide changes in the appropriate yeast genome. Our results provide the highest resolution to date of the molecular basis of a quantitative trait, showing that the interaction of a few genetic variants can have a profound phenotypic effect.
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Acknowledgements
We thank L. David, J. Dean, C. Nislow, G. Giaever, K. Gurley, W. Lee, L. Steinmetz, M. Drmanac and D. Richards for assistance and discussions. This work was supported by a National Human Genome Research Institute grant (to R.W.D.).
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Supplementary information
Supplementary Fig. 1
Inheritance of congenic strains. (PDF 301 kb)
Supplementary Fig. 2
RME1 allelic exchange. (PDF 186 kb)
Supplementary Fig. 3
TAO3 allelic exchange. (PDF 186 kb)
Supplementary Fig. 4
Phenotyping yeast sporulation efficiency. (PDF 166 kb)
Supplementary Table 1
Strain list. (PDF 119 kb)
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Deutschbauer, A., Davis, R. Quantitative trait loci mapped to single-nucleotide resolution in yeast. Nat Genet 37, 1333–1340 (2005). https://doi.org/10.1038/ng1674
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DOI: https://doi.org/10.1038/ng1674
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