Nature Genetics 37, 1333 - 1340 (2005)
Published online: 6 November 2005; | doi:10.1038/ng1674
Quantitative trait loci mapped to single-nucleotide resolution in yeastAdam M Deutschbauer1, 2
& Ronald W Davis1, 21
Department of Biochemistry, Stanford University School of Medicine, Stanford, California, 94305, USA. 2
Stanford Genome Technology Center, Palo Alto, California, 94304-1103, USA.
Correspondence should be addressed to Adam M Deutschbauer AMDeutschbauer@lbl.gov or Ronald W Davis dbowe@stanford.edu 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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