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Book Summary:
The budding yeast Saccharomyces cerevisiae has long served as a model eukaryote for molecular biology studies. The work described here takes advantage of yeast functional genomics to address three fundamental biological issues: the prevalence and mechanism of haploinsufficiency, the extent to which gene expression and mutant phenotype are correlated, and the molecular basis of quantitative traits. Using the tagged deletion collection, we measured fitness values for every heterozygous strain to identify all haploinsufficient genes in the yeast genome under standard laboratory conditions. Our analysis of haploinsufficiency indicates that this phenomenon largely results from insufficient protein production rather than the toxic consequences of stoichiometric imbalance among protein complex subunits. In addition to fitness profiling, we report the genome-wide identification of sporulation efficiency mutants via parallel deletion profiling of the homozygous diploid collection. This study represents one of the first whole-genome comparisons of gene expression versus mutant phenotype and reveals a small positive correlation between the two approaches. Finally, I describe efforts to map the genetic determinants underlying a quantitative, complex trait in yeast: sporulation efficiency. Our approach to systematically dissect three quantitative trait loci (QTL) on different chromosomes is relevant to mammalian QTL analysis and the results provide valuable insight into how simple polymorphisms can have a profound phenotypic effect. |
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