Causes and consequences of regulatory genetic variation

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Project Summary / Abstract Genetic variation among individuals shapes important phenotypes, including the risk for common human diseases. In particular, regulatory genetic variation causes inter-individual differences in gene expression. The resulting gene expression differences account for a substantial portion of variation in many genetically complex traits. In spite of the critical importance of regulatory variation, many fundamental questions remain open. A particularly critical open question is that we only have a crude understanding of how the differences in gene expression that result from regulatory variation affect organismal phenotypes. This question is a key focus of the research program funded by the parent award for this equipment supplement. Under the parent award, research in my laboratory addresses these critical gaps in knowledge. Our work combines computational biology, quantitative and statistical genetics with experimental genome-wide approaches. We use the yeast Saccharomyces cerevisiae as a powerful and tractable model system for regulatory variation. This equipment supplement removes a critical roadblock in our research program. In our work, we construct libraries of thousands of strains. This award will support the purchase of a high-throughput phenotyping platform that will enable us to rigorously collect trait data from these strains. These data will allow us link genotype and phenotype rapidly and with quantitative precision. The requested instrument is in service of our long-term vision to improve our understanding of regulatory variation to the point at which it becomes possible to accurately predict the consequences of the DNA variants in an individual’s genome. This ability will be valuable for fundamental research and personalized approaches for improving human health.