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ANALYSIS OF GENETICALLY & ENVIRONMENTALLY OVERLAPPING YEAST QUANTITATIVE TRAITS

$349,638R01FY2010GMNIH

Duke University, Durham NC

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Abstract

DESCRIPTION (provided by applicant): Broad long-term objectives: The broad long-term objectives of this work are to improve our understanding of quantitative traits/genetics and genetic diversity, focusing on specific quantitative traits in S. cerevisiae. Improved understanding of quantitative traits requires better understanding of transcriptional/translational regulation, pleiotropy, phenotypic heterogeneity, and gene-environment interactions, all of which are addressed in this proposal. Specific Aims: Specific Aim 1 of this work is to identify in S. cerevisiae quantitative trait loci, quantitative trait genes/nucleotides controlling high temperature growth, mitochondrial genome maintenance, sporulation and flocculation. Specific Aim 2 of this work is to identify the targets and interactors of two of our high temperature growth quantitative trait genes, MKT1 and SSD1 that are translational regulators. Specific Aim 3 of this work is to assess the contributions of our quantitative trait genes in multiple genetic backgrounds. Relevance: The understanding of quantitative traits requires better understanding of transcriptional/translational regulation, pleiotropy, phenotypic heterogeneity, and gene-environment interactions. The health relatedness of this project is two-fold. First, most of the genetically based disease burden in humans is quantitative in nature. Therefore, an improved understanding of quantitative traits in a simple eukaryote such as yeast will aid the understanding of quantitative traits in humans. Second, S. cerevisiae is an emerging opportunistic pathogen and virulence is a quantitative trait. Therefore, an improved understanding of quantitative traits will aid our understanding of how a harmless commensal/saprophytic yeast can become an opportunistic pathogen.

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