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.
| Muller, L A H; Lucas, J E; Georgianna, D R et al. (2011) Genome-wide association analysis of clinical vs. nonclinical origin provides insights into Saccharomyces cerevisiae pathogenesis. Mol Ecol 20:4085-97 |
| Muller, Ludo A H; McCusker, John H (2011) Nature and distribution of large sequence polymorphisms in Saccharomyces cerevisiae. FEMS Yeast Res 11:587-94 |
| Esberg, Anders; Muller, Ludo A H; McCusker, John H (2011) Genomic structure of and genome-wide recombination in the Saccharomyces cerevisiae S288C progenitor isolate EM93. PLoS One 6:e25211 |
| Muller, Ludo A H; McCusker, John H (2009) Microsatellite analysis of genetic diversity among clinical and nonclinical Saccharomyces cerevisiae isolates suggests heterozygote advantage in clinical environments. Mol Ecol 18:2779-86 |
