Genetic dissection of complex quantitative traits in yeast

• Applicant: Professor Lars Steinmetz, Ph.D.
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5434714

We propose to identify major effect genes underlying two quantitative traits in yeast, one of high-temperature growth and another of growth on non-fermentable carbon sources, using genome-wide mapping and our newly developed approach of reciprocal hemizygosity analysis. The identification of the genes underlying complex quantitative traits has been extremely difficult. The development of new genomic technologies however promises advances. Our first application of functional genomic technologies to the dissection of a quantitative trait of high temperature growth, uncovered an unexpectedly complex genetic architecture with three quantitative trait genes in an single 32-kb mapped interval. Now, using backcross lines and microarray analysis we will identify additional QTLs. We will finemap QTLs and then test mapped intervals by sequence analysis, expression analysis and reciprocal hemizygosity analysis genome-wide in the absence of linkage information. Theses approaches applied to patient-derived clinical isolates of yeast for the above mentioned traits will identify genes relevant to the pathogenesis of fungi. Knowledge about the genetic architecture of complex quantitative traits gained by this study will also provide information needed to approach complex genetic diseases in humans.

• DFG Programme: Independent Junior Research Groups