Complex Traits in Yeast Many phenotypes in nature, including human diseases, result from interactions between multiple genes. In contrast to Mendelian traits, the molecular bases of complex traits have been difficult to unravel. We have two goals: to know the number and types of polymorphisms causing natural phenotypic variation, and to understand the molecular basis of genetic interactions (epistasis). As a complement to the large international consortiums focused on humans (eg. The HapMap Project, The SNP Consotium), we are using yeast as a model system to study the genetic basis of complex traits. We have a collection of natural isolates of S. cerevisiae that show quantitative differences in the efficiencies to which they sporulate (undergo meiosis). To rapidly analyze variation in this trait, we developed a reporter gene that fluoresces only in cells that have undergone sporulation (shown at right). Like many variable human phenotypes, this quantitative trait is polygenic and displays the hallmarks of epistasis. We are using a combination of functional genomics and quantitative genetics to identify the naturally occurring sequence polymorphisms causing differences in sporulation efficiency. We hope to gain an understanding of the genetic architecture of this trait that is sufficient to quantitatively predict the effects of allelic combinations we have not previously observed.