Yeast Genetics and Molecular Biology 2000
University of Washington
Seattle, Washington USA
July 2000

Name: Steinmetz, Lars
Mailing Address: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA
Email Address: larsms@leland.stanford.edu
Phone & FAX numbers: (650) 723-6287 & (650) 725-6044

#052

Genome-wide mapping of alleles underlying the multigenic high-temperature-growth phenotype of a pathogenic isolate of yeast.
Lars Steinmetz (1), Daniel Richards (1), John McCusker (2), Kevin White (3), Jamie Spiegelman (3), Peter Oefner (3), Ronald Davis (1)
(1) Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA; (2) Department of Microbiology, 3020, Duke University Medical Center, Durham, NC 27710, USA; (3) Stanford Sequencing and Technology Center, 855 California Avenue, Palo Alto, CA 94304, USA

The pathogenicity of clinical S. cerevisiae isolates (Goldstein and McCusker) is probably dependent on their ability to grow at high temperature. However, the complex genetics of high-temperature growth (Htg) have hampered the identification of the underlying genes. By hybridizing total genomic DNA to high-density oligonucleotide arrays, the inheritance of 3714 biallelic markers has been determined for 18 Htg+ segregants derived from a cross between pathogenic (Htg+) and laboratory (Htg-) strains. The high-density genome-wide marker data showed that two chromosomal intervals on chromosomes XIV and XVI co-segregate with the Htg+ phenotype 96% and 67%, respectively. Additional markers, identified and scored in 104 Htg+ segregants by DHPLC, have been used to fine-map the candidate regions to ~15 and ~50 Kb resolution, respectively. Comparison of polymorphism distributions in the chrXIV interval among independent clinical isolates demonstrated a larger number of shared missense mutations than shared non-coding polymorphisms. The strong association of these mutations with the Htg trait suggests that they may account for a significant proportion of the phenotype. Competition experiments with different dominant drug resistance plasmids are being employed to demonstrate the phenotypic contribution of independent mutations within the chrXIV interval. Ultimately, the dissection of complex traits in yeast will serve as a model for understanding complex traits in other organisms.

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