Complex trait analysis in yeast

Most of our knowledge of how sequence variants affect phenotype is based on the study of traits and diseases that are conditioned by single genes. However in nature, only a small proportion of the diversity in a population can be attributed to single gene variants. The vast majority of phenotypic variation results from multiple genetic and or environmental influences. Since the phenotypes themselves are often quantitative and their inheritance follows non-Mendelian or complex patterns identifying the underlying genes has been difficult.
We developed a new approach to quantitative trait dissection named reciprocal hemizygosity analysis that successfully identified 4 genes involved in high-temperature growth and 3 genes involved in sporulation efficiency in yeast. Our goal is to further apply and develop this technology to identify additional genetic variants for quantitative traits to achieve the most comprehensive genetic description of a quantitative trait achieved to date.

Personnel

Lars Steinmetz
Michelle Nguyen
Raquel Kuehn
Adam Deutschbauer
Patrick Flaherty
Ulrich Schlecht
Ronald W. Davis

Relevant publications:

  • Sequential elimination of major-effect contributors identifies additional quantitative trait Loci conditioning high-temperature growth in yeast. Sinha H, David L, Pascon RC, Clauder-Münster S, Krishnakumar S, Nguyen M, Shi G, Dean J, Davis RW, Oefner PJ, McCusker JH, Steinmetz LM. Genetics. 2008 Nov;180(3):1661-70. Epub 2008 Sep 9. [PubMed]
  • Complex genetic interactions in a quantitative trait locus. Sinha H, Nicholson BP, Steinmetz LM, McCusker JH. PLoS Genet. 2006 Feb;2(2):e13. Epub 2006 Feb 3. [PubMed], [Publisher Full Text]
  • Quantitative trait loci mapped to single-nucleotide resolution in yeast. Deutschbauer AM, Davis RW. Nat Genet. 2005 Dec;37(12):1333-40. Epub 2005 Nov 6. [PubMed]
  • Dissecting the architecture of a quantitative trait locus in yeast. Steinmetz LM, Sinha H, Richards DR, Spiegelman JI, Oefner PJ, McCusker JH, Davis RW. Nature. 2002 Mar 21;416(6878):326-30. [Publisher Full Text]
 
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