dSLAM analysis of genome-wide genetic interactions in Saccharomyces cerevisiae

Xuewen Pan, Daniel S. Yuan, Siew Loon Ooi, Xiaoling Wang, Sharon Sookhai-Mahadeo, Pamela Meluh, Jef D. Boeke

Research output: Contribution to journalArticle

Abstract

Analysis of genetic interactions has been extensively exploited to study gene functions and to dissect pathway structures. One such genetic interaction is synthetic lethality, in which the combination of two non-lethal mutations leads to loss of organism viability. We have developed a dSLAM (heterozygote diploid-based synthetic lethality analysis with microarrays) technology that effectively studies synthetic lethality interactions on a genome-wide scale in the budding yeast Saccharomyces cerevisiae. Typically, a query mutation is introduced en masse into a population of ∼6000 haploid-convertible heterozygote diploid Yeast Knockout (YKO) mutants via integrative transformation. Haploid pools of single and double mutants are freshly generated from the resultant heterozygote diploid double mutant pool after meiosis and haploid selection and studied for potential growth defects of each double mutant combination by microarray analysis of the "molecular barcodes" representing each YKO. This technology has been effectively adapted to study other types of genome-wide genetic interactions including gene-compound synthetic lethality, secondary mutation suppression, dosage-dependent synthetic lethality and suppression.

Original languageEnglish (US)
Pages (from-to)206-221
Number of pages16
JournalMethods
Volume41
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Compound-gene interactions
  • Genetic interaction
  • Genome-wide analysis
  • Microarrays
  • Molecular barcodes
  • Synthetic lethality

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Pan, X., Yuan, D. S., Ooi, S. L., Wang, X., Sookhai-Mahadeo, S., Meluh, P., & Boeke, J. D. (2007). dSLAM analysis of genome-wide genetic interactions in Saccharomyces cerevisiae. Methods, 41(2), 206-221. https://doi.org/10.1016/j.ymeth.2006.07.033