Genetic interactions underlie all biology, including complex traits such as susceptibility to common human diseases. This proposal to examine genetic interactions globally has simple overarching goals that characterize both the original and renewal proposals.
We aim to determine for each of the -12,500,000 double mutant combinations possible among viable knockout (YKO) mutations in budding yeast, the subset of those pairwise interactions that result in inviability or reduced growth. This set of pair-wise interaction data will allow us to construct a genetic interaction map of the yeast genome. By combining this dataset with other large-scale datasets, in particular protein interaction and transcriptional regulation datasets, we aim to allow the larger community to benefit from thousands of new interactions discovered, and to work with the community to generate a complete description of the """"""""cellular wiring diagram"""""""". In the first phase of the project, now complete, we perfected the needed technology, generated a production protocol, constructed two new complete collections of YKO mutants that will allow the project to be carried out as well as facilitate a multitude of projects in other labs. While other groups have reported limited maps of approximately 2% of the possible synthetic lethal interactions in yeast, those methods are too costly to be applied genome scale. The method we developed during the initial funding period is in production and can be applied genome scale. Thus, to our knowledge, we are the only group that can complete the remaining 98% of the yeast synthetic lethal interaction map. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG002432-05
Application #
7283802
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Feingold, Elise A
Project Start
2002-02-06
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2007
Total Cost
$2,251,157
Indirect Cost
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Darby, Miranda M; Serebreni, Leo; Pan, Xuewen et al. (2012) The Saccharomyces cerevisiae Nrd1-Nab3 transcription termination pathway acts in opposition to Ras signaling and mediates response to nutrient depletion. Mol Cell Biol 32:1762-75
Pan, Xuewen; Reissman, Stefanie; Douglas, Nick R et al. (2010) Trivalent arsenic inhibits the functions of chaperonin complex. Genetics 186:725-34
Li, Fuyang; Dong, Junchao; Pan, Xuewen et al. (2008) Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol Cell 30:325-35
Lin, Yu-yi; Qi, Yan; Lu, Jin-ying et al. (2008) A comprehensive synthetic genetic interaction network governing yeast histone acetylation and deacetylation. Genes Dev 22:2062-74
Peyser, Brian D; Irizarry, Rafael; Spencer, Forrest A (2008) Statistical analysis of fitness data determined by TAG hybridization on microarrays. Methods Mol Biol 416:369-81
Meluh, Pamela B; Pan, Xuewen; Yuan, Daniel S et al. (2008) Analysis of genetic interactions on a genome-wide scale in budding yeast: diploid-based synthetic lethality analysis by microarray. Methods Mol Biol 416:221-47
Pan, Xuewen; Yuan, Daniel S; Ooi, Siew-Loon et al. (2007) dSLAM analysis of genome-wide genetic interactions in Saccharomyces cerevisiae. Methods 41:206-21
Zurita-Martinez, Sara A; Puria, Rekha; Pan, Xuewen et al. (2007) Efficient Tor signaling requires a functional class C Vps protein complex in Saccharomyces cerevisiae. Genetics 176:2139-50
Yuan, Daniel S; Irizarry, Rafael A (2006) High-resolution spatial normalization for microarrays containing embedded technical replicates. Bioinformatics 22:3054-60
Pan, Xuewen; Ye, Ping; Yuan, Daniel S et al. (2006) A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell 124:1069-81

Showing the most recent 10 out of 18 publications