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Trends Genet. 2006 Jan;22(1):56-63. Epub 2005 Nov 23.

Global synthetic-lethality analysis and yeast functional profiling.

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High Throughput Biology Center, Institute of Genetic Medicine, Department of Biostatistics, Johns Hopkins University School of Medicine, 339 Broadway Research Building, 733 North Broadway, Baltimore, MD 21205, USA.


The Saccharomyces genome-deletion project created >5900 'molecularly barcoded' yeast knockout mutants (YKO mutants). The YKO mutant collections have facilitated large-scale analyses of a multitude of mutant phenotypes. For example, both synthetic genetic array (SGA) and synthetic-lethality analysis by microarray (SLAM) methods have been used for synthetic-lethality screens. Global analysis of synthetic lethality promises to identify cellular pathways that 'buffer' each other biologically. The combination of global synthetic-lethality analysis, together with global protein-protein interaction analyses, mRNA expression profiling and functional profiling will, in principle, enable construction of a cellular 'wiring diagram' that will help frame a deeper understanding of human biology and disease.

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