Gene function is often obscured or modified by other genes. The most dramatic examples of such """"""""gene interactions"""""""" are those that result in cell death (""""""""synthetic lethality""""""""), since these often signal the existence of parallel or redundant pathways in the architecture of a vital physiological system. Our goal is to construct a comprehensive map of synthetic lethal gene interactions in yeast, the organism for which genetic screens for synthetic lethality are most highly developed. Populations of cells carrying defined deletion mutations are being systematically mutated at a second defined locus, and the viability of the resulting double mutants is being assessed in parallel using microarrays. This proposal describes (1) the testing of a novel microarray design for sharpening the precision of our experimental results, and (2) the development of an object database for facilitating access to our functional genomic data across multiple levels of abstraction. The classification of gene interactions that will eventually emerge from this project is fundamental to the study of all polygenic traits and will provide an improved basis for characterizing the roles of common genetic variants in human disease.
| Yuan, Daniel S; Irizarry, Rafael A (2006) High-resolution spatial normalization for microarrays containing embedded technical replicates. Bioinformatics 22:3054-60 |
| Pan, Xuewen; Yuan, Daniel S; Xiang, Dong et al. (2004) A robust toolkit for functional profiling of the yeast genome. Mol Cell 16:487-96 |
