BIOINFORMATICS OF A GENE INTERACTION MAP

描述(申请人提供)：基因功能经常被其他基因遮盖或修改。这种“基因相互作用”最戏剧性的例子是那些导致细胞死亡(“合成致命性”)的例子，因为这些通常表明在一个重要的生理系统的结构中存在平行或冗余的通路。我们的目标是构建酵母中合成致死基因相互作用的综合图谱，酵母是对合成致死基因筛查最发达的生物。携带已定义的缺失突变的细胞群体正在第二个已定义的位置被系统地突变，所产生的双突变体的生存能力正在使用微阵列进行平行评估。这项建议描述了(1)测试一种新的微阵列设计，以提高我们实验结果的精确度，以及(2)开发一个目标数据库，以促进对我们跨多个抽象级别的功能基因组数据的访问。这个项目最终将出现的基因相互作用的分类是研究所有多基因特征的基础，并将为确定常见基因变异在人类疾病中的作用提供更好的基础。

DESCRIPTION (provided by applicant): 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.