BIOINFORMATICS OF A GENE INTERACTION MAP

描述（由申请人提供）：基因功能通常被其他基因掩盖或修饰。这种“基因相互作用”最引人注目的例子是那些导致细胞死亡（“合成致死”）的基因相互作用，因为这些基因相互作用通常表明在生命生理系统的结构中存在平行或冗余的途径。我们的目标是构建一个全面的地图合成致死基因的相互作用在酵母，生物体的合成致死性的遗传筛选是最高度发达的。携带确定的缺失突变的细胞群体在第二个确定的基因座处被系统地突变，并且使用微阵列平行地评估所产生的双突变体的活力。该提案描述了（1）测试一种新的微阵列设计，以提高我们实验结果的精度，以及（2）开发一个对象数据库，以便于在多个抽象层次上访问我们的功能基因组数据。该项目最终将产生的基因相互作用的分类是研究所有多基因性状的基础，并将为描述人类疾病中常见遗传变异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.