FUNCTIONAL MAP OF THE YEAST GENOME

1996年4月完成的酵母基因组测序开启了全基因组探索基因功能的时代。该项目的目标是制作一个详细的酵母基因组“功能图”。 许多功能属性可以自然地映射到基因组序列提供的框架上。 总体目标是将任何可能有助于理解基因组的信息映射到这个框架上，并理解基因组序列中的静态信息如何在生物体中产生生命。 大多数拟议的工作依赖于几年前在本实验室开发的DNA微阵列技术，该技术为在全基因组基础上研究基因和DNA序列的不同特性提供了方便、通用和经济的工具。 设想了三个主要项目：1。全球基因表达计划的全面调查。 将确定数千种条件对每个酵母基因表达的影响，包括不同的环境和遗传干扰以及内源性遗传程序。 本研究将对酵母基因组中每个可能的调控基因所调控的靶基因进行系统的研究。 计算工具，已经在开发中，将被用来从每个基因的表达模式的功能推断，并确定候选人的顺式调控元件，占观察到的表达模式。 2.一个详细的地图，在体内模式的蛋白质结合到酵母基因组将开发。3.将开发一种新的基于微阵列的方法，用于在基因组规模上分析显性突变的后果。 这一程序将首先应用于定义的后果，每个酵母基因的过表达的健身在一组不同的选择性条件。 在这项工作的整个过程中，我们将继续我们正在进行的努力，发明和发现新的方法来使用DNA微阵列技术和其他实验方法来探索基因组。

The completion of the yeast genome sequence in April 1996 inaugurated the era of genome-wide exploration of gene function. The goal of this project is to produce a detailed "functional map" of the yeast genome. A great many functional attributes can naturally be mapped onto the framework that the genome sequence provides. The overarching goal is to map onto this framework any kind of information that might be useful in understanding the genome, and understanding how the static information in the genome sequence comes to life in the living organism. Most of the proposed work relies on the DNA microarray technology that was developed in this laboratory a few years ago, which provides a convenient, versatile and economical tool for investigating diverse properties of genes and DNA sequences on a genome-wide basis. Three principal projects are envisioned: 1. A comprehensive survey of global gene expression programs. The effects on expression of every yeast gene of thousands of conditions, including diverse environmental and genetic perturbations as well as endogenous genetic programs, will be determined. A systematic survey will be conducted, aimed at identifying the target genes regulated by each putative regulatory gene in the yeast genome. Computational tools, already under development, will be used to draw inferences of function from the patterns of expression of each gene, and to identify candidate cis-regulatory elements that account for the observed expression patterns. 2. A detailed map of the in vivo pattern of protein binding to the yeast genome will be developed. 3. A new microarray-based method for analyzing the consequences of dominant mutations on a genomic scale will be developed. This procedure will be applied initially to define the consequences of overexpression of each yeast gene on fitness under a diverse set of selective conditions. Throughout the course of this work, we will continue our ongoing efforts to invent and discover new ways to use DNA microarray technology and other experimental approaches to explore the genome.