MAPPING NETWORKS OF GENE INTERACTIONS IN YEAST

绘制酵母基因相互作用网络图

基本信息

批准号：
2896474
负责人：
RONALD A BUTOW
金额：
$ 32.83万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-15 至 2001-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2896474
关键词：
Saccharomyces cerevisiae biological transport biomedical equipment biomedical equipment development fungal genetics gene expression gene interaction genetic mapping microorganism culture nucleic acid hybridization

项目摘要

The overall objective of the proposed research is to identify and map networks of gene interactions in Saccharomyces cerevisiae. The strategy is to identify genes whose mRNA abundance is altered as a consequence of directed gene perturbations; initially, these will be single-gene replacements. The basic method to be used is the hybridization of cDNAs derived from wild-type and experimental strains to arrays of all known and predicted yeast genes. The hybridization signals will be quantified to obtain values of relative gene expression among the different experimental samples. As a model system, we will analyze gene interactions in a complex, poorly understood, interorganelle communication network called the retrograde response, in which changes in the functional state of mitochondria result in changes in expression of a large but unidentified subset of nuclear genes. Four specific aims are proposed: 1) to construct a high throughput microdisplay system, patterned after an existing design, for the analysis of expression of all known and predicted yeast genes; 2) to identify genes and pathways that constitute the retrograde response; 3) to develop general methodology for the identification, analysis and presentation of networks of gene interactions; and 4) to make the technology, reagents and data available to the scientific community. The general methodology will involve tabulation and graphical analysis of the data to obtain, as a long range goal, i) the relative expression value of any given gene in the yeast genome as it samples all viable single-gene replacements, and, as a short term goal, ii) an array of genes organized as nested sets whose expression changes in response to a given single-gene replacement, beginning with known genes in the retrograde response pathways. These studies are aimed at furthering our understanding of polygenic interactions that underlie poorly understood genetic phenomena such as penetrance and quantitative traits.

拟议研究的总体目的是识别和映射酿酒酵母中基因相互作用的网络。策略是为了确定其mRNA丰度而改变的基因定向基因扰动；最初，这些将是单基因替换。要使用的基本方法是CDNA的杂交源自野生型和实验菌株到所有已知的阵列并预测酵母基因。杂交信号将被量化获得不同基因表达的值实验样品。作为模型系统，我们将分析基因在复杂的，鲜为人知的互动中的相互作用通信网络称为逆行响应，其中更改在线粒体的功能状态下导致表达变化核基因的大量但身份不明的子集。四个具体目标提出：1）要构建高吞吐量微型播放系统，在现有设计之后进行了图案，以分析表达所有已知和预测的酵母基因； 2）识别基因和途径构成逆行响应； 3）发展一般识别，分析和呈现的方法基因相互作用网络； 4）为了制作技术，试剂和科学界可用的数据。一般方法将涉及数据的制表和图形分析，以获得，作为一个长距离目标，i）任何给定的相对表达值酵母基因组中的基因，因为它采样了所有可行的单基因替换，作为短期目标，ii）一系列基因组织为嵌套集，其表达在响应A的响应中变化给定单基因替换，从已知基因开始逆行响应途径。这些研究旨在进一步理解多基因相互作用的理解不足遗传现象，例如外渗和定量性状。