Phenomic analysis of the murine hippocampus

小鼠海马的表型分析

• 批准号: 7058197
• 负责人: Richard S Nowakowski
• 金额: $ 35.11万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058197
• 关键词: bioinformatics; biotechnology; brain morphology; computational biology; developmental neurobiology; functional /structural genomics; gene expression; genetic mapping; genetic strain; hippocampus; laboratory mouse; microarray technology; neurogenesis; neurogenetics; phenotype; statistics /biometry

DESCRIPTION (provided by applicant): The mouse and human genomes have now been sequenced, but the task of linking genes to functions is just beginning. We will combine old and new technologies as a generalized method of linking genetic loci to functions and also as a method of linking disparate functions to each other. The proposed project depends on the existence of resources that have been produced by mouse geneticists over the past century, including the numerous inbred, recombinant inbred (RI), consomic, and congenic strains. These resources are a rich source of genetic diversity that remains essentially untapped for studies of the central nervous system. In this project we will exploit this genetic diversity to begin to define the set of traits that comprise the "hippocampal phenotype," i.e., what might be termed the hippocampal "phenome." We call this approach a "phenomic analysis." This project will focus on traits that involve inter-strain variation in adult neurogenesis and in hippocampal morphology and development. The general strategy will be to: 1) Identify multiple genetic traits that vary among a set of inbred strains and to use network construction (i.e., a novel approach consisting of a collection of statistical methods and data visualization techniques) to generate hypotheses about the potential relationships among these diverse traits (Specific Aim 1); 2) exploit existing mouse genetic resources, i.e., RI strains and consomic strains, to test the hypotheses generated from the network analysis and simultaneously to map the genetic loci responsible for the identified traits (Specific Aim 2); and 3) to determine the developmental basis for the traits identified as significant and/or possible related from the network analysis of the traits identified in adult animals (Specific Aim 3). As described in Preliminary Results, we have made some progress towards each of these steps, and it is clear that there are numerous genetic traits that we will be able to study and map simultaneously. This "moderate throughput" approach, in effect, provides a genetic dissection of hippocampal structure, function, and development

描述（由申请人提供）：现在已经对小鼠和人类基因组进行了测序，但是将基因与功能联系起来的任务才刚刚开始。我们将将旧技术和新技术结合在一起，作为将遗传基因座与函数联系起来的广义方法，也将彼此之间的不同功能联系起来。拟议的项目取决于小鼠遗传学家在过去一个世纪中产生的资源的存在，包括众多近交，重组的近交（RI），康斯综合菌株和与众菌株。这些资源是遗传多样性的丰富来源，对于中枢神经系统的研究，基本上仍未开发。在这个项目中，我们将利用这种遗传多样性开始定义构成“海马表型”的一组特征，即可能称为海马“现象”。我们称这种方法为“现象分析”。该项目将重点放在涉及成人神经发生以及海马形态和发育中的紧密差异的特征上。一般策略将是：1）确定在一组近交菌株之间变化的多种遗传特征，并使用网络构建（即，一种由统计方法和数据可视化技术集合组成的新方法）来产生有关这些多样性性质之间潜在关系的假设（特定目标1）； 2）利用现有的小鼠遗传资源，即RI菌株和综合菌株，以同时测试网络分析产生的假设，以绘制负责确定性状的遗传基因座（特定目标2）； 3）确定与成年动物中鉴定的性状的网络分析相关的特征的发展基础（特定目标3）。如初步结果中所述，我们在每个步骤中都取得了一些进步，很明显，我们将能够同时研究和映射许多遗传特征。实际上，这种“中等吞吐量”方法提供了海马结构，功能和发育的遗传解剖