Phenomic analysis of the murine hippocampus

描述（由申请人提供）：小鼠和人类基因组现已测序，但将基因与功能联系起来的任务才刚刚开始。我们将把联合收割机和新技术结合起来，作为一种将基因位点与功能联系起来的通用方法，也作为一种将不同功能相互联系起来的方法。建议的项目取决于存在的资源，已产生的小鼠遗传学家在过去的世纪，包括众多的近交系，重组近交系（RI），同源，和同类品系。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尚未开发。在这个项目中，我们将利用这种遗传多样性来开始定义构成“海马表型”的一组特征，即，这可以被称为海马体“现象组”。我们称这种方法为“表型分析”。“该项目将重点关注涉及成年神经发生和海马形态和发育中的品系间变异的特征。一般策略将是：1）鉴定在一组近交系中变化的多个遗传性状，并使用网络构建（即，一种由统计方法和数据可视化技术的集合组成的新方法）来产生关于这些不同性状之间的潜在关系的假设（具体目标1）; 2）利用现有的小鼠遗传资源，即，RI品系和同源体品系，以测试从网络分析产生的假设，并同时定位负责所鉴定的性状的遗传基因座（具体目标2）;和3）确定从成年动物中鉴定的性状的网络分析鉴定为显著和/或可能相关的性状的发育基础（具体目标3）。正如初步结果中所描述的，我们在这些步骤中的每一步都取得了一些进展，很明显，我们将能够同时研究和绘制许多遗传性状。这种“中等通量”的方法实际上提供了海马结构、功能和发育的遗传解剖

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