COMPARATIVE GENOMIC ANALYSIS OF CARDIOVASCULAR GENE REGU

心血管(CV)系统的障碍通常是由于颞叶或 一组数量较大但有限的基因表达的数量变化。 非编码顺式调控序列在基因调控中起着核心作用 表达和物种间(即人/鼠)基因组序列比较 作为一种快速而准确的手段来识别这种非编码调控 元素。这次PGA的中心目标将是使用比较基因组 首先要确定方法，并确定它们的功能要素 调节影响CV系统的基因的表达。的活动 这个PGA的中心不是发现新的基因，而是使用 比较基因组学以了解顺式调节元件在 CV研究人员已经在研究基因的表达。在这 从基因组角度探索CV基因调控的综合计划，200 人类基因组间隔(=~200BAC)，每个包含一个CV基因(S)，将是 比较有特点的。该计划的组成部分将包括：(1) 获得同源的人/鼠和其他哺乳动物基因组 一组优先排序的CV基因的序列。序列将被访问 来自公共资助的数据库，或由 这个职业高尔夫球协会。(2)心血管比较基因组数据库的建立 它将包含经过广泛注释的人类和老鼠序列，包括 保守的非编码元件在研究得很好的附近的定位 CV基因。(3)全基因组表达谱发现共调控基因 并识别共享的非编码调控元件，通过 种内分析。(4)在保守的非物种中识别SNPs 编码序列，并分析其对Cv基因表达的影响 人类。(5)在基因工程小鼠中分析一组优先的 保守的非编码元件在CV基因表达中的作用。(6) 年为心血管研究人员建立了一个教育项目 基因组数据库和工具的使用。

Disorders of the cardiovascular (CV) system are frequently due to temporal or quantitative changes in the expression of a large, but finite set of genes. Noncoding cis regulatory sequences play a central role in controlling gene expression and inter-species (i.e., human/mouse) genomic sequence comparisons serve as a rapid and accurate means for identifying such noncoding regulatory elements. The central goal of this PGA will be to use a comparative genomic approach first to identify, and them to determine the function of elements regulating the expression of genes affecting the CV system. The activities of this PGA are not centered on the discovery of new genes, but rather upon using comparative genomics to understand the role of cis regulating elements in the expression of genes already being studied by CV researchers. In this integrated program to "genomically" explore the regulation of CV genes, 200 human genomic intervals (=~200 BACs), each containing a CV gene(s), will be comparatively characterized. The components of this program will include: (1) The acquisition of orthologous human/mouse and other mammalian genomic sequence for a set of prioritized CV genes. Sequences will either be accessed from publicly funded databases or generated by the sequencing component of this PGA. (2) The creation of a cardiovascular comparative genomic database that will contain extensively annotated human and mouse sequences including the localization of conserved noncoding elements in proximity to well studied CV genes. (3) Genome-wide expression profiling to discover genes co-regulated with CV genes and identify shared noncoding regulatory elements, through intra-species analysis. (4) The identification of SNPs within conserved non- coding sequences, and analysis of their effect on CV gene expression in humans. (5) Analysis in genetically engineered mice of a prioritized set of the conserved noncoding elements for their role in CV gene expression. (6) The establishment of an educational program for cardiovascular researchers in the use of genomic databases and tools.