CORE--FUNCTIONAL ANALYSIS /EXPRESSION

核心--功能分析/表达

• 批准号: 6845950
• 负责人: DAVID FITZPATRICK
• 金额: $ 8.29万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845950
• 关键词: British Isles; biomedical facility; cleft lip; cleft palate; developmental genetics; disease /disorder etiology; functional /structural genomics; gene expression; genetic mapping; high throughput technology

Cleft lip and palate is a major birth defect commonly used as a model for complex genetic diseases of human embryogenesis. Our current understanding of the coordination and function of the pathways driving craniofacial development is limited and biased by particular well-studied examples. The ability to integrate site- and stage- specific expression patterns of individual genes in a comprehensive representation of the developing face in model organisms is a critical first step towards dissection of these pathways. The functional analysis/expression core will combine this approach with the recent advances in functional 'knockdown" analysis to assist the projects in examining evidence of non-redundant gene-function during clinically important morphogenetic events. This core will use innovative technologies to provide resources to the other projects and cores of this P50 to enhance the process of gene discovery and improve our understanding of how genes interact in complex pathways that play a role in normal and abnormal facial development. The core will present the resulting data in an intuitive, publicly-accessible manner that can be used for both research and educational purposes. Specific aims will be to: 1. To develop whole-mount RNA in situ hybridization data generated by Projects 0003, 0004, 0005 and Pilot into a 4-dimensional atlas of craniofacial development in mouse embryos. 2. To construct developmental expression profiles for all genes within a human genomic region (9q) with strong evidence of linkage to CL/P. 3. To assess the use of self-organizing maps in predicting candidate genes from transcriptional profiles generated by microarray analysis 4. To determine the function of specific candidate genes in palate development using a high-throughput gene knockdown approach.

唇裂和腭裂是一种主要的出生缺陷，通常用作人类胚胎发生的复杂遗传疾病的模型。我们目前对驱动颅面发育的通路的协调和功能的理解受到特定的充分研究的例子的限制和偏见。将单个基因的位点和阶段特异性表达模式整合到模型生物体发育面孔的综合表示中的能力是剖析这些途径的关键的第一步。功能分析/表达核心将这种方法与功能“击倒”分析的最新进展相结合，以协助项目检查临床重要形态发生事件期间非冗余基因功能的证据。该核心将使用创新技术为这 该 P50 的其他项目和核心旨在增强基因发现过程并改善我们的 了解基因如何在复杂的通路中相互作用，这些通路在正常和异常的面部发育中发挥作用。核心将以直观、可公开访问的方式呈现结果数据， 用于研究和教育目的。具体目标是： 1. 将0003、0004、0005和Pilot项目产生的全RNA原位杂交数据开发成小鼠胚胎颅面发育的4维图谱。 2. 构建人类基因组区域 (9q) 内所有基因的发育表达谱，并提供与 CL/P 关联的有力证据。 3. 评估自组织图谱在根据微阵列分析生成的转录谱预测候选基因中的应用 4. 使用高通量基因敲低方法确定特定候选基因在上颚发育中的功能。