CORE--FUNCTIONAL ANALYSIS /EXPRESSION

核心--功能分析/表达

• 批准号: 7666244
• 负责人: Michael Lovett
• 金额: $ 8.97万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666244
• 关键词: Advisory Committees; Affect; Animal Model; Atlases; Automobile Driving; Candidate Disease Gene; Clinical; Complex; Congenital Abnormality; Data; Development; Dissection; Embryo; Embryonic Development; Event; Face; Family; Four-dimensional; Genes; Genetic; Genomics; Hereditary Disease; Human; In Situ Hybridization; Individual; Laboratories; Maps; Microarray Analysis; Modeling; Molecular Profiling; Mus; Palate; Pathway interactions; Pattern; Play; Processed Genes; Purpose; RNA; Research; Resources; Role; Site; Staging; TNFRSF5 gene; cleft lip and palate; craniofacial; gene discovery; gene function; improved; innovative technologies; knock-down; programs

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pa裂是一种主要的先天缺陷，通常用作人类胚胎发生复杂遗传疾病的模型。我们目前对推动颅面发育的途径的协调和功能的理解受到了特定的例子的限制和偏见。将单个基因的位点和阶段特定表达模式整合到模型生物体中发育面的全面表示中的能力是迈向这些途径的关键第一步。功能分析/表达核心将将这种方法与功能“敲低”分析的最新进展相结合，以帮助项目检查临床重要的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来为资源提供资源为 该P50的其他项目和核心，以增强基因发现过程并改善我们的 了解基因如何在复杂的途径中相互作用，这些途径在正常和异常面部发育中起作用。核心将以直观的，公共的访问方式呈现结果数据，可以是 用于研究和教育目的。具体目标是： 1。要开发由项目0003、0004、0005生成的原位原位杂交数据，并将驾驶液用于小鼠胚胎中颅面发育的4维地图集。 2。构建人类基因组区域内所有基因（9Q）中所有基因的发育表达谱，并有很强的证据与Cl/p连接。 3。评估自组织图在通过微阵列分析产生的转录曲线预测候选基因中的使用 4。使用高通量基因敲低方法来确定特定候选基因在口感发育中的功能。