CLONING AND CHARACTERIZATION OF THE VAN DER WOUDE GENE

VAN DER WOUDE 基因的克隆和表征

• 批准号: 6027902
• 负责人: BRIAN C SCHUTTE
• 金额: $ 32.3万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6027902
• 关键词: animal genetic material tag; cleft lip; cleft palate; clinical research; congenital oral /facial /cranial defect; developmental genetics; disease /disorder etiology; family genetics; gene complementation; gene environment interaction; gene expression; gene interaction; gene mutation; genetic mapping; genetic screening; genetically modified animals; genotype; high throughput technology; human genetic material tag; human subject; laboratory mouse; molecular cloning; northern blottings; nucleic acid sequence; polymerase chain reaction; single strand conformation polymorphism

DESCRIPTION (Adapted from investigator's abstract): Cleft lip and palate (CL/P) is a major congenital structural anomaly that is notable for significant lifelong morbidity and complex etiology. The extensive psychological, surgical, speech and dental involvement emphasize the importance of understanding the underlying causes. Cleft lip and palate, like other complex diseases, provides a challenge in determining the multiple genetic, stochastic, and environmental factors that lead to its phenotype. In this proposal, the P.I. will pursue the complex causes of cleft lip and palate through investigations of a genetic form of clefting, Van der Woude syndrome (VDWS). VDWS is an excellent model of the more than 300 syndromic forms of CL/P. VDWS is the most prevalent syndromic form of CL/P and its clinical presentation is most similar to nonsyndromic classes. The main goal of this proposal is to discover the structure and function of the VDWS gene. A more long-term goal is to identify gene-gene and gene-environment interactions. These goals will be achieved with the following experiments: 1) Identification of the VDWS gene. A Taqman assay will be used to screen for disease-causing microdeletions that may further restrict the region that contains the VDWS gene. Gene-finding techniques, including the sequence analysis of the entire 600 kb critical region, will be used to identify transcriptional units. Mutation screens will be used to find disease-causing changes in the DNA. 2) Characterization of the VDWS gene and its mouse homologue, including complete cDNA and genomic sequence analysis, the study of temporal and tissue-specific expression to identify developmental pathways that require the VDWS gene function and screens for gene homologues which may function in the same pathway 3) identification of sequences that regulate VDWS gene expression and the development of transgenic mouse models, including a mouse knockout that will be used in 4) long-term studies that will include complementation experiments to identify other genes in the pathway and investigate the effects of environmental factors on the VDWS gene.

描述（根据调查员的摘要改编）：唇唇和味觉（Cl/p） 是一种主要的先天性结构异常，值得注意 终身发病率和复杂的病因。广泛的心理，外科手术， 言语和牙科参与强调了理解的重要性 根本原因。嘴唇和pape裂，与其他复杂疾病一样， 确定多重遗传，随机和环境的挑战 导致其表型的因素。在此提案中，P.I。将追求 通过研究一种遗传形式的复杂原因唇裂和味 Clefting，Van der Woude综合征（VDWS）。 VDWS是 300多种综合征的Cl/p。 VDW是最普遍的综合症 Cl/P及其临床表现的形式与非综合症最相似 课程。该提议的主要目标是发现结构和 VDWS基因的功能。一个更长期的目标是确定基因基因和 基因环境相互作用。这些目标将通过以下 实验：1）VDWS基因的鉴定。塔克人测定将习惯 筛选引起疾病的微缺失，可能进一步限制该地区 其中包含VDWS基因。基因调查技术，包括序列 对整个600 KB关键区域的分析将用于识别 转录单元。突变筛查将用于发现引起疾病的筛查 DNA的变化。 2）VDWS基因及其小鼠的表征 同源物，包括完整的cDNA和基因组序列分析，研究 时间和组织特异性表达以识别发育途径 需要VDWS基因功能和筛选基因同源物 在同一途径中的功能3）识别调节VDW的序列 基因表达和转基因小鼠模型的发展，包括A 鼠标敲除将在4）长期研究中使用 互补实验，以鉴定途径中的其他基因 研究环境因素对VDWS基因的影响。