CLONING AND CHARACTERIZATION OF THE VAN DER WOUDE GENE

VAN DER WOUDE 基因的克隆和表征

• 批准号: 6379968
• 负责人: BRIAN C SCHUTTE
• 金额: $ 28.58万
• 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/6379968
• 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（改编自研究者的摘要）：唇腭裂 (CL/P) 是一种主要的先天性结构异常，其显着特征是 终生发病且病因复杂。广泛的心理、外科、 言语和牙科参与强调了理解的重要性 根本原因。与其他复杂疾病一样，唇裂和腭裂会导致 确定多重遗传、随机和环境因素的挑战 导致其表型的因素。在此提案中，P.I.将追求 通过研究遗传形式找出唇裂和腭裂的复杂原因 唇裂、范德沃德综合征 (VDWS)。 VDWS 是一个优秀的模型 超过 300 种 CL/P 综合征形式。 VDWS 是最常见的综合征 CL/P 的形式及其临床表现与非综合征最相似 类。该提案的主要目标是发现结构和 VDWS 基因的功能。更长期的目标是识别基因与基因 基因-环境相互作用。这些目标将通过以下方式实现 实验：1)VDWS基因的鉴定。 Taqman 检测将用于 筛查可能进一步限制该区域的致病微缺失 含有 VDWS 基因。基因查找技术，包括序列 分析整个 600 kb 关键区域，将用于识别 转录单位。突变筛查将用于发现致病因素 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，以确定发育途径 需要 VDWS 基因功能并筛选可能的基因同源物 在同一途径中发挥作用 3) 调节 VDWS 的序列的鉴定 基因表达和转基因小鼠模型的开发，包括 小鼠基因敲除将用于 4) 长期研究，其中包括 互补实验来识别该途径中的其他基因 研究环境因素对 VDWS 基因的影响。