CLONING AND CHARACTERIZATION OF THE VAN DER WOUDE GENE

描述（改编自研究者摘要）：唇腭裂（CL/P） 是一种主要的先天性结构异常， 终身发病率和复杂的病因。广泛的心理，外科， 语言和牙齿的参与强调了理解的重要性， 根本原因唇腭裂，像其他复杂的疾病，提供 在确定多个遗传，随机和环境的挑战， 导致其表型的因素。在这份提案中，P.I.将实行 唇腭裂的治疗方法有哪些？ 货车der Woude综合征（VDWS）。VDWS是一个很好的模型， 超过300种综合征形式的CL/P。VDWS是最普遍的综合征 CL/P的形式及其临床表现与非综合征型最相似 班该提案的主要目标是发现结构和 VDWS基因的功能。一个更长远的目标是确定基因-基因， 基因与环境的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。将使用Taqman测定法， 筛选致病微缺失，可能进一步限制该地区 含有VDWS基因的病毒基因发现技术，包括 分析整个600 kb的关键区域，将用于鉴定 转录单位突变筛查将用于发现致病基因 DNA的变化。2)VDWS基因及其小鼠的特性分析 同源物，包括完整的cDNA和基因组序列分析， 时间和组织特异性表达来鉴定发育途径， 需要VDWS基因功能，并筛选基因同源物， 3）鉴定调节VDWS的序列 基因表达和转基因小鼠模型的发展，包括 小鼠基因敲除将用于4）长期研究，包括 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。

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.