MOLECULAR STUDIES IN NONSYNDROMIC CLEFT LIP AND PALATE

描述(改编自《调查员摘要》)：具体目的 这项提案中描述的研究之一是定义分子 导致或易患非综合征性唇裂的机制 伴/不伴腭裂(NSCLP)。NSCLP是最常见的 出生缺陷，发病率约为每1000名活产儿中就有一名。 这种疾病的病因尚不清楚，尽管最近有 是遗传病因学的证据。申请人已报告证据 家族性非小细胞肺癌与19号染色体上bcl3基因连锁分析 39个家庭，并表示她处于一个独特的位置 完成目标，因为她的实验室已经确定了60个家庭的特征 NSCLP，基因组图谱的技术现在已经成熟，并且 已经确定了一些与生物相关的候选基因。 目前的申请描述了旨在识别 NSCLP新的多重和简单家系的遗传图谱 用候选基因和基因组两种方法检测引起NSCLP的基因座 基于PCR的Weber-CHLC标记筛选集的广泛方法 (版本8)。该计划是研究至少42个候选基因，这些基因可能 可能在头面部胚胎发生中起作用，以及随机 基因组标记。非子宫内膜异位症和子宫内膜异位症统计方法 将用于优化候选基因的连锁检测和标记 基因将被识别出来。家庭研究将进行测试，以确认 或者排除两个不同种族人群中的联系。其中一个 目标是跟进之前的数据，其中17个家庭与 通过在BCL3的子集中进行突变分析来检测BCL基因座 有证据表明唇腭裂与bcl3相关的家庭。

DESCRIPTION (Adapted from investigator's Abstract): The specific aim of the investigations described in this proposal is to define molecular mechanisms that cause, or predispose, to non-syndromic cleft lip with/without cleft palate (NSCLP). NSCLP is one of the most common birth defects with a prevalence of approximately 1 in 1000 live births. The etiology of this disorder has been unclear although recently there is evidence of genetic etiology. The applicant has reported evidence of linkage between familial NSCLP and BCL3 gene on chromosome 19 in 17 of 39 families, and states that she is in a unique position to accomplish the goals because her lab has characterized 60 families with NSCLP, the technology for genomic mapping is now mature, and that a number of biologically relevant candidate genes have been identified. The current application describes experiments aimed at identification of new multiplex and simples families with NSCLP, and to map genetic loci causing NSCLP using both candidate gene approaches and a genome wide approach with the Weber-CHLC screening set of PCR based markers (version 8). The plan is to study at least 42 candidate genes that may possibly have a role in craniofacial embryogenesis as well as random gnomic markers. Both non-perimetria and perimetria statistical methods will be used to optimize linkage detection and markers of candidate genes are to be identified. Family studies will be tested to confirm or exclude linkage in two ethnically diverse populations. One of the aims is to follow up on prior data in which 17 families were linked to the BCL locus by performing mutation analysis at BCL3 in the subset of families with evidence of linkage with cleft lip and palate to BCL3.