MOLECULAR STUDIES IN NONSYNDROMIC CLEFT LIP AND PALATE

描述（改编自研究者摘要）：具体目的 本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 有/无腭裂（NSCLP）。 NSCLP是最常见的 出生缺陷的发生率约为千分之一。 这种疾病的病因一直不清楚，虽然最近有 是遗传病因学的证据 申请人报告了证据 17例家族性NSCLP与19号染色体BCL 3基因连锁 39个家庭，并指出，她是在一个独特的位置， 因为她的实验室已经描述了60个家庭的特征， NSCLP，基因组作图技术现已成熟， 已经鉴定了许多生物学相关的候选基因。 本申请描述了旨在鉴定 新的多重和简单的家庭与NSCLP，并绘制遗传图谱 使用候选基因方法和基因组方法引起NSCLP的基因座 基于PCR标记的Weber-CHLC筛选集的广泛方法 （第8版）。 该计划是研究至少42个候选基因， 可能在颅面胚胎发育中起作用， 格言标记。 非周长和周长统计方法 将用于优化连锁检测和候选标记 基因是要识别的。 家庭研究将进行测试，以确认 或排除两个不同种族群体的联系。 之一 目的是跟踪先前的数据，其中17个家庭与 BCL基因座，通过在以下子集中的BCL 3处进行突变分析： 有证据表明唇腭裂与BCL 3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.