MAPPING NONSYNDROMIC CLEFT LIP AND PALATE GENETIC LOCI

描述(申请人提供)：非综合征性唇腭裂(NSCLP)是一种常见的出生缺陷，每年影响美国约4000名新生儿和全球100万名新生儿。多学科方法改善了对这些儿童的照顾，但长期存在的问题仍然存在，并与面部畸形和语言障碍有关。医疗保健成本很高。大量研究支持NSCLP是一种复杂的疾病，遗传因素在其发展中起着重要的病因学作用。现在的挑战是确定NSCLP基因座。为了实现这一目标，我们已经积累了一批多基因家系和单链三联体，并采用候选基因和基因组扫描相结合的方法成功地识别了12个染色体区域和几个候选基因进行询问。最令人兴奋的是在一个非洲裔美国人大家庭中发现了8号染色体上一个20 cM的区域，最高LOD得分为2.84。在这些持续的研究中，我们将进一步细化已识别的染色体区域，并充分表征我们的候选基因。我们将继续收集非小细胞肺癌家系和单纯非小细胞肺癌三联体，以进一步扩大我们的数据集，并将收集一个基于人群的病例对照数据集，用于验证性研究。最后，我们将在资助周期的第三年将我们的扩展样本集提交给高密度基因组扫描。本研究的结果将为鉴定影响非小细胞肺癌表型的基因(S)提供必要的数据。识别高危基因类型可导致在选定人群中制定预防计划，并可能建议基于基因的预防策略。

DESCRIPTION (provided by applicant): Nonsyndromic cleft lip and palate (NSCLP) is a common birth defect affecting approximately 4,000 newborns each year in the US and a million worldwide. Multidisciplinary approaches have improved the care of these children but long-term problems persist and are related to facial dysmorphism and speech impediments. The health care costs are significant. Numerous studies support the idea that NSCLP is a complex disorder and that genetic factors play an important etiologic role in its development. The challenge now is to identify the NSCLP loci. Towards this goal, we have amassed a collection of multiplex families and simplex trios and we have employed a combination of candidate gene and genome scan approaches to successfully identify 12 chromosomal regions and several candidate genes to interrogate. Most exciting is the identification of a 20cM region on chromosome 8 with a maximum LOD score of 2.84 in a single large African-American family. In these continuing studies, we will further refine the identified chromosomal regions and fully characterize our candidate genes. We will continue to collect NSCLP families and simplex NSCLP trios to further expand our data set and will assemble a population based case-control data set for use in confirmatory studies. Finally we will submit our expanded sample set to a high-density genome scan during the third year of the funding cycle. The results of this study will provide data essential to the identification of the gene(s) contributing to the NSCLP phenotype. Identification of high-risk genotypes can lead to the development of prevention programs in selected populations and may suggest gene-based prevention strategies.