MAPPING NONSYNDROMIC CLEFT LIP AND PALATE GENETIC LOCI

描述（由申请人提供）：非综合征性唇腭裂（NSCLP）是一种常见的出生缺陷，每年在美国影响约4，000名新生儿，在全球影响100万名新生儿。多学科方法改善了对这些儿童的照顾，但长期问题仍然存在，与面部畸形和言语障碍有关。医疗保健费用很高。许多研究支持NSCLP是一种复杂疾病的观点，遗传因素在其发展中起着重要的病因作用。现在的挑战是确定NSCLP基因座。为了实现这一目标，我们已经积累了一系列的多重家庭和简单的三人组，我们采用了候选基因和基因组扫描方法的组合，成功地确定了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，在8号染色体上鉴定出一个20 cM的区域，最大LOD得分为2.84。在这些持续的研究中，我们将进一步完善已鉴定的染色体区域，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重奏，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，用于确证性研究。最后，我们将在资助周期的第三年提交我们扩大的样本集进行高密度基因组扫描。本研究的结果将提供鉴定导致NSCLP表型的基因所必需的数据。高风险基因型的识别可以导致在选定的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.