SNP DISCOVERY AND ANALYSIS IN CRANIOFACIAL BIRTH DEFECTS

描述(改编自申请人的描述)：本申请 建议使用高通量来定位单核苷酸多态SNPs 从已证实的Or基因中扩增出的基因组PCR产物的测序 推定与人类先天缺陷有关。对此进行高通量筛选 SNPs小组将首先应用于一组特征良好的亲本- 通过一例非综合征口腔面部病例确诊子女三人组 唇裂(OFC)，包括伴有或不伴有腭裂的唇裂(夹片)和 使用高通量筛查过程的腭裂(CP)，第二个 非综合征性颅缝早闭患者。这些病例父母三人组是 取自对口腔裂或颅缝早闭的单独研究，旨在 确定与这种常见出生缺陷的病因学有关的基因 并测试可能与环境暴露的相互作用。这个案子- 本文提出的亲本三联设计在有联动的情况下进行联动测试 不平衡，以及这些DNA样本在大量 病例-父母三人组将允许立即对SNP标记进行检测 是这项提议的一部分。在OFC研究之后，调查人员将延长 一组颅缝早闭患者及其父母的SNP筛查 来自调查人员之前进行的一项研究 由疾病中心赞助的出生缺陷研究和预防 控制(CDC)。

DESCRIPTION (Adapted from the Applicant's Description): This application proposes to locate single nucleotide polymorphisms SNPs using high throughput sequencing of genomic PCR products amplified from genes with demonstrated or presumed relevance to human birth defects. High throughput screening for this panel of SNPs will be applied first to a well characterized set of parent- offspring trios ascertained through a case with non-syndromic oral-facial clefts (OFC), including cleft lip with or without cleft palate (CLIP) and cleft palate (CP) using a high-throughput screening process, and second to patients with non-syndromic craniosynostosis. These case-parent trios are drawn from separate studies of oral clefts or craniosynostosis designed to identify genes involved in the etiology of this common group of birth defects and test for possible interaction with environmental exposures. The case- parent trio design proposed here tests for linkage in the presence of linkage disequilibrium, and the availability of these DNA samples on a large number of case-parent trios will allow immediate tests for the SNP markers developed as part of this proposal. Following the OFC study the investigators will extend SNP screening to a collection of craniosynostosis patients and their parents from a previous study conducted by the investigators and from the Centers of Birth Defect Research and Prevention sponsored by the Centers for Disease Control (CDC).