SNP DISCOVERY AND ANALYSIS IN CRANIOFACIAL BIRTH DEFECTS

说明书（改编自申请人的说明书）：本申请 建议使用高通量定位单核苷酸多态性SNP 对从已证实或 与人类出生缺陷有关高通量筛选 一组SNP将首先应用于一组特征良好的亲本- 通过一例非综合征性口面部畸形确定后代三胞胎 裂（OFC），包括唇裂伴或不伴腭裂（CLIP）， 腭裂（CP）使用高通量筛选过程，其次， 非综合征性颅缝早闭患者。这些家长三人组 从单独的研究中提取的口裂或颅缝早闭， 确定与这组常见出生缺陷病因有关的基因 并测试与环境暴露的可能相互作用。这件案子- 这里提出的亲本三重设计在存在连锁的情况下检验连锁 不平衡，以及这些DNA样本在大量 病例亲本三重奏将允许立即测试开发的SNP标记， 这一提案的一部分。在OFC研究之后， 颅缝早闭患者及其父母的SNP筛查 从研究者之前进行的一项研究中， 出生缺陷研究和预防由疾病中心赞助 对照（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).