SNP DISCOVERY AND ANALYSIS IN CRANIOFACIAL BIRTH DEFECTS

颅面出生缺陷中的 SNP 发现和分析

• 批准号: 6380016
• 负责人: ALAN F SCOTT
• 金额: $ 88.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6380016
• 关键词: cleft lip; cleft palate; clinical research; craniosynostosis; family genetics; genetic disorder diagnosis; genetic polymorphism; genetic screening; high throughput technology; human subject; linkage disequilibriums; linkage mapping; polymerase chain reaction; single strand conformation polymorphism

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).

描述（改编自申请人的描述）：本申请 提议使用高通量定位单核苷酸多态性 SNP 对从已证实或已证实的基因扩增的基因组 PCR 产物进行测序 推测与人类出生缺陷有关。为此进行高通量筛选 SNP 组将首先应用于一组经过充分表征的亲本 通过一例非综合征性口面部病例确定后代三人组 唇裂（OFC），包括伴有或不伴有腭裂的唇裂（CLIP）和 使用高通量筛选过程来检测腭裂 (CP)，其次是 非综合征性颅缝早闭患者。这些案例家长三人组是 来自口腔裂或颅缝早闭的单独研究，旨在 识别与这组常见出生缺陷的病因有关的基因 并测试与环境暴露可能发生的相互作用。该案—— 这里提出的父三重奏设计在存在链接的情况下测试链接 不平衡，以及这些 DNA 样本在大量的可用性 病例-亲本三人组将允许立即测试开发的 SNP 标记 本提案的一部分。 OFC 研究结束后，研究人员将延长 对一批颅缝早闭患者及其家长进行 SNP 筛查 根据研究人员和研究中心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（疾病预防控制中心）。