Screening to Find Genes Causing Cleft Lip and Palate

筛查寻找导致唇裂和腭裂的基因

• 批准号: 7115858
• 负责人: Pieter J. de Jong
• 金额: $ 23.45万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115858
• 关键词: artificial chromosomes; cleft lip; cleft palate; clinical research; comparative genomic hybridization; developmental genetics; family genetics; functional /structural genomics; gene rearrangement; genetic screening; human genetic material tag; human tissue; in situ hybridization

Cleft lip with or without cleft palate (CL/P) are very common structural birth defects. CL/P is predominantly sporadic in occurrence and about 22 percent of patients with facial clefts have a genetic origin. Linkage analysis and/or association studies have allowed narrowing down several candidate regions, but not sufficiently to indicate likely candidate genes for re-sequencing from patients. The goal of this proposal is to survey the genome for candidate regions by searching for micro-deletions/duplications and to compare the relative efficacy of this approach with the more conventional genetic association studies to identify candidate genes for CL/P. Our approach is based on comparative genomic hybridization (CGH) using very-high resolution BAG arrays to screen for genomic segments involved in copy-number changes. The specific aims are to: (1) Perform array CGH from 200 patient DNA samples over 2 years; (2) Identify sporadic deletions/duplications possibly shared between multiple patients; (3) Search for candidate genes from the common deletion region through public databases. (4) Confirm alleged genomic rearrangements in a representative set of samples by fluorescent in situ hybridization of BACs to the chromosomes from patients and parents.

带有或没有裂口的唇裂（Cl/p）是非常常见的结构出生缺陷。 Cl/P的发生主要是零星的，大约22％的面部裂口患者具有遗传来源。连锁分析和/或关联研究使得缩小了几个候选区域，但不足以表明可能从患者重新进行后续进来的候选基因。该提案的目的是通过搜索微缺失/重复来调查候选区域的基因组，并将这种方法的相对疗效与更传统的遗传关联研究进行比较以识别候选人 Cl/p的基因。我们的方法是基于比较基因组杂交（CGH）的方法，该方法使用非常高的分辨率袋阵列来筛选涉及拷贝数变化的基因组段。具体目的是：（1）在2年内从200名患者DNA样本中执行阵列CGH； （2）确定可能在多名患者之间共享的零星缺失/重复； （3）通过公共数据库搜索从公共删除区域中搜索候选基因。 （4）通过荧光原位对患者和父母的染色体进行荧光原位杂交，证实了一组代表性样品中所谓的基因组重排。