Screening to Find Genes Causing Cleft Lip and Palate

唇裂伴或不伴腭裂（CL/P）是非常常见的结构性出生缺陷。CL/P主要是散发性的，大约22%的面裂患者有遗传起源。连锁分析和/或关联研究已经允许缩小几个候选区域，但不足以指示来自患者的用于重新测序的可能候选基因。该提案的目标是通过搜索微缺失/重复来调查基因组中的候选区域，并将该方法的相对功效与更传统的遗传关联研究进行比较，以确定候选区域。 CL/P基因。我们的方法基于比较基因组杂交（CGH），使用极高分辨率BAG阵列来筛选涉及拷贝数变化的基因组片段。具体目标是：（1）在2年内从200个患者DNA样本中进行阵列CGH;（2）鉴定多个患者之间可能共有的零星缺失/重复;（3）通过公共数据库从共同缺失区域中搜索候选基因。(4)通过BAC与患者和父母染色体的荧光原位杂交，在一组代表性样本中确认所谓的基因组重排。

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.