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主要是零星发生的，约22%的面裂患者有遗传起源。连锁分析和/或关联研究已经缩小了几个候选区域的范围，但还不足以指出患者可能需要重新测序的候选基因。这项建议的目标是通过搜索微缺失/复制来调查候选区域的基因组，并比较这种方法与更传统的遗传关联研究的相对有效性，以确定候选区域 我们的方法是基于比较基因组杂交(CGH)，使用非常高分辨率的BAG阵列来筛选与拷贝数变化有关的基因组片段。其具体目标是：(1)在2年多的时间里对200例患者的DNA样本进行阵列计算；(2)识别多个患者之间可能共享的零星缺失/复制；(3)通过公共数据库从共同缺失区域中寻找候选基因。(4)通过将BAC与患者和父母的染色体进行荧光原位杂交，在一组具有代表性的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.