视盘小凹（ODP）是一种罕见的单基因遗传病，小凹可与黄斑部视网膜下腔相通，形成局限性的视网膜浆液性脱离，黄斑区水肿及色素紊乱，导致视力严重下降，甚致盲。ODP的发生可能与视盘原始细胞的异常分化所致胚裂不完全闭合相关，但发病机制目前尚不清楚。我们前期收集了一个常显遗传ODP家系，通过全基因组连锁分析发现了一个新的遗传位点，位于14号染色体q11.2-q22.1区域内约27.35cM范围。本课题拟在上述系统研究的基础上，采用外显子测序、连锁区域内候选基因大片段缺失/插入和拷贝数异常检测等方法来定位克隆新的ODP基因，并初步分析该基因的时空表达谱。通过研究ODP人类疾病模型，鉴定影响视神经发育的重要功能基因，定位克隆新的致病基因，对揭示ODP的分子遗传学机制提供重要线索和价值。

Optic disc pit (ODP) is a rare ocular monogenic disorder, leading to serious visual impairment even blindness for that is frequently associated with macular lesions such as schisis-related macular detachment, macular edema or changes in macular pigment. Here, we ascertained a autosomal dominant inherited family with ODP phenotype mapped to a novel locus within a 27.35 Mb region of chromosome 14q11.2-q22.1 after a initial genome-wide screening and linkage analysis. Based on these important findings, in this project, we propose to identify and clone the novel gene by the exome sequencing, detection of large deletions / insertions and copy number variations of possible candidate genes on the linkaged interval. Furthermore, the temporal and spatial expression profile in tissue and cell types and of the novel gene will be evaluated. Cloning and identification of a new gene responsible for ODP would be valuable for the understanding of the molecular and genetic mechanism of ODP.