The Genetics of Eye Disease

描述（由申请人提供）：该项目的长期目标是确定对人眼和视觉系统的发育和维持重要的基因，了解它们的正常作用和相互作用，以及这些作用和相互作用如何失败，导致视觉系统异常。这些将在洞穴鱼模型系统（Astyanax mexicanus）中进行研究，其中可以绘制和识别导致眼睛和视觉障碍的基因。该项目有三个具体目标：首先，我们将对洞穴/地表杂交的异常眼睛进行组织学检查并进行QTL定位，以便更好地表征异常表型并了解其遗传基础。这将使我们能够认识到与已知人眼疾病的相似之处，并增加我们对其原因的了解。其次，我们将绘制已知影响眼睛发育或在眼睛中表达的基因。其中一些基因将被证明是QTL候选者，我们的分析将增加我们对它们在控制眼睛发育或维持方面的作用方式的理解。第三个目标是对两个不同洞穴种群杂交后眼睛结构和功能的恢复进行组织学和遗传学分析。了解通过两个有缺陷的基因组的相互作用恢复正常表型的方式，将增加我们对涉及人类眼睛发育和疾病的遗传途径的理解。

DESCRIPTION (provided by applicant): The long-term objectives of this project are to identify genes important for the development and maintenance of the human eye and visual system, to understand their normal actions and interactions, and how these may fail, leading to abnormalities of the visual system. These will be studied in the cave fish model system (Astyanax mexicanus) in which genes causing eye and visual disorders can be mapped and identified. The project has three specific aims: first, we will examine the abnormal eyes of cave/surface hybrids histologically and do QTL mapping in order to better characterize the abnormal phenotypes and understand their genetic bases. This will allow us to recognize similarities to known human eye disorders and increase our knowledge of their causes. Second, we will map genes known to affect eye development or to be expressed in the eye. Some of these genes will prove to be QTL candidates and our analyses will increase our understanding of the ways in which they function in controlling eye development or maintenance. The third aim is to do histological and genetic analyses on the restoration of eye structure and function that occurs in hybrids between two different cave populations. An understanding of the ways in which normal phenotype can be restored by the interaction of elements from two flawed genomes will increase our understanding of the genetic pathways involved in human eye development and disease.