The Molecular Genetics of Pigmentary Glaucoma

描述（由申请人提供）：本申请的目标是将John Fingert博士培养为独立的临床科学家。埃德温·斯通博士和华莱士·阿尔沃德博士将担任导师，以确保他在遗传研究和眼科领域的发展取得成功。这项建议的核心是强化训练遗传方法研究遗传形式的青光眼。青光眼合并色素弥散综合征（PDS）由于其独特的临床特征而受到特别关注。PDS是常见的（影响高达2.5%的美国人），由于发病年龄较早，其对个人和社会的影响可能比许多其他眼科疾病更长。PDS的定义特征是从虹膜释放色素，导致许多患者发展为色素性青光眼和视力丧失。虽然结构和解剖因素显然有助于PDS的发展，流行病学和动物研究提供了强有力的证据，这种情况的病理生理学的一个重要的遗传成分。PDS的遗传基础尚不清楚，然而，爱荷华州大学拥有独特的资源，可以促进PDS致病基因的发现，包括世界一流的眼科遗传学研究实验室和大量具有临床特征的PDS患者和家系。该提议的主要假设是，腹透综合症可能是由参与虹膜色素产生的基因缺陷引起的。为了验证这一假设，我们将搜索PDS疾病的基因与三种方法：首先，我们将使用定位克隆，以确定致病基因在一个大的PDS家系。第二，我们将用遗传标记对PDS患者和对照组进行基因分型，以寻找这些标记的等位基因与PDS之间的关联。第三，我们将筛选PDS患者和对照组中与色素产生相关的致病基因突变。这些不同的方法将有助于发现导致PDS的基因，并深入了解这种疾病的发病机制，最终目标是促进改善这种疾病的诊断和治疗。“青光眼是一种常见的致盲性疾病，具有遗传风险因素。一种形式的疾病（色素性青光眼）是由眼睛内虹膜色素的释放引起的。我们正在研究与色素产生有关的基因，这是这种青光眼的原因。"

DESCRIPTION (provided by applicant): The goal of this application is to develop Dr. John Fingert into an independent clinician-scientist. Drs. Edwin Stone and Wallace Alward will assume responsibility as mentors to ensure success in his development in the fields of genetic research and ophthalmology. The core of this proposal is intensive training in genetic approaches to studying inherited forms of glaucoma. Glaucoma associated with pigment dispersion syndrome (PDS) is of particular interest for research due to its unique clinical features. PDS is common (affecting up to 2.5% of Americans) and due to the early age of onset, its effects on individuals and society may be felt for decades more than many other eye diseases. The defining characteristic of PDS is the release of pigment from the iris that causes many patients to develop pigmentary glaucoma and vision loss. Although structural and anatomical factors clearly contribute to the development of PDS, epidemiological and animal studies have provided strong evidence for a significant genetic component to the pathophysiology of this condition. The genetic basis of PDS is unknown, however, the University of Iowa has unique resources to facilitate the discovery of PDS-causing genes including a world class ophthalmic genetics research laboratory and a large collection of clinically-characterized PDS patients and pedigrees. The principle hypothesis of this proposal is that PDS may be caused by defects in genes involved in iris pigment production. To test this hypothesis we will search for PDS disease genes with three approaches: First, we will use positional cloning to identify the disease-causing gene in a large PDS pedigree. Second, we will genotype large cohorts of PDS patients and controls with genetic markers in search of an association between alleles of these markers and PDS. Third, we will screen our cohorts of PDS patients and controls for disease-causing mutations in genes associated with pigment production. These diverse approaches will facilitate the discovery of PDS-causing genes and provide insight into the pathogenesis of this disease, with the ultimate goal of facilitating improvements in the diagnosis and treatment of this condition. "Glaucoma is a common, blinding condition with genetic risk factors. One form of disease (pigmentary glaucoma) is caused by release of iris pigment within the eye. We are studying genes involved in pigment production as a cause of this form of glaucoma."