Genetics of Age-Related Maculopathy

年龄相关性黄斑病的遗传学

• 批准号: 6644237
• 负责人: MICHAEL B GORIN
• 金额: $ 75.34万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644237
• 关键词: biotechnology; clinical research; disease /disorder classification; disease /disorder onset; eye disorder diagnosis; family genetics; gene frequency; genetic disorder; genetic disorder diagnosis; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human genetic material tag; human old age (65+); human subject; linkage disequilibriums; linkage mapping; macular degeneration; molecular pathology; nucleic acid sequence; phenotype; polymerase chain reaction; single strand conformation polymorphism

DESCRIPTION (provided by applicant): Age-related maculopathy (ARM) is the leading cause of irreversible blindness in the elderly population and heredity is clearly the most important risk factor. Treatment for this group of conditions is extremely limited and primarily focused on minimizing the further loss of vision in patients with advanced disease. The long range objective of this project is to identify the genetic contributions to age-related maculopathy (ARM). The goal is to better understand the causes of this condition so that eventually preventive therapies can be developed and tested in at-risk individuals. We have established a rigorous diagnosis scheme for ARM, screened a series of 12 candidate loci, completed two autosomal 10 cM genome-wide scans on a total of 400 ARM families, and, by the end of the current funding period, will have completed a third 10 cM genome-wide scan on an additional set of 200 ARM families. We have one of the largest datasets of ARM families in the world for molecular genetic studies. While we are preparing to undertake our final genome-wide scan of ARM families with CIDR, we are initiating the investigation of the six regions of potential linkage that we have already identified. We will collect additional ARM families, as well as sporadic ARM cases and matched controls (from spouses) for additional testing using linkage and association methods. Microsatellite genotyping of ARM families will be done to further refine potential regions of interest. We will then use single nucleotide polymorphisms (SNPs) and association methods to study the two most promising regions that contain genes involved in ARM. From these studies, we can then proceed to evaluated individual candidate genes for their potential role in this condition. We will also use our large set of ARM subjects, families and controls to test candidate genes that are tentatively identified from other research studies.

描述（由申请人提供）：与年龄相关的大肿瘤（ARM）是老年人口不可逆转的失明的主要原因，而遗传显然是最重要的危险因素。这组疾病的治疗极为有限，主要集中于最大程度地减少晚期疾病患者的进一步视力丧失。该项目的远距离目标是确定对年龄相关的刺激（ARM）的遗传贡献。目的是更好地了解这种情况的原因，以便最终可以在高危人群中开发和测试预防疗法。我们已经为ARM建立了一项严格的诊断方案，筛选了一系列的12个候选基因座，在总共400个ARM家族中完成了两次常染色体10 cm全基因组的扫描，并且在当前资金结束时，将完成第三次10 cm基因组基因组扫描，并在另一组200个ARM家族中完成。我们拥有世界上最大的ARM家族数据集之一，用于分子遗传研究。当我们准备通过CIDR对ARM家族进行最终的全基因组扫描时，我们正在对我们已经确定的六个潜在联系区域进行调查。我们将收集其他ARM系列，以及零星的ARM病例和匹配的对照（来自配偶），以使用连锁和关联方法进行额外的测试。将对ARM家族进行微卫星基因分型，以进一步完善潜在的感兴趣区域。然后，我们将使用单核苷酸多态性（SNP）和关联方法来研究包含ARM基因的两个最有前途的区域。从这些研究中，我们可以继续评估单个候选基因在这种情况下的潜在作用。我们还将使用大量的ARM受试者，家庭和控件来测试从其他研究中暂时确定的候选基因。