Unraveling the 10q AMD Risk Locus

揭开 10 季度 AMD 风险轨迹

基本信息

批准号：
9762936
负责人：
EDWIN M STONE
金额：
$ 49.58万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9762936
关键词：
10q 10q26 Affect Age Age related macular degeneration Alleles Biochemical Biopsy Blindness Cells Chromosomes Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 10 Clustered Regularly Interspaced Short Palindromic Repeats Computer Analysis Computer-Assisted Image Analysis DNA Sequence Alteration Development Diagnostic Procedure Disease Endothelial Cells Eye Eye Development Functional disorder Genes Genetic Genetic Polymorphism Genotype Goals Heritability Human Image Individual Insulin-Like Growth Factor I Life Molecular Molecular Analysis Molecular Genetics Morphology Mutation Pathogenesis Pathway interactions Patient imaging Patients Phenotype Photoreceptors Physiological Play Population Prevalence Protocols documentation Publishing Regulation Resolution Retinal Risk Role Skin Stem cells Susceptibility Gene Testing Therapeutic Intervention Tissues United States Variant base clinical imaging cohort complement system disease mechanisms study effective therapy genetic association genetic manipulation genetic risk factor genome editing high risk induced pluripotent stem cell insight interdisciplinary approach macula new therapeutic target patient population postnatal research study retinal imaging risk variant societal costs transcriptome

项目摘要

ABSTRACT Age-related macular degeneration (AMD) is the most common cause of severe visual loss in the developed world, affecting more than 10 million people in the United States alone. Approximately 1 in 3 people over the age of 75 are affected to some degree. A significant fraction of this disease is genetic, with major genetic risk factors on chromosomes 1 and 10. In this study, we will take advantage of molecular genetics, state of the art computer-assisted image analysis, large patient populations, well characterized donor eye tissue, induced pluripotent stem cells and CRISPR based genome editing to determine the molecular basis of how variations in AMD loci increase risk of AMD. These studies will provide new insight into the pathophysiologic mechanisms of AMD that will be valuable for the development of more specific diagnostic methods and more effective therapies.

抽象的与年龄相关的黄斑变性（AMD）是发达的严重视觉丧失的最常见原因世界，仅在美国就会影响超过1000万人。大约三分之一的人 75岁的年龄在某种程度上受到影响。这种疾病的很大一部分是遗传的，具有重大遗传风险染色体1和10的因素。在这项研究中，我们将利用分子遗传学的优势，即最先进的计算机辅助图像分析，大量的患者人群，表征良好的供体眼组织，诱导多能干细胞和CRISPR 基于基因组编辑，以确定AMD基因座变化如何增加AMD风险的分子基础。这些研究将为AMD的病理生理机制提供新的见解，这将对开发更具体的诊断方法和更有效的疗法。