A joint linkage/association strategy to interrogate AMD genetic susceptibility

描述（由申请人提供）： 视网膜相关性黄斑变性（AMD）是一种复杂的疾病，其中多种遗传和环境成分影响临床表型。这种情况现在是美国老年人法律的失明的主要原因。了解完整的遗传流行病学将有助于开发新的治疗方法和预防策略。 已经确定了与AMD相关的几种常见遗传变异。我们假设，其余的病因是由一些个别不太常见，但功能显着的遗传变异解释。 该项目是凯西眼科研究所/俄勒冈州健康与科学大学黄斑变性中心与西南生物医学研究基金会遗传学系之间新的令人兴奋的合作的开始。新的AMD易感基因将通过使用一个强大的联合全基因组连锁和关联策略，在我们预先存在的150个家系收集丰富的AMD易感性。我们将通过使用存储的视网膜图像仔细量化表型来识别与基因作用更密切相关的生物学特征，从而增加识别易感性相关遗传变异的可能性。 在高密度SNP阵列基因分型后，显示每个AMD相关表型的最佳证据的基因将在无关的AMD病例和对照中复制。还将进行全外显子组下一代测序，以确定家族中存在的罕见或潜在的私人突变。贝叶斯QTN和生物信息学分析将用于预测功能变体。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a complex disease in which multiple genetic and environmental components influence the clinical phenotype. The condition is now the major cause of legal blindness in older people in the USA. Understanding the complete genetic epidemiology will enable the development of new therapies and preventive strategies. Several common genetic variants associated with AMD have been identified. We hypothesize that the remaining etiology is explained by a number of individually less common, but functionally significant genetic variants. This project is the beginning of a new and exciting collaboration between the Macular Degeneration Center at the Casey Eye Institute/Oregon Health and Science University and the Department of Genetics to accomplish at the Southwest Foundation for Biomedical Research. Novel AMD-susceptibility genes will be identified by using a powerful joint genome-wide linkage and association strategy in our pre-existing collection of 150 pedigrees enriched for their susceptibility to AMD. We will increase the likelihood of identifying susceptibility-related genetic variation by careful quantification of the phenotype using stored retinal images to identify biological characteristics more closely related to the action of genes. Genes showing the best evidence for each AMD-related phenotype following high-density SNP-array genotyping will be replicated in unrelated AMD cases and controls. Whole Exome Next Generation sequencing will also be undertaken to identify rare or potentially private mutations present in the families. Bayesian QTN and bioinformatics analysis will be used to predict functional variants.