Core G: Genetics

核心G：遗传学项目摘要/摘要 一百年前，痴呆症是根据其临床表现和 神经病理学。21世纪的希望是，我们将能够对这些疾病进行分类 根据遗传原因或遗传风险因素，基于病因学而不是症状学的分类。在.期间 在过去的二十年里，许多基因被证明是导致常染色体显性形式的早发性疾病的原因 精神错乱的疾病。这些罕见的疾病为更多的 相同疾病的常见变种。1993年，载脂蛋白E(APOE)基因的一个多态是 被确定为阿尔茨海默病的第一遗传危险因素。APOE4等位基因的剂量依赖效应现在已经成为 这是所有AD研究中的一个重要变量。在过去的五年中，全基因组关联研究和下一步 世代测序研究已经开始识别AD的许多新的危险因素。遗传学的目标 骑士ADRC的核心是提供关于所有ADRC的遗传信息和有用的生物材料 参与者。我们将获得所有ADRC的家族史、血浆、血清、DNA、RNA和APOE基因型别 参与者。所有参与者的血液样本将被送往NCRAD。许多参与者还将拥有GWA， 外显子组阵列和整个外显子组/基因组序列数据，通过国家和国际倡议以及ADRC Goate博士和Cruchaga博士持有的附属项目。这些数据将存储在主ADRC数据库中 并应要求提供给调查人员。我们将识别和评估新的多重亲缘关系。那些家庭 符合其他资助项目的标准，如DIAN、NIA-LOAD和LEFFTDS将被邀请参与 这些研究。核心将支持骑士ADRC的项目1、2和3，并将继续支持 健康老龄化、老年痴呆症和成年儿童研究计划项目补助金(JC Morris，PI) 接下来的五年。在这个应用程序中，我们将收集携带特定基因的目标个体的皮肤活检 阿尔茨海默病的遗传风险因素，我们将开始每年采集血液进行RNA表达和DNA甲基化 能够在外周组织中实现新的生物标记物计划的研究。

Core G: Genetics Project Summary/Abstract One hundred years ago, dementing illnesses were classified based upon their clinical presentation and neuropathology. The promise of the twenty-first century is that we will be able to classify these same diseases by the genetic cause or genetic risk factors, a classification based upon etiology not symptomatology. During the last two decades many genes have been shown to cause autosomal dominant forms of early onset dementing illnesses. These rare disorders have provided enormous insight into the pathogenesis of more common variants of the same diseases. In 1993, a polymorphism in the apolipoprotein E (APOE) gene was identified as the first genetic risk factor for AD. A dose-dependent effect of the APOE4 allele has now become an important variable in all studies of AD. During the last five years genome-wide association studies and next generation sequencing studies have begun to identify many novel risk factors for AD. The goal of the Genetics Core of the Knight ADRC is to provide genetic information and useful biological materials on all ADRC participants. We will obtain family history data, plasma, serum, DNA, RNA, and APOE genotypes on all ADRC participants. Blood samples on all participants will be sent to NCRAD. Many participants will also have GWAS, exome array and whole exome/genome sequence data through national and international initiatives and ADRC affiliated projects held by Drs. Goate and Cruchaga. These data will be stored in the master ADRC database and provided to investigators upon request. We will identify and assess novel multiplex kindreds. Families that meet criteria for other funded projects such as DIAN, NIA-LOAD and LEFFTDS will be invited to participate in these studies. The Core will support Projects 1, 2 and 3 of the Knight ADRC and will continue to support the Health Aging and Senile Dementia and Adult Children Study Program Project Grants (JC Morris, PI) during the next five years. New in this application we will collect skin biopsies from targeted individuals carrying specific genetic risk factors for AD and we will begin to collect blood annually for RNA expression and DNA methylation studies to enable novel biomarker programs in peripheral tissues.