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进行分类的， 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，基于病因学而非病理学的分类。期间 在过去的二十年里，许多基因已被证明会导致常染色体显性形式的早发性 精神错乱的疾病这些罕见的疾病提供了巨大的洞察更多的发病机制， 相同疾病的常见变种。在1993年，载脂蛋白E（APOE）基因的多态性， 被认为是AD的第一个遗传风险因素。APOE 4等位基因的剂量依赖性效应现已成为 是所有AD研究中的重要变量。在过去的五年里，全基因组关联研究和未来的研究 世代测序研究已经开始鉴定AD的许多新的危险因素。遗传学的目标 Knight ADRC的核心是提供所有ADRC上的遗传信息和有用的生物材料 参与者我们将获得所有ADRC的家族史数据、血浆、血清、DNA、RNA和APOE基因型 参与者所有受试者的血样将被送往NCRAD。许多参与者也将拥有GWAS， 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和ADRC Goate博士和Cruchaga博士主持的附属项目。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。我们将确定和评估新型多重激酶。的家庭 符合其他资助项目的标准，如DIAN，NIA-LOAD和LEFFTDS将被邀请参加 这些研究。核心将支持Knight ADRC的项目1、2和3，并将继续支持 健康老龄化和老年痴呆症和成年儿童研究计划项目赠款（JC莫里斯，PI）在 未来五年在这项新的应用中，我们将收集皮肤活检从目标个人携带特定的 我们将开始每年收集血液用于RNA表达和DNA甲基化 研究，使新的生物标志物程序在外周组织。

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.