Core--Genetic

核心--遗传

• 批准号: 6842198
• 负责人: MATTHEW J FARRER
• 金额: $ 23.03万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6842198
• 关键词: Parkinson' s disease; biomedical facility; family genetics; fluorescent in situ hybridization; gene mutation; genetic markers; genotype; human genetic material tag; linkage disequilibriums; linkage mapping; molecular cloning; neurogenetics; statistics /biometry

The Genetic Core will assess the genetic contribution to familial Parkinson's disease and atypical parkinsonism. It will aid in molecular diagnosis for the Cinical and Neuropathology Cores and will serve Projects by Farrer and Dickson. Genes implicated in a phenotype of parkinsonism are to be sequenced and quantitatively assessed using Taqman/ABI3100 and fluorescent in-situ hybridization. Analysis will include all exons of the PRKN and DJ-1 genes in early-onset parkinsonism (<50 years at onset), as well as genes indirectly implicated either biochemically within a common pathway or through linkage/association analyses. The frequency of any variant found will be assessed in a large number of appropriate population controls. Genes/mutations will be cloned and made publically accessible to other researchers. Power analysis will prioritize family collections for the Clinical Core and guide pedigree expansion. Known loci will be examined through limited marker genotyping in regions implicated in previous genome searches, but for which the gene has yet to be identified (PARK3, 6, 8-11). The genetic contribution to disease in large multi-incident families, excluded from known loci, will subsequently be explored by genome-wide genotyping and model-based linkage and haplotype analyses. For smaller sets of families (2+ affecteds) or without a clearly demonstrable mode of inheritance, non-parametric allele sharing methods may be employed. Support will go into genetic analysis software, a package of perl scripts/open source statistical algorithms running on Linux OS, for wider distribution to other groups.

遗传学核心将评估家族性帕金森病和非典型帕金森病的遗传贡献 帕金森症。它将有助于临床和神经病理学核心的分子诊断，并将为法雷尔和迪克森的项目服务。与帕金森症表型有关的基因将被测序，并使用Taqman/ABI3100和荧光原位杂交进行定量评估。分析将包括早发性帕金森病(发病50年)的PRKN和DJ-1基因的所有外显子，以及通过共同途径或通过连锁/关联分析间接涉及的生化基因。将在大量适当的人口控制措施中评估发现的任何变异的频率。基因/突变将被克隆，并向其他研究人员公开。能力分析将优先考虑临床核心的家系收集，并指导谱系扩展。已知的基因座将通过在以前的基因组搜索中涉及的、但基因尚未确定的区域的有限标记基因分型来检查(Park3、6、8-11)。基因对疾病的贡献，排除在已知的基因座之外，将在多个事件的大家庭中起作用 随后通过全基因组基因分型和基于模型的连锁和单倍型进行探索 分析。对于较小的家庭组(2个以上受影响的家庭)或没有明显可演示的模式 可以采用遗传、非参数等位基因共享方法。支持将进入基因 分析软件，一个运行在Linux操作系统上的Perl脚本/开源统计算法包，用于向其他组进行更广泛的分发。