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.

遗传核心将评估对家族性帕金森氏病和非典型的遗传贡献 帕金森主义。它将有助于电影和神经病理学核心的分子诊断，并将为Farrer和Dickson提供服务。涉及帕金森氏症表型的基因将进行测序，并使用Taqman/Abi3100和荧光原位杂交进行定量评估。分析将包括早期帕金森氏症中PRKN和DJ-1基因的所有外显子（发病时<50年），以及在共同途径或通过链接/关联分析中间接涉及生化的基因。发现的任何变体的频率将在大量适当的人群控制中进行评估。基因/突变将被克隆并使其他研究人员公开访问。功率分析将优先考虑临床核心的家庭收集，并指导血统的扩展。已知的基因座将通过与先前基因组搜索有关的区域中有限的标记基因分型进行检查，但尚未确定基因（Park3，6，8-11）。在已知基因座不包括的大型多物种家庭中对疾病的遗传贡献将 随后通过全基因组基因分型和基于模型的连锁和单倍型探索 分析。对于较小的家庭（2+受影响）或没有明显证明的模式 可以采用继承，非参数等位基因共享方法。支持将成为遗传 分析软件是在Linux OS上运行的PERL脚本/开源统计算法的包，用于更广泛的分布到其他组。