Core--Genetic

遗传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。 帕金森综合征它将有助于临床和神经病理学核心的分子诊断，并将服务于Farrer和Dickson的项目。将使用Taqman/ABI 3100和荧光原位杂交对帕金森综合征表型中涉及的基因进行测序和定量评估。分析将包括早发性帕金森综合征（发病时<50岁）中PRKN和DJ-1基因的所有外显子，以及在共同途径内或通过连锁/关联分析间接涉及的基因。将在大量适当的人群对照中评估发现的任何变体的频率。基因/突变将被克隆，并使其他研究人员可以通过计算机访问。功效分析将优先考虑临床核心的家族收集，并指导谱系扩展。将通过在先前基因组搜索中涉及的区域中的有限标记基因分型来检查已知基因座，但是对于这些区域，基因尚未被鉴定（PARK 3，6，8-11）。排除已知基因位点，在多发病的大家族中， 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（2+受影响的）或没有明确的可证明的模式， 遗传，可以采用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，用于更广泛地分发给其他群体。

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.