Genetic Analysis Of Non-alzheimer Dementias

我们使用基于密集SNP的连锁图谱来识别与家族性额颞叶痴呆相关的新的基因座。这项工作表明，9号染色体上现有的一个基因座重叠，我们现在知道这也是肌萎缩侧索硬化症的一个危险基因。这项定位克隆工作是由特雷诺博士的团队领导的(另有报告)。我们正在进行的路易体痴呆症和帕金森氏病痴呆症的工作主要集中在分析我们在阿尔茨海默病和帕金森氏病的全基因组关联研究中确定的基因座，以查看我们是否可以梳理出这些疾病中痴呆症的遗传基础，这些疾病在神经病理学上位于阿尔茨海默氏症和帕金森氏病之间；此外，这项工作已扩展到分析痴呆症/帕金森氏病的遗传风险基因座对神经病理学的影响。作为大型合作努力的一部分，我们最近撰写了一篇论文，描述了进行性核上性瘫痪的新风险基因；目前正在进行一项分析，以剖析这种疾病和帕金森病之间MAPT风险单倍型的差异。

We have used dense SNP based linkage mapping to identify novel loci associated with familial frontotemporal dementia. This work shows linkage overlapping an extant locus on chromosome 9 which we now is understand is also a risk locus for amyotrophic lateral sclerosis. This positional cloning effort is being lead by Dr. Traynor's group (separate report). Our ongoing work on dementia with Lewy bodies and Parkinson's disease with dementia primarily focuses on analysis of loci identified in our genome wide association studies in Alzheimer's disease and Parkinson's disease to see if we can tease out the genetic basis of dementia in these disorders which neuropathologically sit between Alzheimer's and Parkinson's disease; further this work has been extended to analyze the effects of genetic risk loci for dementia/parkinson's disease on neuropathology. As a part of a large collaborative effort we have recently authored a paper describing novel risk loci for Progressive Supranuclear Palsy; and are currently working on an analysis to dissect the differences in MAPT risk haplotypes between this disease and Parkinson's disease.