Brain Bank Seq

我们之前已经使用定制的神经芯片基因分型阵列对约翰·霍普金斯脑库的神经退行性疾病病例中的致病变异进行了遗传分析。从物流的角度来看，这项研究展示了我们与整个脑库合作的能力。从科学上讲，我们的分析揭示了耐人寻味的基因-表型相关性，例如LRRK2与进行性核上性麻痹的分子关系，从而拓宽了疾病表型，并突出了基因组学在分子诊断目的中的用途。与基因分型阵列相比，基因组序列数据可以被分析以发现新的基因变化。 接下来，我们将使用Illumina NovaSeq 6000平台进行测序。该项目将生成范围广泛的痴呆症和密切相关的神经退行性疾病的高质量数据，如阿尔茨海默病、路易体疾病、FTD/ALS、复杂痴呆症(由患有一种以上神经退行性疾病的个人组成)和罕见的神经退行性痴呆症综合征。每个样本都有详细的表型和神经病理数据。

We have previously performed a genetic analysis of pathogenic variants in neurodegenerative disease cases from the Johns Hopkins Brain Bank using the custom-generated NeuroChip genotyping array. From a logistics perspective, this study demonstrates our ability to work with an entire brain bank. Scientifically, our analysis revealed intriguing genotype-phenotype correlations, such as the molecular relationship of LRRK2 and progressive supranuclear palsy, thereby broadening disease phenotypes and highlighting the utility of genomics for molecular diagnostic purposes. In contrast to genotyping arrays, genome sequence data can be analyzed to discover new genetic changes. We will next perform sequencing with the Illumina NovaSeq 6000 platform. This project will generate high-quality data across a wide range of dementias and closely related neurodegenerative diseases, such as Alzheimer's disease, Lewy body diseases, FTD/ALS, complex dementia cases (consisting of individuals with more than one neurodegenerative disease), and rare neurodegenerative dementia syndromes. Detailed phenotype and neuropathological data are available for each sample.