Brain Bank Genome Sequencing - Exploring Alzheimer's disease related dementias

神经退行性疾病是残疾的常见原因，给受影响的个人、护理人员和社区带来巨大的身体、情感和经济负担。随着人口老龄化，神经退行性疾病的患病率正在增加，引起重大的公共卫生问题。不幸的是，我们目前对分子基础的了解是有限的，治疗本质上是支持性的。虽然疾病途径越来越多地被认识到，但对受影响个体大脑中最常见的蛋白质沉积的遗传驱动因素知之甚少。BrainBankSeq计划旨在通过将现代定量遗传工具应用于病理学特征良好的患者来解决我们知识中的这一关键空白。病理学定义的患者的基因组测序代表了一种强有力的方法来解开与年龄相关的神经系统疾病的分子原因。这项工作的样本来自两个大脑银行，即约翰霍普金斯大脑资源中心和班纳健康大脑和组织银行。事实上，这是全基因组测序第一次广泛应用于整个大脑银行的收藏。在过去的一年里，我们的研究工作集中在生成全基因组序列数据上。这是与克利夫顿达尔加德和美国基因组中心在统一服务大学合作完成的。大部分样本已处理完毕，其余样本将于短期内完成。下一步将是分析这个完整的数据集，以找到这些神经病理实体背后的基因。在此过程中，我们还将为研究界提供丰富的数据资源，作为未来系统生物学调查和转化研究工作的跳板。

Neurodegenerative diseases are common causes of disability that place an enormous physical, emotional, and financial burden on affected individuals, caregivers, and the community. The prevalence of neurodegenerative diseases is increasing as the population ages, causing major public health concerns. Unfortunately, our current knowledge of the molecular underpinnings is limited, and treatments are essentially supportive in nature. Although disease pathways are increasingly recognized, little is known about genetic drivers for the most common protein depositions found in the brain in affected individuals. The BrainBankSeq initiative is designed to address this critical gap in our knowledge by applying modern quantitative genetic tools to pathologically well-characterized patients. Genome-sequencing of pathologically defined patients represents a powerful approach to unravel the molecular causes of age-related neurological conditions. The samples for this effort come from two brain banks, namely the Johns Hopkins Brain Resource Center and the Banner Health Brain & Tissue Bank. Indeed, this is the first time that whole-genome sequencing has been applied broadly to entire brain bank collections. Over the last year, we have focused our research efforts on generating the whole-genome sequence data. This has been done in collaboration with Clifton Dalgard and The American Genomic Center at the Uniformed Services University. The majority of samples have been processed, and the remainder will be completed shortly. The next step will be to analyze this complete dataset to find the genes underlying these neuropathological entities. In the process, we will also generate a data-rich resource for the research community that will act as a springboard for future systems biology investigations and translational research efforts.