Exploring the Role of Transcriptome Variation in Cognitive Decline

描述（由申请人提供）：在本项目中，我们将研究人脑组织的转录组，以解析导致衰老人脑认知能力下降过程的RNA转录本和功能变体。我们使用下一代RNA测序来创建这些转录组的方法将允许对大脑转录调控的复杂性进行无与伦比的透视，大脑是一种具有最多样化的可变剪接转录本和非编码RNA分子内容之一的组织，其中许多可能以前没有被发现。此外，相同受试者的全基因组基因型数据的可用性为我们提供了探索遗传对RNA表达的影响的独特机会。因此，我们不仅可以深入了解衰老人脑的转录组多样性，还可以了解与临床认知障碍相关的遗传变异对人脑产生功能性影响的方式。! !

DESCRIPTION (provided by applicant): In this project, we will investigate the transcriptomes of a human brain tissue to resolve RNA transcripts and functional variants that contribute to the process of cognitive decline in the aging human brain. Our approach using next generation RNA sequencing to create these transcriptomes will allow an unparalleled perspective on the complexity of transcriptional regulation of the brain, which is a tissue with one of the most diverse content of alternatively spliced transcripts and non-coding RNA molecules, many of which may not have been previously discovered. Further, the availability of genome-wide genotype data on the same subjects gives us a unique opportunity to explore the genetic effects on RNA expression. Thus, we may gain insight not only into the transcriptome diversity of the aging human brain but also into the manner in which genetic variation associated with clinically impaired cognition exert a functional consequence on the human brain. ! !