Exploring the Role of Transcriptome Variation in Cognitive Decline

探索转录组变异在认知衰退中的作用

• 批准号: 8397265
• 负责人: Towfique Raj
• 金额: $ 5.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8397265
• 关键词: Affect; Age-associated memory impairment; Aging; Alzheimer' s Disease; Base Sequence; Biostatistical Methods; Brain; Cessation of life; Clinical; Cognition; Cognition Disorders; Cohort Studies; Computational Biology; Computing Methodologies; DNA; Data; Dementia; Disease; Exons; Functional RNA; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Risk; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; Goals; Human; Impaired cognition; Individual; Investigation; Knowledge acquisition; Measures; Mediating; Mediation; Mentors; Methods; Modeling; Neurobiology; Neurodegenerative Disorders; Neurology; Phenotype; Predisposition; Prefrontal Cortex; Process; Protein Isoforms; RNA; RNA Sequences; RNA Splicing; Research; Research Personnel; Risk; Role; Signal Transduction; Spliced Genes; Statistical Methods; Testing; Tissues; Training; Transcript; Transcriptional Regulation; Variant; Work; age related; brain tissue; career; cognitive function; cohort; genetic variant; genome wide association study; genome-wide; genotyping technology; high throughput analysis; insight; next generation; novel; pre-clinical; prevent; prospective; skills; statistics; transcriptomics

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. ! ! PUBLIC HEALTH RELEVANCE: The goal of this proposal is to understand which molecules of a brain tissue are involved in the cognitive decline in older individuals. In understanding how these molecules relate to genetic risk for aging and human cognitive function will allow investigators to better understand the onset of cognitive decline and diseases of cognition, such as Alzheimer's disease (AD). This may help to develop clinical tests that may be able to predict who is at risk of developing AD and to develop new treatments to delay or prevent onset of cognitive decline and AD.

描述(申请人提供)：在这个项目中，我们将研究人脑组织的转录本，以解析导致人类大脑老化的认知衰退过程的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本的方法，将允许以无与伦比的视角来了解大脑转录调控的复杂性，大脑是一个组织，其内容最多样化，包括选择性剪接的转录本和非编码的RNA分子，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获得性给了我们一个独特的机会来探索遗传对RNA表达的影响。因此，我们不仅可以洞察老化人脑的转录组多样性，还可以洞察与临床认知受损相关的基因变异对人脑产生功能影响的方式。！！ 与公共健康相关：这项提议的目标是了解脑组织中的哪些分子与老年人的认知能力下降有关。了解这些分子如何与衰老和人类认知功能的遗传风险相关，将使研究人员更好地了解认知衰退和认知疾病的发生，如阿尔茨海默病(AD)。这可能有助于开发临床测试，或许能够预测谁有患阿尔茨海默病的风险，并开发新的治疗方法，以延缓或预防认知能力下降和阿尔茨海默病的发病。