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: 8568593
• 负责人: Towfique Raj
• 金额: $ 3.54万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8568593
• 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; High-Throughput Nucleotide Sequencing; 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; 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. ! !

描述（由申请人提供）：在这个项目中，我们将研究人脑组织的转录组，以解析导致衰老人脑认知衰退过程的RNA转录物和功能变异。我们使用下一代 RNA 测序来创建这些转录组的方法将为大脑转录调控的复杂性提供无与伦比的视角，大脑是具有最多样化内容的选择性剪接转录物和非编码 RNA 分子的组织之一，其中许多这可能是以前没有发现的。此外，同一受试者的全基因组基因型数据的可用性为我们提供了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受损相关的遗传变异对人脑产生功能影响的方式。 ！ ！

项目成果

Intersection of population variation and autoimmunity genetics in human T cell activation.

• DOI: 10.1126/science.1254665
• 发表时间: 2014-09-12
• 期刊: Science (New York, N.Y.)
• 作者: Ye CJ;Feng T;Kwon HK;Raj T;Wilson MT;Asinovski N;McCabe C;Lee MH;Frohlich I;Paik HI;Zaitlen N;Hacohen N;Stranger B;De Jager P;Mathis D;Regev A;Benoist C
• 通讯作者: Benoist C

Common risk alleles for inflammatory diseases are targets of recent positive selection.

• DOI: 10.1016/j.ajhg.2013.03.001
• 发表时间: 2013-04
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: T. Raj;Manik Kuchroo;J. Replogle;S. Raychaudhuri;B. Stranger;P. D. De Jager