编码和非编码变异对进行性核上性麻痹的影响-猫眼课题宝

编码和非编码变异对进行性核上性麻痹的影响

批准号：

10252910

负责人：

DENNIS WILLIAM DICKSON

金额：

$88.39万

依托单位：

UNIVERSITY OF CALIFORNIA LOS ANGELES

依托单位国家：

美国

项目类别：

财政年份：

2017

资助国家：

美国

项目状态：

已结题

起止时间：

2017-09-25 至 2023-07-31

来源：

https://reporter.nih.gov/project-details/10252910

关键词：

17q21 ATAC-seq Affect Agreement Algorithms Biological Assay Biology Brain Characteristics Clinic Clinical Cloud Computing Code Collaborations Collection Complex Data Data Analyses Disease Disease susceptibility Epigenetic Process Foundations Frontotemporal Dementia Frontotemporal Lobar Degenerations Gene Expression Regulation Genetic Genetic Determinism Genetic Transcription Genetic Variation Genome Genomic Segment Genomics Goals Heritability Infrastructure Knowledge Methods Nerve Degeneration Neurons Occipital lobe Parkinson Disease Pathogenicity Pathologic Pathology Patients Phase Phenotype Play Predisposition Privatization Process Progressive Nonfluent Aphasias Progressive Supranuclear Palsy Proteomics Resources Risk Factors Role Sampling Severities Single Nucleotide Polymorphism Site Structure Syndrome Tauopathies Thalamic structure Tissue Sample Untranslated RNA Validation Variant accurate diagnosis base bioinformatics pipeline brain tissue corticobasal syndrome disorder risk follow-up genetic architecture genetic risk factor genetic variant genome sequencing high throughput screening member neuron loss novel risk variant tau Proteins transcriptome sequencing transcriptomics whole genome

项目摘要

项目成果

DENNIS WILLIAM DICKSON的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

Progressive supranuclear palsy (PSP) is the most common frontotemporal lobar degeneration associated with tau pathology. While rare pathogenic variants, common risk factors, and – more recently – rare risk-associated variants have been identified in PSP, a significant proportion of the heritability for neurodegenerative tauopathies and other frontotemporal lobar degenerations remains unexplained, strongly suggesting that additional genetic risk factors await discovery. In this application, we propose to identify novel genetic variation associated with PSP using a multi-stage strategy. First, we will detect variants through whole-genome sequencing of neuropathologically characterized PSP. Second, we will prioritize pathological brain tissue samples for a multidimensional screen that includes transcriptional, proteomics, and epigenetic assays. Through recursive application of a prioritization algorithm, regions and variants most likely to have a high impact on disease risk will be identified. Finally, we will follow up on these variants using a high-throughput functional screen. This project taps unprecedented pathologic resources of PSP, leverages a pathologic and genetic infrastructure created with support from private foundations, and offers to transform our understanding of the genetic architecture of PSP and to advance towards the biology and downstream effects of this prototypical tauopathy downstream effects of this prototypical tauopathy.

期刊论文(19)

专著(0)

科研奖励(0)

会议论文