Using long-range technologies as a multi-omic approach to understand Alzheimer's disease in brain tissue

使用远程技术作为多组学方法来了解脑组织中的阿尔茨海默病

• 批准号: 10030834
• 负责人: Mark T W Ebbert
• 金额: $ 61.93万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2020-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10030834
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Automobile Driving; Biology; Brain; Brain Diseases; Clinic; Complement; Complex; DNA; DNA Structure; DNA mapping; DNA sequencing; Data; Data Set; Detection; Development; Diagnostic; Disease; Genes; Goals; Grant; Individual; Intervention; Methods; Modification; Molecular; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Nucleotides; Optics; Phenotype; Play; Protein Isoforms; Proteins; RNA; RNA Splicing; Research Personnel; Role; Sampling; Symptoms; Technology; The Sun; Therapeutic; Validation; Variant; Work; advanced disease; brain health; brain tissue; cohort; design; differential expression; disease diagnosis; frontal lobe; gain of function; genome-wide; insight; mind control; multiple omics; outcome forecast; programs; targeted treatment; transcriptome sequencing

PROJECT SUMMARY/ABSTRACT Our long-term goal is to help develop a meaningful therapeutic and pre-symptomatic diagnostic for Alzheimer’s disease because, while a disease-altering therapeutic is essential, it will not be sufficient without a diagnostic that identifies disease before symptoms onset. We seek to contribute to these long-term goals by helping identify specific molecular modifications, and therefore specific mechanisms, driving disease using long-range optical DNA mapping and sequencing technologies. Unfortunately, most Alzheimer’s disease genes are only implicated through common non-functional variants, and it is still unclear how most Alzheimer’s disease genes are involved in disease. Likewise, individual RNA isoforms in diseased brains for top Alzheimer’s disease genes and their involvement in disease are poorly understood. Functional variants and RNA sequencing at the isoform level in diseased brain tissue will provide specific mechanisms to target for therapeutics and diagnostics. Large short-read sequencing efforts are already ongoing to identify small functional variants involved in Alzheimer’s disease, but structural DNA variants—many of which directly affect downstream RNA and proteins—also cause neurodegenerative diseases. We hypothesize that undiscovered SVs and aberrant RNA isoforms play a direct role in Alzheimer’s disease. A thorough study in diseased brain using long-range DNA and RNA technologies will complement current short-read efforts, providing important disease insights.

项目总结/文摘