Telomere Length Measurements: Strengths and Limitations

端粒长度测量：优点和局限性

基本信息

批准号：
10171754
负责人：
ABRAHAM AVIV
金额：
$ 11.77万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10171754
关键词：
Address Adult Air Pollutants Atherosclerosis Biological Biology Cardiovascular Diseases Categories Cells Cessation of life Clinical Communities Companions Conflict (Psychology)Disease Dyskeratosis Congenita Elements Energy Intake Environmental Exposure Environmental Risk Factor Epidemiology Exposure to Funding Future Genomics Goals Health Hematopoietic Stem Cell Transplantation Hematopoietic System Heritability Human Individual Laboratories Length Leukocytes Longitudinal Studies Malignant Neoplasms Measurement Measures Mediating Methods Mission Modality Mutation Outcome Pathogenesis Patient-Focused Outcomes Patients Play Population Population Research Practice Guidelines Protocols documentation Psyche structure Recommendation Recording of previous events Research Research Design Risk Role Savings Science Services Single Nucleotide Polymorphism Skeletal Muscle Southern Blotting Standardization Stress Suggestion Techniques Testing Time Tissues United States National Institutes of Health age related arm base cardiovascular disorder risk cell type cigarette smoking comparative epidemiology study genome sequencing improved insight personalized medicine population based premature stem cells telomere whole genome

项目摘要

PROJECT SUMMARY Converging lines of evidence suggest that telomere biology plays a central role in the pathogenesis of cancer and cardiovascular disease, the two leading killers in the USA. Telomere length (TL) is heritable, but environmental exposures influence TL dynamics, i.e., TL and its age- dependent shortening. These findings bring into sharp focus the opportunities and challenges facing population-based telomere research. High throughput TL measurements and TL imputations from whole genome sequencing have opened up possibilities that once seemed unattainable in population research. However, questions have been raised regarding the indiscriminate reliance on such modalities and their shortcomings compared to labor-intensive techniques of TL measurements used in small populations and specialized clinical settings. RFA- AG-19-023 and a companion RFA-AG-022 have called for developing standards of TL measurements in epidemiological research. This U01 proposal responds to the first RFA. Its Aims are two-tiered: Aims 1 and 2 (the proposal’s first arm) will compare the abilities of two TL measurements (Southern blotting of the terminal restriction fragments and qPCR-based analysis) to capture elements of TL dynamics and TL-related outcomes in two longitudinal studies. Aims 3- 5 (the proposal’s second arm) address the standardization and collaborative protocols that meet the goals and central mission of the Telomere Research Network (TRN) established by RFA-AG- 19-023. If reliable TL measurements predicting disease can be identified or developed, they might become a component of the individual’s biogenetic health profile, envisioned to drive personalized medicine in the future.

项目概要多种证据表明，端粒生物学在癌症和心血管疾病（美国的两个主要杀手）的发病机制。长度（TL）是可遗传的，但环境暴露会影响 TL 动态，即 TL 及其年龄这些发现使人们更加关注相关的机遇和挑战。面向基于人群的端粒研究。全基因组测序的估算开辟了曾经看似的可能性然而，人们对这一点提出了质疑。不加区别地依赖此类方式及其与劳动密集型方式相比的缺点 TL 技术用于小群体和专门的临床测量环境。 AG-19-023 和配套的 RFA-AG-022 呼吁制定 TL 标准该 U01 提案响应了第一个 RFA 的目标。分为两层：目标 1 和 2（该提案的第一部分）将比较两个 TL 的能力测量（末端限制性片段的 Southern 印迹和基于 qPCR 的分析）在两项纵向研究中捕捉 TL 动态和 TL 相关结果的要素目标 3-。 5（该提案的第二部分）解决了满足以下要求的标准化和协作协议 RFA-AG 建立的端粒研究网络 (TRN) 的目标和中心使命- 19-023 如果能够识别或开发出预测疾病的可靠 TL 测量值，他们可能会成为个人生物遗传健康状况的一部分，旨在推动个性化未来的医学。