Telomere Length Measurements: Strengths and Limitations

项目总结 越来越多的证据表明，端粒生物学在 癌症和心血管疾病的发病机制是美国的两大杀手。端粒 长度(TL)是可遗传的，但环境暴露会影响TL的动态变化，即TL及其年龄。 从属缩写。这些发现突出了机遇和挑战 面临基于群体的端粒研究。高通量TL测量和TL 来自全基因组测序的推论开启了曾经看似 在人口研究中是无法达到的。然而，有人提出了关于 与劳动密集型相比，不分青红皂白地依赖这种模式及其缺点 在小人口和专门临床环境中使用的TL测量技术。RFA- AG-19-023和配套的RFA-AG-022呼吁制定TL的标准 流行病学研究中的测量。这份U01提案回应了第一个RFA。它的目的 是两级的：目标1和目标2(提案的第一个臂)将比较两个TL的能力 测量(末端限制性片段的Southern blotting和基于qPCR的分析) 在两个纵向研究中获取目标语言动力学和与目标语言相关的结果的要素。AIMS 3- 5(提案的第二部分)解决符合以下条件的标准化和协作协议 RFA-AG建立的端粒研究网络(TRN)的目标和中心任务- 19-023.如果能够识别或开发预测疾病的可靠的TL测量，它们可能会 成为个人生物遗传健康档案的组成部分，旨在推动个性化 未来的医学。

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.