Telomere Length Measurements: Strengths and Limitations

项目摘要 越来越多的证据表明，端粒生物学在人类基因组中起着核心作用。 癌症和心血管疾病的发病机制，在美国的两个主要杀手。端粒 长度（TL）是可遗传的，但环境暴露影响TL动态，即，他的年龄和他的年龄-- 依赖性缩短这些调查结果使人们更加清楚地看到， 面对基于人群的端粒研究。高通量TL测量和TL 来自全基因组测序的估算开启了曾经似乎 在人口研究中是无法实现的。然而，有人提出了关于 不分青红皂白地依赖这种模式及其缺点相比，劳动密集型 TL测量技术用于小人群和专业临床环境。射频消融- AG-19-023和配套的RFA-AG-022呼吁制定TL标准 流行病学研究中的测量。本U 01提案响应第一份RFA。其目标 目标1和目标2（提案的第一个分支）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（该提案的第二个分支）解决满足以下要求的标准化和协作协议： 由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测量方法， 成为个人生物遗传健康档案的一个组成部分， 医学在未来

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.