Cancer Prevention and Control Program, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC 20057, USA.
Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
Nucleic Acids Res. 2024 Oct 28;52(19):e96. doi: 10.1093/nar/gkae812.
The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach was developed to measure the base-pair (bp) lengths of single telomeres. On average 32000 telomeres were measured per DNA sample with one microarray chip assaying 96 test DNA samples. Various telomere parameters, i.e. aTL and the frequency of short/long telomeres, were computed to delineate TL distribution. The intra-assay and inter-assay coefficient of variations of aTL ranged from 1.37% to 3.98%. The correlation coefficient (r) of aTL in repeated measurements ranged from 0.91 to 1.00, demonstrating high measurement precision. aTLs measured by DNA-array-FISH predicted aTLs measured by terminal restriction fragment (TRF) analysis with r ranging 0.87-0.99. A new accurate and high-throughput method has been developed to measure the bp lengths of single telomeres. The large number of single TL data provides an opportunity for an in-depth analysis of telomere dynamics and the complex relationship between telomere and age-related diseases.
人类端粒系统具有高度动态性。白细胞平均端粒长度（aTL）无论是缩短还是延长，都会增加患癌症和早逝的风险，这说明了端粒与人类健康之间的复杂关系，以及用单端粒分析评估端粒分布的重要性。本文开发了一种 DNA 微阵列和端粒荧光原位杂交（DNA-array-FISH）方法来测量单个端粒的碱基对（bp）长度。每个 DNA 样本平均测量 32000 个端粒，一个微阵列芯片可检测 96 个测试 DNA 样本。计算各种端粒参数，如 aTL 和短/长端粒的频率，以描绘端粒分布。aTL 的组内和组间变异系数范围为 1.37%至 3.98%。aTL 在重复测量中的相关系数（r）范围为 0.91 至 1.00，表明测量精度高。DNA-array-FISH 测量的 aTL 与末端限制性片段（TRF）分析测量的 aTL 之间的 r 值范围为 0.87-0.99。本文开发了一种准确、高通量的方法来测量单个端粒的 bp 长度。大量的单端粒数据为深入分析端粒动力学和端粒与年龄相关疾病之间的复杂关系提供了机会。
