In humans, the telomere consists of tandem 5′TTAGGG3′ DNA repeats on both ends of all 46 chromosomes. Telomere shortening has been linked to aging and age-related diseases. Similarly, telomere length changes have been associated with chemical exposure, molecular-level DNA damage, and tumor development. Telomere elongation has been associated to tumor development, caused due to chemical exposure and molecular-level DNA damage. The methods used to study these effects mostly rely on average telomere length as a biomarker. The mechanisms regulating subtelomere-specific and haplotype-specific telomere lengths in humans remain understudied and poorly understood, primarily because of technical limitations in obtaining these data for all chromosomes. Recent studies have shown that it is the short telomeres that are crucial in preserving chromosome stability. The identity and frequency of specific critically short telomeres potentially is a useful biomarker for studying aging, age-related diseases, and cancer. Here, we will briefly review the role of telomere length, its measurement, and our recent single-molecule telomere length measurement assay. With this assay, one can measure individual telomere lengths as well as identify their physically linked subtelomeric DNA. This assay can also positively detect telomere loss, characterize novel subtelomeric variants, haplotypes, and previously uncharacterized recombined subtelomeres. We will also discuss its applications in aging cells and cancer cells, highlighting the utility of the single molecule telomere length assay.

在人类中，端粒由所有 46 条染色体两端串联的 5'TTAGGG3' DNA 重复序列组成。端粒缩短与衰老和与年龄相关的疾病有关。同样，端粒长度的变化与化学暴露、分子水平 DNA 损伤和肿瘤发展有关。端粒伸长与肿瘤的发展有关，这是由于化学暴露和分子水平的 DNA 损伤引起的。用于研究这些影响的方法主要依靠平均端粒长度作为生物标志物。调节人类亚端粒特异性和单倍型特异性端粒长度的机制仍未得到充分研究和了解，这主要是因为获取所有染色体的这些数据的技术限制。最近的研究表明，短端粒对于保持染色体稳定性至关重要。特定的极短端粒的特性和频率可能是研究衰老、与年龄相关的疾病和癌症的有用生物标志物。在这里，我们将简要回顾端粒长度的作用、其测量以及我们最近的单分子端粒长度测量测定。通过这种测定，人们可以测量单个端粒长度并识别其物理连接的亚端粒 DNA。该测定还可以积极检测端粒丢失，表征新的亚端粒变异、单倍型和先前未表征的重组亚端粒。我们还将讨论其在衰老细胞和癌细胞中的应用，重点介绍单分子端粒长度测定的实用性。