Human telomere length is chromosome end-specific and conserved across individuals

• 成果类型: Article
• 署名作者: Karimian, Kayarash; Groot, Aljona; Huso, Vienna; Kahidi, Ramin; Tan, Kar-Tong; Sholes, Samantha; Keener, Rebecca; McDyer, John F.; Alder, Jonathan K.; Li, Heng; Rechtsteiner, Andreas; Greider, Carol W.
• 署名单位: Johns Hopkins University; Johns Hopkins University; University of California System; University of California Santa Cruz; University of Calgary; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Johns Hopkins University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Merck & Company; Merck & Company USA
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13246
• DOI: 10.1126/science.ado0431
• 发表日期: 2024-05-03
• 页码: 533-539
• 关键词: tert promoter mutations; dna; subpopulations; ORGANIZATION; subsets; cohesin; rif1p; rif2p; trf1; ctcf

摘要

Short telomeres cause age-related disease, and long telomeres contribute to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, which we call Telomere Profiling, to determine telomere length at nearly single-nucleotide resolution. Mapping telomere reads to chromosome ends showed chromosome end-specific length distributions that could differ by more than six kilobases. Examination of telomere lengths in 147 individuals revealed that certain chromosome ends were consistently longer or shorter. The same rank order was found in newborn cord blood, suggesting that telomere length is determined at birth and that chromosome end-specific telomere length differences are maintained as telomeres shorten with age. Telomere Profiling makes precision investigation of telomere length widely accessible for laboratory, clinical, and drug discovery efforts and will allow deeper insights into telomere biology.