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

Kayarash Karimian; Aljona Groot; Vienna Huso; Ramin Kahidi; Kar-Tong Tan; Samantha Sholes; Rebecca Keener; John F McDyer; Jonathan K Alder; Heng Li; Andreas Rechtsteiner; Carol W Greider

doi:10.1126/science.ado0431

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

Science. 2024 Apr 11:eado0431. doi: 10.1126/science.ado0431. Online ahead of print.

Authors

Kayarash Karimian^{1

2}, Aljona Groot³, Vienna Huso^{1

2}, Ramin Kahidi⁴, Kar-Tong Tan^{5

6

7}, Samantha Sholes^{1

2}, Rebecca Keener^{2

8}, John F McDyer⁹, Jonathan K Alder⁹, Heng Li^{10

11}, Andreas Rechtsteiner³, Carol W Greider^{1

3}

Affiliations

¹ Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
⁴ Health Sciences Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁵ Department of Genetics, Harvard Medical School, Boston, MA, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁷ Cancer Program, The Broad Institute, Cambridge, MA, USA.
⁸ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁹ Pulmonary, Allergy, Critical Care, and Sleep Medicine Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
¹¹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.

PMID: 38603523
DOI: 10.1126/science.ado0431

Abstract

Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, 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. Telomere lengths in 147 individuals showed 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 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.