IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48917-7.html
   My bibliography  Save this article

High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer

Author

Listed:
  • Tobias T. Schmidt

    (Salk Institute for Biological Studies)

  • Carly Tyer

    (Inc.)

  • Preeyesh Rughani

    (Inc.)

  • Candy Haggblom

    (Salk Institute for Biological Studies)

  • Jeffrey R. Jones

    (Salk Institute for Biological Studies)

  • Xiaoguang Dai

    (Inc.)

  • Kelly A. Frazer

    (University of California, San Diego)

  • Fred H. Gage

    (Salk Institute for Biological Studies)

  • Sissel Juul

    (Inc.)

  • Scott Hickey

    (Inc.)

  • Jan Karlseder

    (Salk Institute for Biological Studies)

Abstract

Telomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres’ repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies’ native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution.

Suggested Citation

  • Tobias T. Schmidt & Carly Tyer & Preeyesh Rughani & Candy Haggblom & Jeffrey R. Jones & Xiaoguang Dai & Kelly A. Frazer & Fred H. Gage & Sissel Juul & Scott Hickey & Jan Karlseder, 2024. "High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48917-7
    DOI: 10.1038/s41467-024-48917-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48917-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48917-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Joe Nassour & Lucia Gutierrez Aguiar & Adriana Correia & Tobias T. Schmidt & Laura Mainz & Sara Przetocka & Candy Haggblom & Nimesha Tadepalle & April Williams & Maxim N. Shokhirev & Semih C. Akincila, 2023. "Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis," Nature, Nature, vol. 614(7949), pages 767-773, February.
    2. Suneet Agarwal & Yuin-Han Loh & Erin M. McLoughlin & Junjiu Huang & In-Hyun Park & Justine D. Miller & Hongguang Huo & Maja Okuka & Rosana Maria dos Reis & Sabine Loewer & Huck-Hui Ng & David L. Keefe, 2010. "Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients," Nature, Nature, vol. 464(7286), pages 292-296, March.
    3. Tsung-Po Lai & Ning Zhang & Jungsik Noh & Ilgen Mender & Enzo Tedone & Ejun Huang & Woodring E. Wright & Gaudenz Danuser & Jerry W. Shay, 2017. "A method for measuring the distribution of the shortest telomeres in cells and tissues," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    4. Riham Smoom & Catherine Lee May & Vivian Ortiz & Mark Tigue & Hannah M. Kolev & Melissa Rowe & Yitzhak Reizel & Ashleigh Morgan & Nachshon Egyes & Dan Lichtental & Emmanuel Skordalakes & Klaus H. Kaes, 2023. "Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Wen-Wei Liao & Mobin Asri & Jana Ebler & Daniel Doerr & Marina Haukness & Glenn Hickey & Shuangjia Lu & Julian K. Lucas & Jean Monlong & Haley J. Abel & Silvia Buonaiuto & Xian H. Chang & Haoyu Cheng , 2023. "A draft human pangenome reference," Nature, Nature, vol. 617(7960), pages 312-324, May.
    6. Ting Wang & Lucinda Antonacci-Fulton & Kerstin Howe & Heather A. Lawson & Julian K. Lucas & Adam M. Phillippy & Alice B. Popejoy & Mobin Asri & Caryn Carson & Mark J. P. Chaisson & Xian Chang & Robert, 2022. "The Human Pangenome Project: a global resource to map genomic diversity," Nature, Nature, vol. 604(7906), pages 437-446, April.
    7. Joe Nassour & Robert Radford & Adriana Correia & Javier Miralles Fusté & Brigitte Schoell & Anna Jauch & Reuben J. Shaw & Jan Karlseder, 2019. "Autophagic cell death restricts chromosomal instability during replicative crisis," Nature, Nature, vol. 565(7741), pages 659-663, January.
    8. Karen H. Miga & Sergey Koren & Arang Rhie & Mitchell R. Vollger & Ariel Gershman & Andrey Bzikadze & Shelise Brooks & Edmund Howe & David Porubsky & Glennis A. Logsdon & Valerie A. Schneider & Tamara , 2020. "Telomere-to-telomere assembly of a complete human X chromosome," Nature, Nature, vol. 585(7823), pages 79-84, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Timothy K. Turkalo & Antonio Maffia & Johannes J. Schabort & Samuel G. Regalado & Mital Bhakta & Marco Blanchette & Diana C. J. Spierings & Peter M. Lansdorp & Dirk Hockemeyer, 2023. "A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Rishi Kumar Nageshan & Raquel Ortega & Nevan Krogan & Julia Promisel Cooper, 2024. "Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Wolfram Höps & Tobias Rausch & Michael Jendrusch & Jan O. Korbel & Fritz J. Sedlazeck, 2024. "Impact and characterization of serial structural variations across humans and great apes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Santiago E. Sanchez & Yuchao Gu & Yan Wang & Anudeep Golla & Annika Martin & William Shomali & Dirk Hockemeyer & Sharon A. Savage & Steven E. Artandi, 2024. "Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Sean A. Misek & Aaron Fultineer & Jeremie Kalfon & Javad Noorbakhsh & Isabella Boyle & Priyanka Roy & Joshua Dempster & Lia Petronio & Katherine Huang & Alham Saadat & Thomas Green & Adam Brown & John, 2024. "Germline variation contributes to false negatives in CRISPR-based experiments with varying burden across ancestries," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Zhikun Wu & Zehang Jiang & Tong Li & Chuanbo Xie & Liansheng Zhao & Jiaqi Yang & Shuai Ouyang & Yizhi Liu & Tao Li & Zhi Xie, 2021. "Structural variants in the Chinese population and their impact on phenotypes, diseases and population adaptation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    7. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Robin Aguilar & Conor K. Camplisson & Qiaoyi Lin & Karen H. Miga & William S. Noble & Brian J. Beliveau, 2024. "Tigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    10. Alyssa R Lindrose & Lauren W Y McLester-Davis & Renee I Tristano & Leila Kataria & Shahinaz M Gadalla & Dan T A Eisenberg & Simon Verhulst & Stacy Drury, 2021. "Method comparison studies of telomere length measurement using qPCR approaches: A critical appraisal of the literature," PLOS ONE, Public Library of Science, vol. 16(1), pages 1-23, January.
    11. Kunpeng Li & Peng Xu & Jinpeng Wang & Xin Yi & Yuannian Jiao, 2023. "Identification of errors in draft genome assemblies at single-nucleotide resolution for quality assessment and improvement," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Mohamed Awad & Xiangchao Gan, 2023. "GALA: a computational framework for de novo chromosome-by-chromosome assembly with long reads," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Tuomas Hämälä & Christopher Moore & Laura Cowan & Matthew Carlile & David Gopaulchan & Marie K. Brandrud & Siri Birkeland & Matthew Loose & Filip Kolář & Marcus A. Koch & Levi Yant, 2024. "Impact of whole-genome duplications on structural variant evolution in Cochlearia," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Joanna Hård & Jeff E. Mold & Jesper Eisfeldt & Christian Tellgren-Roth & Susana Häggqvist & Ignas Bunikis & Orlando Contreras-Lopez & Chen-Shan Chin & Jessica Nordlund & Carl-Johan Rubin & Lars Feuk &, 2023. "Long-read whole-genome analysis of human single cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    15. Can Luo & Yichen Henry Liu & Xin Maizie Zhou, 2024. "VolcanoSV enables accurate and robust structural variant calling in diploid genomes from single-molecule long read sequencing," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Souren Paul & Mark H. Kaplan & Dinesh Khanna & Preston M. McCourt & Anjan K. Saha & Pei-Suen Tsou & Mahek Anand & Alexander Radecki & Mohamad Mourad & Amr H. Sawalha & David M. Markovitz & Rafael Cont, 2022. "Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Riham Smoom & Catherine Lee May & Vivian Ortiz & Mark Tigue & Hannah M. Kolev & Melissa Rowe & Yitzhak Reizel & Ashleigh Morgan & Nachshon Egyes & Dan Lichtental & Emmanuel Skordalakes & Klaus H. Kaes, 2023. "Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    18. Yilei Fu & Sergey Aganezov & Medhat Mahmoud & John Beaulaurier & Sissel Juul & Todd J. Treangen & Fritz J. Sedlazeck, 2024. "MethPhaser: methylation-based long-read haplotype phasing of human genomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    19. Sarah Morrison-Smith & Christina Boucher & Aleksandra Sarcevic & Noelle Noyes & Catherine O’Brien & Nazaret Cuadros & Jaime Ruiz, 2022. "Challenges in large-scale bioinformatics projects," Palgrave Communications, Palgrave Macmillan, vol. 9(1), pages 1-9, December.
    20. Cristian Groza & Carl Schwendinger-Schreck & Warren A. Cheung & Emily G. Farrow & Isabelle Thiffault & Juniper Lake & William B. Rizzo & Gilad Evrony & Tom Curran & Guillaume Bourque & Tomi Pastinen, 2024. "Pangenome graphs improve the analysis of structural variants in rare genetic diseases," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48917-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.