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  1. Article: Human telomere length is chromosome specific and conserved across individuals.

    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

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. To probe these mechanisms, we developed a nanopore sequencing method, Telomere Profiling, that is easy to ... ...

    Abstract Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. To probe these mechanisms, we developed a nanopore sequencing method, Telomere Profiling, that is easy to implement, precise, and cost effective with broad applications in research and the clinic. We sequenced telomeres from individuals with short telomere syndromes and found similar telomere lengths to the clinical FlowFISH assay. We mapped telomere reads to specific chromosome end and identified both chromosome end-specific and haplotype-specific telomere length distributions. In the T2T HG002 genome, where the average telomere length is 5kb, we found a remarkable 6kb difference in lengths between some telomeres. Further, we found that specific chromosome ends were consistently shorter or longer than the average length across 147 individuals. The presence of conserved chromosome end-specific telomere lengths suggests there are new paradigms in telomere biology that are yet to be explored. Understanding the mechanisms regulating length will allow deeper insights into telomere biology that can lead to new approaches to disease.
    Language English
    Publishing date 2024-01-13
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.21.572870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Human telomere length is chromosome end-specific and conserved across individuals.

    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

    Science (New York, N.Y.)

    2024  Volume 384, Issue 6695, Page(s) 533–539

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Telomere/genetics ; Infant, Newborn ; Fetal Blood ; Telomere Homeostasis ; Telomere Shortening ; Chromosomes, Human/genetics ; Nanopore Sequencing/methods ; Male ; Adult
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.ado0431
    Database MEDical Literature Analysis and Retrieval System OnLINE

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