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

Tobias T. Schmidt, Carly Tyer, Preeyesh Rughani, Candy Haggblom, Jeffrey R. Jones, Xiaoguang Dai, Kelly A. Frazer, Fred H. Gage, Sissel Juul, Scott Hickey () and Jan Karlseder ()
Additional contact information
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

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48917-7

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