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Towards single-cell chromosome-specific single-base measurement of telomeres with nanopores


Telomeres protect the ends of chromosomes from DNA repair processes. Somatic cells reach senescence as a protective mechanism when telomeres have become critically short. Under certain conditions, a small subset of cells can continue dividing to the point where telomeres are no longer adequately protected, leading to chromosome instability or crisis, at which point the cell is fated to either apoptosis or carcinogenesis. Senescence can be triggered by a single telomere if it is sufficiently short. Chromosomes have been shown to have telomere lengths, and telomere length regulatory factors that can be inherited. Studies on the influence and dynamics of these factors provide insight that is limited by the resolution of tools currently available. Single-cell chromosome-specific techniques are time-consuming, while scalable single-cell methods can only probe the telomere length averaged across all chromosomes. Nanopores have the capability to measure single-molecule telomere lengths with high throughput, and we have developed methods and tools to bring us closer to realizing their potential for this application.

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