Tobias T. Schmidt from the Salk Institute for Biological Studies presented at the Nanopore Community Meeting in Houston on “Telomere dynamics in aging and cancer by nanopore long-read sequencing.” Schmidt is a postdoc working on sequencing and described how telomeres protect the end of linear eukaryotic chromosomes. Telomeres shorten with every round of replication in human somatic cells. Terminal restriction fragment analysis (TRF) can be used to analyze sizes. If telomeres get too short, they trigger a p53 + Rb response. Cancer cells activate telomere maintenance mechanisms. Telomeres are repetitive, long, and often difficult to analyze. Some cancer cell lines have very long telomeres. To sequence telomeres, Schmidt used nanopore long-read sequencing on a GridION. The approach was to ligate adapters to be able to sequence telomeres. Their proof of principle for Telo-seq was to try HG002. The team performed the assay in duplicate and obtained reproducible results. Interestingly, their approach indicated that different chromosome arms had different telomere lengths. Schmidt and the team concluded that allele-specific telomere length differences contribute to heterogeneity. Using a fibroblast cell line, they used the Telo-seq approach to sequence telomere length in bulk and study telomere shortening. Linear regression analysis and a donor set of DNA indicated that telomere length decreased with donor age. There may be chromosome-specific factors that affect length. The goal is to use Talo-seq to distinguish between TERT and Alt cancer cells. Additionally, since they are using native DNA, epigenetic information may lead to new regressions and analyses!
