Nanopore sequencing reveals conservation of chromosome end-specific telomere lengths

Abstract
Short telomeres cause age-related disease and long telomeres predispose to cancer, yet the mechanisms regulating telomere length are unclear. We first developed telomere length measurement in yeast using Oxford Nanopore technology. Here, we describe a telomere profiling assay for human cells using nanopore sequencing that is easy to implement, precise, and cost effective. The method has broad applications for research and potentially the clinic in the future. Using patient samples our method returned similar length measurements to the clinical standard of FlowFISH. We mapped telomere length distributions to specific chromosome ends and identified both chromosome-specific and haplotype-specific telomere lengths. For HG002, which showed a global mean telomere length of 4.4 kb, for some chromosome ends there was a remarkable 6 kb difference in mean telomere length between maternal and paternal haplotypes. We examined telomere length across 150 individuals and found that specific chromosome ends were consistently shorter or longer than the average length. Our data call for development of new models of telomere length regulation. Understanding the mechanisms regulating conserved chromosome end-specific telomere lengths will allow deeper insights into telomere biology that can lead to new approaches to disease.

Biography

Carol Greider is a Distinguished Professor of Molecular, Cell and Developmental Biology at University California, Santa Cruz (UCSC). She received a B.A. from UC Santa Barbara and a PhD from UC Berkeley. In 1984, working with Dr. Elizabeth Blackburn, she discovered telomerase, the enzyme that maintains telomeres. Carol was an independent fellow before joining the faculty at Cold Spring Harbor Laboratory, New York between 1988 and 1997, then she moved to Johns Hopkins University School of Medicine. Carol shared the 2009 Nobel Prize in Physiology or Medicine with Dr. Elizabeth Blackburn and Dr. Jack Szostak for their work on telomeres and telomerase. In 2020, Carol moved to UCSC where her group studies telomere length regulation.