Nanopore sequencing of telomere length unlocks new insights into age-related degeneration, cancer and disease prevention

Oxford Nanopore Technologies (Oxford Nanopore) sequencing technology has been used in a breakthrough study unlocking new ways to measure human telomere length, providing key insights into the correlation between telomeres and age-related disease or predisposition to cancer. The researchers behind the study, led by Nobel laureate Professor Carol Greider, demonstrated that the length of telomeres – the caps at the ends of chromosomes -- are determined at birth and that human health is profoundly affected by it, highlighting the utility of telomere profiling as a potentially powerful area of investigation for preventative health and drug discovery efforts.

The nucleus of every human cell contains chromosomes which carry genetic instructions that guide human growth and development. Telomeres play a critical role in cell renewal in health and disease with short telomeres often manifesting in age-related degenerative diseases and long telomeres predisposing to cancer. However, the detailed mechanism of length regulation has been poorly understood, until now.

In a new publication in the journal Science, a team of researchers led by Professor Carol Greider of University of California Santa Cruz, a telomere scientist who was awarded the Nobel Prize in Physiology or Medicine in 2009, in collaboration with the Johns Hopkins University School of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, and University of Pittsburgh, outlined a new method to examine telomere length in detail. Over the past 30 years, research by Greider and others has confirmed that short telomeres can lead to degenerative disease and that telomere lengths can vary significantly. The new study builds on that knowledge, examining the individual telomere lengths of 147 people to show that most telomere lengths vary wildly not only amongst people but also amongst chromosomes within the same person.

In results that Greider described as “jaw dropping” in a press release , they also found that across the 147 individuals, the same telomeres were often the shortest or longest, implying telomeres on specific chromosome ends may be the first to trigger stem-cell failure – and offer insight into specific targets for more clinical study and possible drug discovery.

Nanopore sequencing’s precise native DNA reads enabled Greider’s team to pinpoint the area where the enzyme, telomerase, regulates length. Greider said those regions, and the proteins that bind there, could serve as potential targets for new drugs to prevent disease. In addition, the process of “telomere profiling” via nanopore sequencing could serve as a model for the development of additional MinION-based assays for high-throughput drug screening.

This breakthrough research was only made possible because of nanopore sequencing’s unique features, which for the first-time enabled scientists to see long telomere-length reads at ultra-rich, nearly single nucleotide resolution. This capability has led to an increase in telomere-based interest. In November 2023, a team led by Oxford Nanopore and the Karlseder lab at Salk Institute for Biological Studies published a pre-print demonstrating the utility of a new workflow, Telo-seq, to study telomere biology during development, aging and cancer at unprecedented resolution.

Telo-seq is now available to researchers in early access. To find out more or register your interest, click here: https://register.nanoporetech.com/telo-seq

Gordon Sanghera, CEO, Oxford Nanopore Technologies, commented:

"Today marks a significant milestone not just for Oxford Nanopore but for the field of genomics. This breakthrough illustrates that what you’re missing matters in genomics, showcasing the benefits of richer insights to capture more types of genetic variation and unravel the mysteries of biology. It's also a step towards new healthcare solutions, offering novel avenues for the prevention and treatment of age-related diseases and cancer. We are proud to be at the forefront of this research, empowering scientists worldwide with tools that unlock unprecedented genomic insight.

Sissel Juul, VP of Applications, Oxford Nanopore Technologies, commented:

“The findings from this study highlight a path forward in understanding complex genetic mechanisms surrounding telomere-length variation. It was made possible only because of the unique benefits of nanopore sequencing, which enabled long, native, unbiased reads that are able to solve the complexity of telomeres and would have been impossible with other sequencing technology.”

Join us for our annual customer event, London Calling! This year we will be celebrating the 10-year anniversary of our annual community event in London. Carol Greider will be giving a keynote discussing nanopore sequencing and its use in the study of telomere lengths. To find out more and register, click here: https://nanoporetech.com/about/events/conferences/lc24/agenda