A recent study published in Science reveals that telomere lengths do not follow the previously understood pattern. Instead of all chromosomes having a general range of shortest to longest telomere lengths, this study has found that different chromosomes have unique end-specific telomere length distributions.We rely on our cells to be able to multiply and divide for various purposes such as repairing sunburnt skin and replenishing our blood supply. Chromosomes contain our genetic instructions and must be accurately copied during cell division. Telomeres, which cap the ends of chromosomes, are crucial for this process and have a significant impact on our health and susceptibility to diseases. The enzyme telomerase is essential for maintaining the length of telomeres as chromosomes replicate during cell division. Caro, a professor at UC Santa Cruz, is studying the specific distribution of telomere lengths.l Greider has dedicated over 30 years to researching telomeres and telomerase, and her discoveries played a significant role in her Nobel Prize in Physiology or Medicine in 2009, which she shared with two colleagues. Despite her extensive knowledge in the field, Greider was surprised by the findings of her latest study on telomeres, which was published online in Science. The study revealed that telomere lengths do not follow the previously understood pattern of falling under one general range from shortest to longest across all chromosomes. Instead, the study found that different chromosomes have separate patterns for telomere lengths.The discovery of rate end-specific telomere-length distributions highlights our incomplete understanding of the molecular process that controls telomere lengths. This is significant because telomere lengths play a crucial role in human health. According to Greider, when telomeres become too short, it can lead to age-related degenerative diseases such as pulmonary fibrosis, bone-marrow failure, and immunosuppression. Conversely, excessively long telomeres can predispose individuals to certain types of cancer. Kayarash Karimian, the lead author of the paper, was a former Ph.D. student in Greider’s lab at Johns Hopkins University School.The study was conducted by researchers at the University of California, Santa Cruz, the Dana-Farber Cancer Institute, Harvard Medical School, and the University of Pittsburgh. Elizabeth Blackburn, a distinguished professor of molecular, cell, and developmental biology at UC Santa Cruz, and a University Professor at Johns Hopkins, was the senior author of the paper and led the study.
Importance of telomere length
If telomerase is not present, telomeres will shorten with each cell division. Research over the past 30 years has confirmed the link between short telomeres and degenerative diseases.Disease – as well as research has indicated that telomere lengths vary within a specific range.
However, this study challenges the established scientific agreement by demonstrating that a single range for telomere length is too broad. By examining the telomeres of 147 individuals, the scientists discovered that the average telomere length across all chromosomes was 4,300 bases of DNA in one person. However, when they examined specific chromosomes, they found that most telomere lengths varied significantly from this average. In one instance, the lengths varied by as much as 6,000 bases, which Greider describes as “astonishing.”
In addition, the researchers observed that the same pattern was present in all 147 individuals.Telomeres were frequently found to be either the shortest or longest, suggesting that the telomeres on specific ends of chromosomes might be the first to cause stem cell failure. The technique of nanopore sequencing, developed at UC Santa Cruz, was used by Greider’s team to make precise molecular-level measurements. This revolutionary method for reading DNA and RNA has had a huge impact on genomics research since it was introduced to the market as MinION in 2014. Nanopore technology has led to major advances in genomic research.The field has seen significant advancements, including the completion of a continuous human genome and the sequencing of COVID-19 genomes. This has become crucial in the fight against the pandemic. UC Santa Cruz licensed the idea for nanopore-sequencing technology to the UK-based company Oxford Nanopore Technologies, which created the MinION, the first hand-held DNA sequencer.
In the eyes of the inventors of nanopore sequencing, Greider’s study demonstrates that the technique’s potential to advance scientific research is still unfolding. Mark Akeson, emeritus professor of biomolecular engineering at UC Santa Cruz, highlights two preprint studies that support the basic findings of Greider.The paper by UC Santa Cruz researchers Akeson and Deamer has also been published online. Akeson stated, “In my opinion, this is the most important nanopore-based paper focused on human biology since the MinION was introduced. It is easy to envision broad use of their telomere-length assay in the clinic.” Akeson and David Deamer were honored at the Library of Congress last year for inventing nanopore sequencing. Their colleague Daniel Branton, a Harvard biologist and co-inventor of the technology, was also honored. This research has implications for disease prevention.
The precise DNA analysis conducted by Greider’s team allowed them to identify the specific sequences near telomeres. This led to the hypothesis that these areas are where telomerase controls the length of telomeres. If this is accurate, Greider noted that these regions and the proteins that bind to them could be potential targets for new drugs aimed at preventing disease.
Furthermore, the “telomere profiling” process using nanopore sequencing could be a valuable model for creating additional MinION-based assays for high-throughput drug screening.
Greider emphasized that this accessible technique has the potential to be widely used in research, diagnostics, and drug development.The author stated that this research suggests that there are still unknown methods for regulating the length of telomeres. Exploring these methods will provide new insights into cancer and certain degenerative diseases.”
The research titled “Human telomere length is chromosome end-specific and conserved across individuals,” was financially supported by grants from the National Institutes of Health (R35CA209974 to Greider and R01HL166265), the Johns Hopkins Bloomberg Distinguished Professorship, and the National Science Foundation Graduate Research Fellowship Program.
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