Going to New Lengths to Measure Chromosome Ends
A novel sequencing-based method revealed chromosome-specific telomere lengths, challenging prior models.
Telomeres protect crucial functional regions of DNA, however the regulation of their length remains poorly understood. One model suggests that all telomeres are maintained around an average length but another model points to chromosome-specific lengths. This discrepancy is in part due to the difficulty in accurately measuring telomeres.
To overcome these limitations, one group adapted nanopore sequencing to quantify individual telomere lengths. The new method, Telomere Profiling, and study findings, published in Science, demonstrated that telomere lengths are specific to chromosomes and not globally maintained.1
“It's very exciting because it gives us an inroad into understanding new mechanisms that might be involved in telomere length regulation,” said Carol Greider, a molecular biologist and geneticist at the University of California, Santa Cruz and study author.
Greider’s team isolated all telomeres from peripheral blood mononuclear cells (PBMCs) from volunteers spanning a range of ages using biotin-labeled tags, sequenced them, and quantified the distance from the chromosome end to the subtelomere region. They observed that telomere lengths varied in an age-dependent manner. When they compared Telomere Profiling to two other telomere measuring techniques, Southern blot and flow cytometry fluorescent in situ hybridization, and observed similar measurements.
The researchers then measured individual chromosome telomeres in a cell line with a reference genome and identified chromosome-specific length distributions. They found a similar trend when they applied Telomere Profiling to PBMCs from 147 volunteers. Additionally, they observed that certain chromosomes were consistently shorter or longer than others and that these lengths were present at birth.
“[This method] will allow more detailed studies of these length differences,” said Peter Lansdorp, a stem cell biologist at the BC Cancer Research Centre and cofounder of Repeat Diagnostics, a telomere testing service for medical professionals. He said that the method could be more accessible than other techniques and more accurate than quantitative PCR, a currently used approach. “[This approach] opens up new avenues for trying to understand where these chromosome-specific differences in telomere length come from.”
- Karimian K, et al. Science. 2024;384(6695):533-539.