Measuring Exact Telomere Length

OVERVIEW

Researchers at Georgetown University’s Department of Oncology developed a novel DNA fluorescent in situ hybridization (DNA-FISH) assay to rapidly measure the absolute lengths (base pairs) of single telomere molecules using conventional fluorescent microscopy with high precision and sensitivity. The method can measure telomeres as small as 100 base-pairs, with high accuracy, and is compatible with all non-degraded sources of DNA. The method is relatively inexpensive and is well suited for high-throughput use and large population studies. Furthermore, it is capable of measuring telomere length distribution, generating four telomere parameters. These parameters provide a depiction not only of telomere lengths but also length distributions, and are improved telomere biomarkers to delineate the relationships between telomere characteristics and environmental exposures, psychosocial stress, aging, disease susceptibility and progression.

BACKGROUND

Despite intense interest in the relationships between telomere biology and human disease, a method that can truly assess the changes in telomere constitution using DNA samples is currently not available. A number of methods exist for measuring telomere lengths, but most are either too laborious, unable to provide absolute measurement of individual telomere lengths, or limited to certain chromosomes or cell types.

Benefit

• Method determines telomere length using fluorescent probes and digital image analysis
• Relatively inexpensive and well suited for high-throughput use and large population studies
• Ability to determine at least one of the following for each sample of genomic DNA, and each chromosomal arm—average telomere length per telomere, telomere length variation, frequency of short telomeres (≤1 kb in length), and frequency of long telomeres (≥15 kb in length)
• High accuracy—using a series of cloned telomere molecules (0.1, 0.2, 0.4, 0.9, 1.2 and 2.4 kb), the correlation between telomere length measured by DNA-FISH and telomere length measured by sequencing is 0.99
• Efficiency and compatibility—this DNA-FISH method of telomere length measurement uses a small amount (e.g., 200 ng) of DNA and the works well with all sources of non-degraded genomic DNA, as no enzymatic reaction is required

Market Application

A novel diagnostic method for obtaining patient telomere length data through the collection, processing, and analysis of genomic DNA derived from a biological sample.

Publications

• Fluorescence spectroscopic detection and measurement of single telomere molecules (DOI: https://doi.org/10.1093/nar/gky627) (link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212783/)
• U.S. Patent no. 17/630,424