PhD defence
Decoding Telomere Gene Variation through Saturation Genome Editing: From Functional Genomics to Clinical Interpretation
- S. Obolenski-Koenig
- Date
- Thursday 24 September 2026
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prof.dr. R van Doorn
- dr. D.J. Adams
Summary
Telomeres protect the ends of our chromosomes and help prevent DNA damage. Changes in genes that regulate telomeres, such as POT1 and TINF2, can increase the risk of cancer and other telomere-related disorders. However, genetic testing often identifies variants whose effects are unknown. This can leave patients and their families without a clear diagnosis or appropriate advice about medical monitoring.
In this thesis, I investigated whether saturation genome editing, a method that allows thousands of genetic variants to be tested simultaneously in human cells, can improve the interpretation of these uncertain variants. I created detailed functional maps for POT1 and TINF2, showing which variants disrupt the normal function of these genes.
The results show that harmful variants are particularly concentrated in regions of the proteins that are important for binding DNA or interacting with other telomere proteins. For POT1, loss of function was associated with telomere damage and a higher occurrence of cancer. For TINF2, the findings supported a broader tumour spectrum, including melanoma, thyroid cancer, kidney cancer, sarcoma and brain tumours.
This research is distinctive because it combines laboratory experiments, telomere measurements, patient information and population-level data. The resulting functional maps could help improve the interpretation of genetic test results, reduce the number of variants classified as uncertain, and provide patients and families with clearer information about their potential cancer risk.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
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