External Seminar : Jia-Xing Yue

Gianni LITI invites : Jia-Xing Yue – State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

« Telomere variation and inheritance at individual and population scales« 

Abstract: Telomeres are specialized repetitive DNA sequences located at the termini of eukaryotic nuclear chromosomes, protecting them from end-to-end fusion. Telomeres have important implications for genome integrity, aging, and cancer. Therefore, it is highly valuable to characterize their genomic variation and evolutionary dynamics at population scales. Towards this goal, we developed both targeted sequencing and computational profiling methods for comprehensive characterization of the length, sequence, and methylation variation of telomeres with chromosome-end-specific resolution. We validated both methods using a range of organisms with diverse telomeric repeat properties (e.g., human, mouse, and yeast), demonstrating impressive robustness and accuracy. Next, we applied our methods to characterize the haplotype-resolved telomere diversity of 233 representative human individuals enrolled in the Human Pangenome Reference Consortium (HPRC), revealing how geographical and ethnical origins shape the global variation landscapes of telomere lengths and sequences in human. Beyond characterizing natural telomere variation, we applied our methods to investigate telomere characteristics and neotelomere landscapes across TERT+ (telomerase positive) and ALT+ (alternative lengthening of telomeres) human cancer cell lines, revealing distinct mutational signatures underlying these two telomere maintenance mechanisms. Finally, with mouse and yeast models, we also looked into the telomere dynamics upon organismal aging and perturbations of genome integrity respectively. Taken together, we anticipate that our methods and findings will facilitate telomere studies at both individual and population levels across diverse organisms.