Telomeres and Human Disease

Telomeres, the long nucleotide repeats, and protein complex at chromosome ends, are central to genomic integrity. Telomere length (TL) varies widely between populations due to germline genetics, environmental exposures, and other factors. Very short telomeres caused by pathogenic germline variants in telomere maintenance genes cause the telomere biology disorders, a spectrum of life-threatening conditions including bone marrow failure, liver and lung disease, cancer, and other complications. Cancer predisposition with long telomeres is caused by rare pathogenic germline variants in components of the shelterin telomere protection protein complex and associated primarily with elevated risk of melanoma, thyroid cancer, sarcoma, and lymphoproliferative malignancies. In the middle, studies of the general population at risk of common illnesses, such as cardiovascular disease and cancer, have found statistically significant differences in TL but uncertain clinical applicability. This work reviews connections between telomere biology and human disease focusing on similarities and differences across the phenotypic spectrum.