Tell me more – telomere biology and understanding telomere defects

Abstract

Telomeres are DNA-protein structures at the ends of chromosomes that maintain chromosome stability and protects them from damage during mitosis and prevents abnormal fusion with adjacent chromosomes. They are non-coding repeats of the (TTAGGG)n nucleotide sequence. Telomere length affects cell replication potential and cell senescence. There are numerous proteins and enzymes that protect and maintain telomere length. Telomere disorders are a heterogenous group of diseases caused by germline pathogenic variants in genes involved in telomere maintenance. The clinical features are variable but often include bone marrow failure, idiopathic pulmonary fibrosis (IPF), liver cirrhosis, premature greying of hair, and dysplastic nails. However, incomplete penetrance and variable expressivity influence the clinical phenotype in individuals, which results is underdiagnosis or late diagnosis for many patients. At birth, telomere length on average in white blood cells (WBCs) is estimated to be 10Kb and the rate of attrition ranges from 27–41 base pairs each year. There are many factors that affect telomere length but genetics plays a significant role. Also, telomere length can vary in different cells in the same individual based on variable local gene expression. Idiopathic pulmonary fibrosis (IPF) is the most common telomere defect and approximately 30% of patients with sporadic or familial IPF have genetic defects in telomere-related genes. This talk will cover fundamental concepts of telomeres and discuss short and long telomere defects and measurement of telomere length in the clinical laboratory.