ABSTRACT Telomere-associated diseases, including telomere biology disorders (TBD), are prevalent among the aging population. TBD represent a group of most common premature aging syndromes, including dyskeratosis congenita (DC), aplastic anemia, and idiopathic pulmonary fibrosis (IPF), etc. The diagnosis of TBDs can be challenge due to the variable, complex, and time-dependent nature of clinical manifestations. Genetic testing may be inconclusive because a significant portion of patients do not have an identifiable genetic cause. Telomere length testing has been shown to aid in DC diagnostics. However, a low-cost and accurate telomere length test is not available as a first line diagnostic or screening tool for the early detection of TBDs and other telomere-associated diseases. We propose to develop a DNA array and fluorescent in situ hybridization (FISH)-based method to measure the absolute lengths of individual telomeres. The goal is to develop a low-cost, accurate, and high-throughput telomere test that uses a small amount of DNA, thus the test will be applicable to any cell/tissue type which DNA can be extracted from. This next-generation telomere test not only measures average telomere length, but also telomere length distribution, thus providing a detailed telomere length profile for a patient. We anticipate that additional details in telomere length distribution will enhance the diagnostic accuracy of telomere-associated diseases because it is well documented that accumulation of critically short telomeres during aging or by environmental assaults is responsible for the telomere-driven pathologies. In this phase I study, we propose the following two aims: 1) validate the optimized experimental conditions for accuracy in the measurement of telomere length; 2) determine the impact of DNA extraction methods on telomere length measurement. Phase I aims will lay the foundation for the Phase II study which will establish a new, accurate, low-cost, and high-throughput telomere length assay and generate a marketable telomere diagnostic test to enhance the diagnosis and management of telomere-associated diseases. Given the rapid increase in the aging population and the relevance of telomere biology in human aging-related diseases, we anticipate the potential market for the test will be large.