| Grant number: | 11/16177-1 |
| Support type: | Scholarships in Brazil - Master |
| Effective date (Start): | March 01, 2012 |
| Effective date (End): | February 28, 2014 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal researcher: | Rodrigo do Tocantins Calado de Saloma Rodrigues |
| Grantee: | Fernanda Gutierrez Rodrigues |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract Telomeres consist of long TTAGGG tandem repeats coated by DNA-binding proteins (shelterins) at the end of chromosomes. Telomeres have important functions in the stability and replication of chromosomes and in the maintenance of cell proliferative capacity, preventing the activation of DNA-damage responses and genome instability. That DNA polymerase is intrinsically unable to fully duplicate telomeres during cell division causes telomere shortening after every mitosis. The gradual loss of telomere repeats contributes to replicative senescence, apoptosis, and neoplastic transformation. To avoid telomere attrition, germ-line cells and some somatic cells produce an enzyme termed telomerase. Mutations in the telomerase complex genes or in the telomere-protecting proteins (shelterin) cause telomere erosion and, thus yielding dysfunctional telomeres. The pathologic bone marrow failure, hepatic cirrhosis, idiopathic pulmonary fibrosis, and a proclivity to cancer, now termed "telomere diseases". Telomere length measurement has important implications for diagnosis, clinical management, and therapy in telomere diseases. For all these reasons, an accurate and efficient telomere length measurement method has particular importance to understand the fundamental biology of telomere maintenance as well to contribute to the improvement of diagnostic services. Several techniques can be used to measure telomeres: Southern blot, quantitative PCR, FISH and Flow-FISH. However, the method that appears to be more accurate and reproducible in the clinic is Flow-FISH. In Brazil, there is no clinical laboratory that measures telomere length for clinical purposes and flow-FISH is still restricted to a few laboratories in Canada and Europe. The main goal of the present study is to evaluate the flow-FISH performance for telomere length measurement in nucleated blood cells from patients with marrow failure syndromes and idiopathic pulmonary fibrosis, aiming to implement this technique as an instrumental in the diagnostic service of these diseases. (AU) | |
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