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|Title:||Inter-individual genetic variability in the expression frequency of the common fragile site FRAXB among healthy persons||Authors:||Ahmad Nachar, Baraah Al||Advisors:||Achkar, Eliane El||Subjects:||Cancer--Molecular aspects
Cancer is a genetic disease characterized by uncontrolled cellular proliferation and reprogramming of genetic information. Oncogenic stress found in cancers is associated with genomic instability triggering DNA breakages that seem to colocalize with preferential sites called fragile sites (FS). FS are site-specific breaks, gaps or decondensations expressed on metaphase chromosomes when cells are cultured under replication stress. They are classified according to their frequency into rare and common fragile sites (CFS). CFS are present in all individuals and are mainly induced by aphidicolin (APH), a partial inhibitor of DNA polymerases , and . Previous cytogenetic studies suggested that there is variation in CFS expression frequency among individuals. However, no molecular studies have been done to detect if there is CFS expression variability at hotspots of breakage between normal individuals. In this study, we propose to determine the expression frequency of FRAXB, a CFS located at Xp22.31 and one of the most CFS expressed in the human genome, in healthy persons of different ages. Blood samples from 11 donors were collected, cultured for 4 days and lymphocytes were then treated with 0.2 µg/ml of APH. RP11-483M24, a BAC probe specific for a hotspot of breakage within FRAXB was used in FISH in order to detect breaks on this site. One hundred fluorescent signals were analyzed per donor using fluorescence microscopy. The results show that the percentage of breakage ranges from 6% to 25% with several folds increase among 6 females in the twenties and from 3% to 19% among 3 males of the same age suggesting the presence of a variability among individuals of same age and gender. . In addition, the percentage of breakage in a male in forties and a female in fifties are 7% and 10% respectively, suggesting that the expression of FRAXB is age independent. Such inter-individual variability in CFS expression could be due to difference in the genetic background of these subjects and can explain why there is variability in cancer incidence among individuals with the same age subjected to the same environmental conditions and same mutagens. This finding can be used as a biomarker for cancer prevention.
Includes bibliographical references (p.76-94).
Supervised by Dr. Eliane El Achkar.
|URI:||https://scholarhub.balamand.edu.lb/handle/uob/4238||Rights:||This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder||Ezproxy URL:||Link to full text||Type:||Thesis|
|Appears in Collections:||UOB Theses and Projects|
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