A chromosomal fragile site is a specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break [1]when the cell is exposed to partial replication stress. [2] Based on their frequency, fragile sites are classified as "common" or "rare".[3] To date, more than 120 fragile sites have been identified in the human genome.[3][4]
Common fragile sites are considered part of normal chromosome structure and are present in all (or nearly all) individuals in a population. Under normal conditions, most common fragile sites are not especially prone to spontaneous breaks. Common fragile sites are of interest in cancer studies because they are frequently affected in cancer and they can be found in healthy individuals. Sites FRA3B (harboring the FHIT gene) and FRA16D (harboring the WWOX gene) are two well known examples and have been a major focus of research.
Rare fragile sites are found in less than 5% of the population, and are often composed of two- or three-nucleotide repeats. They are often susceptible to spontaneous breakage during replication, frequently affecting neighboring genes. Clinically, the most important rare fragile site is FRAXA, which is associated with the fragile X syndrome, the most common cause of hereditary mental retardation.
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