Chromosomal fragile site

Silencing of the FMR1 Gene in Fragile X Syndrome
Silencing of the FMR1 gene in Fragile X syndrome. FMR1 co-localizes with a rare fragile site, visible here as a gap on the long arms of the X chromosome.

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 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 in the FMR1 gene, which is associated with the fragile X syndrome, the most common cause of hereditary intellectual disability.

For a database of fragile sites in human chromosomes, see [5]

  1. ^ Sutherland, GR and Hecht, F: Fragile Sites on Human Chromosomes. New York and Oxford: Oxford University Press, 280 pages (1985).
  2. ^ Schwartz, M.; Zlotorynski, E.; Kerem, B. (2005), "The molecular basis of common and rare fragile sites", Cancer Letters, 232 (1): 13–26, doi:10.1016/j.canlet.2005.07.039, PMID 16236432
  3. ^ a b Lukusa, T.; Fryns, J.P. (2008), "Human chromosome fragility", Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1779 (1): 3–16, doi:10.1016/j.bbagrm.2007.10.005, PMID 18078840
  4. ^ Durkin, S.G.; Glover, T.W. (2007), "Chromosome fragile sites", Annual Review of Genetics, 41: 169–192, doi:10.1146/annurev.genet.41.042007.165900, PMID 17608616
  5. ^ Kumar, R.; Nagpal, G.; Kumar, V.; Usmani, S.S.; Agrawal, P.; Raghava, G. (2019), "HumCFS: a database of fragile sites in human chromosomes", BMC Genomics, 9 (Suppl 9): 985, doi:10.1186/s12864-018-5330-5, PMC 7402404, PMID 30999860