Fragile Sites


Fragile sites are specific points on chromosomes that show nonrandom gaps or breaks when the cells from which the chromosomes have been prepared have been exposed to a specific chemical agent or condition of tissue culture. Hence a fragile site is an area of chromatin which is not compacted when viewed in mitosis.

Keywords: fragile X syndrome; Jacobsen syndrome; trinucleotide repeat; fragile site; FRAXA; FRAXE

Figure 1.

Partial metaphases showing the appearance of various fragile sites (arrowed): (a) the fragile X (FRAXA); (b) common fragile site FRA3B; (c) common BrdU‐inducible fragile site FRA6D; (d) rare distamycin A‐inducible fragile site FRA16B showing duplication of chromosome material distal to the fragile site; (e) rare folate‐sensitive fragile site FRA22A; and (f) rare folate‐sensitive fragile site FRA2B. (Courtesy of Elizabeth Baker.)



Hewett DR, Handt O, Hobson L et al. (1998) FRA10B structure reveals common elements in repeat expansion and chromosomal fragile site genesis. Molecular Cell 1: 773–781.

Human Genome Nomenclature Database (2006)‐bin/nomenclature/ (Lists approved names, literature aliases and withdrawn symbols, with links to further information).

Inoue H, Ishii H, Alder H et al. (1997) Sequence of the FRA3B common fragile region: implications for the mechanisms of FHIT deletion. Proceedings of the National Academy of Sciences of the USA 94: 14584–14589.

Nolin SL, Brown WT, Glicksman A et al. (2003) Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. American Journal of Human Genetics 72: 454–464.

Ried K, Finnis M, Hobson L et al. (2000) Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Human Molecular Genetics 9: 1651–1663.

Sherman SL (2000) Premature ovarian failure in the fragile X syndrome. American Journal of Medical Genetics 97: 189–194.

Sherman SC, Jacobs PA, Morton NE et al. (1985) Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Human Genetics 69: 289–299.

Sutherland GR (1991) The detection of fragile sites on human chromosomes. In: Adolph KW (ed.) Advanced Techniques in Chromosome Research, pp. 203–222. New York, NY: Marcel Dekker

Sutherland GR (1993) Human fragile sites. In: O’Brien SJ (ed.) Genetic Maps, vol. VI, pp. 5.264–5.267. Woodbury, NY: Cold Spring Harbor Laboratory Press

Turner G, Webb T, Wake S and Robinson H (1996) Prevalence of fragile X syndrome. American Journal of Medical Genetics 64: 196–197.

Willemsen R, Mientjes E and Oostra BA (2005) FXTAS: a progressive neurologic syndrome associated with Fragile X premutation. Current Neurology and Neuroscience Reports 5: 405–410.

Yu S, Mangelsdorf M, Hewett D et al. (1997) Human chromosomal fragile site FRA16B is an amplified AT‐rich minisatellite repeat. Cell 88: 367–374.

Further Reading

Gecz J and Sutherland GR (2003) (eds) Nucleotide and protein expansions and human disease. Cytogenetics and Genome Research 100: 1–298.

Hagerman RJ and Cronister A (1996) Fragile X Syndrome, 2nd edn Baltimore, MD: Johns Hopkins University Press.

NCBI (2006) Fragile site, folic acid type, rare, fra(X)(q28) (FRAXE); Locus ID: 2481. LocusLink:

NCBI (2006) Fragile site, folic acid type, rare, fra(11)(q23.3) (FRA11B); Locus ID: 2439. LocusLink:

NCBI (2006) Fragile X mental retardation 1 (FMR1); Locus ID: 2332. LocusLink:

OMIM (2006) Fragile site, folic acid type, rare, fra(X)(q28) (FRAXE); MIM number: 309548.‐post/Omim/ dispmim?309548

OMIM (2006) Fragile site, folic acid type, rare, fra(11)(q23.3) (FRA11B); MIM number: 600651.‐post/Omim/ dispmim?600651

OMIM (2006) Fragile X mental retardation 1 (FMR1); MIM number: 309550.‐post/Omim/ dispmim?309550

Schwartz M, Zlotorynski E and Kerem B (2006) The molecular basis of common and rare fragile sites. Cancer Letters 232: 13–26.

Sutherland GR, Baker E and Richards RI (1996) Fragile sites. Encyclopedia of Molecular Biology and Molecular Medicine, vol. 2, pp. 313–318. New York, NY: Wiley‐Interscience.

Sutherland GR and Hecht F (1985) Fragile Sites on Human Chromosomes. New York, NY: Oxford University Press.

Sutherland GR and Richards RI (1999) Fragile sites – cytogenetic similarity with molecular diversity. American Journal of Human Genetics 64: 354–359.

Wells RD and Warren ST (1998) Genetic Instabilities and Hereditary Neurological Diseases. San Diego, CA: Academic Press.

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How to Cite close
Sutherland, Grant R(Apr 2007) Fragile Sites. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005547.pub2]