Expanding Mutations/Genetic Anticipation


Expanding or dynamic mutations are caused by the abnormal expansion of simple repetitive sequences, which are scattered throughout the genome. The phenotypic effects will depend on the localization of the unstable sequence (exonic, intronic, in the promoter or intergenic region), on the size of the expansion, on the lack of interruptions and on the sequence of the repeat unit, which may favour the formation of secondary structures. More than 20 genetic disorders due to expanding (or ‘dynamic’) mutations have been reported to date.

Keywords: simple repetitive sequences; trinucleotide repeats; dynamic mutations; genetic anticipation; chromosomal instability

Figure 1.

Expansion disorders due to SRS outside coding sequences.

Figure 2.

Expansion disorders due to SRS encoding polyglutamine (poly‐Q) tracts.

Figure 3.

Expansion disorders due to SRS encoding polyalanine (poly‐A) tracts.

Figure 4.

Slipped strand mispairing and small expansions/deletions.

Figure 5.

Multiple slippage events and larger expansions.



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Further Reading

Cummings CJ and Zoghbi HY (2000) Fourteen and counting: unraveling trinucleotide repeat diseases. Human Molecular Genetics 9: 909–916.

Parniewski P and Staczek P (2003) Molecular Mechanisms of TRS Instability. Georgetown, TX: Landes Bioscience.


Richards RI (2001) Dynamic mutations: a decade of unstable expanded repeats in human genetic disease. Human Molecular Genetics 10: 2187–2194.

Web pages on DNA repeat sequences and disease by the Neuromuscular Disease Center of the Washington University, St Louis, MO, USA. http://www.neuro.wustl.edu/neuromuscular/mother/dnarep.htm.

Web site of the Simple Sequence Repeat Database for the Human Genome, maintained at the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India. http://www.ccmb.res.in/ssr/.

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How to Cite close
Chiurazzi, Pietro, and Oostra, Ben A(Jan 2006) Expanding Mutations/Genetic Anticipation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001463]