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Repeat instability as the basis for human diseases and as a potential target for therapy

Nature Reviews Molecular Cell Biology volume 11, pages 165–170 (2010)Cite this article

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Abstract

Expansions of repetitive DNA sequences cause numerous human neurological and neuromuscular diseases. Ongoing repeat expansions in patients can exacerbate disease progression and severity. As pathogenesis is connected to repeat length, a potential therapeutic avenue is to modulate disease by manipulating repeat expansion size — targeting DNA, the root-cause of symptoms. How repeat instability is mediated by DNA replication, repair, recombination, transcription and epigenetics may explain its contribution to pathogenesis and give insights into therapeutic strategies to block expansions or induce contractions.

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Figure 1: Contributors to trinucleotide repeat instability.
Figure 2: Repair and somatic repeat instability.

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Acknowledgements

We apologize to colleagues whose work could not be cited owing to size limitations. Many citations are included in Supplementary information S1 and S2. Work in the Pearson laboratory is supported by the Muscular Dystrophy Association, USA, the Canadian Institutes of Health Research (CIHR) and the University of Rochester Paul Wellstone Muscular Dystrophy Cooperative Research Center, with support from the National Institutes of Health (U54NS48843), a CIHR fellowship (JDC) and the Hospital for Sick Children Research Training Centre (ALC).

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Authors and Affiliations

  1. Arturo López Castel, John D. Cleary and Christopher E. Pearson are at the Program of Genetics & Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15-312, TMDT Toronto, Ontario, Canada, M5G 1L7.,

    Arturo López Castel, John D. Cleary & Christopher E. Pearson

  2. John D. Cleary and Christopher E. Pearson are also at the Department of Molecular Genetics, University of Toronto, Canada.,

    John D. Cleary & Christopher E. Pearson

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  1. Arturo López Castel
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Correspondence to Christopher E. Pearson.

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DATABASES

OMIM

DM1

FRAXA

FRAXE

FRDA

HD

SBMA

SCA7

SCA8

SCA10

SCA31

FURTHER INFORMATION

Christopher E. Pearson's homepage

Unstable microsatellites and human disease

Human DNA repair genes

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López Castel, A., Cleary, J. & Pearson, C. Repeat instability as the basis for human diseases and as a potential target for therapy. Nat Rev Mol Cell Biol 11, 165–170 (2010). https://doi.org/10.1038/nrm2854

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