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Budworth H, McMurray CT. Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity. Rare Dis. 2016;4(1):e1131885doi: 10.1080/21675511.2015.1131885.
Budworth, H., & McMurray, C. T. (2016). Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity. Rare diseases (Austin, Tex.), 4(1), e1131885. https://doi.org/10.1080/21675511.2015.1131885
Budworth, Helen, and McMurray, Cynthia T. "Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity." Rare diseases (Austin, Tex.) vol. 4,1 (2016): e1131885. doi: https://doi.org/10.1080/21675511.2015.1131885
Budworth H, McMurray CT. Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity. Rare Dis. 2016 Feb 18;4(1):e1131885. doi: 10.1080/21675511.2015.1131885. eCollection 2016. PMID: 27141411; PMCID: PMC4838321.
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Rare Dis. 2016 Feb 18;4(1):e1131885. doi: 10.1080/21675511.2015.1131885. eCollection 2016.

Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity.

Rare diseases (Austin, Tex.)

Helen Budworth, Cynthia T McMurray

Affiliations

  1. Life Sciences Division, Lawrence Berkeley National Laboratory , Berkeley, CA, USA.

PMID: 27141411 PMCID: PMC4838321 DOI: 10.1080/21675511.2015.1131885

Abstract

Huntington's Disease is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. Whether somatic expansion contributed to toxicity was unknown. From extensive work from multiple laboratories, it has been made clear that toxicity depended on length of the inherited allele, but whether preventing or delaying somatic repeat expansion in vivo would be beneficial was unknown, since the inherited disease allele was still expressed. In Budworth et al., we provided definitive evidence that suppressing the somatic expansion in mice substantially delays disease onset in littermates that inherit the same disease-length allele. This key discovery opens the door for therapeutic approaches targeted at stopping or shortening the CAG tract during life. The analysis was difficult and, at times, non-standard. Here, we take the opportunity to discuss the challenges, the analytical solutions, and to address some controversial issues with respect to expansion biology.

Keywords: DNA repair; OGG1 DNA glycosylase; huntington's Disease; oxidative DNA damage; somatic expansion; trinucleotides; triplet repeat expansions

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