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Genetic modifiers of Mendelian disease: Huntington's disease and the trinucleotide repeat disorders

Holmans, Peter A. ORCID:, Massey, Thomas H. ORCID: and Jones, Lesley ORCID: 2017. Genetic modifiers of Mendelian disease: Huntington's disease and the trinucleotide repeat disorders. Human Molecular Genetics 26 (R2) , R83-R90. 10.1093/hmg/ddx261

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In the decades since the genes and mutations associated with the commoner Mendelian disorders were first discovered, technological advances in genetic analysis have made finding genomic variation a much less onerous task. Recently, the global efforts to collect subjects with Mendelian disorders, to better define the disorders and to empower appropriate clinical trials, along with improved genetic technologies, have allowed the identification of genetic variation that does not cause disease, but substantially modifies disease presentation. The advantage of this is it identifies biological pathways and molecules, that, if modified in people, might alter disease presentation. In Huntington’s disease (HD), caused by an expanded CAG repeat tract in HTT, genetic variation has been uncovered that is associated with change in the onset or progression of disease. Some of this variation lies in genes that are part of the DNA damage response, previously suggested to be important in modulating expansion of the repeat tract in germline and somatic cells. The genetic evidence implicates a DNA damage response-related pathway in modulating the pathogenicity of the repeat tracts in HD, and possibly, in other trinucleotide repeat disorders. These findings offer new targets for drug development in these currently intractable disorders.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Oxford University Press
ISSN: 0964-6906
Date of First Compliant Deposit: 25 July 2017
Date of Acceptance: 3 July 2017
Last Modified: 07 Mar 2023 16:32

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