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Over a disease-gene carrier's life, the length of the repeat can expand in somatic cells, through the process of somatic expansion which is hypothesised to drive disease progression. Despite being monogenic, individual REDs are phenotypically variable, and exploring what genetic modifying factors drive this phenotypic variability has illuminated key pathogenic mechanisms that are common to this group of diseases. Disease phenotypes are affected by the cognate gene in which the expansion is found, the location of the repeat sequence in coding or non-coding regions and by the presence of repeat sequence interruptions. Human genetic data, mouse models and in vitro models have implicated the disease-modifying effect of DNA repair pathways via the mechanisms of somatic mutation of the repeat tract. As such, developing an understanding of these pathways in the context of expanded repeats could lead to future disease-modifying therapies for REDs.<\/jats:p>","DOI":"10.1042\/etls20230015","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T11:04:16Z","timestamp":1697799856000},"page":"325-337","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Genetic modifiers of repeat expansion disorders"],"prefix":"10.1042","volume":"7","author":[{"given":"Sangeerthana","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"1UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, U.K."},{"name":"2UK Dementia Research Institute, University College London, London WCC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Donaldson","sequence":"additional","affiliation":[{"name":"1UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, U.K."},{"name":"2UK Dementia Research Institute, University College London, London WCC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Flower","sequence":"additional","affiliation":[{"name":"1UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, U.K."},{"name":"2UK Dementia Research Institute, University College London, London WCC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina J.","family":"Hensman Moss","sequence":"additional","affiliation":[{"name":"1UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, U.K."},{"name":"2UK Dementia Research Institute, University College London, London WCC1N 3BG, U.K."},{"name":"3St George's University of London, London SW17 0RE, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-2208","authenticated-orcid":false,"given":"Sarah J.","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"1UCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, U.K."},{"name":"2UK Dementia Research Institute, University College London, London WCC1N 3BG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2023,10,20]]},"reference":[{"key":"2023121411240772800_ETLS-2023-0015CC1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.gde.2017.01.012","article-title":"A genomic view of short tandem repeats","volume":"44","year":"2017","journal-title":"Curr. 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