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What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Although most lymphoblastoid cell lines (88%) showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting <jats:italic>in cis<\/jats:italic> to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2350-10-11","type":"journal-article","created":{"date-parts":[[2009,2,11]],"date-time":"2009-02-11T19:14:30Z","timestamp":1234379670000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["DNA instability in replicating Huntington's disease lymphoblasts"],"prefix":"10.1186","volume":"10","author":[{"given":"Milena","family":"Cannella","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Maglione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Martino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Ragona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Frati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Squitieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,2,11]]},"reference":[{"key":"425_CR1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","volume":"72","author":"The Huntington's Disease Collaborative Research Group","year":"1993","unstructured":"The Huntington's Disease Collaborative Research Group: A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. 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