Show simple item record

dc.creatorFlower, Michael
dc.creatorLomeikaite, Vilija
dc.creatorCiosi, Marc
dc.creatorCumming, Sarah
dc.creatorMorales Montero, Fernando
dc.creatorLo, Kitty
dc.creatorHensman Moss, Davina
dc.creatorJones, Lesley
dc.creatorHolmans, Peter A.
dc.creatorTRACK-HD Investigators
dc.creatorOPTIMISTIC Consortium
dc.creatorMonckton, Darren G.
dc.creatorTabrizi, Sarah J.
dc.date.accessioned2020-01-17T20:06:56Z
dc.date.available2020-01-17T20:06:56Z
dc.date.issued2019-07
dc.identifier.citationhttps://academic.oup.com/brain/article/142/7/1876/5520687es_ES
dc.identifier.issn1460-2156
dc.identifier.issn0006-8950
dc.identifier.urihttp://hdl.handle.net/10669/80324
dc.description.abstractHuntington’s disease and myotonic dystrophy type 1. A recent Huntington’s disease genome-wide association study found rs557874766, an imputed single nucleotide polymorphism located within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated with progression in Huntington’s disease. Using Illumina sequencing in Huntington’s disease and myotonic dystrophy type 1 subjects, we show that rs557874766 is an alignment artefact, the minor allele for which corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of somatic CAG CTG expansion (P = 0.004) and delayed disease onset (P = 0.003) in both Huntington’s disease and myotonic dystrophy type 1, and slower progression (P = 3.86 10 7) in Huntington’s disease. RNA-Seq of whole blood in the Huntington’s disease subjects found that repeat variants are associated with MSH3 and DHFR expression. A transcriptome-wide association study in the Huntington’s disease cohort found increased MSH3 and DHFR expression are associated with disease progression. These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion and disease phenotype in Huntington’s disease and myotonic dystrophy type 1, and suggests a common DNA repair mechanism operates in both repeat expansion diseases.es_ES
dc.description.sponsorshipUK DementiaResearch Institute/[]//Reino Unidoes_ES
dc.description.sponsorshipMedical Research Council/[MR/L010305/1]/MRC/Reino Unidoes_ES
dc.description.sponsorshipEuropean Union’s Seventh Framework Programme/[2012-305121]/FP7 2007-2013/Unión Europeaes_ES
dc.description.sponsorshipRosetrees Trust/[JS16/M574]//Reino Unidoes_ES
dc.language.isoen_USes_ES
dc.sourceBrain, vol. 142(7), 1876-1886es_ES
dc.subjectHuntington’s diseasees_ES
dc.subjectmyotonic dystrophyes_ES
dc.subjecttranscriptomicses_ES
dc.subjectmovement disorderses_ES
dc.subjectassociation studyes_ES
dc.titleMSH3 modifies somatic instability and disease severity in Huntington’s and myotonic dystrophy type 1es_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doihttps://doi.org/10.1093/brain/awz115
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)es_ES


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record