Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/20476

TitleSequence analysis of 5' regulatory regions of the Machado-Joseph Disease gene (ATXN3)
Author(s)Bettencourt, C.
Raposo, Mafalda
Kazachkova, Nadiya
Santos, Cristina
Kay, Teresa
Vasconcelos, João
Maciel, P.
Donis, Karina
Pereira, Maria Luiza Saraiva
Jardim, Laura
Sequeiros, Jorge
Armas, Jácome Bruges
Lima, M.
KeywordsAtaxin-3
5′ regulatory regions
5′ UTR
MJD
Promoter
SCA3
Issue dateMar-2012
PublisherSpringer
JournalCerebellum
Abstract(s)Machado–Joseph disease (MJD) is a late-onset autosomal dominant neurodegenerative disorder, which is caused by a coding (CAG)n expansion in the ATXN3 gene (14q32.1). The number of CAG repeats in the expanded alleles accounts only for 50 to 75 % of onset variance, the remaining variation being dependent on other factors. Differential allelic expression of ATXN3 could contribute to the explanation of different ages at onset in patients displaying similar CAG repeat sizes. Variation in 5′ regulatory regions of the ATXN3 gene may have the potential to influence expression levels and, ultimately, modulate the MJD phenotype. The main goal of this work was to analyze the extent of sequence variation upstream of the ATXN3 start codon. A fragment containing the core promoter and the 5′ untranslated region (UTR) was sequenced and analyzed in 186 patients and 59 controls (490 chromosomes). In the core promoter, no polymorphisms were observed. In the 5′ UTR, only one SNP (rs3814834) was found, but no improvements on the explanation of onset variance were observed, when adding its allelic state in a linear model. Accordingly, in silico analysis predicted that this SNP lays in a nonconserved position for CMYB binding. Therefore, no functional effect could be predicted for this variant.
TypeArticle
URIhttp://hdl.handle.net/1822/20476
DOI10.1007/s12311-012-0373-7
ISSN1473-4222
1473-4230
Publisher versionhttp://www.springerlink.com/
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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