Linked Life Data

19676102

Source:http://linkedlifedata.com/resource/pubmed/id/19676102

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-26
pubmed:abstractText
The spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by gait and limb ataxia. This disease is caused by the expansion of a (CAG)(n) located in the ATXN2, that encodes a polyglutamine tract of more than 34 repeats. Lately, alleles with 32-33 CAGs have been associated to late-onset disease cases. Repeat interruptions by CAA triplets are common in normal alleles, while expanded alleles usually contain a pure repeat tract. To investigate the mutational origin and the instability associated to the ATXN2 repeat, we performed an extensive haplotype study and sequencing of the CAG/CAA repeat, in a cohort of families of different geographic origins and phenotypes. Our results showed (1) CAA interruptions also in expanded ATXN2 alleles; (2) that pathological CAA interrupted alleles shared an ancestral haplotype with pure expanded alleles; and (3) higher genetic diversity in European SCA2 families, suggesting an older European ancestry of SCA2. In conclusion, we found instability towards expansion in interrupted ATXN2 alleles and a shared ancestral ATXN2 haplotype for pure and interrupted expanded alleles; this finding has strong implications in mutation diagnosis and counseling. Our results indicate that interrupted alleles, below the pathological threshold, may be a reservoir of mutable alleles, prone to expansion in subsequent generations, leading to full disease mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1552-485X
pubmed:author
pubmed:copyrightInfo
(c) 2009 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
153B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
524-31
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (SCA2).
pubmed:affiliation
UnIGENe, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't