Polyalanine and polyserine frameshift products in Huntington's disease.
J Med Genet
; 43(11): 893-6, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-16801344
ABSTRACT
Codon reiteration disorders are caused by abnormal expansions of either polyglutamine or polyalanine tracts within the coding region of a protein. These mutations impair normal protein folding, resulting in aggregate formation in the affected tissues. Huntington's disease is the most common of the nine disorders caused by polyglutamine expansion mutations. The most extensively studied polyalanine expansion disorder is oculopharyngeal muscular dystrophy. There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations as it has been shown that the expanded CAG/polyglutamine tract within the SCA3 gene can shift to the GCA[corrected]/polyalanine frame. Here, we show that this frameshifting phenomenon is more widespread and occurs in Huntington's disease. We have shown both +1 frameshift and +2 frameshift products (which may contain polyalanine or polyserine tracts, respectively) in human postmortem Huntington's disease brains and in a transgenic mouse model of Huntington's disease. Our data suggest that +1 and +2 frameshift products are generated at low levels. This may be relevant to the pathogenesis of human Huntington's disease, as we have previously shown that both polyserine and polyalanine-containing proteins are modifiers of mutant huntingtin toxicity, with low expression levels of polyalanine-containing proteins having a protective effect.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Mutação da Fase de Leitura
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Doença de Huntington
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Expansão das Repetições de Trinucleotídeos
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article