Journal Article

Simultaneous Analysis of Expression of the Three Myotonic Dystrophy Locus Genes in Adult Skeletal Muscle Samples: The CTG Expansion Correlates Inversely with <i>DMPK</i> and <i>59</i> Expression Levels, but Not <i>DMAHP</i> Levels

Maria Eriksson, Tor Ansved, Lars Edström, Maria Anvret and Nessa Carey

in Human Molecular Genetics

Volume 8, issue 6, pages 1053-1060
Published in print June 1999 | ISSN: 0964-6906
Published online June 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.6.1053
Simultaneous Analysis of Expression of the Three Myotonic Dystrophy Locus Genes in Adult Skeletal Muscle Samples: The CTG Expansion Correlates Inversely with DMPK and 59 Expression Levels, but Not DMAHP Levels

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The causative mutation in the majority of cases of myotonic dystrophy has been shown to be the expansion of a CTG trinucleotide repeat, but the mechanism(s) by which this repeat leads to the very complex symptomatology in this disorder remains controversial. We have developed a highly sensitive and quantifiable assay, based on competitive RT-PCR, to test the hypothesis that the expansion disrupts the expression of the genes in its immediate vicinity, DMPK, 59 and DMAHP. In order to avoid cell culture-induced artifacts we performed these experiments using adult skeletal muscle biopsy samples and analysed total cytoplasmic poly(A)+ mRNA levels for each gene simultaneously, as this is more physiologically relevant than allele-specific levels. There was considerable overlap between the expression levels of the three genes in myotonic dystrophy patient samples and samples from control individuals. However, in the myotonic dystrophy samples we detected a strong inverse correlation between the repeat size and the levels of expression of DMPK and 59.This is the first report of a possible effect of the CTG expansion on gene 59. Our results indicate that whilst a simple dosage model of gene expression in the presence of the mutation is unlikely to be sufficient in itself to explain the complex molecular pathology in this disease, the repeat expansion may be a significant modifier of the expression of these two genes.

Journal Article.  5547 words.  Illustrated.

Subjects: Genetics and Genomics

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