Understanding Somatic Mosaicism in Myotonic Dystrophy Type 1

Hogg, Grant Fraser (2000) Understanding Somatic Mosaicism in Myotonic Dystrophy Type 1. MSc(R) thesis, University of Glasgow.

Abstract

Myotonic dystrophy type 1 is caused by an unstable CTG repeat expansion in the 3' UTR of the DM1 protein kinase gene on chromosome 19. A neuromuscular disease with a broad spectrum of symptoms, DM1 also exhibits anticipation whereby disease severity increases through successive generations. Increasing measured allele size between patients correlates with an increased severity of symptoms and an earlier age of onset. However, this correlation is not precise and therefore measured allele length caimot be used as an accurate indicator of age of onset. This suggests that repeat length may not be the major determinant of disease severity. There is a high level of somatic mosaicism shown by the mutation and failure to take into account age-dependent somatic mosaicism in patients may have compromised the accuracy of clinical correlations. The aim of this project was to investigate simple approaches for correcting for age-dependent somatic mosaicism and also to develop computer software to allow us to simulate the progression of age-dependent somatic mosaicism. We have demonstrated that employing alternative approaches in both molecular diagnoses and statistical comparison can yield significantly improved repeat length / age of onset correlations. This conclusively shows that repeat length is by far the major determinant in DM1 disease onset. Simulation software was also successfully developed and preliminary results suggest that DM1 repeat instability is amenable to mathematical modelling in the future.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Additional Information: Adviser: Darren G Monckton
• Keywords: Genetics
• Date of Award: 2000
• Depositing User: Enlighten Team
• Unique ID: glathesis:2000-76136
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 16:36
• Last Modified: 19 Nov 2019 16:36
• URI: https://theses.gla.ac.uk/id/eprint/76136