Modelling dynamic DNA in mytonic dystrophy

Higham, C., Wilcox, D., Haydon, D. , Cobbold, C. and Monckton, D. (2009) Modelling dynamic DNA in mytonic dystrophy. In: Sixth International Workshop on Computational Systems Biology, WCSB 2009, Aarhus, Denmark, 10-12 Jun 2009, pp. 63-66.

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Publisher's URL: http://www.cs.tut.fi/wcsb09/

Abstract

<p>Myotonic dystrophy type 1 is the most common of about 20 human diseases associated with inheriting an abnormally large unstable DNA simple sequence repeat. New quantitative data, collected by single molecule analysis of repeat length in blood cells from 145 patients reveals the extent and nature of the genetic cell to cell variation within (somatic mosaicism) and between patients.</p> <p>We are developing discrete-state continuous-time mathematical models and stochastic simulation techniques that capture key features of the mutation mechanism underlying repeat length evolution. Modern Bayesian techniques involving Markov chain Monte Carlo are employed to calibrate our models against the biological data and test model hypotheses. This work has the potential to improve prognostic information for patients, as well as providing deeper understanding of the underlying biological process.</p> <p>We report here an initial finding that the distribution of repeat length is better described by a threshold birth and death process model than by a traditional pure birth process. This suggests that the underlying biological mechanism consists of both expansions and contractions and that the observed tendency towards repeat expansion is the net result of many more expansion and contraction mutations than previously thought. Our estimates for expansion and contraction give only a slight bias (2%) in favour of repeat expansion and they predict that mutation events occur at a much greater rate than a pure birth model would allow.</p>

Item Type:Conference Proceedings
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Higham, Dr Catherine and Cobbold, Dr Christina and Monckton, Professor Darren and Haydon, Professor Daniel and Wilcox, Dr Douglas
Authors: Higham, C., Wilcox, D., Haydon, D., Cobbold, C., and Monckton, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Science and Engineering > School of Mathematics and Statistics > Mathematics

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