DNA diagnostics and exon skipping

The predominate form of DNA diagnostics remains nucleic acid sequencing in the research and clinical setting. While DNA sequencing allows a mutation to be correctly identified, only RNA sequencing can confirm the effect of that mutation on the resulting mRNA transcript. In the absence of RNA sequencing, predictions are reliant on either experimental studies or bioinformatic modelling. While each of these approaches provides insights into cellular splicing choices, of which exon skipping is but one, both possess inherent weaknesses. A method which is able to integrate and appropriately weigh the various factors influencing cellular splicing choices into an accurate, comprehensive modelling tool still remains elusive.In this overview chapter, the current methods utilised for DNA diagnostics and the impact of the emerging next-generation sequencing techniques are considered. We explore why RNA remains a problematic medium with which to work. To understand how exon skipping can be predicted from a DNA sequence, the key cis-acting elements influencing splicing are reviewed. Finally, the current methods used to predict exon skipping including RNA-based studies, experimental studies, and bioinformatic modelling approaches are outlined.