Detection of Mutation-Hotspots and Exon-Deletions using Digital Signal Processing in Duchenne Muscular Dystrophy (DMD) Gene

Duchenne muscular dystrophy (DMD) is a life threatening disease which mostly occurs due to deletions in the dystrophin gene. The deletions are reported to be clustered in two main regions in the gene involving nearly one fourth of exons. These regions also represent major meiotic recombination hotspots. The detection of deletions/mutation-hotspots in the coding sequences (exons) is not much possible till date due to the gene specific-potential variations or the complex organization of introns and exons in the gene. A Digital signal processing (DSP) method based on antinotch filter that exploits the period-3 property of a DNA sequence is applied for the identification of exons in DNA sequences by providing concerned peaks in magnitude-plot. A two digit numerical representation has been proposed for generating indicator sequence. In our approach to detect deletion in DMD gene, all-exon-sequence was taken and analyzed through digital filter to obtain normal peaks in the plot, which was than compared with the plots obtained after deletion of hotspot exons one by one. It was found that most of the hotspot exons share the peaks and deletions are marked by significant modifications in peaks. Thus, it was known that the peaks in filter-plot of DMD gene are associated with the location of the hotspots and their modifications/absence can be utilized to detect the deletions of exons.