Abstract: 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.
Keywords: Exon, exon-deletion, hotspot, DMD, antinotch filter.
[1] A.G. Engel and E. Ozawa, Dystrophinopathies, in A.G. Engel and L. C. Franzini-Armstrong, (Ed.) Myology. Basic and clinical, 3rd ed. Vol 2. (New York: McGraw Hill, 2004) 961-1025.
[2] R. Howard and M.E. Lewis, The Home Medical Manual (G-O) Time, Vol. III (New York: Doubleday & company, Inc., 1986). PP. 180.
[3] A. Drousiotou, P. Ioannou, T. Georgiou, et al., Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus, Genet Test., 2, 1998, 55–60.
[4] D. Bradley and E. Parsons, Newborn screening for Duchenne muscular dystrophy. Semin Neonatol., 3, 1998, 27–34.
[5] A.E. Emery, Population frequencies of inherited neuromuscular diseases—a world survey, Neuromuscul Disord, 1991, 1: 19–29.
[6] A.P. Monaco, R. L. Neve, C. Colletti-Feener, et al., Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene, Nature, Oct 16-22. 323(6089), 1986, 646-650.
[7] M. Koenig, E. P. Hoffman, C. J. Bertelson, et al., Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals, Cell, 50, Issue 3, 1987, 509-517.
[8] A. H. Ahn, L. M. Kunkel, The structural functional diversity of dystrophin, Nature Genetics, 3(4), 1993, 283-91.
[9] J. Yan, J. Feng, C. H., Buzin, et al., Three-tiered noninvasive diagnosis in 96% of patients with Duchenne muscular dystrophy (DMD), Hum Mutat., 23, 2004, 203–204.
[10] K. M. Dent, D.M., Dunn, A. C. von Niederhausern, et al., Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort, Am J Med Genet A, 134, 2005, 295–298.