TDK conference 2010

Duchenne Muscular Dystrophy (DMD) is caused by the absence of the protein dystrophin in the muscle tissue. The larger part of the dystrophin as well as in the closely related protein utrophin is composed of spectrin type repeats (STRs). Possible treatment methods such as exon skipping and gene therapy involve editing these repeats. We analysed all of the spectrin repeats of human dystrophin (24 repeats) and utrophin (22 repeats) using various bioinformatical methods. We found a distinctive pattern in the rod region of human dystrophin based on isoelectic points, which upon further inspection proved to be conserved in mammals, and to some extent in every vertebrate. We modelled the structure of the STRs and examined the distribution of the surface electrostatic charge which proved consistent with our previous findings. Finally, we estimated the selective pressure on the various regions in dystrophin, and especially the locations of the basic amino acids composing the basic sites in the repeats D3, D5, D7 and D10-17 and found that these basic locations are under a different type of selection, namely under positive Darwinian selection as opposed to the other regions in dystrophin. Our findings may help in deciding which STRs may be edited without important functional loss.