Bioinformatic analysis of Rp1 gene causing visual disparity in humans

Abstract

Retinitis pigmentosa (RP) is a group of inherited diseases that damage rod and cone cells located in human retina. A nonsense mutation R677X has been identified in RP1 gene which not only causes mRNA degradation but also results in truncated protein production leading towards visual disparity in humans. Secondary structure of RP1 gene was determined in order to elucidate the structural changes conferred due to nonsense mutation R677X. The structural differences among non mutated and mutated RP1 gene range from 23 to 43%. Similarly, the truncated protein also resulted in the loss of certain functional as well as active sites which were identified by predicting motifs. A detailed comparison between non mutated and mutated RP1 gene revealed the significance of R677X mutation causing significant structural (helix, turn, sheet and coil) as well as functional loss. Four domains of RP1 gene were predicted using ModWeb and SWISS – MODEL Comparative Modeling Server. The 3D structures of the domains were determined based upon the crystal structure of the homologous templates. The 3D structures were then verified using PROCHECK protein structure validation and verification tool. The quality of the structures obtained was good. This is also useful for future work for annotating the functions of protein using their structures.

Keywords: Retinitis pigmentosa, secondary structure, comparative modeling