Bioinformatics Evaluation of the KRT Gene’s Effects on Epidermolysis Bullosa Disease

The Epidermolysis Bullosa (EB) disease may be caused by mutations in the KRT۱۴ and KRT۵ genes, thatlead to abnormal polymerization of the middle fibers in the keratinocyte layer and result to weak epidermal[۱,۲]. The mutation in keratine (KRT) gene mediated by Single Nucleotide Polymorphisms (SNP) and micro-RNA (miRNA) change some alleles that result in EB. The SNPs residing within miRNA at the ۳’UTR ofgenes may, impair miRNA biogenesis and alter target selection have potentially profound [۴,۵]. In the currentstudy, we aimed to investigate the process of EB disease bioinformatically through SNPs and microRNAaffecting the disease. For this purpose, miRNASNP and LncRNASNP۲ databases were studied in order tofind the effective SNPs in EB and profile changes of genome. The results indicated that the most importantgenes involve in EB were KRT۱۰ and KRT۵. The conversions of alleles A to G, T to C and A to C wereobserved in SNPs rs۷۸۰۲۷۷۸۰۲, rs۷۷۴۸۶۲۹۲۰ and rs۷۷۳۱۰۰۴۷۴ respectively. The occurrence of these SNPson miRNA sequence may have potentially profound biological effect and lead to changes in chromosomalstructure. Bioinformatics analysis revealed that frequent mutations in chromosomes ۱۷ and ۱۲ lead tomutations in KRT۱۴ and KRT۵ genes due to interaction of SNPs and miRNAs. In detail, the occurrence ofrs۷۸۰۲۷۷۸۰۲ within hsa-miR-۱۰۶a-۵p, rs۷۷۴۸۶۲۹۲۰ on hsa-miR-۲۰a-۵p, and rs۷۷۳۱۰۰۴۷۴ on the sequencesof hsa-miR-۱۷-۵p on ۳’UTR of KRT۵ gene may lead the cells to tumorigenesis. In this study and previousstudies, it was observed that the main causes of EB is abnormal production of protein and keratin due tointeraction of SNPs and mRNA in KRT genes. Overall, it is concluded that the EB phenotype harbor aspectrum of mRNA (hsa-miR-۲۰a-۵p) and SNP (rs۷۷۴۸۶۲۹۲۰) mutations in the KRT۵ gene.

Keywords:

Skin disease , EB , KRT genes , bioinformatics