مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Bioinformatic analysis of COL7A1 gene mutations in Epidermolysis bullosa (EB) disease
Bioinformatic analysis of COL7A1 gene mutations in Epidermolysis bullosa (EB) disease
Mahdis Kashani,1,*Zahra Rezvani,2
1. Department of Cell and Molecular Biology, Univesity of Kashan, Kashan, Iran 2. Department of Cell and Molecular Biology, Univesity of Kashan, Kashan, Iran
Introduction: The epidermolysis bullosa (EB) family of inherited diseases is characterized by blistering in response to mechanical trauma. EB can produce painful wounds and erosions in skin, eyes, and mucosal tissues; can be mild or severe; and can heal with severe scarring or no scarring at all. Over 30 subtypes are recognized, grouped into four major categories, based predominantly on the plane of cleavage within the skin and reflecting the underlying molecular abnormality: EB simplex, junctional EB, dystrophic EB and Kindler EB. To date, pathogenetic mutations in 16 distinct genes have been implicated in EB, encoding proteins influencing cellular integrity and adhesion. COL7A1 is one of the genes that impact on this disease. This gene encodes the alpha chain of type VII collagen.
Methods: In this study, mutations reported for COL7A1 gene of EB disease were collected through UniProt and ClinVar databases. Then, by using SIFT and Polyphen-2 tools, the possible impact of an amino acid substitution on the structure and function of a human protein for epidermolysis bullosa disease was investigated separately, and common mutations were extracted and analyzed in the form of a statistical chart. Ultimately, we used NCBI to detect where the most regions had mutation.
Results: Based on VarSome, Most of the mutations that led to pathogenicity included Start loss, Nonsense, Frameshift and Splice junction loss. Based on SIFT tool, we found approximately 60 single nucleoutide polymorphism (SNP) with score between 0_0.03 that was deleterious and had pathogenicity records in UniProt and ClinVar databases and and by analyzing the data by polyphen we got the damage rate in replacing amino acids with each other. The results showed that most of them were malignant and only 2 benign samples were found. A common region for mutations affects the amino acid residues 2000-2835 that includes glycine rich domains and collagen triple helix repeat. Glycine and arginine were the most substituted amino acids.
Conclusion: In this research, we analyzed COL7A1 gene mutations and their pathogenicity. Mutations in arginine and glycine regions can cause different types of EB disease, which are very dangerous. dominant dystrophic epidermolysis bullosa usually involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice-site mutations may underlie some cases. The recessive dystrophic epidermolysis bullosa mutations include nonsense mutations, splice site mutations, deletions or insertions, ‘silent’ glycine substitutions within the triple helix and non-glycine missense mutations within the triple helix domain. We can demonstrate the utility of bioinformatics in mutation detection and predict EB in a consanguineous family at risk for recurrence.