Mohamed A. Abdelrahim
Daoud Research Group, Sudan
Title: Computational Analysis of Single Nucleotide Polymorphism (SNPs) in Human ATP7B Gene of Wilson's disease from Functional Analysis to Polymorphisms in microRNA
Biography
Biography: Mohamed A. Abdelrahim
Abstract
Background: Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism with a worldwide prevalence of one per 30,000. It is caused by homozygous or compound heterozygous mutations in the ATP7B gene. Studying ATP7B function has been always difficult due to the complexity of the large membrane protein. Design and methods: In order to investigate ATP7B nonsynonymous substitutions, we used a computational analysis approach. Specifically, we used SIFT (Sorting Intolerant from Tolerant) and PolyPhen online softwares to predict possible impact of an amino acid substitution on both structure and function of proteins. Protein structural analysis of amino acid variants was performed by Chimera 1.8 and Project Hope. PolymiRTS was used to analyze the SNPs in the 3'UTR region. Functions and interaction of ATP7B with functional similar gene was predicted using Gene MANIA software. Results: We analyzed 5631 Single Nucleotide Polymorphisms (SNPs) from National Center for Biological Information SNPs database, out of which 838 were coding SNPs, 111 occurred in the mRNA 3′ UTR. The nsSNP; rs28942074, rs28942075, rs28942076, rs41292782, rs60003608 and rs60431989 were identified as deleterious and damaging by the SIFT and PolyPhen programs. Five microRNA binding sites were found to be highly affected due to 3′UTR SNPs. Conclusions: This study suggested that R778L, D765N, G943S, T991M, I967F and I1148T variants of ATP7B protein could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks thus explaining the functional deviations of protein to some extent. That can facilitate early diagnosis and treatment of WD.