IN – SILICO ANALYSIS OF NON- SYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS OF ACTIVATION- INDUCED CYTIDINE DEAMINASE (AICDA) GENE
Journal Title: European Journal of Biomedical and Pharmaceutical Sciences - Year 2019, Vol 6, Issue 10
Abstract
Introduction: The activation- induced cytidine deaminase (AICDA) enzyme is responsible for converting the immunoglobulin IgM to other classes (IgG, IgA and IgE).Immunodeficiency type2 with hyper serum IgM (HIGM2) is due to failure of AICDA gene to convert the IgM to other classes. The aim of this study was to investigate the effect of nsSNPs in the function and stability of (AICDA) gene using computational tools. Methods: Various software were used to investigates the functional effect of ns SNPs of AICDA gene. Interactions of this gene with other genes was investigated using Gene MANIA. SNPs in the gene were obtained from dbSNP database. For functional analysis various softwares were used including SIFT, Polyphen-2, PROVEAN and SNPs &GO and PHD-SNP. In SIFT the amino acid substitution is predicted deleterious if the score is ≤0.05, and tolerated if the score is >0.05. Regarding polyphen-2 the outcome is shown as probably damaging (score=1) (more confident) possibly damaging(less confident) and PROVEAN prediction, the PROVEAN threshold is (-2.5) if the protein variant is ≤ -2.5 predicted to have a "deleterious" effect. If the PROVEAN score is above the threshold, the variant is predicted to have a "neutral" effect. Also to investigate the disease related SNPs (SNPs & GO and (PhD-SNP) were used. The variation can be classified disease-related or neutral. The stability effect of the SNPs on the protein was investigated using I-mutant suite version3.0, the reliability index:0-10,where 0 is lowest reliability and 10 is the highest. The out put is either increase or decrease stability. Lastly Project hope was used to investigate the effect of amino acids substitution in the protein structure and function. Results: Gene interaction using GeneMANIA showed that AICDA gene has an interaction with 20 other genes mainly two genes: namely SPTY2D1, and STAT4. SIFT predication revealed 200 nsSNPs in the gene. A total of 131 were in the coding region,61 were in 3´ UTR,and 8 were in 5´UTR. Out of these, 10 SNPs were determined to deleterious.Polyphen-2 predicted that the 10 nsSNPs were probably damaging and with high score ( ≥ 0.9). Likewise PROVEAN showed that all 10 SNPs were deleterious. To predict the association with disease using SNPs&GO and PHD-SNP, the former showed that 6 mutations were disease related while 4 mutations were neutral while the latter showed that 9 mutations were disease related while 1 (one) mutation was neutral. Prediction of protein stability using I-Mutant3.0 revealed that 9 SNPs lead to decrease protein stability while one mutation showed an increased stability effect. The change in the chemical nature of amino acid and how it effects the protein structure was analyzed using Project Hope. Overall five highly deleterious and damaging mutations were predicted namely, R24W (rs104894324), W80R (rs104894320), L106P (rs104894321) M139T(rs200858797) F151S (rs104894327). Conclusion: This study showed, after using various computer software, five highly deleterious and damaging SNPs in AICDA gene. These SNPs can be considered as candidate SNPs in people with HIGM2 after further conformation using laboratory techniques.
Authors and Affiliations
Ahmed Musa Abdullah
Keywords
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