Background. Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. We aimed to identify the pathogenic SNPs in MEFV by computational analysis software. Methods. We carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function. Result. 23 novel mutations out of 857 nsSNPs are found to have deleterious effect on the MEFV structure and function. Conclusion. This is the first in silico analysis of MEFV gene to prioritize SNPs for further genetic mapping studies. After using multiple bioinformatics tools to compare and rely on the results predicted, we found 23 novel mutations that may cause FMF disease and it could be used as diagnostic markers for Mediterranean basin populations.

Background: Genetic polymorphisms in the HEXA gene are associated with a neurodegenerative disorder called Tay-Sachs disease (TSD) (GM2 gangliosidosis type 1). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools. Methods: SNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of the hexosaminidase A protein.Results: Fifty nine mutations were found to be highly damaging to the structure and function of the HEXA gene protein.Conclusion: According to this study, thirty two novel nsSNP in HEXA are predicted to have possible role in Tay-Saches Disease using different bioinformatics tools. Our findings could help in genetic study and diagnosis of Tay-Saches Disease.Keywords: Tay-Sachs disease (TSD), GM2 gangliosidosis, hexosaminidase A, HEXA, a neurodegenerative disorder, bioinformatics, single nucleotide polymorphisms (SNPs), computational, insilico. ganglioside which is caused by mutations in HEXA gene the highest concentration of GM2 ganglioside found in neuronal cells and they are the main glycolipids of neuronal cell's plasma membranes responsible of the normal cellular activities. Patients with HexA deficiency suffer from GM2 ganglioside accumulates inside neural's lysosomes. Therefore, HexA deficiency primarily affects the nervous system [1,2,4,[6][7][8][9][10][11][12][13][14].According to the disease onset age, TSD is differentiated into three types which are: acute infantile, juvenile, and late-onset. Acute infantile TSD is the most common type. It causes progressive weakness and motor skills lost in the infected infants. This progression occurs between the ages of six months to three years. In addition, the infected infant progressively suffers from diminished attentiveness and an exaggerated startle response. As TSD continues to destroy the brain infant suffers from seizures, blindness, and death which usually occurs before four years of age [8,9,11,[13][14][15].The human HEXA gene [OMIM *606869] encodes the alpha subunit of the lysosomal hexosaminidase A isozyme (HexA) which is located on chromosome 15 q23-q24 and contains 14 exons. More than two hundred mutations have been reported in the HEXA gene to cause TSD and its variants. These mutations include single base substitutions, small deletion, duplications, insertions splicing alterations, complex gene rearrangement, partial large duplications, partial deletion, splicing mutations, nonsense mutations and missense mutations that lead to the disruption of transcription, translation, folding, dimerization of monomers and catalytic dysfunction of HexA protein [4,8,11,15,16].

Background: Single Nucleotide Polymorphisms (SNPs) in the HEXB gene are associated with a neurodegenerative disorder called Sandhoff disease (SD) (GM2 gangliosidosis-O variant). This study aimed to predict the possible pathogenic SNPs of this gene and their impact on the protein using different bioinformatics tools. Methods: SNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different algorithms collectively predicted the effect of single nucleotide substitution on both structure and function of beta subunit beta subunit of both hexosaminidase A and hexosaminidase B proteins. Results: Forty nine mutations were found to be extremely damaging to the structure and function of the HEXB gene protein.Conclusion: According to this study, forty two novel nsSNP in HEXB are predicted to have possible role in Sandhoff disease using different bioinformatics tools, beside two SNPs found to have effect on miRNAs binding site affecting expression of HEXB gene. Our findings may assist in genetic study and diagnosis of Sandhoff disease.

Background: X linked severe combined immunodeficiency (X-SCID) is a lifethreatening disorder. It is due to mutation of the interleukin two receptor gamma-chain (IL2RG) gene. Nonsynonymous SNPs (nsSNPs) are the most common polymorphism, known to be deleterious or disease-causing variations because they alter protein sequence, structure, and function. Objective: is to reveal the effect of harmful SNPs in the function and structure of IL2RG protein. Method: Data on IL2RG was investigated from dbSNP/NCBI database. Prediction of damaging effect was done using sift, polyphen, provean and SNAP2.more software were used for more analysis: phd-snp, and and go, Pmut, Imutant.modeling was done using chimera and project hope. Gene interaction was done by gene mania.3UTR prediction was done using polymiRTS software. Result: The in-silico prediction identified 1479 SNPs within IL2RG gene out of which 253 were coding SNPs, 50 took place in the miRNA 3 UTR, 21 occurred in 5 UTR region and 921 occurred in intronic regions. a total of 12 missense nsSNPs were found to be damaging by both a sequence homology-based tool (SIFT) and a structural homology-based method (3UTR region were predicted to disrupt miRNAs binding sites and affect the gene expression. Conclusions: Computational analysis of SNPs has become a very valuable tool in order to discriminate neutral SNPs from damaging SNPs. This study revealed 5 novel nsSNPs in the IL2RG gene by using different software and 21 SNPs in 3UTR. These SNPs could be considered as important candidates in causing diseases related to IL2RG mutation and could be used as diagnostic markers.Keywords: X linked severe combined immunodeficiency (X-SCID), interleukin 2 receptor gamma-chain (IL2RG), single nucleotide polymorphism (SNP), nonsynonymous Single Nucleotide Polymorphisms (nsSNPs), bioinformatics.

Background: AB variant of GM2 gangliosidosis caused as a result of mutations in GM2 activator gene (GM2A) which is regarded as neurodegenerative disorder. This study aimed to predict the possible damaging SNPs of this gene and their impact on the protein using different bioinformatics tools. Methods: SNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different tools collectively predicted the effect of single nucleotide substitution on both structure and function of GM2 activator. Results: Three novel mutations were found to be highly damaging to the structure and function of the GM2A gene. Conclusion: Four SNPs were found to be highly damaging SNPs that affect function, structure and stability of GM2A protein, which they are: C99Y, C112F, C138S and C138R, three of them are novel SNPs (C99Y, C112F and C138S). Also 46 SNPs were predicted to affect miRNAs binding sites on 3'UTR leading to abnormal expression of the resulting protein. These SNPs should be considered as important candidates in causing AB variant of GM2 gangliosidosis and may help in diagnosis and genetic screening of the disease.