Background: Myelodysplastic syndrome/Acute myeloid leukemia (MDS/AML) is a highly heterogeneous malignant disease; affects children and adults of all ages. AML is one of the main causes of death in children with cancer. However, It is the most common acute leukemia in adults, with a frequency of over 20 000 cases per year in the United States of America alone. Methods: The SNPs were retrieved from the dbSNP database. this SNPs were submitted into various functional analysis tools that done by SIFT, PolyPhen-2, PROVEAN, SNAP2, SNPs&GO, PhD-SNP and PANTHER, while structural analysis were done by I-mutant3 and MUPro. The most damaging SNPs were selected for further analysis by Mutation3D, Project hope, ConSurf and BioEdit softwares. Results: A total of five novel nsSNPs out of 248 missense mutations were predicted to be responsible for the structural and functional variations of CEBPA protein. Conclusion: In this study the impact of functional SNPs in the CEBPA gene was investigated through different computational methods, which determined that (R339W, R288P, N292S N292T and D63N) are novel SNPs have a potential functional effect and can thus be used as diagnostic markers and may facilitate in genetic studies with a special consideration of the large heterogeneity of AML among the different populations.

Background: Hereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. The comprehensive in silico analysis of coding SNPs, and their functional impacts on protein level, still remains unknown. In this study, we aimed to identify the pathogenic SNPs in PRSS1 gene by computational analysis approach. Materials and Methods: We carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict Single-nucleotide polymorphisms influence on protein structure and function. Result: Two novel mutations out of 339 nsSNPs that are found be deleterious effect on the PRSS1 structure and function. Conclusion: This is the first in silico analysis in PRSS1 gene, which will be a valuable resource for future targeted mechanistic and population-based studies.

Background: Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a rare immunodeficiesncy disease that classically presents in early childhood, characterized by eczematoid dermatitis, characteristic facies, pneumatoceles, hyperextensibility of joints, multiple bone fractures, scoliosis, atopic dermatitis and elevated levels of serum IgE (>2000 IU/ml). The term Autosomal dominant hyper-IgE syndrome has primarily been associated with mutations in STAT3 gene, Located in human chromosome 17q21. Methods: The human STAT3 gene was investigated in dbSNP/NCBI, 962 SNPs were Homo sapiens; of which 255 were missense SNPs. This selected for in silico analysis by multiple in silico tools to investigate the effect of SNPs on STAT3 protein's structure and function. Result: Eleven novel mutations out of 255 nsSNPs that are found to be deleterious effect on the STAT3 structure and function. Conclusion: A total of eleven novel nsSNPs were predicted to be responsible for the structural and functional modifications of STAT3 protein .The newly recognized genetic cause of the hyper-IgE syndrome affects complex, compartmentalized somatic and immune regulation. This study will opens new doors to facilitate the development of novel diagnostic markers for associated diseases.

Early infantile epileptic encephalopathy 1 (EIEE1) is a rare but devastating neurologic disorder that displays concomitant cognitive and motor impairment, and is often presented in the first months of life with severe intellectual disability. The objective of this study is to classify the most deleterious nsSNPs in ARX gene that may cause EIEE1 disease .Despite the reported association of ARX gene mutations with vulnerability to several neurologic condition, there is lack of in silico analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the ARX at protein level. Therefore, the pathogenic nsSNPs in the human ARX obtained from NCBI were analyzed for their functional and structural impact using bioinformatics tools like SIFT, Polyphen, PROVEAN , I-Mutant, and MUPro. The effects of the mutations on tertiary structure of the human ARX protein were predicted using RaptorX and visualized by UCSF Chimera while STRING was used to investigate its protein-protein interaction. Our extensive in silico analysis revealed 11 mutations that will significantly alter the structure of human ARX protein; that may disturb the domain which will affect the function of the protein.Extensive in silico analysis of the functional and structural consequences of SNPs in human ARX gene revealed 11 mutations (L535Q, R528S, R380L, V374D, L343Q, T333N, T333S, R332H, R330H, G34R and L33P) that may cause EIEE1.Therefore, can be used as diagnostic markers for EIEE1. Keywords: ARX gene; Early infantile epileptic encephalopathy 1 (EIEE1); neurologic disease; in silico analysis; SNPs. PolyPhen-2:PolyPhen 2 sever (Polymorphism Phenotyping v2), was used to study the potential effects of each amino acid substitution on the structural and functional properties of ARX protein by applying physical and comparative approaches [19]. PROVEAN:PROVEAN is a trained functional online tool that depends on alignment-based score.Mutations are predicted to have neutral or deleterious effects based on their alignment score being more or less than -2.5 respectively. [20]. SNAP2:SNAP2 is a trained functional tool that is based on neural network. It differentiates between disease and benign mutations by taking a variety of features into account. it got an accuracy of 83% [21]. SNPs&GO:It is a support vector machine (SVM) based on the method to accurately predict the disease-related mutations from protein sequence. The probability score higher than 0.5 reveals the disease-related effect of mutation on the parent protein function. [22]. SNPs&GO has another tool impeded with it called PHD-SNP which classifies the results into deleterious or neutral mutation [23]. P-Mut:P-Mut is a functional web-based tool which permits swift and accurate results (80%) of the compulsive features of each SNP based on neural networks intelligence [24]. Condel:Condel is a method to assess the outcome of non-synonymous single nucleotide variants SNVs using consensus deleteriousness score that combines various tools (SIFT, Polyphen2, Mutation Assessor, and F...

BackgroundCLL: Chronic lymphocytic leukemia is a chronic type of haematological malignancies that evoked from lymph proliferative origin of bone marrow and secondary lymphoid tissue, resultant in proliferation and progressive accumulation of distinct monoclonal CD5 /CD19 /CD23 B lymphocytes in the bone marrow, peripheral blood, and lymphatic organs. CD38 is a multifunctional ecto-enzyme, known to be a direct contributor in pathogenesis of CLL by poorly understood mechanism. Even though, it highly expressed in CLL. At specific position of CD38 gene sequence, substitution of single nucleotide may result in change in amino acid that ends by consequent alteration of protein structure.AimTo study CD38 polymorphism and to predict its effect on structure and subsequently function of CD38 molecule.Methodology and ResultThe bioinformatic analysis of CD38 gene had been carried out by using several soft wares. Functional analysis by SIFT, Polyphen2, and PROVEAN reveled 12 deleterious SNPs. These SNPs were further analyzed by SNAP2, SNP@GO. PMut, STRING and other soft wars. Furthermore, Stability analysis was done using I-Mutant and MUpro software where seven SNPs were found to decrease the stability of the protein by I-Mutant, while two SNPs increase it. At the same time, eight SNPs were found to decrease the stability by Mupro software while only one SNP is predicted to increase it. Finally, Physiochemical analysis was done using Project Hope.ConclusionIn summary, CD38 genotype seems to have twelve SNP that possibly will result in deleterious effect on Protein Structure. This genetic variation eventually will lead to alteration in potential molecule functions. Which effect the progression of CLL By the end.