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.

BackgroundAn astonishing observation is that aggressive behavior is actually a highly heritable. Recent experimental work and behavior research has linked individual variation in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to the occurrence of anger-driven aggression. Aggressive antisocial and violent behavior has become a regularly debated topic in the scientific community; the impending question is what is the source of aggressive behavior, is it genetic or environmental or is it just an individual choice. This study aims to analyses the SNPs found in MAOA gene and it is possible association to aggressive behavior.MethodVarious bioinformatics software (SIFT, PolyPhen-2, PROVEAN, SNAP22, SNP&GO and PMut)is used to analyses the SNPs within the MAOA gene to study the structural and functional implication on the associated protein, which is further clarified using chimera software. Then gene-gene interaction is studied with geneMANIA software. Furthermore, conservation and annotation studies were done through the ConSurf server and Variant Effect Predictor (VEP) respectively.ResultSix missense SNPs were found to affect the structural and functional prospect of MAOA protein.ConclusionGenetic mutation within MAOA is likely to be associated with aggressive behavior; this will enrich future management and screening possibilities for this behavior.

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...