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Elbager, S. G.

Publications and source records attributed to Elbager, S. G..

2 recordsLinked to original sources
bioRxiv2020

Bio-informatic Analysis of Missense Single Nucleotide Polymorphisms (SNPs) in Human CD38 Gene Associated with B-Chronic Lymphocytic Leukemia

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.

bioinformatics↗
bioRxiv2019

In silico analysis of Missense Variants in Human MPL Gene Associated with Essential Thrombocythemia

IntroductionThe proto-oncogene (MPL) gen encodes the receptor for thrombopoietin (TPO-R), a member of hematopoietic receptor superfamily. Thrombopoietin (TPO), the primary cytokine regulating self-renewal of hematopoietic stem cells, thrombopoiesis and megakaryocytopoiesis. TPO binding to TPO-R induces activation of Janus Kinase 2 (JAK2). Activated JAK2 triggers the activation of downstream positive signaling pathways, leading to the survival, proliferation, and differentiation of hematopoietic cells. Mutations in MPL gene possibly will alter the normal regulatory mechanisms. Numerous MPL mutations have been observed in various hematopoietic cancers such as essential thrombocythemia and primary myelofibrosis and leukemias. In this study, we performed a comprehensive in silico analysis of the functional and structural impact of non-synonymous (nsSNP) that are deleterious to TPO-R structure and function.\n\nMethodologyThe data on human MPL gene was retrieved from dbSNP/NCBI. Nine prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Condel, PhD-SNP, I-Mutant, Mutpred. RaptorX and Chimera were used to analyzing the effect of nsSNPs on functions and structure of the TPO-R. STRING and KEGG database were used for TPO-R protein-protein interaction.\n\nResults and DiscussionAs per dbSNP database, the human MPL gene contained 445 missense mutations. A total 5 nsSNPs (D295G, R257C, Y252H, R537W and D128Y) were predicted to have the most damaging effects on TPO-R structure and function. STRING and KEGG revealed that MPL had strong interactions with proteins that involved in cell growth, apoptosis, signal transduction pathway, some cancers pathways such as colorectal cancer, lung cancer, pancreas cancers, and skin cancer. A literature search revealed that Y252H has contribute to the development of essential thrombocythemia.\n\nConclusionThese in silico predictions will provide useful information in selecting the target SNPs that are likely to have functional impact on the TPO-R and moreover could act as potential targets in genetic association studies. Keywords: In Silico analyses; JAK2; Missense Variants; MPL gene; Thrombopoietin (TPO); Single nucleotide polymorphism (SNP).

bioinformatics↗