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

ABSTRACT Background: CLL: 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. Aim: To study CD38 polymorphism and to predict its effect on structure and subsequently function of CD38 molecule. Methodology and Result: The 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. Conclusion: In 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. Keywords: B-Chronic lymphocytic leukemia, missense single nucleotide polymorphism, and CD38 gene.