In Silico Genetics Revealing Novel Mutations in CEBPA Gene Associated with Acute Myeloid Leukemia

Abstract

BackgroundMyelodysplastic 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.\n\nMethodsThe 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.\n\nResultsA total of five novel nsSNPs out of 248 missense mutations were predicted to be responsible for the structural and functional variations of CEBPA protein.\n\nConclusionIn 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.