title: Computational Screening and Exploration of Disease-Associated Genes in Alzheimer's Disease.
abstract: Alzheimer's is a neurodegenerative disease affecting large populations worldwide characterized mainly by progressive loss of memory along with various other symptoms. The foremost cause of the disease is still unclear, however various mechanisms have been proposed to cause the disease that include amyloid hypothesis, tau hypothesis, and cholinergic hypothesis in addition to genetic factors. Various genes have been known to be involved which are APOE, PSEN1, PSEN2, and APP among others. In the present study, we have used computational methods to examine the pathogenic effects of non-synonymous single nucleotide polymorphisms (SNPs) associated with ABCA7, CR1, MS4A6A, CD2AP, PSEN1, PSEN2, and APP genes. The SNPs were obtained from dbSNP database followed by identification of deleterious SNPs and prediction of their functional impact. Prediction of disease-associated mutations was performed and the impact of the mutations on the stability of the protein was carried out. To study the structural significance of the computationally prioritized mutations on the proteins, molecular dynamics simulation studies were carried out. On analysis, the SNPs with IDs rs76282929 ABCA7; CR1 rs55962594; MS4A6A rs601172; CD2AP rs61747098; PSEN1 rs63750231, rs63750265, rs63750526, rs63750577, rs63750687, rs63750815, rs63750900, rs63751037, rs63751163, rs63751399; PSEN2 rs63749851; and APP rs63749964, rs63750066, rs63750734, and rs63751039 were predicted to be deleterious and disease-associated having significant structural impact on the proteins. The current study proposes a precise computational methodology for the identification of disease-associated SNPs. J. Cell. Biochem. 118: 1471-1479, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India.
authors.forename: Salma
authors.initials: S
authors.lastname: Jamal
authors.affiliation: Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India.|Bioinformatics Programme, Centre for Biological Sciences, Central University of South Bihar, BIT Campus, Patna, Bihar, India.
authors.forename: Asheesh
authors.initials: A
authors.lastname: Shanker
authors.affiliation: School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D056004:Molecular Dynamics Simulation; D020641:Polymorphism, Single Nucleotide; D053764:Presenilin-1 / Q000737:chemistry / Q000235:genetics; D053766:Presenilin-2 / Q000737:chemistry / Q000235:genetics; D055550:Protein Stability; D017463:Receptors, Complement 3b / Q000737:chemistry / Q000235:genetics
chemical_list: C411895:ABCA7 protein, human; C545487:APP protein, human; D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C114545:CD2-associated protein; C509991:CR1 protein, human; D003598:Cytoskeletal Proteins; C574492:MS4A6A protein, human; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D017463:Receptors, Complement 3b
keywords: ALZHEIMER'S; MOLECULAR DYNAMICS; MUTATIONS; PATHOGENIC; SINGLE NUCLEOTIDE POLYMORPHISMS