title: Exploration of deleterious single nucleotide polymorphisms in late-onset Alzheimer disease susceptibility genes.
abstract: Non-synonymous single nucleotide polymorphisms (nsSNPs) are considered as biomarkers to disease susceptibility. In the present study, nsSNPs in CLU, PICALM and BIN1 genes were screened for their functional impact on concerned proteins and their plausible role in Alzheimer disease (AD) susceptibility. Initially, SNPs were retrieved from dbSNP database, followed by identification of potentially deleterious nsSNPs and prediction of their effect on proteins by PolyPhen and SIFT. Protein stability and the probability of mutation occurrence were predicted using I-Mutant and PANTHER respectively. SNPs3D and FASTSNP were used for the functional analysis of nsSNPs. The functional impact on the 3D structure of proteins was evaluated by SWISSPDB viewer and NOMAD-Ref server. On analysis, 3 nsSNPs with IDs rs12800974 (T158P) of PICALM and rs11554585 (R397C) and rs11554585 (N106D) of BIN1 were predicted to be functionally significant with higher scores of I-Mutant, SIFT, PolyPhen, PANTHER, FASTSNP and SNPs3D. The mutant models of these nsSNPs also showed very high energies and RMSD values compared to their native structures. Current study proposes that the three nsSNPs identified in this study constitute a unique resource of potential genetic factors for AD susceptibility.
authors.affiliation: Department of Biotechnology, K L University, Andhra Pradesh, India. tahamasoodi@gmail.com
authors.forename: Tariq Ahmad
authors.initials: TA
authors.lastname: Masoodi
authors.forename: Sulaiman A
authors.initials: SA
authors.lastname: Al Shammari
authors.forename: May N
authors.initials: MN
authors.lastname: Al-Muammar
authors.forename: Adel A
authors.initials: AA
authors.lastname: Alhamdan
authors.forename: Venkateswar Rao
authors.initials: VR
authors.lastname: Talluri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D051152:Clusterin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D030561:Databases, Nucleic Acid; D030562:Databases, Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D034041:Monomeric Clathrin Assembly Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D020539:Sequence Analysis, Protein; D012984:Software; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; C495242:CLU protein, human; D051152:Clusterin; D034041:Monomeric Clathrin Assembly Proteins; D009687:Nuclear Proteins; C439003:PICALM protein, human; D025521:Tumor Suppressor Proteins