Determination of Deleterious SNPs in APH1A Gene Related to Alzheimers Disease by In Silico Methods

• Main Authors: Ebru OZKAN OKTAY, TuGba KAMAN, Omer Faruk KARASAKAL, Korkut ULUCAN, Muhsin KONUK, Nevzat TARHAN
• Format: Article
• Language: English
• Published: Suleyman Demirel University 2019-08-01
• Series: Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi
• Online Access: http://dergipark.org.tr/tr/download/article-file/784617
• ISSN: 1300-7688; 1308-6529

Alzheimers disease (AD) is a progressive neurodegenerative disease characterized by pathological accumulation of ?-amyloid (A?) senile plaques and neurofibrillary tangles. ?-secretase produces the amyloid ? peptide (A?), which causes AD. ?-secretase is a macromolecular complex and the protein encoded by the APH1A gene is located in this complex. In this study, it was aimed to determine the possible deleterious effects of missense single nucleotide polymorphisms (SNPs) in APH1A gene on the protein structure and stabilization via in silico methods. PolyPhen-2 and SIFT were used to predict deleterious SNPs, I-Mutant 2.0 software was used to detect protein stabilization changes and Project HOPE software tool was used to make three-dimensional modeling of wild and mutant type proteins. The results showed that 257 SNPs among a total of 3567 SNPs in the APH1A gene were missense SNPs. According to the in silico analysis of the 257 SNPs it has been determined that rs11548266, rs74126634, rs145324799, rs199961673, rs370361277, rs370719475 and rs376071112 polymorphisms may have deleterious effects. The results of in silico analysis provide data for genotyping of SNPs which have deleterious effects on protein structure and stabilization rather than genotyping of entire 3567 SNPs in the APH1A gene associated with Alzheimer's disease. Therefore, deleterious SNPs may be used in the selection of SNPs and experimental design which are the most important stages of genotyping studies. Thus, we envisaged that the obtained results will contribute to the further studies either experimental or in silico on Alzheimers disease.