Tuğba KAMAN, Ebru ÖZKAN OKTAY, Ömer Faruk KARASAKAL, Muhsin KONUK, Korkut ULUCAN

In silico approach to the analysis of SNPs in the human APAF1 gene

The apoptotic protease activating factor 1 (APAF1) gene encodes a cytoplasmic protein that initiates apoptosis and is a crucialfactor in the mitochondria-dependent death pathway. APAF1 is implicated in many pathways such as apoptosis, neurodegenerativediseases, and cancer. The purpose of this study was to predict deleterious/damaging SNPs in the APAF1 gene via in silico analysis. Tothis end, APAF1 missense SNPs were obtained from the NCBI dbSNP database. In silico analysis of the missense SNPs was carriedout by using publicly available online software tools. The stabilization and three-dimensional modeling of mutant proteins were alsodetermined by using the I-Mutant 2.0 and Project HOPE webservers, respectively. In total, 772 missense SNPs were found in the APAF1gene from the NCBI dbSNP database, 18 SNPs of which were demonstrated to be deleterious or damaging. Of those, 13 SNPs had adecreasing effect on protein stability, while the other 5 SNPs had an increasing effect. Based on the modeling results, some dissimilaritiesof mutant type amino acids from wild-type amino acids such as size, charge, and hydrophobicity were revealed. The SNPs predicted tobe deleterious in this study might be used in the selection of target SNPs for genotyping in disease association studies. Therefore, wecould suggest that the present study could pave the way for future experimental studies.

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