Comprehensive In silico Analysis of Single Nucleotide Polymorphisms (SNPs) in Human BDNF Gene

Abstract

Since a number of single nucleotide polymorphisms (SNPs) are associated with the BDNF gene mutations involved in different diseases. Hence, it is important to find out the probable functional SNPs before planning a larger population study. So, to look out for the functional nsSNPs (non-synonymous single nucleotide polymorphisms) in BDNF gene, existing data present in the dbSNP database and different bioinformatics tools like SIFT, PolyPhen, nsSNPAnalyzer, F-SNP, I-mutant, Pymol were used for the analysis. The results showed that out of the total 2929 SNPs, 58 were nsSNPs (non-synonymous single nucleotide polymorphisms), 44 occurred in the mRNA 3′ UTR, 108 occurred in 5′ UTR region, 257 occurred in intronic regions and the rest were other types of SNPs. SIFT and PolyPhen programs predicted 3 out of 58 nsSNPs (rs8192466, rs1048218, and rs77787410) as not tolerable, deleterious and damaging. F-SNP revealed that the rs1048221, rs1048220, rs1048218, rs6265 and rs8192466 SNP in the non-synonymous coding region may have protein-coding and splicing regulator functions. PDBSum and UniProtKB predicted the number of protein structures, sharing 100% similarity with the BDNF amino acid sequence. Moreover, I-Mutant and nsSNPAnalyzer showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant and PyMOL. This study suggested that three nsSNPs, rs8192466, rs1048218, and rs77787410 were identified as deleterious, thus destabilizing the protein stability, amino acid interactions, and hydrogen bond networks of the protein directly or indirectly. Hence, these SNPs can explain the functional deviation of protein to some extent. Keywords: BDNF, F-SNP, I-Mutant, nsSNPAnalyzer, PolyPhen, SIFT, SNP