Computational Analysis of Single Nucleotide Polymorphism (SNPs) in Human GRM4 Gene

Abstract

Background: L-glutamate is one of the most common amino acid in nature and it acts as excitatory neurotransmitter in the central nervous system. GRM4 is a large gene located in chromosome 6 and consists of 7217 bp (NCBI) divided into 10 exons. The location of GRM4 (chromosomal segment 6p21.3) is tentative susceptibility loci for Juvenile Myoclonic Epilepsy so many studies investigate the association of GRM4 polymorphism with myoclonic epilepsy juvenile. Design and methods: GRM4 gene was investigated in dbSNP/NCBI database NCBI and we used computational analysis approach. Deleterious nsSNPs were predicted by SIFT and Polyphen soft wares then the damaging nsSNPs were submitted to I mutant tool. Protein structural analysis of amino acid variants was performed by Chimera 1.8 and Project Hope. Results: We analyze 29854 SNPs from NCBI; 8561 of them found on homosapiens; of which 330 were missense, of which 208 were in the coding region, 334 were non-synonymous SNPs (nsSNPs), 232 were in the 3'un-translated region. These SNPs were analyzed using different soft wares; SIFT, Polyphen-2, Imutant3.0, PhD-SNP, PolymiRTs, Project Hope and GENEMAIA to investigate the effect of SNPs mutations on GRM4 protein structure and function. Conclusions: Computational tools were used to analyze deleterious SNPs in GRM4 gene. Out of 8561 SNPs, the SNPs (rs184636998), (rs199744441), (rs199744441), (rs149277708), (rs144660534), (rs139236496) were identified as highly damaging in coding region confirmed by using bioinformatics tools . In 3'un-translated region two SNPs (rs188406833) and (rs192860479) contained (C) allele had 4 miRSite as target binding site can be disrupts a conserved miRNA and one SNPs (rs77415386) contained (D) allele had 6 miRSite as derived allele that disrupts a conserved miRNA site. Further study must be done to detect the effect of these SNPs on the protein structure and function.