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

Afra Abd Elhamid Fadlalla Elshaikh^1, , Mosab Mohamed Gasemelseed^{1, 2}, Marwa Mohamed Osman¹, Samah Ahmed Ibrahim Shokri¹, Samia Othman massad¹, Nahid Ebrahim Merghani Fadl¹, Arafa Habiballa Ibrahim³, Selma Shiekh Idris⁴, Maab Mohamed Abdalla⁵ and Mohamed Ahmed Salih⁶

¹Department of Bioinformatics, Africa city of technology, Sudan

²Alneelain University Faculty of Medical Laboratory Sciences, Sudan

³Department of haeatology, Elnehoud teaching Hospital, Sudan

⁴Medical Lab Manager, Tyba Hospital, Sudan

⁵Institute of Endemic Diseases, Khartoum University, Sudan

⁶Head Department of Biotechnology, Biotechnology Park, Africa city of technology, Sudan

Cite this paper:
Afra Abd Elhamid Fadlalla Elshaikh, Mosab Mohamed Gasemelseed, Marwa Mohamed Osman, Samah Ahmed Ibrahim Shokri, Samia Othman massad, Nahid Ebrahim Merghani Fadl, Arafa Habiballa Ibrahim, Selma Shiekh Idris, Maab Mohamed Abdalla and Mohamed Ahmed Salih. Computational Analysis of Single Nucleotide Polymorphism (SNPs) in Human GRM4 Gene. American Journal of Biomedical Research. 2016; 4(3):61-73. doi: 10.12691/ajbr-4-3-2

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.

Keywords:
glutamate neurotransmitter ionotropic metabotropic Myoclonic Epilepsy SNPs

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References:

[1]	Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, Cui Y. PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. J Nucleic Acids Res (2007); 35: 1-4.
[2]	Capriotti E., Calabrese R. and Casadio R.. Predicting the insurgence of human genetic disease associated to single point protein mutation with Support Vector Machines and evolutionary information.. Bioinformatics.2006 ; 22: 2729-2734.
[3]	C.N. Pauline, H. Steven. SIFT: predicting amino acid changes that affect protein function. J Nucleic Acids Res (2003); 31: 3812-3814.
[4]	E. Capriotti, P. Fariselli, R. Casadio. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure. J Nucleic Acid Res (2005); 33:306-310.
[5]	Goddard TD1, Huang CC, Ferrin. TE Software extensions to UCSF chimera for interactive visualization of large molecular assemblies. J Structure (2005); 13(3):473-82.
[6]	González-Pérez A1, López-Bigas N. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. J Am Hum Genet (2011); 88: 440-449.
[7]	http://www.ncbi.nlm.nih.gov/snp.
[8]	http://www.ncbi.nlm.nih.gov/gene/2914.
[9]	Makoff A, Lelchuk R, Oxer M, Harrington K, Emson P. Molecular characterization and localization of human metabotropic glutamate receptor type 4 .J Brain Research. Molecular Brain Research (1996); 37 (1-2): 239-48.
[10]	Muhle H1, von Spiczak S, Gaus V, Kara S, Helbig I, Hampe J, Franke A, Weber Y, Lerche H, Kleefuss-Lie AA, Elger CE, Schreiber S, Stephani U, Sander T. Role of GRM4 in idiopathic generalized epilepsies analysed by genetic association and sequence analysis. J Epilepsy Res (2010);89(2-3):319-26.
[11]	Venselaar, H., T. A. te Beek, R. K. Kuipers, M. L. Hekkelman and G. Vriend. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. J BMC bioinformatics (2010); 11(1): 548.
[12]	Warde-Farley D1, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, Maitland A, Mostafavi S, Montojo J, Shao Q, Wright G, Bader GD, Morris Q. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. J Nucleic Acids Res (2010); 38:214-20.
[13]	Wong CG1, Scherer SW, Snead OC 3rd, Hampson DR. Localization of the human mGluR4 gene within an epilepsy susceptibility locus. J Brain Res Mol Brain Res (2001); 19 (1): 109-16.
[14]	Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, Johnson BG, Schoepp DD, Belagaje RM. Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. J Brain Research. Molecular Brain Research (1998); 53 (1-2): 88-97.