title: In Silico Analysis of FMR1 Gene Missense SNPs.
abstract: The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1-related diseases.
authors.affiliation: School of Health, Ahi Evran University, Kirsehir, Turkey. akintekcan@hotmail.com.
authors.forename: Akin
authors.initials: A
authors.lastname: Tekcan
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008958:Models, Molecular; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: FMR1; Fragile X syndrome; In silico analysis; Missense SNP