Abstract
Single Nucleotide Polymorphisms (SNPs) are the most common candidate mutations in human beings that play a vital role in the genetic basis of certain diseases. Previous studies revealed that Solute Carrier Family 26 Member 4 (SLC26A4) being an essential gene of the multi-faceted transporter family SLC26 facilitates reflexive movement of Iodide into follicular lumen through apical membrane of thyrocyte. SLC26A4 gene encodes Pendred protein, a membrane glycoprotein, highly hydrophobic in nature, present at the apical membrane of thyrocyte functioning as transporter of iodide for thyroid cells. A minor genetic variation in SLC26A4 can cause Pendred syndrome, a syndrome associated with thyroid glands and deafness. In this study, we performed in-silico analysis of 674 missense SNPs of SLC26A4 using different computational platforms. The bunch of tools including SNPNEXUS, SNAP-2, PhD-SNP, SNPs&GO, I-Mutant, ConSurf, and ModPred were used to predict 23 highly confident damaging and disease causing nsSNPs (G209V, G197R, L458P, S427P, Q101P, W472R, N392Y, V359E, R409C, Q235R, R409P, G139V, G497S, H723R, D87G, Y127H, F667C, G334A, G95R, S427C, R291W, Q383H and E384G) that could potentially alter the SLC26A4 gene. Moreover, protein structure prediction, protein-ligand docking and Molecular Dynamics simulation were performed to confirm the impact of two evident alterations (Y127H and G334A) on the protein structure and function.
Highlights
In last few years, genome-wide association studies (GWAS) tested a huge number of SNPs in thousands of people and highlighted reproducibly distinguished numerous relationships among the common genetic variants and diseases with their traits [1]
The nucleotide sequence in FASTA format (Accession number: NC_000007. 14), Pendrin protein amino acid sequence (NP_000432.1) were downloaded from NCBI and datasets related to SNPs of SLC26A4 gene were obtained from NCBI database of SNPs
Human SLC2A46 gene contains a total number of 14473 single nucleotide polymorphisms)
Summary
Genome-wide association studies (GWAS) tested a huge number of SNPs in thousands of people and highlighted reproducibly distinguished numerous relationships among the common genetic variants and diseases with their traits [1]. These studies have advanced from measuring 100,000 SNPs to one million, and test sizes have increased significantly as the need of variations that make the analysis of diseases easier has escalated [2]. The studies to detect SNPs along with the mutagenesis analysis complement each other to identify the amino acid substitutions in the protein coding regions, as each variation can potentially alter the function or structure of a protein [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
