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A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene
Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to com...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916122/ https://www.ncbi.nlm.nih.gov/pubmed/27390651 http://dx.doi.org/10.1186/s40064-016-2543-4 |
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author | Kalia, Namarta Sharma, Aarti Kaur, Manpreet Kamboj, Sukhdev Singh Singh, Jatinder |
author_facet | Kalia, Namarta Sharma, Aarti Kaur, Manpreet Kamboj, Sukhdev Singh Singh, Jatinder |
author_sort | Kalia, Namarta |
collection | PubMed |
description | Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency ≥0.10 were considered for the present study. These 37 SNPs includes one in 3′ near gene, nine in 3′ UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5′ near gene. From these 37 SNPs, 11 non-coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases. |
format | Online Article Text |
id | pubmed-4916122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-49161222016-07-07 A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene Kalia, Namarta Sharma, Aarti Kaur, Manpreet Kamboj, Sukhdev Singh Singh, Jatinder Springerplus Research Mannose binding lectin (MBL) is a liver derived protein which plays an important role in innate immunity. Mannose binding lectin gene 2 (MBL2) polymorphisms are reported to be associated with various diseases. In spite of being exhaustively studied molecule, no attempt has been made till date to comprehensively and systematically analyze the SNPs of MBL2 gene. The present study was carried out to identify and prioritize the SNPs of MBL2 gene for further genotyping and functional studies. To predict the possible impact of SNPs on MBL structure and function SNP data obtained from dbSNP database were analyzed using various bioinformatics tools. Out of total 661 SNPs, only 37 validated SNPs having minor allele frequency ≥0.10 were considered for the present study. These 37 SNPs includes one in 3′ near gene, nine in 3′ UTR, one non-synonymous SNP (nsSNP), thirteen intronic SNPs and thirteen in 5′ near gene. From these 37 SNPs, 11 non-coding SNPs were identified to be of functional significance and evolutionary conserved. Out of these, 4 SNPs from 3′ UTR were found to play role in miRNA binding, 7 SNPs from 5′ near and intronic region were predicted to involve in transcription factor binding and expression of MBL2 gene. One nsSNP Gly54Asp (rs1800450) was found to be deleterious and damaging by both SIFT and Polyphen-2 servers and thus affecting MBL2 protein stability and expression. Protein structural analysis with this amino acid variant was performed by using I-TASSER, RAMPAGE, Swiss-PdbViewer, Chimera and I-mutant. Information regarding solvent accessibility, molecular dynamics and energy minimization calculations showed that this variant causes clashes with neighboring amino acids residues that must interfere in the normal triple helix formation of trimeric subunit and further with the normal assembly of MBL oligomeric form, hence decrease in stability. Thus, findings of the present study indicated 12 SNPs of MBL2 gene to be functionally important. Exploration of these variants may provide novel remedial markers for various diseases. Springer International Publishing 2016-06-21 /pmc/articles/PMC4916122/ /pubmed/27390651 http://dx.doi.org/10.1186/s40064-016-2543-4 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Kalia, Namarta Sharma, Aarti Kaur, Manpreet Kamboj, Sukhdev Singh Singh, Jatinder A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title | A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title_full | A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title_fullStr | A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title_full_unstemmed | A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title_short | A comprehensive in silico analysis of non-synonymous and regulatory SNPs of human MBL2 gene |
title_sort | comprehensive in silico analysis of non-synonymous and regulatory snps of human mbl2 gene |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916122/ https://www.ncbi.nlm.nih.gov/pubmed/27390651 http://dx.doi.org/10.1186/s40064-016-2543-4 |
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