Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.
Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The...
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| Format: | Article |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4503774?pdf=render |
| _version_ | 1818689005635502080 |
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| author | Dorota M Nowak Marzena Gajecka |
| author_facet | Dorota M Nowak Marzena Gajecka |
| author_sort | Dorota M Nowak |
| collection | DOAJ |
| description | Despite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T12:03:14Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-2e6812e1c58446689f67af8041b6ecab2022-12-21T21:49:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013214310.1371/journal.pone.0132143Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci.Dorota M NowakMarzena GajeckaDespite numerous studies, the causes of both development and progression of keratoconus remain elusive. Previous studies of this disorder focused mainly on one or two genetic factors only. However, in the analysis of such complex diseases all potential factors should be taken into consideration. The purpose of this study was a comprehensive analysis of known keratoconus loci to uncover genetic factors involved in this disease causation in the general population, which could be omitted in the original studies. In this investigation genomic data available in various databases and experimental own data were assessed. The lists of single nucleotide variants and miRNA genes localized in reported keratoconus loci were obtained from Ensembl and miRBase, respectively. The potential impact of nonsynonymous amino acid substitutions on protein structure and function was assessed with PolyPhen-2 and SIFT. For selected protein genes the ranking was made to choose those most promising for keratoconus development. Ranking results were based on topological features in the protein-protein interaction network. High specificity for the populations in which the causative sequence variants have been identified was found. In addition, the possibility of links between previously analyzed keratoconus loci was confirmed including miRNA-gene interactions. Identified number of genes associated with oxidative stress and inflammatory agents corroborated the hypothesis of their effect on the disease etiology. Distribution of the numerous sequences variants within both exons and mature miRNA which forces you to search for a broader look at the determinants of keratoconus. Our findings highlight the complexity of the keratoconus genetics.http://europepmc.org/articles/PMC4503774?pdf=render |
| spellingShingle | Dorota M Nowak Marzena Gajecka Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. PLoS ONE |
| title | Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. |
| title_full | Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. |
| title_fullStr | Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. |
| title_full_unstemmed | Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. |
| title_short | Nonrandom Distribution of miRNAs Genes and Single Nucleotide Variants in Keratoconus Loci. |
| title_sort | nonrandom distribution of mirnas genes and single nucleotide variants in keratoconus loci |
| url | http://europepmc.org/articles/PMC4503774?pdf=render |
| work_keys_str_mv | AT dorotamnowak nonrandomdistributionofmirnasgenesandsinglenucleotidevariantsinkeratoconusloci AT marzenagajecka nonrandomdistributionofmirnasgenesandsinglenucleotidevariantsinkeratoconusloci |