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Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases
The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SN...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235176/ https://www.ncbi.nlm.nih.gov/pubmed/34208629 http://dx.doi.org/10.3390/ijms22126454 |
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author | Degtyareva, Arina O. Antontseva, Elena V. Merkulova, Tatiana I. |
author_facet | Degtyareva, Arina O. Antontseva, Elena V. Merkulova, Tatiana I. |
author_sort | Degtyareva, Arina O. |
collection | PubMed |
description | The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study. Then, we brief the recent comprehensive examples of rSNPs studied from the discovery of the changes in the TFBS sequence as a result of a nucleotide substitution to identification of its effect on the target gene expression and, eventually, to phenotype. We also describe state-of-the-art genome-wide approaches to identification of regulatory variants, including both making molecular sense of genome-wide association studies (GWAS) and the alternative approaches the primary goal of which is to determine the functionality of genetic variants. Among these approaches, special attention is paid to expression quantitative trait loci (eQTLs) analysis and the search for allele-specific events in RNA-seq (ASE events) as well as in ChIP-seq, DNase-seq, and ATAC-seq (ASB events) data. |
format | Online Article Text |
id | pubmed-8235176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82351762021-06-27 Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases Degtyareva, Arina O. Antontseva, Elena V. Merkulova, Tatiana I. Int J Mol Sci Review The vast majority of the genetic variants (mainly SNPs) associated with various human traits and diseases map to a noncoding part of the genome and are enriched in its regulatory compartment, suggesting that many causal variants may affect gene expression. The leading mechanism of action of these SNPs consists in the alterations in the transcription factor binding via creation or disruption of transcription factor binding sites (TFBSs) or some change in the affinity of these regulatory proteins to their cognate sites. In this review, we first focus on the history of the discovery of regulatory SNPs (rSNPs) and systematized description of the existing methodical approaches to their study. Then, we brief the recent comprehensive examples of rSNPs studied from the discovery of the changes in the TFBS sequence as a result of a nucleotide substitution to identification of its effect on the target gene expression and, eventually, to phenotype. We also describe state-of-the-art genome-wide approaches to identification of regulatory variants, including both making molecular sense of genome-wide association studies (GWAS) and the alternative approaches the primary goal of which is to determine the functionality of genetic variants. Among these approaches, special attention is paid to expression quantitative trait loci (eQTLs) analysis and the search for allele-specific events in RNA-seq (ASE events) as well as in ChIP-seq, DNase-seq, and ATAC-seq (ASB events) data. MDPI 2021-06-16 /pmc/articles/PMC8235176/ /pubmed/34208629 http://dx.doi.org/10.3390/ijms22126454 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Degtyareva, Arina O. Antontseva, Elena V. Merkulova, Tatiana I. Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title | Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title_full | Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title_fullStr | Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title_full_unstemmed | Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title_short | Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases |
title_sort | regulatory snps: altered transcription factor binding sites implicated in complex traits and diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235176/ https://www.ncbi.nlm.nih.gov/pubmed/34208629 http://dx.doi.org/10.3390/ijms22126454 |
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