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Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions

Definitive molecular diagnoses in disorders apparently due to genetic or genomic defects are still lacking in a significant number of investigated cases, despite use of studies designed to discover defects in the protein coding regions of the genome. Increasingly studies are being designed to search...

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Detalles Bibliográficos
Autores principales: Smith, Moyra, Flodman, Pamela L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277798/
https://www.ncbi.nlm.nih.gov/pubmed/30542652
http://dx.doi.org/10.3389/fmolb.2018.00101
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author Smith, Moyra
Flodman, Pamela L.
author_facet Smith, Moyra
Flodman, Pamela L.
author_sort Smith, Moyra
collection PubMed
description Definitive molecular diagnoses in disorders apparently due to genetic or genomic defects are still lacking in a significant number of investigated cases, despite use of studies designed to discover defects in the protein coding regions of the genome. Increasingly studies are being designed to search for defects in the non-protein coding genome, and for alterations in gene expression. Here we review new insights into genomic elements involved in control of gene expression, including methods to analyze chromatin that is accessible for transcription factor binding, enhancers, chromatin looping, transcription, RNA binding proteins, and alternative splicing. We review new studies on levels of genome organization, including the occurrence of transcriptional domains and their boundary elements. Information is presented on specific malformation syndromes that arise due to structural genomic changes that impact the non-protein coding genome and sometimes impact specific transcriptional domains. We also review convergence of genome-wide association with studies of gene expression, discoveries related to expression quantitative trait loci and splicing quantitative trait loci and the relevance of these to specific complex common diseases. Aspects of epigenetic mechanisms and clinical applications of analyses of methylation signatures are also discussed.
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spelling pubmed-62777982018-12-12 Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions Smith, Moyra Flodman, Pamela L. Front Mol Biosci Molecular Biosciences Definitive molecular diagnoses in disorders apparently due to genetic or genomic defects are still lacking in a significant number of investigated cases, despite use of studies designed to discover defects in the protein coding regions of the genome. Increasingly studies are being designed to search for defects in the non-protein coding genome, and for alterations in gene expression. Here we review new insights into genomic elements involved in control of gene expression, including methods to analyze chromatin that is accessible for transcription factor binding, enhancers, chromatin looping, transcription, RNA binding proteins, and alternative splicing. We review new studies on levels of genome organization, including the occurrence of transcriptional domains and their boundary elements. Information is presented on specific malformation syndromes that arise due to structural genomic changes that impact the non-protein coding genome and sometimes impact specific transcriptional domains. We also review convergence of genome-wide association with studies of gene expression, discoveries related to expression quantitative trait loci and splicing quantitative trait loci and the relevance of these to specific complex common diseases. Aspects of epigenetic mechanisms and clinical applications of analyses of methylation signatures are also discussed. Frontiers Media S.A. 2018-11-27 /pmc/articles/PMC6277798/ /pubmed/30542652 http://dx.doi.org/10.3389/fmolb.2018.00101 Text en Copyright © 2018 Smith and Flodman. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Smith, Moyra
Flodman, Pamela L.
Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title_full Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title_fullStr Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title_full_unstemmed Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title_short Expanded Insights Into Mechanisms of Gene Expression and Disease Related Disruptions
title_sort expanded insights into mechanisms of gene expression and disease related disruptions
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277798/
https://www.ncbi.nlm.nih.gov/pubmed/30542652
http://dx.doi.org/10.3389/fmolb.2018.00101
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