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From Genotype to Phenotype: Through Chromatin

Advances in sequencing technologies have enabled the exploration of the genetic basis for several clinical disorders by allowing identification of causal mutations in rare genetic diseases. Sequencing technology has also facilitated genome-wide association studies to gather single nucleotide polymor...

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Autores principales: Romanowska, Julia, Joshi, Anagha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410296/
https://www.ncbi.nlm.nih.gov/pubmed/30678090
http://dx.doi.org/10.3390/genes10020076
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author Romanowska, Julia
Joshi, Anagha
author_facet Romanowska, Julia
Joshi, Anagha
author_sort Romanowska, Julia
collection PubMed
description Advances in sequencing technologies have enabled the exploration of the genetic basis for several clinical disorders by allowing identification of causal mutations in rare genetic diseases. Sequencing technology has also facilitated genome-wide association studies to gather single nucleotide polymorphisms in common diseases including cancer and diabetes. Sequencing has therefore become common in the clinic for both prognostics and diagnostics. The success in follow-up steps, i.e., mapping mutations to causal genes and therapeutic targets to further the development of novel therapies, has nevertheless been very limited. This is because most mutations associated with diseases lie in inter-genic regions including the so-called regulatory genome. Additionally, no genetic causes are apparent for many diseases including neurodegenerative disorders. A complementary approach is therefore gaining interest, namely to focus on epigenetic control of the disease to generate more complete functional genomic maps. To this end, several recent studies have generated large-scale epigenetic datasets in a disease context to form a link between genotype and phenotype. We focus DNA methylation and important histone marks, where recent advances have been made thanks to technology improvements, cost effectiveness, and large meta-scale epigenome consortia efforts. We summarize recent studies unravelling the mechanistic understanding of epigenetic processes in disease development and progression. Moreover, we show how methodology advancements enable causal relationships to be established, and we pinpoint the most important issues to be addressed by future research.
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spelling pubmed-64102962019-03-26 From Genotype to Phenotype: Through Chromatin Romanowska, Julia Joshi, Anagha Genes (Basel) Review Advances in sequencing technologies have enabled the exploration of the genetic basis for several clinical disorders by allowing identification of causal mutations in rare genetic diseases. Sequencing technology has also facilitated genome-wide association studies to gather single nucleotide polymorphisms in common diseases including cancer and diabetes. Sequencing has therefore become common in the clinic for both prognostics and diagnostics. The success in follow-up steps, i.e., mapping mutations to causal genes and therapeutic targets to further the development of novel therapies, has nevertheless been very limited. This is because most mutations associated with diseases lie in inter-genic regions including the so-called regulatory genome. Additionally, no genetic causes are apparent for many diseases including neurodegenerative disorders. A complementary approach is therefore gaining interest, namely to focus on epigenetic control of the disease to generate more complete functional genomic maps. To this end, several recent studies have generated large-scale epigenetic datasets in a disease context to form a link between genotype and phenotype. We focus DNA methylation and important histone marks, where recent advances have been made thanks to technology improvements, cost effectiveness, and large meta-scale epigenome consortia efforts. We summarize recent studies unravelling the mechanistic understanding of epigenetic processes in disease development and progression. Moreover, we show how methodology advancements enable causal relationships to be established, and we pinpoint the most important issues to be addressed by future research. MDPI 2019-01-23 /pmc/articles/PMC6410296/ /pubmed/30678090 http://dx.doi.org/10.3390/genes10020076 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Romanowska, Julia
Joshi, Anagha
From Genotype to Phenotype: Through Chromatin
title From Genotype to Phenotype: Through Chromatin
title_full From Genotype to Phenotype: Through Chromatin
title_fullStr From Genotype to Phenotype: Through Chromatin
title_full_unstemmed From Genotype to Phenotype: Through Chromatin
title_short From Genotype to Phenotype: Through Chromatin
title_sort from genotype to phenotype: through chromatin
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410296/
https://www.ncbi.nlm.nih.gov/pubmed/30678090
http://dx.doi.org/10.3390/genes10020076
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