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Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions

More than 30 human genetic diseases are linked to tri-nucleotide repeat expansions. There is no known mechanism that explains repeat expansions in full, but changes in the epigenetic state of the associated locus has been implicated in the disease pathology for a growing number of examples. A compre...

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Autores principales: Essebier, Alexandra, Vera Wolf, Patricia, Cao, Minh Duc, Carroll, Bernard J., Balasubramanian, Sureshkumar, Bodén, Mikael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782033/
https://www.ncbi.nlm.nih.gov/pubmed/27013954
http://dx.doi.org/10.3389/fnins.2016.00092
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author Essebier, Alexandra
Vera Wolf, Patricia
Cao, Minh Duc
Carroll, Bernard J.
Balasubramanian, Sureshkumar
Bodén, Mikael
author_facet Essebier, Alexandra
Vera Wolf, Patricia
Cao, Minh Duc
Carroll, Bernard J.
Balasubramanian, Sureshkumar
Bodén, Mikael
author_sort Essebier, Alexandra
collection PubMed
description More than 30 human genetic diseases are linked to tri-nucleotide repeat expansions. There is no known mechanism that explains repeat expansions in full, but changes in the epigenetic state of the associated locus has been implicated in the disease pathology for a growing number of examples. A comprehensive comparative analysis of the genomic features associated with diverse repeat expansions has been lacking. Here, in an effort to decipher the propensity of repeats to undergo expansion and result in a disease state, we determine the genomic coordinates of tri-nucleotide repeat tracts at base pair resolution and computationally establish epigenetic profiles around them. Using three complementary statistical tests, we reveal that several epigenetic states are enriched around repeats that are associated with disease, even in cells that do not harbor expansion, relative to a carefully stratified background. Analysis of over one hundred cell types reveals that epigenetic states generally tend to vary widely between genic regions and cell types. However, there is qualified consistency in the epigenetic signatures of repeats associated with disease suggesting that changes to the chromatin and the DNA around an expanding repeat locus are likely to be similar. These epigenetic signatures may be exploited further to develop models that could explain the propensity of repeats to undergo expansions.
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spelling pubmed-47820332016-03-24 Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions Essebier, Alexandra Vera Wolf, Patricia Cao, Minh Duc Carroll, Bernard J. Balasubramanian, Sureshkumar Bodén, Mikael Front Neurosci Genetics More than 30 human genetic diseases are linked to tri-nucleotide repeat expansions. There is no known mechanism that explains repeat expansions in full, but changes in the epigenetic state of the associated locus has been implicated in the disease pathology for a growing number of examples. A comprehensive comparative analysis of the genomic features associated with diverse repeat expansions has been lacking. Here, in an effort to decipher the propensity of repeats to undergo expansion and result in a disease state, we determine the genomic coordinates of tri-nucleotide repeat tracts at base pair resolution and computationally establish epigenetic profiles around them. Using three complementary statistical tests, we reveal that several epigenetic states are enriched around repeats that are associated with disease, even in cells that do not harbor expansion, relative to a carefully stratified background. Analysis of over one hundred cell types reveals that epigenetic states generally tend to vary widely between genic regions and cell types. However, there is qualified consistency in the epigenetic signatures of repeats associated with disease suggesting that changes to the chromatin and the DNA around an expanding repeat locus are likely to be similar. These epigenetic signatures may be exploited further to develop models that could explain the propensity of repeats to undergo expansions. Frontiers Media S.A. 2016-03-08 /pmc/articles/PMC4782033/ /pubmed/27013954 http://dx.doi.org/10.3389/fnins.2016.00092 Text en Copyright © 2016 Essebier, Vera Wolf, Cao, Carroll, Balasubramanian and Bodén. 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) or licensor 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 Genetics
Essebier, Alexandra
Vera Wolf, Patricia
Cao, Minh Duc
Carroll, Bernard J.
Balasubramanian, Sureshkumar
Bodén, Mikael
Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title_full Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title_fullStr Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title_full_unstemmed Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title_short Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions
title_sort statistical enrichment of epigenetic states around triplet repeats that can undergo expansions
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782033/
https://www.ncbi.nlm.nih.gov/pubmed/27013954
http://dx.doi.org/10.3389/fnins.2016.00092
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