Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782419881891725312 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4782033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT essebieralexandra statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions AT verawolfpatricia statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions AT caominhduc statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions AT carrollbernardj statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions AT balasubramaniansureshkumar statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions AT bodenmikael statisticalenrichmentofepigeneticstatesaroundtripletrepeatsthatcanundergoexpansions |