Statistical enrichment of epigenetic states around triplet repeats that can undergo expansions

Essebier, Alexandra, Wolf, Patricia Vera, Cao, Minh Duc, Carroll, Bernard J., Balasubramanian, Sureshkumar and Boden, Mikael (2016) Statistical enrichment of epigenetic states around triplet repeats that can undergo expansions. Frontiers in Neuroscience, 10 MAR: 92.1-92.12. doi:10.3389/fnins.2016.00092

Author Essebier, Alexandra
Wolf, Patricia Vera
Cao, Minh Duc
Carroll, Bernard J.
Balasubramanian, Sureshkumar
Boden, Mikael
Title Statistical enrichment of epigenetic states around triplet repeats that can undergo expansions
Journal name Frontiers in Neuroscience   Check publisher's open access policy
ISSN 1662-453X
Publication date 2016-03-08
Year available 2016
Sub-type Article (original research)
DOI 10.3389/fnins.2016.00092
Open Access Status DOI
Volume 10
Issue MAR
Start page 92.1
End page 92.12
Total pages 12
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2017
Language eng
Formatted abstract
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.
Keyword Short tandem repeat
Histone modification
DNA methylation
Genome sequence
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
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