title: Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions.
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.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland St Lucia, QLD, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Essebier
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland St Lucia, QLD, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vera Wolf
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland St Lucia, QLD, Australia.
authors.forename: Minh Duc
authors.initials: MD
authors.lastname: Cao
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland St Lucia, QLD, Australia.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Carroll
authors.affiliation: School of Biological Sciences, Monash University Melbourne, VIC, Australia.
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland St Lucia, QLD, Australia.
authors.forename: Mikael
authors.initials: M
authors.lastname: Bodén
keywords: DNA methylation; bioinformatics; epigenetics; genome sequence; histone modification; short tandem repeat