Title |
Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome
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Published in |
Epigenetics & Chromatin, March 2017
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DOI | 10.1186/s13072-017-0118-4 |
Pubmed ID | |
Authors |
Laila C. Schenkel, Kristin D. Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J. Ainsworth, David I. Rodenhiser, Guillaume Pare, Nathalie G. Bérubé, Cindy Skinner, Kym M. Boycott, Charles Schwartz, Bekim Sadikovic |
Abstract |
Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the ATRX gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers. We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity. Most significant methylation changes in the 14 genomic loci provide a unique epigenetic signature for this syndrome that may be used as a highly sensitive and specific diagnostic biomarker to support the diagnosis of ATR-X, particularly in patients with phenotypic complexity and in patients with ATRX gene sequence variants of unknown significance. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 20% |
United Kingdom | 1 | 20% |
Canada | 1 | 20% |
United States | 1 | 20% |
Unknown | 1 | 20% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 80% |
Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 86 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 16 | 19% |
Student > Ph. D. Student | 12 | 14% |
Student > Bachelor | 7 | 8% |
Student > Master | 5 | 6% |
Student > Doctoral Student | 5 | 6% |
Other | 16 | 19% |
Unknown | 25 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 23 | 27% |
Medicine and Dentistry | 12 | 14% |
Agricultural and Biological Sciences | 5 | 6% |
Neuroscience | 5 | 6% |
Nursing and Health Professions | 3 | 3% |
Other | 9 | 10% |
Unknown | 29 | 34% |