dc.contributor.author |
Lu, Ake T |
|
dc.contributor.author |
Narayan, Pritika |
|
dc.contributor.author |
Grant, Matthew J |
|
dc.contributor.author |
Langfelder, Peter |
|
dc.contributor.author |
Wang, Nan |
|
dc.contributor.author |
Kwak, Seung |
|
dc.contributor.author |
Wilkinson, Hilary |
|
dc.contributor.author |
Chen, Richard Z |
|
dc.contributor.author |
Chen, Jian |
|
dc.contributor.author |
Simon Bawden, C |
|
dc.contributor.author |
Rudiger, Skye R |
|
dc.contributor.author |
Ciosi, Marc |
|
dc.contributor.author |
Chatzi, Afroditi |
|
dc.contributor.author |
Maxwell, Alastair |
|
dc.contributor.author |
Hore, Timothy A |
|
dc.contributor.author |
Aaronson, Jeff |
|
dc.contributor.author |
Rosinski, Jim |
|
dc.contributor.author |
Preiss, Alicia |
|
dc.contributor.author |
Vogt, Thomas F |
|
dc.contributor.author |
Coppola, Giovanni |
|
dc.contributor.author |
Monckton, Darren |
|
dc.contributor.author |
Snell, Russell G |
|
dc.contributor.author |
William Yang, X |
|
dc.contributor.author |
Horvath, Steve |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2023-07-13T01:25:56Z |
|
dc.date.available |
2023-07-13T01:25:56Z |
|
dc.date.issued |
2020-09 |
|
dc.identifier.citation |
(2020). Nature Communications, 11(1), 4529-. |
|
dc.identifier.issn |
2041-1723 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/64731 |
|
dc.description.abstract |
Although Huntington's disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10<sup>-7</sup>) associated with 33 CpG sites, including the HTT gene (p = 6.5 × 10<sup>-26</sup>). These Htt/HTT associations were replicated in the Q175 Htt knock-in mouse model (p = 6.0 × 10<sup>-8</sup>) and in the transgenic sheep model (p = 2.4 × 10<sup>-88</sup>). We define a measure of HD motor score progression among manifest HD cases based on multiple clinical assessments. EWAS of motor progression in manifest HD cases exhibits significant (p < 10<sup>-7</sup>) associations with methylation levels at three loci: near PEX14 (p = 9.3 × 10<sup>-9</sup>), GRIK4 (p = 3.0 × 10<sup>-8</sup>), and COX4I2 (p = 6.5 × 10<sup>-8</sup>). We conclude that HD is accompanied by profound changes of DNA methylation levels in three mammalian species. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Nature communications |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Animals |
|
dc.subject |
Animals, Genetically Modified |
|
dc.subject |
Sheep |
|
dc.subject |
Humans |
|
dc.subject |
Mice |
|
dc.subject |
Huntington Disease |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Disease Progression |
|
dc.subject |
Recombinant Proteins |
|
dc.subject |
Severity of Illness Index |
|
dc.subject |
Registries |
|
dc.subject |
Longitudinal Studies |
|
dc.subject |
Follow-Up Studies |
|
dc.subject |
Prospective Studies |
|
dc.subject |
Cross-Sectional Studies |
|
dc.subject |
Behavior, Animal |
|
dc.subject |
DNA Methylation |
|
dc.subject |
Epigenesis, Genetic |
|
dc.subject |
CpG Islands |
|
dc.subject |
Mutation |
|
dc.subject |
Adolescent |
|
dc.subject |
Adult |
|
dc.subject |
Aged |
|
dc.subject |
Aged, 80 and over |
|
dc.subject |
Middle Aged |
|
dc.subject |
Female |
|
dc.subject |
Male |
|
dc.subject |
Genome-Wide Association Study |
|
dc.subject |
Young Adult |
|
dc.subject |
Gene Knock-In Techniques |
|
dc.subject |
Genetic Loci |
|
dc.subject |
Huntingtin Protein |
|
dc.subject |
Global Burden of Disease |
|
dc.subject |
Brain Disorders |
|
dc.subject |
Neurosciences |
|
dc.subject |
Rare Diseases |
|
dc.subject |
Orphan Drug |
|
dc.subject |
Human Genome |
|
dc.subject |
Huntington's Disease |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
Genetics |
|
dc.subject |
2 Aetiology |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
Neurological |
|
dc.subject |
Science & Technology |
|
dc.subject |
Multidisciplinary Sciences |
|
dc.subject |
Science & Technology - Other Topics |
|
dc.subject |
GENE |
|
dc.subject |
AGE |
|
dc.subject |
ONSET |
|
dc.subject |
METAANALYSIS |
|
dc.subject |
AGGREGATION |
|
dc.subject |
EXPRESSION |
|
dc.subject |
PACKAGE |
|
dc.subject |
LENGTH |
|
dc.subject |
0604 Genetics |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
Biotechnology |
|
dc.title |
DNA methylation study of Huntington's disease and motor progression in patients and in animal models. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41467-020-18255-5 |
|
pubs.issue |
1 |
|
pubs.begin-page |
4529 |
|
pubs.volume |
11 |
|
dc.date.updated |
2023-06-30T00:04:20Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
32913184 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/32913184 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Multicenter Study |
|
pubs.subtype |
Journal Article |
|
pubs.subtype |
Observational Study |
|
pubs.elements-id |
816893 |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
pubs.org-id |
Statistics |
|
dc.identifier.eissn |
2041-1723 |
|
dc.identifier.pii |
10.1038/s41467-020-18255-5 |
|
pubs.number |
4529 |
|
pubs.record-created-at-source-date |
2023-06-30 |
|
pubs.online-publication-date |
2020-09-10 |
|