|
| Status |
Public on Oct 09, 2019 |
| Title |
Differential 5-methylcytosine and 5-hydroxymethylcytosine in Parkinson’s and Alzheimer’s Disease. |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
|
| Summary |
Background: 5-methylcytosine (5-mC) and its oxidized form, 5-hydroxymethylcytosine (5-hmC), are distinct epigenetic marks that help regulate gene expression in the mammalian brain. Existing studies have identified associations between 5-mC and neurodegenerative disease, but little work has examined the potential role of 5-hmC in Parkinson’s disease (PD) or Alzheimer’s disease (AD). Here, we utilized PD postmortem brain tissue and a public dataset from postmortem AD brains to analyze the effect of neurodegenerative disease on paired 5-mC and 5-hmC levels. Results: In PD samples, we measured genome-wide 5-mC and 5-hmC from control (n=3) and PD (n=6) brains using the Illumina EPIC array combined with bisulfite and oxidative bisulfite treatments (BS/oxBS-EPIC). In publicly sourced data, genome-wide 5-mC and 5-hmC were measured from control (n=25) and AD (n=62) human entorhinal cortex tissue using the Illumina 450K array combined with bisulfite and oxidative bisulfite treatment (BS/oxBS-450K). Paired 5-mC and 5-hmC beta values were generated using a custom pipeline of bioinformatics tools, and we modeled the effect of disease on paired 5-mC and 5-hmC data using a mixed effects beta regression model with a random effect for ID and an interaction term between disease category and DNA modification category (“5-mC” or “5-hmC”). We identified a number of CpG probes (AD: n=699, PD: total n = 80) that showed a significant interaction between disease status and DNA modification category (p-value < 2.4x10-7). Conclusions: While our PD data requires additional validation, our analyses suggest that there are widespread shifts in the balance between 5-mC and 5-hmC in Parkinson’s and Alzheimer’s disease.
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| Overall design |
Control (n=3) and PD (n=6) postmortem brain tissue samples from two tissues -- parietal and cingulate cortex. Total n=18 (n=9 per tissue type). Samples were both bisulfite treated and oxidative bisulfite treated to generate paired 5-mC and 5-hmC. Total number of data files = 36 (n=18 per method).
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| Contributor(s) |
Kochmanski J, VanOeveren SE, Adams M, Gearing M, Bernstein AI |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R00 ES024570 |
Epigenetic effects of adult and developmental exposure to Parkinsonian toxicants |
MICHIGAN STATE UNIVERSITY |
Alison Bernstein |
|
| Submission date |
Oct 08, 2019 |
| Last update date |
Oct 11, 2019 |
| Contact name |
Alison I Bernstein |
| E-mail(s) |
bernst79@msu.edu
|
| Phone |
6162340957
|
| Organization name |
Michigan State University
|
| Department |
Translational Neuroscience
|
| Lab |
Bernstein Lab
|
| Street address |
400 Monroe Ave NW
|
| City |
Grand Rapids |
| State/province |
MI |
| ZIP/Postal code |
49503 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA576484 |
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