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| Status |
Public on Nov 24, 2013 |
| Title |
DNA methylation differences between multiple sclerosis and controls in frontal lobe white matter |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis–affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis–affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis–affected brains.
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| Overall design |
47 samples analyzed in total: 17 MS females, age 55.5 ± 10.3 years; 11 MS males, age 55.0 ± 9.9 years; 7 control females, 69.1 ± 9.2 years; 12 control males, 64.7 ± 8.0 years. From each individual, white matter was dissected from the frontal lobe and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.
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| Contributor(s) |
Huynh JL, Garg P, Sharp AJ, Casaccia P |
| Citation(s) |
24270187 |
| Submission date |
Aug 24, 2012 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Patrizia Casaccia |
| E-mail(s) |
pcasaccia@gc.cuny.edu
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| Organization name |
ASRC-CUNY
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| Department |
Neuroscience
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| Street address |
85 St Nicholas Terrace
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10031 |
| Country |
USA |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (47)
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| Relations |
| BioProject |
PRJNA173693 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40360_GenomeStudio_norm_bg.txt.gz |
442.2 Mb |
(ftp)(http) |
TXT |
| GSE40360_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| GSE40360_RAW_nonorm_nobg.txt.gz |
436.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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