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| Status |
Public on Apr 13, 2017 |
| Title |
DNA methylation signature of human fetal alcohol spectrum disorder |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Prenatal alcohol exposure is the leading preventable cause of behavioural and cognitive deficits, which may affect between 2-5% of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with Fetal Alcohol Spectrum Disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date. Genome-wide DNA methylation patterns of buccal epithelial cells were analyzed using the Illumina HumanMethylation450 array on a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip. After correcting for the effects of genetic background, 658 significantly differentially methylated sites between FASD cases and controls remained, with 41 displaying differences in beta greater than 5%. Furthermore, 203 differentially methylated regions containing 2 or more CpGs were also identified, overlapping with 167 different genes. The majority of differentially methylated genes were highly expressed in samples from the Allen Brain Atlas, which showed high correlations with buccal cell DNA methylation patterns. Furthermore, over-representation analysis of the up-methylated genes displayed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders. These findings suggest that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.
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| Overall design |
The Illumina Infinium HumanMethylation450 Beadchip was used to analyze human buccal epithelial cells from children from the NeuroDevNet cohort, assesing genome-wide DNA methylation patterns in children with fetal alcohol spectrum disorder (n=110 ) and controls (n=96) to identify a potential DNA methylation signature of FASD.
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| Contributor(s) |
Portales-Casamar E, Lussier AA, Jones MJ, MacIsaac JL, Edgar R, Mah SM, Barhdadi A, Provost S, Lemieux-Perreault L, Chudley AE, Dubé M, Reynolds JN, Pavlidis P, Kobor MS |
| Citation(s) |
27358653 |
| Submission date |
Apr 13, 2016 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Michael S. Kobor |
| Organization name |
Centre for Molecular Medicine and Therapeutics / University of British Columbia
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| Department |
Medical Genetics
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| Lab |
Kobor
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| Street address |
950 West 28th Avenue
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (216)
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| Relations |
| BioProject |
PRJNA318420 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80261_RAW.tar |
1.9 Gb |
(http)(custom) |
TAR (of IDAT) |
| GSE80261_unmethylated_and_methylated_signal.txt.gz |
825.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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