The data is big,please wait a moment......
| EWAS ID | EWAS717 |
| GSE ID | GSE74486 |
| EWAS Title | Trans-effects of chromosome aneuploidies on DNA methylation patterns: DNA methylation analysis of Down syndrome in human brain tissues and cells |
| Disease/Phenotype | down syndrome (DS) |
| Group1 | Down syndrome(Adult;Cerebellar cortex;Whole grey matter) |
| Group2 | Normal(Adult;Cerebellar cortex;Whole grey matter) |
| Group1 Sample Size | 13 |
| Group2 Sample Size | 10 |
| Summary | Background: Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results: Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T-lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in brain cells. Some genes show brain-specific DS-DM, while others show stronger DS-DM in T cells. Both 5-methyl-cytosine and 5-hydroxy-methyl-cytosine contribute to the DS-DM. Thirty percent of genes with DS-DM in adult brain cells also show DS-DM in fetal brains, indicating early onset of these epigenetic changes, and we find early maturation of methylation patterns in DS brain and lymphocytes. Some, but not all, of the DS-DM genes show differential expression. DS-DM preferentially affected CpGs in or near specific transcription factor binding sites, implicating a mechanism involving altered transcription factor binding. Methyl-seq of brain DNA from mouse models with sub-chromosomal duplications mimicking DS reveals partial but significant overlaps with human DS-DM and shows that multiple chromosome 21 genes contribute to the downstream epigenetic effects. Conclusions: These data point to novel biological mechanisms in DS and have general implications for trans effects of chromosomal duplications and aneuploidies on epigenetic patterning. |
| Contributor | Mendioroz M, Do C, Jiang X, Liu C, Darbary HK, Lang CF, Lin J, Thomas A, Abu-Amero S, Stanier P, Temkin A, Yale A, Liu M, Li Y, Salas M, Kerkel K, Capone G, Silverman W, Yu E, Moore G, Wegiel J, Tycko B |
| Public date | Public on Oct 30, 2015 |
| Citation (PubMed ID) | 26607552 |
| Browse ALL Significant Marker | Browse (the result is searched from a big database. It may be a potentially slow. Please be patient.) |
| Browse ALL Significant KEGG Pathways | Browse (the result is searched from a big database. It may be a potentially slow. Please be patient.) |
| Browse ALL Significant GO Categories | Browse (the result is searched from a big database. It may be a potentially slow. Please be patient.) |