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| Status |
Public on Dec 13, 2016 |
| Title |
Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes. |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Rare variants enriched for functions in chromatin regulation and neuronal synapses have been linked to autism. How chromatin and DNA methylation interact with environmental exposures at synaptic genes in autism etiologies is currently unclear. Using whole-genome bisulfite sequencing in brain tissue and a neuronal cell culture model carrying a 15q11.2-q13.3 maternal duplication, we find that significant global DNA hypomethylation is enriched over autism candidate genes and affects gene expression. The cumulative effect of multiple chromosomal duplications and exposure to the pervasive persistent organic pollutant PCB 95 altered methylation of more than 1,000 genes. Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A.Z was altered by PCB 95 and duplication. These results demonstrate the compounding effects of genetic and environmental insults on the neuronal methylome that converge upon dysregulation of chromatin and synaptic genes.
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| Overall design |
Examination of DNA Cytosine methylation in human brain and cell culture;
Brain_Control: 11 different post-mortem human brains with no diagnosed neurological disorders
Brain_Dup15: 9 different post-mortem human brains diagnosed with Dup15q Syndrome
Brain_PWS: 5 different post-mortem human brains diagnosed with Prader-Willi Syndrome
Brain_Angelman: 3 different post-mortem human brains diagnosed with Angelman Syndrome
Brain_Downs: 4 different post-mortem human brains diagnosed with Downs Syndrome
Brain_IdioAut: 6 different post-mortem human brains diagnosed with Idiopathic Autism
BraindfBA_Control: 2 different post-mortem human Control brains that are the same biological sample as those found in Brain_Control but a different Brodmann Area
BraindfBA_Dup15: A post-mortem human Dup15q brain that are the same biological sample as that found in Brain_Dup15 but a different Brodmann Area
Culture_SH: SH-SY5Y human neuroblastoma cell line treated with DMSO for 10 days.
Culture_SHPCB: SH-SY5Y human neuroblastoma cell line treated with PCB 95 in DMSO for 10 days.
Culture_SH15M: SH-SY5Y human neuroblastoma cell line with a duplication of part of chromosome 15 treated with DMSO for 10 days.
Culture_SH15MPCB: SH-SY5Y human neuroblastoma cell line with a duplication of part of chromosome 15 treated with PCB 95 in DMSO for 10 days.
Culture_SHclone: SH-SY5Y human neuroblastoma cell line treated with DMSO for 40 days. Then, single cell cloned and grown for 21 generations.
Culture_SHPCBclone: SH-SY5Y human neuroblastoma cell line treated with PCB 95 in DMSO for 40 days. Then, single cell cloned and grown for 21 generations.
Culture_SH15Mdup22: SH-SY5Y human neuroblastoma cell line with a duplication of part of chromosome 15 treated with DMSO for 40 days. Then, single cell cloned and grown for 21 generations.
Culture_SH15Mdup22PCB: SH-SY5Y human neuroblastoma cell line with a duplication of part of chromosome 15 treated with PCB 95 in DMSO for 40 days. Then, single cell cloned and grown for 21 generations.
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| Contributor(s) |
Dunaway K, LaSalle J |
| Citation(s) |
27974215 |
| |
| Submission date |
May 17, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Keith Dunaway |
| E-mail(s) |
kwdunaway@ucdavis.edu
|
| Organization name |
UC Davis
|
| Department |
MMI
|
| Lab |
LaSalle Lab
|
| Street address |
3318 Tupper Hall
|
| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95616 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (64)
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| Relations |
| BioProject |
PRJNA321909 |
| SRA |
SRP075292 |
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