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Genome-wide methylation profiles of post-mortem tissue samples (human)

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244996 | GEO | 2023/10/22

REPOSITORIES: GEO

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Genome-wide methylation profiles of post-mortem tissue samples (human) 3

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Project description:In this study, 60 post-mortem tissue samples comprising three tissue types (blood, brain, and heart) were collected from autopsies of 20 Koreans aged 18 to 78. 250 ng of genomic DNA (gDNA) was employed to generate DNA methylation profiles utilizing the Illumina Infinium MethylationEPIC BeadChip array (Illumina, San Diego, CA, USA) at Macrogen Inc. (Macrogen, Seoul, Korea).

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Genome-wide methylation profiles of post-mortem tissue samples (human)

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Epigenome wide association study of post-mortem Alzheimer’s Disease samples

Project description:Samples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study (EWAS) to evaluate the epigenetic differences using post-mortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples. We performed an epigenome-wide association study (EWAS) to evaluate the epigenetic differences using post-mortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples.

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Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue.

Project description:Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular aetiology of ASD, we quantified genome-wide patterns of DNA methylation in 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex and cerebellum (CB)] dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the CB. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically defined subtype of ASD, were characterized by striking differences in DNA methylationacross a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.

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DNA methylation and histone post-translational modification stability in post-mortem brain tissue.

Project description:BackgroundEpigenetic (including DNA and histone) modifications occur in a variety of neurological disorders. If epigenetic features of brain autopsy material are to be studied, it is critical to understand the post-mortem stability of the modifications.MethodsPig and mouse brain tissue were formalin-fixed and paraffin-embedded, or frozen after post-mortem delays of 0, 24, 48, and 72?h. Epigenetic modifications frequently reported in the literature were studied by DNA agarose gel electrophoresis, DNA methylation enzyme-linked immunosorbent assays, Western blotting, and immunohistochemistry. We constructed a tissue microarray of human neocortex samples with devitalization or death to fixation times ranging from <?60?min to 5?days.ResultsIn pig and mouse brain tissue, we found that DNA cytosine modifications (5mC, 5hmC, 5fC, and 5caC) were stable for ??72?h post-mortem. Histone methylation was generally stable for ??48?h (H3K9me2/K9me3, H3K27me2, H3K36me3) or ??72?h post-mortem (H3K4me3, H3K27me3). Histone acetylation was generally less stable. The levels of H3K9ac, H3K27ac, H4K5ac, H4K12ac, and H4K16ac declined as early as ??24?h post-mortem, while the levels of H3K14ac did not change at ??48?h. Immunohistochemistry showed that histone acetylation loss occurred primarily in the nuclei of large neurons, while immunoreactivity in glial cell nuclei was relatively unchanged. In the human brain tissue array, immunoreactivity for DNA cytosine modifications and histone methylation was stable, while subtle changes were apparent in histone acetylation at 4 to 5?days post-mortem.ConclusionWe conclude that global epigenetic studies on human post-mortem brain tissue are feasible, but great caution is needed for selection of post-mortem delay matched controls if histone acetylation is of interest.

| S-EPMC6330433 | biostudies-literature

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