Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA737741 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14813700_1.fastq.gz | Fastqsanger.gz | |||
| SRR14813700_2.fastq.gz | Fastqsanger.gz | |||
| SRR14813800_1.fastq.gz | Fastqsanger.gz | |||
| SRR14813800_2.fastq.gz | Fastqsanger.gz | |||
| SRR14813701_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism [WGS]
| PRJNA737757 | ENA
Project description:Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism [WGBS]
| PRJNA737756 | ENA
Project description:Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism [RNA-seq]
| PRJNA737758 | ENA
Project description:Most autism spectrum disorder (ASD) cases involve complex genetics interacting with perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. Here we used whole genome bisulfite sequencing (WGBS) in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene in a co-methylated block at 22q13.33. Differentially methylated region (DMR) analysis identified 139 DMRs common to ASD in placental samples, including a high-confidence 118 kb hypomethylated block at 22q13.33 that replicated in two additional cohorts and identified the novel transcript NHIP as neuronal hypoxia inducible, placenta associated (gene name approved by HGNC). NHIP characterized by high expression in brain, increased expression following neuronal differentiation or hypoxia in vitro, and minimal expression in ASD placenta. Transient NHIP overexpression in cell lines increased cellular proliferation and altered expression of genes regulating synapses and neurogenesis in response to hypoxia, significantly overlapping with NHIP-associated transcript levels in ASD brain and known ASD risk genes. A common Alu insert near a fetal brain enhancer correlated with NHIP placental and brain expression levels and ASD risk, demonstrating a common genetic influence on DNA methylation levels. Together, these results demonstrate a novel environmentally-responsive ASD risk gene relevant to brain development in a hitherto uncharacterized region of the human genome.
2022-01-16 | GSE178204 | GEO
Project description:Most autism spectrum disorder (ASD) cases involve complex genetics interacting with perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. Here we used whole genome bisulfite sequencing (WGBS) in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene in a co-methylated block at 22q13.33. Differentially methylated region (DMR) analysis identified 139 DMRs common to ASD in placental samples, including a high-confidence 118 kb hypomethylated block at 22q13.33 that replicated in two additional cohorts and identified the novel transcript NHIP as neuronal hypoxia inducible, placenta associated (gene name approved by HGNC). NHIP characterized by high expression in brain, increased expression following neuronal differentiation or hypoxia in vitro, and minimal expression in ASD placenta. Transient NHIP overexpression in cell lines increased cellular proliferation and altered expression of genes regulating synapses and neurogenesis in response to hypoxia, significantly overlapping with NHIP-associated transcript levels in ASD brain and known ASD risk genes. A common Alu insert near a fetal brain enhancer correlated with NHIP placental and brain expression levels and ASD risk, demonstrating a common genetic influence on DNA methylation levels. Together, these results demonstrate a novel environmentally-responsive ASD risk gene relevant to brain development in a hitherto uncharacterized region of the human genome.
2022-01-16 | GSE178203 | GEO
Project description:Most autism spectrum disorder (ASD) cases involve complex genetics interacting with perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. Here we used whole genome bisulfite sequencing (WGBS) in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene in a co-methylated block at 22q13.33. Differentially methylated region (DMR) analysis identified 139 DMRs common to ASD in placental samples, including a high-confidence 118 kb hypomethylated block at 22q13.33 that replicated in two additional cohorts and identified the novel transcript NHIP as neuronal hypoxia inducible, placenta associated (gene name approved by HGNC). NHIP characterized by high expression in brain, increased expression following neuronal differentiation or hypoxia in vitro, and minimal expression in ASD placenta. Transient NHIP overexpression in cell lines increased cellular proliferation and altered expression of genes regulating synapses and neurogenesis in response to hypoxia, significantly overlapping with NHIP-associated transcript levels in ASD brain and known ASD risk genes. A common Alu insert near a fetal brain enhancer correlated with NHIP placental and brain expression levels and ASD risk, demonstrating a common genetic influence on DNA methylation levels. Together, these results demonstrate a novel environmentally-responsive ASD risk gene relevant to brain development in a hitherto uncharacterized region of the human genome.
2022-01-16 | GSE178205 | GEO
Project description:BackgroundAutism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome.ResultsWe use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence.ConclusionsTogether, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.
| S-EPMC8848662 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-13 | GSE178206 | GEO
Project description:Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs. Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
2020-10-21 | GSE159526 | GEO
Project description:Advanced paternal age has been shown to be a significant risk factor for neurodevelopmental psychiatric disorders, particularly autism. We have recently shown that mice conceived by old fathers display behavioral abnormalities which resemble key diagnostic symptoms of human autism. De novo mutations and epigenetic alterations increase in the male germ line during ageing and are thought to mediate the effect of paternal age on occurrence of diseases occurrence. Because the placenta carry a predominantly fetal genetic background, age-related mutagenesis and epigenetic errors might negatively influence placental physiology and in turn perturb fetal brain development. Here, we examined the impact of paternal age on placental mRNA transcriptome. This work was supported by Programme FP7-KBBE-2012.1.3-04, GA no. 312097 Acronym: FECUND, to GEP; MIUR/CNR, Programme FIRB. GA n. B81J12002520001 Acronym: GenHome, to PL. This study was also partially financed by the IGAB PAS project (S.III.1.3), Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants N N519 657940 and N N311 604938. We compared gene expression patterns of mouse placentas harvested from either advanced paternal age model (APA) of autism or control animals. We included 2 comparisons: 1) placenta of female APA vs placenta of female control; 2) placenta of male APA vs placenta of male control. Each comparison was composed of 3 biological replicates. To minimize family bias, poolings contained at most one placenta per sex from each dam to a minimum of one and a maximum of three placentas per group/sex.
2015-07-25 | E-GEOD-71322 | biostudies-arrayexpress