Genetic Variants Influence on the Placental-specific Regulatory Landscape
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PROVIDER: PRJNA497169 | ENA |
REPOSITORIES: ENA
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Project description:Genetic Variants Influence on the Placental-specific Regulatory Landscape
| PRJNA497170 | ENA
Project description:From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications. By producing and analyzing DNA sequence variation (n = 303), DNA methylation (n = 303) and mRNA expression data (n = 80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations. These findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.
| S-EPMC6277118 | biostudies-literature
Project description:<p>This study of the regulatory landscape of the placenta relies on the identification of associations between genetic variant and gene expression changes (eQTLs); genetic variant and DNA methylation changes (mQTLs); and, gene expression change and DNA methylation change (eQTMs). It involves the analysis of DNA sequence variation (n=303), DNA methylation (n=303) and mRNA expression data (n=80) from placentas from healthy women. Such studies are crucial to fully apprehend the complexity of the regulatory landscape and to support further analysis focusing and disease driven phenotype.</p>
| phs001717 | dbGaP
Project description:Genome-wide association studies (GWAS) have boosted our knowledge of genetic risk variants in autoimmune diseases (AIDs). Most of the risk variants are located within or near genes with immunological functions, and the majority is found to be non-coding, pointing towards a regulatory role. We have performed a cis expression quantitative trait locus (eQTL) screen to investigate whether single nucleotide polymorphisms (SNPs) associated with AIDs influence gene expression in thymus. Genotyping was performed using the Immunochip and 353 AID associated SNPs were tested against expression of surrounding genes (+/- 1 Mb) from human thymic tissue (N=42). We identified eight genes where the expression was associated with AID risk SNPs at a study-wide level of significance (P < 2.57x10-5). Five genes (FCRL3, RNASET2, C2orf74, SIRPG and SYS1) displayed cis eQTL signals also in other tissues, while for two loci (NPIPB8 and LOC388814), the eQTL signal appear to be thymus-specific. Since many AID risk variants from GWAS have been subsequently fine-mapped in recent Immunochip projects, we explored the overlap between these novel AID risk variants and the thymic eQTL regions. Moreover, we examined the functional annotation of the seven expression altering SNPs (eSNPs). Our study reveals autoimmune risk variants that act as eQTLs in thymus. We have highlighted functional variants within these genetic regions that potentially can represent causal autoimmune risk variants. Total RNA from 42 human thymic samples were obtained from children undergoing cardiac surgery.
2016-01-21 | E-GEOD-77052 | biostudies-arrayexpress
Project description:The extensive molecular characterization of the transcriptional regulatory landscape within the LCLs of a 3-generation, 17-member kindred was performed to allow for the identification of functional variants. A variant associated with changes in multiple molecular phenotypes was selected for validation through precise CRISPR/Cas9 editing. Edited clones were subsequently tested for reconstitution of function through CRISPR/dCas9 targeted TF activation.
2019-06-04 | GSE117574 | GEO
Project description:The extensive molecular characterization of the transcriptional regulatory landscape within the LCLs of a 3-generation, 17-member kindred was performed to allow for the identification of functional variants. A variant associated with changes in multiple molecular phenotypes was selected for validation through precise CRISPR/Cas9 editing. Edited clones were subsequently tested for reconstitution of function through CRISPR/dCas9 targeted TF activation.
2019-06-04 | GSE117565 | GEO
Project description:The extensive molecular characterization of the transcriptional regulatory landscape within the LCLs of a 3-generation, 17-member kindred was performed to allow for the identification of functional variants. A variant associated with changes in multiple molecular phenotypes was selected for validation through precise CRISPR/Cas9 editing. Edited clones were subsequently tested for reconstitution of function through CRISPR/dCas9 targeted TF activation.
2019-06-04 | GSE117490 | GEO
Project description:The extensive molecular characterization of the transcriptional regulatory landscape within the LCLs of a 3-generation, 17-member kindred was performed to allow for the identification of functional variants. A variant associated with changes in multiple molecular phenotypes was selected for validation through precise CRISPR/Cas9 editing. Edited clones were subsequently tested for reconstitution of function through CRISPR/dCas9 targeted TF activation.
2019-06-04 | GSE117484 | GEO
Project description:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.
2015-04-29 | E-MTAB-3309 | biostudies-arrayexpress
Project description:Identifying the molecular mechanisms by which genome-wide association study (GWAS) loci influence traits remains challenging. Chromatin accessibility quantitative trait loci (caQTL) help identify GWAS loci that may alter GWAS traits by modulating chromatin structure, but caQTL have been identified in a limited set of human tissues. Here we mapped caQTL in human liver tissue in 20 liver samples and identified 3,123 caQTL. The caQTL variants are enriched in liver tissue promoter and enhancer states and frequently disrupt binding motifs of transcription factors expressed in liver. We predicted target genes for 861 caQTL peaks using proximity, chromatin interactions, correlation with promoter accessibility or gene expression, and colocalization with expression QTL. Using GWAS signals for 19 liver function and/or cardiometabolic traits, we identified 110 colocalized caQTL and GWAS signals, 56 of which contained a predicted caPeak target gene. At the LITAF LDL-cholesterol GWAS locus, we validated that a caQTL variant showed allelic differences in protein binding and transcriptional activity. These caQTL contribute to the epigenomic characterization of human liver and help identify molecular mechanisms and genes at GWAS loci.
2021-05-01 | GSE164938 | GEO