From GWAS to PheWAS: Scanning the EMR Phenome for Gene-disease Associations
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PROVIDER: PRJNA428409 | ENA |
REPOSITORIES: ENA
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Project description:From GWAS to PheWAS: Scanning the EMR Phenome for Gene-disease Associations
| PRJNA428408 | ENA
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed RNA-Seq analysis in adult C. elegans nematodes comparing gene expression in wild type and single and double mutants of two components of the NE, EMR-1 and LEM-2. Our data confirm that EMR-1 and LEM-2 facilitate gene repression and that both proteins control the expression of mainly muscle and neuronal genes. mRNA profiles of wild type, emr-1(gk119), lem-2(tm1582) and emr-1(RNAi) lem-2(tm1582) young adult worms were generated by deep sequencing, in triplicate for the wild type and duplicates for the other backgrounds, using Illumina GAIIx.
2013-12-02 | E-GEOD-44682 | biostudies-arrayexpress
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed a genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of two components of the NE, Lamin/LMN-1 and Emerin/EMR-1. Although both proteins were associated to silent DNA, EMR-1 showed a predominant role in the anchoring of muscle and neuronal promoters to the nuclear periphery. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1 association.
2013-12-02 | GSE44188 | GEO
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed RNA-Seq analysis in adult C. elegans nematodes comparing gene expression in wild type and single and double mutants of two components of the NE, EMR-1 and LEM-2. Our data confirm that EMR-1 and LEM-2 facilitate gene repression and that both proteins control the expression of mainly muscle and neuronal genes.
2013-12-02 | GSE44682 | GEO
Project description:Phenome analysis of Mycoplasma pneumoniae
| PRJEB10038 | ENA
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed a genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of two components of the NE, Lamin/LMN-1 and Emerin/EMR-1. Although both proteins were associated to silent DNA, EMR-1 showed a predominant role in the anchoring of muscle and neuronal promoters to the nuclear periphery. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1 association. Comparison of Dam::LMN-1 and Dam::EMR-1 DNA assotiation in wild type strains and Dam::LMN-1 DNA association in wild type, lem-2(tm1582) and emr-1(gk119) mutant backgrounds.
2013-12-02 | E-GEOD-44188 | biostudies-arrayexpress
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125714 | GEO
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125713 | GEO
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125712 | GEO
Project description:Genome-wide association studies (GWASs) have identified many sources of genetic variation associated with bone mineral density (BMD), a clinical predictor of fracture risk and osteoporosis. Aside from the identification of causal genes, other difficult challenges to informing GWAS include characterizing the roles of predicted causal genes in disease and providing additional functional context, such as the cell type predictions or biological pathways in which causal genes operate. Leveraging single-cell transcriptomics (scRNA-seq) can assist in informing BMD GWAS by linking disease-associated variants to genes and providing a cell type context for which these causal genes drive disease. Here, we use large-scale scRNA-seq data from bone marrow–derived stromal cells cultured under osteogenic conditions (BMSC-OBs) from Diversity Outbred (DO) mice to generate cell type-specific networks and contextualize BMD GWAS-implicated genes. Using trajectories inferred from the scRNA-seq data, we identify networks enriched with genes that exhibit the most dynamic changes in expression across trajectories. We discover 21 network driver genes, which are likely to be causal for human BMD GWAS associations that colocalize with expression/splicing quantitative trait loci (eQTL/sQTL). These driver genes, including Fgfrl1 and Tpx2, along with their associated networks, are predicted to be novel regulators of BMD via their roles in the differentiation of mesenchymal lineage cells. In this work, we showcase the use of single-cell transcriptomics from mouse bone-relevant cells to inform human BMD GWAS and prioritize genetic targets with potential causal roles in the development of osteoporosis.
2025-06-10 | GSE269583 | GEO