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Project description:Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single cell Hi-C, combined with genome-wide statistical analysis and structural modeling of single copy X chromosomes, to show that individual chromosomes maintain domain organisation at the megabase scale, but show variable cell-to-cell chromosome territory structures at larger scales. Despite this structural stochasticity, localisation of active gene domains to boundaries of territories is a hallmark of chromosomal conformation, affecting most domains in most nuclei. Single cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organisation underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns. Mouse Th1 single-cell Hi-C maps were produced and paired-end sequenced. 10 single-cell samples and a multi-sample pool together with a population Hi-C sample are included.
2013-09-26 | E-GEOD-48262 | biostudies-arrayexpress
Project description:The analysis of patient blood transcriptional profiles offers a means to investigate the immunological mechanisms relevant to human diseases on a genome-wide scale. In addition, such studies provide a basis for the discovery of clinically relevant biomarker signatures. We designed a strategy for microarray analysis that is based on the identification of transcriptional modules formed by genes coordinately expressed in multiple disease data sets. Mapping changes in gene expression at the module level generated disease-specific transcriptional fingerprints that provide a stable framework for the visualization and functional interpretation of microarray data. These transcriptional modules were used as a basis for the selection of biomarkers and the development of a multivariate transcriptional indicator of disease progression in patients with systemic lupus erythematosus. Thus, this work describes the implementation and application of a methodology designed to support systems-scale analysis of the human immune system in translational research settings. This SuperSeries is composed of the SubSeries listed below.
2008-08-11 | GSE11907 | GEO
Project description:Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately one percent of the general population. Most genetic studies so far focused on disease association with common genetic variation such as single nucleotide polymorphisms, but recently it has become apparent that large-scale genomic copy number variants (CNVs) are involved in disease development as well. To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrix’ GeneChip 250K SNP arrays. Keywords: genomic hybridisation
2008-10-22 | GSE12714 | GEO
Project description:Here we utilized large-scale systematic probing and screening of ~2000 sequence and structural variants based on two long, perfect RNA hairpins to explore the structure and sequence context determining editability.
2021-05-05 | GSE155490 | GEO
Project description:Mammalian genomes are organized into megabase-scale topologically associated domains (TADs) that have been proposed to represent large regulatory units. Here we demonstrate that disruption of TADs can cause rewiring of long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome. RNA-seq profile of developing distal limbs of mutants and WT animals at E11.5
2015-05-08 | E-GEOD-66377 | biostudies-arrayexpress
Project description:Identification of genes involved in trophoblast differentiation is of great interest in understanding cellular and molecular mechanisms involved in placental development and is relevant clinically to fetal development, fertility, and maternal health. To understand, on a global scale, changes in the transcriptome during the differentiation of hESCs down the trophoblast lineage, a large-scale microarray analysis was performed. This work provides an in vitro functional genomic model with which to identify genes involved in trophoblast development.
2011-09-17 | GSE30915 | GEO
Project description:Mammalian genomes are organized into megabase-scale topologically associated domains (TADs) that have been proposed to represent large regulatory units. Here we demonstrate that disruption of TADs can cause rewiring of long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome. Circular Chromosome Conformation Capture (4C seq) at the WNT6/IHH/EPHA4/PAX3 locus in human adult fibroblasts (HAF) of adult patients and controls
2015-05-08 | E-GEOD-66378 | biostudies-arrayexpress
Project description:Mammalian genomes are organized into megabase-scale topologically associated domains (TADs) that have been proposed to represent large regulatory units. Here we demonstrate that disruption of TADs can cause rewiring of long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome. Circular Chromosome Conformation Capture (4C seq) at the Wnt6/Ihh/Epha4/Pax3 locus in developing distal limbs of mutants and WT animals at E11.5
2015-05-08 | E-GEOD-66379 | biostudies-arrayexpress
Project description:We report a genome-wide, multi-scale approach to simultaneously measure the effect that the increased copy of each gene and/or operon has on a desired trait or phenotype. The method involves i) growth selections on a mixture of several different plasmid based genomic libraries of defined insert sizes or SCALEs, ii) micro-array studies of enriched plasmid DNA, and a ii) mathematical multi-scale analysis (MSA) that precisely identifies the relevant genetic elements. This approach allows for identification of all single open reading frames and larger multi-gene fragments within a genomic library that alter the expression of a given phenotype. We have demonstrated this method in E. coli by monitoring, in parallel, a population of >106 genomic library clones of different insert sizes, throughout continuous selections over a period of 100 generations.
2006-10-26 | E-TABM-143 | biostudies-arrayexpress