Quantitative analysis of chromatin interactions upon copy number variation at mouse 4E2
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64360 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA270820
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-03 | E-GEOD-64360 | biostudies-arrayexpress
Project description:The three-dimensional organization of chromatin has a critical impact on the regulation of gene expression. However, little is known about the effect of DNA copy number variants (CNVs) on chromatin organization. We performed an allele-specific chromatin conformation and gene expression analysis of wild-type (WT) mouse chromosome 4 and an engineered 4.3Mb chromosome 4 deletion in mouse embryonic fibroblasts. A newly developed quantitative framework for the analysis of paired-end 4C-seq data revealed a number of significant differentially interacting regions (DIRs) and higher-order chromatin compaction changes present in the deletion chromosome. Selected DIRs were validated by 3D DNA FISH experiments. We discovered a significant enrichment of CTCF and Smc1 binding sites within DIRs, as well as differentially expressed genes determined by RNA-Seq. Together, our findings highlight the complex effects of a 4E2 CNV on chromatin structure and function, both locally in the deletion chromosome and globally in the WT copy. Examination of chromatin contacts and gene expression in wild type chromosome 4 and a 4.3Mb deletion in chromosome 4 in mouse
2016-07-03 | E-GEOD-64359 | biostudies-arrayexpress
Project description:The three-dimensional organization of chromatin has a critical impact on the regulation of gene expression. However, little is known about the effect of DNA copy number variants (CNVs) on chromatin organization. We performed an allele-specific chromatin conformation and gene expression analysis of wild-type (WT) mouse chromosome 4 and an engineered 4.3Mb chromosome 4 deletion in mouse embryonic fibroblasts. A newly developed quantitative framework for the analysis of paired-end 4C-seq data revealed a number of significant differentially interacting regions (DIRs) and higher-order chromatin compaction changes present in the deletion chromosome. Selected DIRs were validated by 3D DNA FISH experiments. We discovered a significant enrichment of CTCF and Smc1 binding sites within DIRs, as well as differentially expressed genes determined by RNA-Seq. Together, our findings highlight the complex effects of a 4E2 CNV on chromatin structure and function, both locally in the deletion chromosome and globally in the WT copy. Examination of chromatin contacts and gene expression in wild type chromosome 4 and a 4.3Mb deletion in chromosome 4 in mouse
2016-07-03 | E-GEOD-64358 | biostudies-arrayexpress
Project description:The three-dimensional organization of chromatin has a critical impact on the regulation of gene expression. However, little is known about the effect of DNA copy number variants (CNVs) on chromatin organization. We performed an allele-specific chromatin conformation and gene expression analysis of wild-type (WT) mouse chromosome 4 and an engineered 4.3Mb chromosome 4 deletion in mouse embryonic fibroblasts. A newly developed quantitative framework for the analysis of paired-end 4C-seq data revealed a number of significant differentially interacting regions (DIRs) and higher-order chromatin compaction changes present in the deletion chromosome. Selected DIRs were validated by 3D DNA FISH experiments. We discovered a significant enrichment of CTCF and Smc1 binding sites within DIRs, as well as differentially expressed genes determined by RNA-Seq. Together, our findings highlight the complex effects of a 4E2 CNV on chromatin structure and function, both locally in the deletion chromosome and globally in the WT copy.
2016-01-01 | GSE64359 | GEO
Project description:The three-dimensional organization of chromatin has a critical impact on the regulation of gene expression. However, little is known about the effect of DNA copy number variants (CNVs) on chromatin organization. We performed an allele-specific chromatin conformation and gene expression analysis of wild-type (WT) mouse chromosome 4 and an engineered 4.3Mb chromosome 4 deletion in mouse embryonic fibroblasts. A newly developed quantitative framework for the analysis of paired-end 4C-seq data revealed a number of significant differentially interacting regions (DIRs) and higher-order chromatin compaction changes present in the deletion chromosome. Selected DIRs were validated by 3D DNA FISH experiments. We discovered a significant enrichment of CTCF and Smc1 binding sites within DIRs, as well as differentially expressed genes determined by RNA-Seq. Together, our findings highlight the complex effects of a 4E2 CNV on chromatin structure and function, both locally in the deletion chromosome and globally in the WT copy.
2016-01-01 | GSE64358 | GEO
Project description:Quantitative analysis of chromatin interactions upon copy number variation at mouse 4E2
| PRJNA270820 | ENA
Project description:Detailed analyses of the clone-based genome assembly reveal that the recent duplication content of mouse (4.94%) is now comparable to that of human (5.5%), in contrast to previous estimates from the whole-genome shotgun sequence assembly. However, the architecture of mouse and human genomes differs markedly: most mouse duplications are organized into discrete clusters of tandem duplications that show depletion of genes and transcripts and enrichment of long interspersed nuclear element (LINE) and long terminal repeat (LTR) retroposons. We assessed copy number variation of the C57BL/6J duplicated regions within 15 mouse strains previously used for genetic association studies, sequencing and the Mouse Phenome Project. We determined that over 60% of these base pairs are polymorphic among the strains (on average, there was 20 Mb of copy-number-variable DNA between different mouse strains). Our data suggest that different mouse strains show comparable, if not greater, copy number polymorphism when compared to human; however, such variation is more locally restricted. We show large and complex patterns of interstrain copy number variation restricted to large gene families associated with spermatogenesis, pregnancy, viviparity, pheromone signaling and immune response.
| S-EPMC2574762 | biostudies-literature
Project description:BackgroundArray comparative genomic hybridization (aCGH) to detect copy number variants (CNVs) in mammalian genomes has led to a growing awareness of the potential importance of this category of sequence variation as a cause of phenotypic variation. Yet there are large discrepancies between studies, so that the extent of the genome affected by CNVs is unknown. We combined molecular and aCGH analyses of CNVs in inbred mouse strains to investigate this question.Principal findingsUsing a 2.1 million probe array we identified 1,477 deletions and 499 gains in 7 inbred mouse strains. Molecular characterization indicated that approximately one third of the CNVs detected by the array were false positives and we estimate the false negative rate to be more than 50%. We show that low concordance between studies is largely due to the molecular nature of CNVs, many of which consist of a series of smaller deletions and gains interspersed by regions where the DNA copy number is normal.ConclusionsOur results indicate that CNVs detected by arrays may be the coincidental co-localization of smaller CNVs, whose presence is more likely to perturb an aCGH hybridization profile than the effect of an isolated, small, copy number alteration. Our findings help explain the hitherto unexplored discrepancies between array-based studies of copy number variation in the mouse genome.
| S-EPMC2943477 | biostudies-literature
Project description:Over recent years small submicroscopic DNA copy-number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease susceptibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed a simple competitive PCR based method to determine DNA copy number which uses the entire genome of a single chimpanzee as a competitor thus eliminating the requirement for competitive sequences to be synthesized for each assay. This results in the requirement for only a single reference sample for all assays and dramatically increases the potential for large numbers of loci to be analysed in multiplex. In this study we establish proof of concept by accurately detecting previously characterized mutations at the PARK2 locus and then demonstrating the potential of quantitative interspecies competitive PCR (qicPCR) to accurately genotype CNVs in association studies by analysing chromosome 22q11 deletions in a sample of previously characterized patients and normal controls.
| S-EPMC2553599 | biostudies-literature
Project description:BackgroundSingle nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE.ResultsWe performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%.ConclusionsOur study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing.
| S-EPMC2600609 | biostudies-literature