Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431246 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6491110.fastq.gz | Fastqsanger.gz | |||
| SRR6491120.fastq.gz | Fastqsanger.gz | |||
| SRR6491130.fastq.gz | Fastqsanger.gz | |||
| SRR6491140.fastq.gz | Fastqsanger.gz | |||
| SRR6491150.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Verification of predicted hotspots of Alu/Alu-mediated rearrangements in the human genome
| PRJNA392240 | ENA
Project description:We report the first genome-wide mapping of fragility hotspots after siRNA-mediated knockdown of the DEAD-box helicase DDX41 in HCT116 cells using sBLISS. DDX41 defficient cells display elevated levels of genomic instability. sBLISS analysis revealed that hotspots for genomic instability in the absence of DDX41 are located around the transcription start site of transcribed genes.
2021-11-17 | GSE183147 | GEO
Project description:Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at nucleotide-level resolution. Accordingly, our aim is to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as array Comparative Genomic Hybridization (aCGH), we have identified the breakpoints and characterized the likely rearrangement mechanism of the NF1 intragenic CNCs in 78 unrelated patients. Unlike the most typical recurrent rearrangements mediated by flanking low copy repeats (LCRs), NF1 intragenic CNCs have diverse breakpoint locations, and are characterized by different rearrangement mechanisms. We propose the DNA replication-based mechanisms comprising FoSTeS/MMBIR and serial replication stalling to be the predominant mechanism leading to NF1 intragenic CNCs. In addition to the loop of a 197-bp palindrome located in intron 40, four Alu elements located in intron 1, 2, 3 and 50 were also identified as significant intragenic rearrangement hotspots within the NF1 gene. However, no clear genotype-phenotype correlations could be identified among the NF1 patients carrying NF1 intragenic CNCs.
2015-07-30 | GSE64869 | GEO
Project description:Genomic rearrangements may cause both Mendelian and complex disorders. Currently, several major mechanisms causing genomic rearrangements have been proposed such as non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR). However, to what extent these mechanisms contribute to gene-specific pathogenic copy-number changes (CNCs) remains understudied. Furthermore, only few studies resolved these pathogenic alterations at nucleotide-level resolution. Accordingly, our aim is to explore which mechanisms contribute to a large, unique set of locus-specific non-recurrent genomic rearrangements causing the genetic neurocutaneous disorder neurofibromatosis type 1 (NF1). Through breakpoint-spanning PCR as well as array Comparative Genomic Hybridization (aCGH), we have identified the breakpoints and characterized the likely rearrangement mechanism of the NF1 intragenic CNCs in 78 unrelated patients. Unlike the most typical recurrent rearrangements mediated by flanking low copy repeats (LCRs), NF1 intragenic CNCs have diverse breakpoint locations, and are characterized by different rearrangement mechanisms. We propose the DNA replication-based mechanisms comprising FoSTeS/MMBIR and serial replication stalling to be the predominant mechanism leading to NF1 intragenic CNCs. In addition to the loop of a 197-bp palindrome located in intron 40, four Alu elements located in intron 1, 2, 3 and 50 were also identified as significant intragenic rearrangement hotspots within the NF1 gene. However, no clear genotype-phenotype correlations could be identified among the NF1 patients carrying NF1 intragenic CNCs. Patient DNA samples with non-overlapping CNCs, as estimated by MLPA, were labeled with Cy3 and Cy5 fluorophores respectively, and hybridized onto the microarray. Alternatively, patient DNA was hybridized versus unrelated individual blood DNA. No hybridizations using biological replicates were performed. In total 6 samples were included. Please note that our experimental setup included a hybridization in which two DNA samples with non-overlapping deletions, from two NF1 patients, were hybridized in one experiment (sample codes: 1253 and 1403). In this specific case, assigning test or reference function to the samples was a matter of arbitrary choice. However, if needed, sample 1253 can be denoted as test, and sample 1403 can be denoted as reference in this experiment.
2015-07-30 | E-GEOD-64869 | biostudies-arrayexpress
Project description:Repetitive sequences are hotspots of evolution at multiple levels. However, due to technical difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content of proteomes and genomes, directly from proteomic and genomic raw sequence data, and applied it to analyze a wide range of tumors and normal tissues. We identify high similarity between the repeat-instability in tumors and their patient-matched normal tissues, but also tumor-specific signatures, both in protein expression and in the genome, that strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We find an inverse relationship between repeat-instability and point mutation load, within and across patients, and independently of other somatic aberrations. Thus, repeat-instability is a distinct, transient and compensatory adaptive mechanism in tumor evolution.
2020-06-02 | PXD012574 | Pride
Project description:Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long span paired-end-tag (PET) sequencing approach using 10 Kb genomic DNA inserts to study human genome structural variations (SVs). The use of 10 Kb insert size allows the identification of breakpoints within repetitive or homology containing regions of a few Kb in size and results in a higher physical coverage compared to small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and 2 non-cancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germline SVs, whereas tandem duplications, unpaired inversions, inter-chromosomal translocations, and complex rearrangements are overrepresented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures which are compatible with breakage-fusion-bridge cycles, and discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers. Structural variations of 15 human cancer samples and 2 human normal samples were identified by long span paired-end sequencing
2011-04-06 | E-GEOD-26954 | biostudies-arrayexpress
Project description:Most sarcomas have complex karyotype and are characterized by multiple chromosomal rearrangements. Moreover, sarcomas very frequently maintain their telomeres by recombination in the process called Alternative Lengthening of Telomeres (ALT) which enables their continuous growth and immortalization. Previously our group showed that orphan receptors bind specifically to the ALT telomeres and that their presence is important for the ALT mechanism. In these studies we focus on the function of orphan receptors at the telomeres and their contribution to telomeric recombination. We demonstrate that orphan receptors induce proximity of their binding sites in telomeric and genomic context and reveal novel aspects of ALT which are telomere-genome rearrangements which can underlie complexity of sarcomas. Our data perturb the dogma of telomere function in protecting the genome integrity. Here we show that in some cases telomeres may in fact drive genomic instability and chromosomal rearrangements by recombination with genomic sites. Characterization of TRF2 and orphan receptor NR2F/C2 binding sites in ALT (-) and ALT (+) cells.
2015-02-23 | E-GEOD-46237 | biostudies-arrayexpress
Project description:DNA replication stress (DRS)-linked genomic instability has emerged as an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability and phenotypic evolution, we mapped chromosomal alterations in a yeast strain with lowered expression of the replicative DNA polymerase δ. At a whole-genome level, we identified both hotspots of mitotic recombination and chromosome-specific aneuploidy dependent on decreased levels of DNA polymerase δ. The high rate of chromosome loss is likely a reflection of reduced DNA repair capacity in strains with low levels of DNA polymerase. Most recombinogenic DNA lesions were introduced during S or G2 phase, presumably as a consequence of broken replication forks.
2016-03-03 | GSE78856 | GEO
Project description:Most sarcomas have complex karyotype and are characterized by multiple chromosomal rearrangements. Moreover, sarcomas very frequently maintain their telomeres by recombination in the process called Alternative Lengthening of Telomeres (ALT) which enables their continuous growth and immortalization. Previously our group showed that orphan receptors bind specifically to the ALT telomeres and that their presence is important for the ALT mechanism. In these studies we focus on the function of orphan receptors at the telomeres and their contribution to telomeric recombination. We demonstrate that orphan receptors induce proximity of their binding sites in telomeric and genomic context and reveal novel aspects of ALT which are telomere-genome rearrangements which can underlie complexity of sarcomas. Our data perturb the dogma of telomere function in protecting the genome integrity. Here we show that in some cases telomeres may in fact drive genomic instability and chromosomal rearrangements by recombination with genomic sites.
2015-02-23 | GSE46237 | GEO
Project description:To identify the genome-wide impact of Alu/Alu-mediated rearrangement (AAMR) on variation and human health, we have developed a bioinformatic approach to characterize Alus involved in mediating CNVs and have predicted genome-wide AAMR hotspot loci. This prediction was validated by performing molecular biological experiments on 89 samples selected by correlating AAMR hotspot genes with a database of ~54,000 chromosomal microarrays.
2017-06-29 | GSE100590 | GEO