Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR125551_1.fastq.gz | Fastqsanger.gz | |||
| ERR125551_2.fastq.gz | Fastqsanger.gz | |||
| ERR125552_1.fastq.gz | Fastqsanger.gz | |||
| ERR125552_2.fastq.gz | Fastqsanger.gz | |||
| ERR125553_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 10 |
Similar Datasets
Project description:Unbalanced translocations are a relatively common type of copy number variation and are a major contributor to neurodevelopmental disorders. We analyzed the breakpoints of 57 unique unbalanced translocations to investigate the mechanisms of how they form. 51 are simple unbalanced translocations between two different chromosome ends, and six rearrangements have more than three breakpoints involving two to five chromosomes. Sequencing 37 breakpoint junctions revealed that simple translocations have between zero and four basepairs (bp) of microhomology (n=26), short inserted sequences (n=8), or paralogous repeats (n=3) at the junctions, indicating that translocations do not arise primarily from non-allelic homologous recombination, but instead form most often via non-homologous end joining or microhomology-mediated break-induced replication. Three simple translocations fuse genes that are predicted to produce in-frame transcripts of SIRPG-WWOX, SMOC2-PROX1, and PIEZO2-MTA1, which may lead to gain of function. Three complex translocations have inversions, insertions, and multiple breakpoint junctions between only two chromosomes. Whole- genome sequencing and fluorescence in situ hybridization analysis of two de novo translocations revealed at least 18 and 33 breakpoints involving five different chromosomes. Breakpoint sequencing of one inherited translocation involving four chromosomes uncovered multiple breakpoints with inversions and insertions. All of these breakpoint junctions had zero to four bp of microhomology consistent with germline chromothripsis, and both de novo events occurred on paternal alleles. Breakpoint sequencing of our large collection of chromosome rearrangements offers a comprehensive analysis of the molecular mechanisms behind germline translocation formation. High resolution array CGH; two-color experiment, clinical patient vs. normal control gDNA; sex mis-matched
2015-04-22 | E-GEOD-68019 | biostudies-arrayexpress
Project description:Unbalanced translocations are a relatively common type of copy number variation and are a major contributor to neurodevelopmental disorders. We analyzed the breakpoints of 57 unique unbalanced translocations to investigate the mechanisms of how they form. 51 are simple unbalanced translocations between two different chromosome ends, and six rearrangements have more than three breakpoints involving two to five chromosomes. Sequencing 37 breakpoint junctions revealed that simple translocations have between zero and four basepairs (bp) of microhomology (n=26), short inserted sequences (n=8), or paralogous repeats (n=3) at the junctions, indicating that translocations do not arise primarily from non-allelic homologous recombination, but instead form most often via non-homologous end joining or microhomology-mediated break-induced replication. Three simple translocations fuse genes that are predicted to produce in-frame transcripts of SIRPG-WWOX, SMOC2-PROX1, and PIEZO2-MTA1, which may lead to gain of function. Three complex translocations have inversions, insertions, and multiple breakpoint junctions between only two chromosomes. Whole- genome sequencing and fluorescence in situ hybridization analysis of two de novo translocations revealed at least 18 and 33 breakpoints involving five different chromosomes. Breakpoint sequencing of one inherited translocation involving four chromosomes uncovered multiple breakpoints with inversions and insertions. All of these breakpoint junctions had zero to four bp of microhomology consistent with germline chromothripsis, and both de novo events occurred on paternal alleles. Breakpoint sequencing of our large collection of chromosome rearrangements offers a comprehensive analysis of the molecular mechanisms behind germline translocation formation.
2015-04-22 | GSE68019 | GEO
Project description:RNA-seq for four neuroblastoma samples (Paired-end protocol). Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we investigated somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries (SRA accession number ERP001414) and RNA-seq. In one cell line and in the two primary tumors, this approach confirmed the localization of the majority of rearrangements within one or two chromosomes, consistent with the phenomenon of chromothripsis. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. RNA-seq analysis allowed the identification of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis.
2013-03-03 | E-MTAB-1367 | biostudies-arrayexpress
Project description:Germline unbalanced translocations arise from diverse mutational mechanisms including chromothripsis
| PRJNA281869 | ENA
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a female carrier to her child. The chromothripsis in the carriers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two carriers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one patient with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy carriers strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease.
2015-01-31 | GSE65452 | GEO
Project description:Large scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology-mediated repair to be the main drivers of interchromosomal structural aberrations. Breakpoint sequences of de novo unbalanced translocations have not yet been investigated systematically. We analyzed 12 de novo translocations and mapped the breakpoints in 9. Surprisingly, in contrast to balanced translocations, we identify non-allelic homologous recombination (NAHR) between (retro)transposable elements and especially long interspersed elements (LINEs) as the main mutational mechanism. This finding implicates (retro)transposons to be a major driver of genomic rearrangements and exposes a profoundly different mutational mechanism compared to balanced chromosomal translocations. Furthermore, we show the existence of compound maternal/paternal derivative chromosomes, reinforcing the hypothesis that human cleavage stage embryogenesis is a cradle of chromosomal rearrangements. In total 36 non-amplified genomic DNA samples (12 patients plus parents) extracted from blood or amniocytes were analyzed by 250K Nsp I SNP arrays (GEO accession number GPL3718).
2012-07-12 | E-GEOD-39303 | biostudies-arrayexpress
Project description:Whole genome sequencing detected structural rearrangements of TERT in 17/75 high stage neuroblastoma with 5 cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted immediate up- and down-stream regions of TERT, placing in 7 cases a super-enhancer close to the breakpoints. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high stage neuroblastoma, each associated with very poor prognosis
2015-10-21 | GSE73537 | GEO
Project description:Chromosomal rearrangements are prevalent events in the human population, occurring both constitutionally in the general population and somatically in the majority of cancers. Detection of balanced rearrangements, such as reciprocal translocations and inversions, is troublesome with many rearrangements remaining undetected. This is particularly detrimental in oncology where rearrangements play diagnostic and prognostic roles and can influence choice and efficacy of treatment protocols. New methods to detect and characterize balanced rearrangements are therefore required for both research and clinical applications. Here we describe the use of the chromosome conformation capture derived method Hi-C as a tool for detection of both balanced and unbalanced chromosomal rearrangements in cell lines and human tumor samples, with the ability to detect gene fusions and define chromosomal breakpoints to base pair resolution. In addition, we show that copy number information can also be obtained from the same data, allowing rearrangements, gains, amplifications and deletions of genomic regions to be detected in a single experiment.
2017-05-23 | GSE81879 | GEO
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. Here, we analyzed one patient-parent-mother's parents quintet to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.
2015-01-31 | E-GEOD-65451 | biostudies-arrayexpress
Project description:Large scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology-mediated repair to be the main drivers of interchromosomal structural aberrations. Breakpoint sequences of de novo unbalanced translocations have not yet been investigated systematically. We analyzed 12 de novo translocations and mapped the breakpoints in 9. Surprisingly, in contrast to balanced translocations, we identify non-allelic homologous recombination (NAHR) between (retro)transposable elements and especially long interspersed elements (LINEs) as the main mutational mechanism. This finding implicates (retro)transposons to be a major driver of genomic rearrangements and exposes a profoundly different mutational mechanism compared to balanced chromosomal translocations. Furthermore, we show the existence of compound maternal/paternal derivative chromosomes, reinforcing the hypothesis that human cleavage stage embryogenesis is a cradle of chromosomal rearrangements.
2012-07-13 | GSE39303 | GEO