Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1289885 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Robertsonian translocations (ROBs) sequencing
| PRJNA1286809 | ENA
Project description:Purpose: determine if gH2AX and H3.3 are enriched at unsynapsed regions of chromosomes involved in translocations in mouse germ line (meiotic prophase I) Methods: testes were isolated from 4-week or 6-week old heterozygous carriers of a single Robertsonian translocation RB(8;12) or 3 Robertsonian translocations RB(8;12), RB(1;3) and RB(9;14) and controls. ChIP assays were conducted as described in Smagulova 2011. Experiments done in triplicate. Results: We find enrichment of gH2AX in the proximal gene-rich regions of translocation-associated chromosomes and reduced enrichment of gH2AX and H3.3 at sex chromosomes
2016-11-19 | GSE75221 | GEO
Project description:The Barcelona Robertsonian system (BRbS) presents mice with standard karyotype (diploid number 40) but also carrying Robertsonian fusions (ehich lead to variable diploid numbers ranging from 28 to 39). To study the heterogeneity of their genetic background and possible genome divergence between them, samples from three populations were genotyped.
2024-04-04 | GSE254746 | GEO
Project description:Robertsonian translocations modify genomic distribution of gH2AX and H3.3 in mouse germ cells
| PRJNA302817 | ENA
Project description:Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., centric) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding, surrounded by pericentromeric LINE/L1 elements. We explored chromosome structure across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible association of centromeric chromatin, and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.
2022-03-30 | GSE199671 | GEO
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:Chromosomal translocations result from joining of DNA double-strand breaks (DSBs) and frequently cause cancer. Yet, the steps linking DSB formation to DSB ligation remain undeciphered. We report that DNA replication timing (RT) directly regulates lymphomagenic Myc translocations during antibody maturation in B-cells downstream of DSBs and independently of DSB frequency. Depletion of minichromosome-maintenance (MCM) complexes alters replication origin activity, decreases translocations and abrogates global RT. Ablating a single origin at Myc causes an early-to-late RT switch, loss of translocations and reduced nuclear proximity with a translocation partner locus, phenotypes that were reversed by restoring early RT. Disruption of shared early RT also reduced tumorigenic translocations in human leukemic cells. Thus, RT constitutes a new, unprecedented mechanism in translocation biogenesis linking DSB formation to DSB ligation
2022-09-13 | PXD034446 | Pride
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:Preimplantation genetic testing for structural rearrangements (PGT-SR) is critical for embryo selection. Most advanced PGT-SR platforms rely on sequence- or marker-based analysis near chromosomal breakpoints, which is costly, labor-intensive, and time-consuming. As a result, clinical practice often defaults to using PGT-A, a platform that cannot detect balanced rearrangements affecting the offspring's reproductive potential. In this study, we introduce Biop-C, a Hi-C–based technique enabling the comprehensive detection of both unbalanced and balanced translocations, including Robertsonian ones, as well as copy number variations (CNV). By developing custom algorithms for translocation detection, we achieved high accuracy in embryo and biopsy samples. We show that using machine-learning-based approaches allows detecting CNVs using low-coverage Hi-C without control euploid human embryos, which are typically unavailable. In a cohort of 88 samples for translocation detection and 78 samples for CNV detection, Biop-C correctly identified over 86% of detected translocations, and 83% of these calls were concordant with the refined reference. Additionally, Biop-C confirmed the aneuploid status in 84% of embryos, with no embryos initially classified as euploid by standard PGT being misclassified as aneuploid. For CNVs, Biop-C detected 72% of reference CNVs, and 95% of all identified CNVs were true positives. Notably, Biop-C identified an unbalanced translocation in an embryo derived from a couple with a previously undiagnosed parental translocation, demonstrating its diagnostic value. We had 36 samples derived from patients carrying balanced chromosomal rearrangements, we identified 4 balanced translocations in samples classified as These findings establish Biop-C as a powerful PGT-SR approach for distinguishing between normal and balanced embryos, with significant implications for embryo selection and genetic counseling in IVF.
2025-12-08 | GSE311964 | GEO
Project description:To study the effect of balanced chromosomal rearrangements on gene expression, we compared the transcriptomes of cell lines from control and t(11;22)(q23;q11) individuals. This translocation between chromosomes 11 and 22 is the only recurrent constitutional non-Robertsonian translocation in humans. The number of differentially expressed transcripts between the translocated and control cohort is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Altered expression is not limited to genes close to the translocation breakpoint suggesting that a long-range effect is operating. Indeed we show that the nuclear position of the derivative chromosome is altered compared to the normal chromosomes. Our results are consistent with recent studies that indicate a functional role for nuclear position in regulating the expression of some genes in mammalian cells. They may also have implications on reproductive separation, as we show that reciprocal translocations not only provide partial isolation for speciation but also significant changes in transcriptional regulation through alteration of nuclear chromosomes territories. Keywords: Genetic modification
2010-03-05 | GSE13122 | GEO