GATA2 deficiency phenotype associated with tandem duplication of the GATA2 locus linked to a common structural variant
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ABSTRACT:
PROVIDER: PRJNA699578 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Typical features of GATA2 deficiency were observed in a individual with wild-type GATA2 sequence. The patient had a de novo tandem duplication of 187Kb spanning GATA2 and RPN1 containing a deletion of 25Kb 5’ of RPN1, inherited from the mother. The deletion is a copy number variant present in about 4% of Europeans (GRCh37: esv2725896 and nsv513733; GRCh38: esv3597711) and removes an alternative 5’ start site of RPN1 at 128,400Kb, associated with CTCF and H3K27ac binding peaks. A second copy of GATA2 is translocated to this region by the tandem duplication. RNA-Seq was underatken in order to identify any gene fussion events resulting from the mutation and to inverstigate differences in gene expression between the patient and controls.
2021-05-10 | GSE166201 | GEO
Project description: Not available
| S-EPMC8714714 | biostudies-literature
Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5’ΔpyrG upstream of the region targeted for tandem chromosomal duplication and 3’ΔpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.
2014-06-30 | GSE57246 | GEO
Project description:We here describe the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had 5M-bM-^@M-^YM-NM-^TpyrG upstream of the region targeted for tandem chromosomal duplication and 3M-bM-^@M-^YM-NM-^TpyrG downstream of the target region. Consequently, strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks (DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under non-selective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method. A. oryzae strain bearing a 210-kb targeted tandem chromosomal duplication, A. oryzae strain bearing a 700-kb targeted tandem chromosomal duplication, and A. oryzae RIB40 (wild type strain), were cultivated in Polypeptone-dextrin medium. After 3 days cultivation, genomic DNAs from the samples were extracted, and array CGH analysis was carried out to confirm the chromosomal duplications in the strains.
2014-06-30 | E-GEOD-57246 | biostudies-arrayexpress
Project description:Interpreting the genomic and phenotypic consequences of copy number variation (CNV) is essential to understand the etiology of genetic disorders. Whereas deletion CNVs obviously lead to haploinsufficiency, duplications may cause disease through triplosensitivity, gene disruption, or gene fusion at breakpoints. The mutational spectrum of duplications has been studied at certain loci and in some cases these copy number gains are complex chromosome rearrangements involving triplications and/or inversions. However, the organization of clinically relevant duplications throughout the genome has not been investigated on a large scale. Here, we fine mapped 184 germline duplications (14.7 kb-25.3 Mb; median 532 kb) ascertained from individuals referred for diagnostic cytogenetics testing. We performed next-generation sequencing (NGS) and whole-genome sequencing (WGS) to sequence 130 breakpoints from 112 subjects with 119 CNVs and found that most (83%) were tandem duplications in direct orientation. The remainder were triplications embedded within duplications (8.4%), adjacent duplications (4.2%), insertional translocations (2.5%), or other complex rearrangements (1.7%). In addition, we predicted six in-frame fusion genes at sequenced duplication breakpoints. Four gene fusions were formed by tandem duplications, one by two interconnected duplications, and one by duplication inserted at another locus. These novel fusion genes could be related to clinical phenotypes and warrant further study. Though most duplications are positioned head-to-tail adjacent to the original locus, those that are inverted, triplicated, or inserted can disrupt or fuse genes in a manner that may not be predicted by conventional copy number analysis. Thus, interpreting the genetic consequences of duplication CNVs requires breakpoint-level analysis.
2014-10-25 | GSE62657 | GEO
Project description:We used a two-component transgene system to study the RNA-dependent DNA methylation (RdDM) and transcriptional gene silencing (TGS) in Arabidopsis. By profiling the small RNA population in mutants defected in RdDM or RNA polymerase II-transcribed trigger for generating silencing siRNA, we investigated how repetitive loci such as tandem repeats were regulated transcriptionally through the action of RNA polymerase IV. Genome-wide small RNA profiling was done by Illumina TruSeq sample preparation followed by high-throughput sequencing with the Illumina HiSeq 2000 platform. The six samples represent mutants and their corresponding control lines.
2014-08-05 | E-GEOD-47852 | biostudies-arrayexpress
Project description:We used a two-component transgene system to study the RNA-dependent DNA methylation (RdDM) and transcriptional gene silencing (TGS) in Arabidopsis. By profiling the small RNA population in mutants defected in RdDM or RNA polymerase II-transcribed trigger for generating silencing siRNA, we investigated how repetitive loci such as tandem repeats were regulated transcriptionally through the action of RNA polymerase IV.
2014-08-05 | GSE47852 | GEO
Project description:Tandem duplication of carbapenemase genes amplifies the gene copy number and enhances carbapenem resistance. These amplifications are often heterogenous, transient, locate in plasmids, which often also contribute to heteroresistance. The duplication is especially important for low-hydrolysis activity enzymes, which is often overlooked or even under controversy. Here we reported an intrinsic oxacillinase duplication mediated by two neighbor ISAba1inserted in the same orientation. The duplication is relatively stable, located in chromosome, and the duplication times is up to twenty-five, much larger than previous reports. We provided genomic, transcriptomic, and proteomic evidence that the duplication resulted oxacillinase overproduction and thus contribute to carbapenem resistance. No other possible carbapenem resistance related changes (point mutations of oxaAb, disturbed expression of porin protein and efflux pump) were found during the duplication process. Furthermore, introducing oxaAb flanked by two ISAba1 to A. baumannii via plasmids, mimicked the in vivo duplication process under carbapenem stress. Taken together, ISAba1 mediated duplication of low activity intrinsic antibiotic hydrolysis enzymes could lead to antibiotic resistance for advanced-generation antibiotics.
2023-01-17 | PXD039528 | iProX