Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15144290_1.fastq.gz | Fastqsanger.gz | |||
| SRR15144290_2.fastq.gz | Fastqsanger.gz | |||
| SRR15144291_1.fastq.gz | Fastqsanger.gz | |||
| SRR15144291_2.fastq.gz | Fastqsanger.gz | |||
| SRR15144292_1.fastq.gz | Fastqsanger.gz |
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Project description:The MLL-PTD mutation is found in patients with MDS and AML, and not in other haematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice present with several MDS-associated features, such as increased self-renewal and apoptosis in HSPCs, expansion of the myeloid progenitor population, ineffective haematopoiesis, and skewed myeloid differentiation. MLL is an epigenetic regulator: its C-terminal Su[var]3–9, enhancer of zeste, trithorax (SET) domain has methyltransferase activity on lysine 4 on histone 3 (H3K4), which is retained in the MLL-PTD mutant. To clarify the effects of MLL-PTD on target gene regulation, we performed H3K4me3 ChIP-Seq analysis of LSKs isolated from WT and Mll-PTD knock-in heterozygous mice.
2018-12-01 | GSE75608 | GEO
Project description:Patients with molar pregnancy are at risk of developing persistent trophoblastic disease (PTD). Previous study indicated that PTD risk was not related to evacuation time of hydatidiform mole (HM), leading to our hypothesis that HM might be pre-programmed before evacuation to determine the PTD risk. Considering the similarity between PTD and tumorigenesis, we investigated the methylation alterations in PTD conceptus using reduced representation bisulfite sequencing (RRBS), in order to identify potential predictors for PTD.
2015-06-01 | GSE65881 | GEO
Project description:In acute myeloid leukemia (AML), the mixed lineage leukemia (MLL) gene may be rearranged to generate a partial tandem duplication (PTD), or fused to partner genes through a chromosomal translocation (tMLL). In this study, we first explored the differentially expressed genes between MLL-PTD and tMLL using gene expression profiling of our cohort (15 MLL-PTD and 10 tMLL) and one published data set. The top 250 probes were chosen from each set, resulting in 29 common probes (21 unique genes) to both sets. The selected genes include four HOXB genes, HOXB2, B3, B5, and B6. The expression values of these HOXB genes significantly differ between MLL-PTD and tMLL cases. Clustering and classification analyses were thoroughly conducted to support our gene selection results. Second, as MLL-PTD, FLT3-ITD, and NPM1 mutations are identified in AML with normal karyotypes, we briefly studied their impact on the HOXB genes. Another contribution of this study is to demonstrate that using public data from other studies enriches samples for analysis and yields more conclusive results.
2011-06-30 | GSE15013 | GEO
Project description:The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1α in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1αFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1α expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1∆/∆ with or without HIF-1α abrogation.
2018-12-23 | GSE86953 | GEO
Project description:Most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus IT-PTD-mutants were introduced into rodent Ba/F3, EML, Rat2 and human TF1 cells to investigate their biological effect. ECD- and PTD-mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT pathways, whereas AKT pathway was only activated by ECD-mutants. Consistently, AKT inhibitor suppressed ECD-mutant-dependent proliferation, clonogenicity and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EMLPTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes.
2010-04-10 | GSE21255 | GEO
Project description:Whole genome microarrays were probed with total mRNA from PTD-DRBD GAPDH siRNA treated H1299 cells at 12 h and 24 h. Using a 1.6x fold increase/decrease filter of cellular mRNAs, we detected a dramatic reduction in the target GAPDH mRNA along with a limited number of both up and down regulated genes. The up regulated genes were reduced in numbers and to nearly background 1.6x levels at 24 h, while the down regulated genes increased slightly in numbers and maintained a similar magnitude at 24 h. In contrast, lipofection treated cells showed both a dramatic increase in both the total number of genes altered and the magnitude of the increase. In addition, the numbers of genes affected increased between 12 h and 24 h, suggesting that lipofection of siRNAs into cells results in a substantial alteration to the transcriptome and may thereby confound interpretation of experimental outcomes. Moreover, the GAPDH specific knockdown was significantly smaller than PTD-DRBD mediated knockdown. Total RNA obtained from H1299 cells treated with PTD-DRBD GAPDH siRNA, Lipofection GAPDH siRNA or PBS (Control) after 12 or 24 hours post-treatment
2010-05-08 | E-GEOD-15723 | biostudies-arrayexpress
Project description:Whole genome microarrays were probed with total mRNA from PTD-DRBD GAPDH siRNA treated H1299 cells at 12 h and 24 h. Using a 1.6x fold increase/decrease filter of cellular mRNAs, we detected a dramatic reduction in the target GAPDH mRNA along with a limited number of both up and down regulated genes. The up regulated genes were reduced in numbers and to nearly background 1.6x levels at 24 h, while the down regulated genes increased slightly in numbers and maintained a similar magnitude at 24 h. In contrast, lipofection treated cells showed both a dramatic increase in both the total number of genes altered and the magnitude of the increase. In addition, the numbers of genes affected increased between 12 h and 24 h, suggesting that lipofection of siRNAs into cells results in a substantial alteration to the transcriptome and may thereby confound interpretation of experimental outcomes. Moreover, the GAPDH specific knockdown was significantly smaller than PTD-DRBD mediated knockdown.
2009-05-22 | GSE15723 | GEO
Project description:MLL-PTD and RUNX1-knockout cooperate to induce MDS phenotypes
| PRJNA343076 | ENA
Project description:<p>Primary torsin dystonias (PTD) are a group of movement disorders characterized by twisting muscle contractures, where dystonia is the only clinical sign (except for tremor) and there is no evidence of neuronal degeneration or an acquired cause. Eleven genes have been mapped for primary dystonia including DYT1 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=1861" target="_blank">TOR1A</a>), <a href="https://www.ncbi.nlm.nih.gov/gene/1862" target="_blank">DYT2</a>, DYT4 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=10382" target="_blank">TUBB4A</a>), DYT6 (<a href="https://www.ncbi.nlm.nih.gov/gene/55145" target="_blank">THAP1</a>), <a href="https://www.ncbi.nlm.nih.gov/gene/?term=1866" target="_blank">DYT7</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=93983" target="_blank">DYT13</a>,, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=100216344" target="_blank">DYT17</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=100885773" target="_blank">DYT21</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=25792" target="_blank">CIZ1</a>, DYT24 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=63982" target="_blank">ANO3</a>), and DYT25 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=2774" target="_blank">GNAL</a>); however, only 3 genes (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=1861" target="_blank">TOR1A</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/55145" target="_blank">THAP1</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/?term=2774" target="_blank">GNAL</a>) have mutations in early onset dystonia patients. Each is inherited as an autosomal dominant trait but with reduced penetrance, meaning that individuals can carry the mutation but do not show clinical symptoms.</p> <p>The most common form of PTD is adult onset focal accounting for about 90% of all cases of dystonia with a prevalence estimated at 30/100,000 in the general population. A small percentage of focal cases are due to mutations in <a href="https://www.ncbi.nlm.nih.gov/gene/?term=25792" target="_blank">CIZ1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=63982" target="_blank">ANO3</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/55145" target="_blank">THAP1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/?term=10382" target="_blank">TUBB4A</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/?term=2774" target="_blank">GNAL</a>, but the vast majority is unaccounted for and is most likely multigenic or multifactorial. In this grant, focusing on early onset PTD, we will uncover genes that influence the penetrance of DYT1 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=1861" target="_blank">TOR1A</a>) dystonia through GWAS and exome sequencing studies. We will identify other genes for early onset PTD using exome sequencing and determine whether variants within the identified early onset PTD genes or the pathways associated with these genes contribute to susceptibility in the most prevalent form of PTD, focal dystonia, using a case:control association study. The proposed research will identify novel PTD risk factors and genes, which in turn should reveal shared and intersecting pathways leading to a better understanding of the molecular basis of PTD and provide the underpinnings for developing new treatments. Additionally, insight into the factors that modulate disease penetrance would be a first step in determine whether these could be modified leading to a reduced incidence of the disease. </p>
| phs001733 | dbGaP
Project description:Most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus IT-PTD-mutants were introduced into rodent Ba/F3, EML, Rat2 and human TF1 cells to investigate their biological effect. ECD- and PTD-mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT pathways, whereas AKT pathway was only activated by ECD-mutants. Consistently, AKT inhibitor suppressed ECD-mutant-dependent proliferation, clonogenicity and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EMLPTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes. Each EML cell line (Del417-419insY mutant and D816V mutant) was cultured with or without 250 ng/mL SCF for 48h. Gene expression profile analysis was performed using whole-genome microarrays. RNA expression profiling of cell lines was done with Affymetrix M430 2.0 mouse oligonucleotide microarrays containing 45.101 probe sets, representing 21.408 transcripts and variants including 17.482 well-characterized mouse genes. Preparation of cRNA, hybridizations, washes, detection and quantification were done as recommended by the supplier. For each sample, synthesis of the first-strand cDNA was done from 3 μg total RNA by T7-oligo(dT) priming, followed by second-strand cDNA synthesis. After purification, in vitro transcription associated with amplification generated cRNA-containing biotinylated pseudouridine. Biotinylated cRNA was purified, quantified and chemically fragmented (95°C for 35 min), then hybridized to microarrays in 200 μL hybridization buffer at 45°C for 16 h. Automated washes and staining with streptavidin-phycoerythrin were done as recommended. Signal amplification was done by biotinylated antistreptavidin antibody with goat-IgG blocking antibody. Scanning was done with Affymetrix GeneArray scanner and quantification with Affymetrix GCOS software.
2010-04-10 | E-GEOD-21255 | biostudies-arrayexpress