Juvenile idiopathic arthritis (JIA) is the most common chronic childhood rheumatic disease in the Western world. To identify novel JIA predisposing loci, a genome-wide association study (GWAS) in 814 Caucasian JIA cases and 3058 Caucasian controls was completed. After adjusting for the most significant HLA associations, the strongest novel associations included rs6479891 (10q21, odds ratio (OR)=1.59, P=1.3x10-8) and rs10761747 (OR=1.34, P=4.0x10-5) within JMJD1C; rs12719740 (15q26, OR=1.47, P=3.3x10-7) near FAM169B; rs4688011 (3q13, OR=1.33, P=1.1x10-4) within C3orf1 and rs4254850 (4q31, OR=0.85, P=7.8x10-3) near IL15. Eleven SNPs were genotyped in Caucasian replication cohorts (1744 cases, 7010 controls) and meta-analysis continued to provide evidence for association with three of the SNPs (rs6479891, P=4.3x10-5; rs12719740, P=5.2x10-4; rs4688011, P=3.6x10-7). Analysis of expression data from 68 JIA cases and 23 controls overlapping in the GWAS cohort1 and published lymphoblastoid cell lines (LCL)2 showed cis eQTL associations for JMJD1C SNPs (P=0.01 and P=1.6x10-6, respectively), and the C3orf1 SNP (P=5.7x10-6).
Genome-wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesIdentification of TBF1-dependent and SA, elf18-responsive genes in Arabidopsis
The HSF-like transcription factor TBF1 is a major molecular switch for plant growth-to-defense transition.
Specimen part, Treatment
View SamplesSingle-cell sorted cells from the osteocytic cell line Ocy454 were screened for high- and low-Sost/sclerostin expression to see changes in other gene expressions related to Sost/sclerostin.
Carbonic anhydrase III protects osteocytes from oxidative stress.
No sample metadata fields
View SamplesAnalysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA
Identification of alternative splicing events regulated by the oncogenic factor SRSF1 in lung cancer.
No sample metadata fields
View SamplesAssessment of mRNA expression levels in fat biopsies from subcutaneous adipose tissue from unrelated individuals.
A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.
Specimen part
View SamplesOverexpression of USF1 in HEK293T cells in vitro to ascertain the genes downstream of USF1. Will identify direct targets as well as indirect targets of USF1.
A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia.
Cell line
View SamplesIndividuals with cystic fibrosis (CF) experience elevated inflammation in multiple organs, but whether this reflects an inherent feature of CF cells or is a consequence of a pro-inflammatory environment is not clear. Using CRISPR/Cas9-mediated mutagenesis of CFTR, 17 subclonal cell lines were generated from Caco-2 cells. Clonal lines with functional CFTR (CFTR+) were compared to those without (CFTR-) to directly address the role of CFTR in inflammatory gene regulation. All lines maintained CFTR mRNA production and formation of tight junctions. CFTR+ lines displayed short circuit currents in response to forskolin, while the CFTR- lines did not. Baseline expression of both cytokines was not different between the lines regardless of CFTR genotype. All lines responded to TNFa and IL1b by increasing IL6 and CXCL8 (IL8) mRNA levels, but the CFTR- lines produced more CXCL8 mRNA than the CFTR+ lines. Transcriptomes of 6 CFTR- and 6 CFTR+ lines, before and after stimulation by TNFa, were compared for differential expression as a function of CFTR genotype. While some genes appeared to be differentially expressed simply because of CFTR's absence, others required stimulation for differences to be apparent. Together, these data suggest cells respond to CFTR's absence by modulating transcriptional networks, some of which are only apparent when cells are exposed to different environmental contexts, such as inflammation. With regards to inflammation, these data suggest a model in which CFTR's absence leads to a poised, pro-inflammatory state of cells that is only revealed by stimulation. Overall design: Compare cells with intact CFTR to cells lacking CFTR for overall gene expression under basal and TNFa-stimulated conditions
Inactivation of CFTR by CRISPR/Cas9 alters transcriptional regulation of inflammatory pathways and other networks.
Specimen part, Treatment, Subject
View SamplesKDM5A/LSD1 is an important epigenetic regulator in medulloblastoma, the most frequent brain tumor of childhood. Here, the response of ONS76 medulloblastoma cells upon siRNA-mediated knockdown of KDM5A is analysed.
The KDM1A histone demethylase is a promising new target for the epigenetic therapy of medulloblastoma.
Specimen part, Cell line, Treatment
View SamplesTo analyze the functional relevance of LSD1 in neuroblastic tumors, SH-SY5Y cells were transiently transfected with siRNA directed against LSD1 or with a scrambled control siRNA. Microarray analysis revealed changes in expression that were consistent with these observations 72 hours after LSD1 knock-down. At this time, 28 genes were significantly induced at least 1.5-fold and 29 genes were significantly repressed at least 1.5-fold. Among the 28 induced genes, 4 are markers of cytoskeletal remodelling (TNS1, TPM1, DNM2, DNAL4), indicating differentiation, and 3 (TPM1, DNM2 and SHANK2) are functionally linked to neurite dynamics and synaptic trafficking. TaqMan quantitative RT-PCR confirmed the expression changes detected via microarray analysis for LSD1, DNAL4, DNM2, TNS1 and TPM1
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy.
No sample metadata fields
View SamplesTo determine genes in FL HSCs that are sensitive to Notch signagling, E14.5 FL cells were cultured on DL1( to stimulate Notch signaling). Cells were cultured in the presence of DMSO (vehicle control) or gamma secretase inhibitor (1uM) for 4 hrs or 10hrs. Gamma secretase inhibitor was used to inhibit Notch signaling. SLAM-LSKs were sorted and used for RNA preparation.
The Notch1 transcriptional activation domain is required for development and reveals a novel role for Notch1 signaling in fetal hematopoietic stem cells.
Specimen part, Treatment, Time
View Samples