EGAD00000000058
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ABSTRACT:
PROVIDER: EGAD00000000058 | EGA |
REPOSITORIES: EGA
Publications
HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
McCormack Mark M Alfirevic Ana A Bourgeois Stephane S Farrell John J JJ Kasperavičiūtė Dalia D Carrington Mary M Sills Graeme J GJ Marson Tony T Jia Xiaoming X de Bakker Paul I W PI Chinthapalli Krishna K Molokhia Mariam M Johnson Michael R MR O'Connor Gerard D GD Chaila Elijah E Alhusaini Saud S Shianna Kevin V KV Radtke Rodney A RA Heinzen Erin L EL Walley Nicole N Pandolfo Massimo M Pichler Werner W Park B Kevin BK Depondt Chantal C Sisodiya Sanjay M SM Goldstein David B DB Deloukas Panos P Delanty Norman N Cavalleri Gianpiero L GL Pirmohamed Munir M
The New England journal of medicine 20110301 12
<h4>Background</h4>Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.<h4>Methods</h4>We performed a genomewide association study of samples obtained from 22 subjects with carbamaze ...[more]
Similar Datasets
Project description:Aggregate results from 43 Carbamazepine-induced hypersensitivity syndrome patients and 1296 1958 British Birth Cohort control samples
| EGAD00000000059 | EGA
Project description:Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress and abnormal cell cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show down-regulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed new light on the molecular mechanisms underlying this severe syndrome and further expand our knowledge of the genomic stress cells experience during the reprogramming process. Gene expression analysis was performed on a total of 6 human cell lines, including WT and NBS Neural progenitor cells (NPCs) and NBS-iPSCs
2016-07-19 | E-GEOD-83686 | biostudies-arrayexpress
Project description:Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress and abnormal cell cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show down-regulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed new light on the molecular mechanisms underlying this severe syndrome and further expand our knowledge of the genomic stress cells experience during the reprogramming process.
2016-07-19 | GSE83686 | GEO
Project description:WTCCC1 project samples from UK National Blood Service
| EGAD00000000002 | EGA
Project description:Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder, first described 1981 in Nijmegen, Holland. The characteristics of NBS include genomic instability (resulting in early onset of malignancies), premature aging, microcephaly and other growth retardations, immune deficiency, and impaired puberty and fertility in females. The consequence of these manifestations is a severe decrease in average life span, caused by cancer or infection of the respiratory and urinary tract. We reprogrammed fibroblasts from NBS patients into induced pluripotent stem cells (iPSCS) to bypass premature senescence and to generate an unlimited cell source for modeling purposes. We screened the influence of antioxidants on intracellular levels of ROS and DNA damage and found that EDHB was able to decrease DNA damage in the presence of high oxidative stress. Furthermore, we found that NBS fibroblasts, but not NBS-iPSCs were more susceptible to the induction of DNA damage than their normal counterparts. We performed global transcriptome analysis comparing NBS to normal fibroblasts and NBS-iPSCs to hESCs. There, we found, that TP53 was activated and cell cycle genes broadly down-regulated in NBS fibroblasts and up-regulation of glycolysis specifically in NBS-iPSCs.
2017-08-18 | GSE94706 | GEO
Project description:Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder, first described 1981 in Nijmegen, Holland. The characteristics of NBS include genomic instability (resulting in early onset of malignancies), premature aging, microcephaly and other growth retardations, immune deficiency, and impaired puberty and fertility in females. The consequence of these manifestations is a severe decrease in average life span, caused by cancer or infection of the respiratory and urinary tract. We reprogrammed fibroblasts from NBS patients into induced pluripotent stem cells (iPSCS) to bypass premature senescence and to generate an unlimited cell source for modeling purposes. We screened the influence of antioxidants on intracellular levels of ROS and DNA damage and found that EDHB was able to decrease DNA damage in the presence of high oxidative stress. Furthermore, we found that NBS fibroblasts, but not NBS-iPSCs were more susceptible to the induction of DNA damage than their normal counterparts. We performed global transcriptome analysis comparing NBS to normal fibroblasts and NBS-iPSCs to hESCs. There, we found, that TP53 was activated and cell cycle genes broadly down-regulated in NBS fibroblasts and up-regulation of glycolysis specifically in NBS-iPSCs.
2017-08-18 | GSE94707 | GEO
Project description:Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder caused by mutations within nibrin (NBN), a DNA damage repair protein. Hallmarks of NBS include chromosomal instability and clinical manifestations such as growth retardation, immunodeficiency, and progressive microcephaly. We employed induced pluripotent stem cell-derived cerebral organoids from two NBS patients to study the etiology of microcephaly. We show that NBS organoids carrying the homozygous 657del5 NBN mutation are significantly smaller with disrupted cyto-architecture. The organoids exhibit premature differentiation, and Neuronatin (NNAT) over-expression. Furthermore, pathways related to DNA damage response and cell cycle are differentially regulated compared to controls. After exposure to bleomycin, NBS organoids undergo delayed p53-mediated DNA damage response and aberrant trans-synaptic signaling, which ultimately leads to neuronal apoptosis. Our data provide insights into how mutations within NBN alters neurogenesis in NBS patients, thus providing a proof of concept that cerebral organoids are a valuable tool for studying DNA damage-related disorders.
2024-10-17 | GSE279611 | GEO
Project description:Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. Dr Tony Holder's laboratory (NIMR, London) has been successful in deleting one of the RH family genes (Py01365) by transfection and insertion of the TgDHFR gene, and cloned the resulting parasite in YM background. The gene expression patterns of the mutant parasite line were compared to that of the wild type YM parasite. ArrayExpress Release Date: 2011-04-25 Publication Title: Targeted Disruption of py235ebp-1: Invasion of Erythrocytes by Plasmodium yoelii Using an Alternative Py235 Erythrocyte Binding Protein Publication Author List: Solabomi A. Ogun, Rita Tewari, Thomas D. Otto, Steven A. Howell, Ellen Knuepfer, Deirdre A. Cunningham, Zhengyao Xu, Arnab Pain, Anthony A. Holder Person Roles: submitter Person Last Name: Service Person First Name: Submission Person Mid Initials: Person Email: datahose@sanger.ac.uk Person Phone: Person Address: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom Person Affiliation: Wellcome Trust Sanger Institute Person Roles: investigator Person Last Name: Holder Person First Name: Anthony Person Mid Initials: A Person Email: aholder@nimr.mrc.ac.uk Person Phone: Person Address: Division of Parasitology, MRC National Institute for Medical Research, London, UK Person Affiliation: MRC National Institute for Medical Research Person Roles: Project Coordinator Person Last Name: Sanders Person First Name: Mandy Person Mid Initials: J Person Email: mjs@sanger.ac.uk Person Phone: 01223 834244 Person Address: Wellcome Trust Genome Campus,Hinxton,Cambridge. CB10 1SA UK Person Affiliation: Wellcome Trust Sanger Institute
2011-07-14 | GSE30620 | GEO
Project description:In traditional Chinese medicine (TCM), blood stasis syndrome (BSS) is mainly manifested by the increase of blood viscosity, platelet adhesion rate and aggregation, and the change of microcirculation, resulting in vascular endothelial injury. It is an important factor in the development of diabetes mellitus (DM). According to the differences in the internal and external environment of the individual disease, BSS were divided into qi-deficiency and blood stasis syndrome (QDBS), qi-stagnation and blood stasis syndrome (QSBS), cold-coagulation and blood stasis syndrome (CCBS), heat-accumulation and blood stasis syndrome (HABS). The aim of this study was to screen out the potential candidate mRNAs in DM patients with BSS by high-throughput sequencing (HTS) and bioinformatics analysis. CRL-1730 human umbilical vein endothelial cells (HUVECs) were incubated with 10% human serum to establish models of DM with BSS, DM without BSS (NBS) and normal control (NC). Total RNA of each sample was extracted and sequenced by the Hiseq2000 platform. Differentially expressed mRNAs (DE-mRNAs) were screened between samples. On the basis of mRNA expression profiles, four comparisons were made, including QDBS vs NBS and NC, QSBS vs NBS and NC, CCBS vs NBS and NC, HABS vs NBS and NC. Then, comparisons with P values <0.05 (Fisher's exact test), false discovery rates (FDR) <0.01 and |log2 ratios|≥1 were considered as DE-mRNAs in BSS. This study screened out the DE-mRNAs in DM patients with BSS by HTS and bioinformatics analysis.
2018-04-03 | GSE109265 | GEO
Project description:WTCCC genome-wide case-control association study for Hypertension (HT) using the 1958 British Birth Cohort and the UK National Blood Service collections as controls.
| EGAS00000000009 | EGA