Genomewide methylation analysis in Silver Russell syndrome patients
ABSTRACT: Genomewide methylation analysis in Silver Russell syndrome patients compared to healthy controls Bisulphite converted DNA from the 24 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately, half of all patients exhibit DNA hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal uniparental disomy of chromosome 7. We meas ...[more]
Project description:Illumina Infinium HumanMethylation450 assay was used to study genome-wide DNA methylation profiles of Silver-Russel sydrome (SRS) patients. Overall design: 44 Silver-Russell syndrome patients, including 21 patients with 11p15 LOM, 10 patients with UPD(7)mat and 13 patients with clinical SRS were analyzed in comparison to 16 control samples. Also one individual with UPD(7)pat was included in the analysis.
Project description:Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk- and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24h of exposure, but with a recovery at 48h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24h, but not at 48h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms. mRNA profiles of whole zebrafish embryos at 24 and 48 hours post-fertilisation (hpf) exposed to silver in nano, bulk and ionic forms were generated by deep sequencing using HT-SuperSAGE (Illumina GA2).
Project description:Chlamydomonas reinhardtii exposed to various concentrations of silver For this experiment,C. reinhardtii were exposed to (4) different concentrations of silver, as biological triplicates
Project description:Custom D. magna gene expression microarray (Design ID: 023710, Agilent Technologies)were used to characterise gene expression profiles of Daphnia magna neoantes exposed to silver nanoparticles ( AgNPs ) or silver nitrate ( AgNO3 ) for 24 hours.
Project description:We investigated the transition from juvenile yellow to the adult sexually maturing, migrating silver eel (Anguilla anguilla) by examining the hypothesis that: The brain is the central organ for the co-ordination of environmental cues (day length, photoperiod, temperature and environmental salinity) with the anatomical and physiological adaptations which accompany pre-migrational morphogenesis and the osmoregulatory plasticity seen in post-migrational, salinity-adapted fish. We have characertised the mRNA expression profiles for the brains of fresh water, yellow and silver eel using a highly representative brain cDNA microarray. The array comprises 5760 cDNA clones from A.anguilla ranging from 0.5 -10 kb and an estimated redundancy of > 5 %.
Project description:Nanoparticles are compounds of emerging concern with largely unknown risks for human and ecological health. It is crucial to evaluate their potential biological impact to prevent unintended adverse effects on human health and the environment. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. We also tested the feasibility of the fathead minnow as an alternative species to elucidate potential adverse effects on humans. Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs for 96h. Microarray analyses were performed on liver and brain. Functional analysis identified potential toxicity pathways and molecular initiating events (MIEs) that were confirmed with functional assays. Data suggested that AgNO3 and PVP-AgNPs had both common and distinct transcriptional effects. The nanoparticles were linked to neurotoxicity and oxidative stress, and identified as a dopamine receptor antagonist. Silver nitrate was also identified as a potential neurotoxicant and was confirmed as adrenergic and cannabinoid receptors antagonist. While silver nitrate and PVP-AgNPs were both potential neurotoxicants, they appeared to act through different MIEs. Fathead minnow is a promising alternative species to elucidate potential adverse effects of relevance to human health. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. FHM were obtained from Aquatic Biosystems (Fort Collins, CO), held in aerated dechlorinated tap water and fed three times daily with Zeigler® AquaTox Feed Gardners, PA, USA). Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs (Luna Innovations, Blackburn, VA) for 96h at 24°C ± 1 with a 90% water change at 48 hours. Microarray analyses were performed on liver and brain.
Project description:We studied twenty-eight growth restricted patients (twenty-two with Silver-Russell syndrome, OMIM#180860) and their parents with the Affymetrix 250K Sty SNP microarray. All patients were molecularly undefined, and thus the aim was to look for copy number alterations that might contribute to the growth restriction. Aberrations found in parents were used to reduce the list of interesting variations to de novo variants.
Project description:CD4 T cell responses are characterized based on a limited number of molecular markers selected from exisiting knowledge. The goal of the experiment was to assess antigenic-peptide specific T-cell responses in vitro without bias using microarrays. PBMCs were isolated from 2 donors with allergy. The cells were stimulated with antigenic peptides derived from silver birch wood and cat for 24 hours. Unstimulated cells were cultured without the peptides for 24 hours.