Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA300698 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PsychENCODE Consortium: Epigenetic Dysregulation in Autism Spectrum Disorder
| PRJNA344520 | ENA
Project description:PsychENCODE Consortium: Epigenetic and Transcriptional Dysregulation in Autism Spectrum
| PRJNA300697 | ENA
Project description:PsychENCODE Consortium: Autism Post-Mortem Brain RNA-Sequencing - SRRM4 Splicing Study
| PRJNA278488 | ENA
Project description:<p>Our current understanding of autism spectrum disorders (ASD) delineates a highly heritable, yet etiologically heterogeneous disease. Forward genetic approaches to find disease associated mutations or common variation have been successful and continue to offer considerable power. Yet, given the accumulating evidence for very significant heterogeneity and environmental influences, complementary approaches to classic forward genetics become necessary. Genetic polymorphism and mutation data to date have identified dozens of causal or contributory variants, yet our preliminary data from autism brain suggest that common molecular pathways are involved in a significant subset of cases. This convergence at the tissue level suggests that other mechanisms, specifically epigenetic changes, combined with genetic background, are contributing to such final common pathways. We further tested this hypothesis by taking a comprehensive and integrative genome-wide approach to assessing brain gene-expression, miRNA levels and the related, causal epigenetic mechanisms in ASD etiology. </p> <p>We performed RNA-seq analyses of four cerebral cortical regions and cerebellum from ASD cases and controls, to assess mRNA, miRNA, and splicing isoform regulation. In parallel, we identified key differences in chromatin state and DNA methylation across multiple brain regions in the same ASD and control individuals used in the expression analyses using ChIP-Seq and MeDIP. We assessed the mechanisms by which changes in DNA methylation, histone modification, and DNA sequence contribute to the observed differences in gene expression. This work, which represents an unprecedented effort to unify these often disparate data (usually produced without integration in mind), delineates potential shared molecular pathways in ASD and the underlying mechanism of these differences at the level of miRNA, the chromatin regulatory apparatus, and DNA methylation.</p> <p>The following substudies are part of the PsychENCODE release at dbGaP and offer additional molecular data: <ul> <li>PsychENCODE: RNA-Sequencing - SRRM4 Splicing Study <a href="study.cgi?study_id=phs000872">phs000872</a></li> <li>PsychENCODE: Global Changes in Patterning, Splicing and lncRNAs <a href="study.cgi?study_id=phs001061">phs001061</a></li> <li>PsychENCODE: Chromatin Contact Map in Fetal Cortical Laminae <a href="study.cgi?study_id=phs001190">phs001190</a></li> <li>PsychENCODE: Epigenetic Dysregulation in Autism Spectrum Disorder <a href="study.cgi?study_id=phs001220">phs001220</a></li> </ul> </p>
| phs001022 | dbGaP
Project description:Identification of transcript dysregulation in patients with Autism Spectrum Disorders
| PRJNA268178 | ENA
Project description:PsychENCODE Consortium: Autism Post-Mortem Brain RNA-Sequencing - Global changes in patterning, splicing and lncRNAs
| PRJNA308995 | ENA
Project description:FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders
| PRJNA261255 | ENA
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders
| PRJNA126395 | ENA