Genome-Wide Association Study Identifies Variants in the MHC Class
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Cytogenomic SNP Microarray - Fetal ARUP Test Code 2002366 Maternal Contamination Study Fetal Spec Fetal Cells
Patient Report |FINAL Client: Example Client ABC123 Patient: Patient, Example 123 Test Drive Salt Lake City, UT 84108 DOB 2/13/1987 UNITED STATES Gender: Female Patient Identifiers: 01234567890ABCD, 012345 Physician: Doctor, Example Visit Number (FIN): 01234567890ABCD Collection Date: 00/00/0000 00:00 Cytogenomic SNP Microarray - Fetal ARUP test code 2002366 Maternal Contamination Study Fetal Spec Fetal Cells Single fetal genotype present; no maternal cells present. Fetal and maternal samples were tested using STR markers to rule out maternal cell contamination. This result has been reviewed and approved by Maternal Specimen Yes Cytogenomic SNP Microarray - Fetal Abnormal * (Ref Interval: Normal) Test Performed: Cytogenomic SNP Microarray- Fetal (ARRAY FE) Specimen Type: Direct (uncultured) villi Indication for Testing: Patient with 46,XX,t(4;13)(p16.3;q12) (Quest: EN935475D) ----------------------------------------------------------------- ----- RESULT SUMMARY Abnormal Microarray Result (Male) Unbalanced Translocation Involving Chromosomes 4 and 13 Classification: Pathogenic 4p Terminal Deletion (Wolf-Hirschhorn syndrome) Copy number change: 4p16.3p16.2 loss Size: 5.1 Mb 13q Proximal Region Deletion Copy number change: 13q11q12.12 loss Size: 6.1 Mb ----------------------------------------------------------------- ----- RESULT DESCRIPTION This analysis showed a terminal deletion (1 copy present) involving chromosome 4 within 4p16.3p16.2 and a proximal interstitial deletion (1 copy present) involving chromosome 13 within 13q11q12.12. This -
Complexin-1 Is a Biomarker of Synucleinopathy
DMM Advance Online Articles. Posted 20 January 2017 as doi: 10.1242/dmm.028035 Access the most recent version at http://dmm.biologists.org/lookup/doi/10.1242/dmm.028035 BLOOD RNA BIOMARKERS IN PRODROMAL PARK4 AND REM SLEEP BEHAVIOR DISORDER SHOW ROLE OF COMPLEXIN-1 LOSS FOR RISK OF PARKINSON’S DISEASE Suna Lahut1,2, Suzana Gispert1, Özgür Ömür1,2, Candan Depboylu3, Kay Seidel4, Jorge Antolio Domínguez-Bautista1, Nadine Brehm1, Hülya Tireli5, Karl Hackmann6, Caroline Pirkevi2, Barbara Leube7, Vincent Ries3, Kerstin Reim8, Nils Brose8, Wilfred F. den Dunnen9, Madrid Johnson10, Zsuzsanna Wolf11, Marc Schindewolf12, Wiebke Schrempf13, Kathrin Reetz14, Peter Young15, David Vadasz3, Achilleas S. Frangakis10, Evelin Schröck6, Helmuth Steinmetz1, Marina Jendrach1, Udo Rüb4, Ayşe Nazlı Başak2¶, Wolfgang Oertel3¶, Georg Auburger1¶ 1Exp. Neurology, Goethe University Medical School, 60590 Frankfurt/Main, Germany; 2NDAL, Boğaziçi University, 34342 Istanbul, Turkey; 3Dept. of Neurology, Philipps University, Baldingerstrasse, 35043 Marburg, Germany; 4Dr. Senckenberg Chronomedical Institute, Goethe University, 60590 Frankfurt/Main, Germany; 5Dept. of Neurology, Haydarpaşa Numune Training and Research Hospital, 34668 Istanbul, Turkey; 6Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany; 7Institute of Human Genetics, Heinrich Heine University, 40225 Düsseldorf, Germany; 8Dept. of Molecular Neurobiology and Center for the Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; 9Dept. of Pathology and Medical Biology, Medical Center, University, 9700 RB Groningen, Netherlands; 10Institut für Biophysik and Frankfurt Institute for Molecular Life Sciences, Goethe University, 60438 Frankfurt/Main, Germany; 11Hemophilia Centre, Medical Clinic III, Institute of Transfusion Medicine and Immunhematology Goethe University, 60590 Frankfurt/Main, Germany; 12Dept. -
Single-Cell RNA-Seq of Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic
bioRxiv preprint doi: https://doi.org/10.1101/148049; this version posted August 31, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Single-cell RNA-seq of dopaminergic neurons informs candidate gene selection for sporadic 2 Parkinson's disease 3 4 Paul W. Hook1, Sarah A. McClymont1, Gabrielle H. Cannon1, William D. Law1, A. Jennifer 5 Morton2, Loyal A. Goff1,3*, Andrew S. McCallion1,4,5* 6 7 1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of 8 Medicine, Baltimore, Maryland, United States of America 9 2Department of Physiology Development and Neuroscience, University of Cambridge, 10 Cambridge, United Kingdom 11 3Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, 12 Maryland, United States of America 13 4Department of Comparative and Molecular Pathobiology, Johns Hopkins University School of 14 Medicine, Baltimore, Maryland, United States of America 15 5Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 16 United States of America 17 *, To whom correspondence should be addressed: [email protected] and [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/148049; this version posted August 31, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. -
Dysregulation of Post-Transcriptional Modification by Copy Number
Yoshikawa et al. Translational Psychiatry (2021) 11:331 https://doi.org/10.1038/s41398-021-01460-1 Translational Psychiatry ARTICLE Open Access Dysregulation of post-transcriptional modification by copy number variable microRNAs in schizophrenia with enhanced glycation stress Akane Yoshikawa1,2,ItaruKushima 3,4, Mitsuhiro Miyashita 1,5,6,KazuyaToriumi 1, Kazuhiro Suzuki 1,5, Yasue Horiuchi 1, Hideya Kawaji 7, Shunya Takizawa8,NorioOzaki 3, Masanari Itokawa1 and Makoto Arai 1 Abstract Previously, we identified a subpopulation of schizophrenia (SCZ) showing increased levels of plasma pentosidine, a marker of glycation and oxidative stress. However, its causative genetic factors remain largely unknown. Recently, it has been suggested that dysregulated posttranslational modification by copy number variable microRNAs (CNV-miRNAs) may contribute to the etiology of SCZ. Here, an integrative genome-wide CNV-miRNA analysis was performed to investigate the etiology of SCZ with accumulated plasma pentosidine (PEN-SCZ). The number of CNV-miRNAs and the gene ontology (GO) in the context of miRNAs within CNVs were compared between PEN-SCZ and non-PEN-SCZ groups. Gene set enrichment analysis of miRNA target genes was further performed to evaluate the pathways affected in PEN-SCZ. We show that miRNAs were significantly enriched within CNVs in the PEN-SCZ versus non-PEN-SCZ groups (p = 0.032). Of note, as per GO analysis, the dysregulated neurodevelopmental events in the two groups may have different origins. Additionally, gene set enrichment analysis of miRNA target genes revealed that miRNAs involved in glycation/oxidative stress and synaptic neurotransmission, especially glutamate/GABA receptor signaling, fi 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; were possibly affected in PEN-SCZ. -
Snareopathies: Diversity in Mechanisms and Symptoms
VU Research Portal SNAREopathies Verhage, Matthijs; Sørensen, Jakob B. published in Neuron 2020 DOI (link to publisher) 10.1016/j.neuron.2020.05.036 document version Publisher's PDF, also known as Version of record document license Article 25fa Dutch Copyright Act Link to publication in VU Research Portal citation for published version (APA) Verhage, M., & Sørensen, J. B. (2020). SNAREopathies: Diversity in Mechanisms and Symptoms. Neuron, 107(1), 22-37. https://doi.org/10.1016/j.neuron.2020.05.036 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 29. Sep. 2021 ll Review SNAREopathies: Diversity in Mechanisms and Symptoms Matthijs Verhage1,2,* and Jakob B. Sørensen3,* 1Department of Functional Genomics, Vrije Universiteit (VU) Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, the Netherlands 2Department of Clinical Genetics, UMC Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, the Netherlands 3Department of Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark *Correspondence: [email protected] (M.V.), [email protected] (J.B.S.) https://doi.org/10.1016/j.neuron.2020.05.036 Neuronal SNAREs and their key regulators together drive synaptic vesicle exocytosis and synaptic transmis- sion as a single integrated membrane fusion machine. -
Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha-Synuclein Pathology
Mol Neurobiol DOI 10.1007/s12035-014-8844-0 Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha-Synuclein Pathology Suzana Gispert & Alexander Kurz & Nadine Brehm & Katrin Rau & Michael Walter & Olaf Riess & Georg Auburger Received: 15 April 2014 /Accepted: 31 July 2014 # The Author(s) 2014. This article is published with open access at Springerlink.com Abstract As the second most frequent neurodegenerative Introduction disorder of the aging population, Parkinson’s disease (PD) is characterized by progressive deficits in spontaneous move- Parkinson’s disease (PD) is the second most frequent age- ment, atrophy of dopaminergic midbrain neurons and aggre- associated brain degeneration disorder, affecting about 1 % gation of the protein alpha-synuclein (SNCA). To elucidate of the population over 65 years of age. The PD-specific molecular events before irreversible cell death, we studied progressive movement deficit is mostly due to the severe synucleinopathy-induced expression changes in mouse brain affliction and cell death of midbrain nigrostriatal dopaminer- and identified 49 midbrain/brainstem-specific transcriptional gic neurons [1]. Surviving neurons in vulnerable regions dysregulations. In particular complexin-1 (Cplx1), Rabl2a and exhibit aggregates predominantly consisting of the protein 14-3-3epsilon (Ywhae) downregulation, as well as upregula- alpha-synuclein, which are visualized as Lewy neurites and tion of the midbrain-specific factor forkhead box P1 (Foxp1) Lewy bodies, both in sporadic late-onset and most familial and of Rabgef1, were interesting as early mRNA level effects early onset PD variants [2]. of alpha-synuclein triggered pathology. The protein levels of Autosomal dominant PD with early clinical manifestation complexin-1 were elevated in midbrain/brainstem tissue of was observed in rare families, leading to the identification of mice with A53T-SNCA overexpression and of mice with alpha-synuclein (SNCA) protein missense mutations such as SNCA-knockout. -
Bisphenol a Exposure in Utero Disrupts Hypothalamic Gene Expression Particularly Genes Suspected in Autism Spectrum Disorders and Neuron and Hormone Signaling
International Journal of Molecular Sciences Article Bisphenol A Exposure in utero Disrupts Hypothalamic Gene Expression Particularly Genes Suspected in Autism Spectrum Disorders and Neuron and Hormone Signaling Anne D. Henriksen 1, Alejandro Andrade 2, Erin P. Harris 3, Emilie F. Rissman 3 and Jennifer T. Wolstenholme 2,* 1 Department of Integrated Science and Technology, James Madison University, Harrisonburg, VA 22807, USA; [email protected] 2 Department of Pharmacology and Toxicology,Virginia Commonwealth University,Richmond, VA23298-0613, USA; [email protected] 3 Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695, USA; [email protected] (E.P.H.); [email protected] (E.F.R.) * Correspondence: [email protected]; Tel.: +1-804-828-4353 Received: 23 March 2020; Accepted: 27 April 2020; Published: 29 April 2020 Abstract: Bisphenol A (BPA) is an endocrine-disrupting compound detected in the urine of more than 92% of humans, easily crosses the placental barrier, and has been shown to influence gene expression during fetal brain development. The purpose of this study was to investigate the effect of in utero BPA exposure on gene expression in the anterior hypothalamus, the basal nucleus of the stria terminalis (BNST), and hippocampus in C57BL/6 mice. Mice were exposed in utero to human-relevant doses of BPA, and then RNA sequencing was performed on male PND 28 tissue from whole hypothalamus (n = 3/group) that included the medial preoptic area (mPOA) and BNST to determine whether any genes were differentially expressed between BPA-exposed and control mice. A subset of genes was selected for further study using RT-qPCR on adult tissue from hippocampus to determine whether any differentially expressed genes (DEGs) persisted into adulthood. -
Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
Journal of Clinical Medicine Article Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis Jacobo Limeres 1 , Candela Serrano 1, Joaquin Manuel De Nova 2, Javier Silvestre-Rangil 3, Guillermo Machuca 4 , Isabel Maura 5, Jose Cruz Ruiz-Villandiego 6, Pedro Diz 1,*, Raquel Blanco-Lago 7 , Julian Nevado 8,9,10 and Marcio Diniz-Freitas 1 1 Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain; [email protected] (J.L.); [email protected] (C.S.); [email protected] (M.D.-F.) 2 Department of Stomatology IV, School of Dentistry, University Complutense de Madrid, 28040 Madrid, Spain; [email protected] 3 Department of Stomatology, University Hospital Doctor Peset-FISABIO, 46017 Valencia, Spain; [email protected] 4 Department of Special Care in Dentistry, School of Dentistry, University of Seville, 41009 Sevilla, Spain; [email protected] 5 Service of Pediatric Dentistry, Barcelona University Children’s Hospital HM Nens, 08009 Barcelona, Spain; [email protected] 6 Service of Special Care in Dentistry, Quirón Hospital, 200012 San Sebastián, Spain; [email protected] 7 Service of Neuropediatrics, University Hospital Central de Asturias, 33011 Oviedo, Spain; [email protected] 8 Medical and Molecular Genetics Institute (INGEMM), La Paz University Hospital, IdiPAZ, 28046 Madrid, Spain; [email protected] 9 Institute of Rare Diseases Research (IIER) & Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain 10 ERN (European Reference Network)-ITHACA, La Paz University Hospital, 28046 Madrid, Spain * Correspondence: [email protected] Received: 24 September 2020; Accepted: 31 October 2020; Published: 4 November 2020 Abstract: Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4. -
Single-Cell Rnaseq Reveals Cell Adhesion Molecule Profiles in Electrophysiologically Defined Neurons
Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons Csaba Földya,b,1, Spyros Darmanisc, Jason Aotoa,d, Robert C. Malenkae, Stephen R. Quakec,f, and Thomas C. Südhofa,f,1 aDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; bBrain Research Institute, University of Zürich, 8057 Zurich, Switzerland; cDepartment of Bioengineering, Stanford University, Stanford, CA 94305; dDepartment of Pharmacology, University of Colorado Denver, Aurora, CO 80045; eNancy Pritzker Laboratory, Stanford University, Stanford, CA 94305; and fHoward Hughes Medical Institute, Stanford University, Stanford, CA 94305 Contributed by Thomas C. Südhof, July 10, 2016 (sent for review May 21, 2016; reviewed by Thomas Biederer, Tamas F. Freund, and Li-Huei Tsai) In brain, signaling mediated by cell adhesion molecules defines the neurexin (Nrxn1 and Nrxn3; presynaptic cell adhesion mole- identity and functional properties of synapses. The specificity of cules) isoforms were expressed cell type-specifically, with re- presynaptic and postsynaptic interactions that is presumably medi- markable consistency in respective cell types (9). We also found ated by cell adhesion molecules suggests that there exists a logic that that genetic deletion of neuroligin-3 (Nlgn3) (postsynaptic cell could explain neuronal connectivity at the molecular level. Despite its adhesion molecule) in PYR cells disabled tonic, cannabinoid importance, however, the nature of such logic is poorly understood, type 1 receptor-mediated, endocannabinoid signaling in RS CCK and even basic parameters, such as the number, identity, and single- synapses, but had no detectable phenotype in FS PV synapses cell expression profiles of candidate synaptic cell adhesion molecules, (10). Thus, although no systematic assessment of cell adhesion are not known. -
Investigating Developmental and Epileptic Encephalopathy Using Drosophila Melanogaster
International Journal of Molecular Sciences Review Investigating Developmental and Epileptic Encephalopathy Using Drosophila melanogaster Akari Takai 1 , Masamitsu Yamaguchi 2,3, Hideki Yoshida 2 and Tomohiro Chiyonobu 1,* 1 Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; [email protected] 2 Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 603-8585, Japan; [email protected] (M.Y.); [email protected] (H.Y.) 3 Kansai Gakken Laboratory, Kankyo Eisei Yakuhin Co. Ltd., Kyoto 619-0237, Japan * Correspondence: [email protected] Received: 15 August 2020; Accepted: 1 September 2020; Published: 3 September 2020 Abstract: Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing. Early infantile epileptic encephalopathy (EIEE) is one of the earliest forms of DEE, manifesting as frequent epileptic spasms and characteristic electroencephalogram findings in early infancy. In recent years, next-generation sequencing approaches have identified a number of monogenic determinants underlying DEE. In the case of EIEE, 85 genes have been registered in Online Mendelian Inheritance in Man as causative genes. Model organisms are indispensable tools for understanding the in vivo roles of the newly identified causative genes. In this review, we first present an overview of epilepsy and its genetic etiology, especially focusing on EIEE and then briefly summarize epilepsy research using animal and patient-derived induced pluripotent stem cell (iPSC) models. The Drosophila model, which is characterized by easy gene manipulation, a short generation time, low cost and fewer ethical restrictions when designing experiments, is optimal for understanding the genetics of DEE. -
Table S1. 103 Ferroptosis-Related Genes Retrieved from the Genecards
Table S1. 103 ferroptosis-related genes retrieved from the GeneCards. Gene Symbol Description Category GPX4 Glutathione Peroxidase 4 Protein Coding AIFM2 Apoptosis Inducing Factor Mitochondria Associated 2 Protein Coding TP53 Tumor Protein P53 Protein Coding ACSL4 Acyl-CoA Synthetase Long Chain Family Member 4 Protein Coding SLC7A11 Solute Carrier Family 7 Member 11 Protein Coding VDAC2 Voltage Dependent Anion Channel 2 Protein Coding VDAC3 Voltage Dependent Anion Channel 3 Protein Coding ATG5 Autophagy Related 5 Protein Coding ATG7 Autophagy Related 7 Protein Coding NCOA4 Nuclear Receptor Coactivator 4 Protein Coding HMOX1 Heme Oxygenase 1 Protein Coding SLC3A2 Solute Carrier Family 3 Member 2 Protein Coding ALOX15 Arachidonate 15-Lipoxygenase Protein Coding BECN1 Beclin 1 Protein Coding PRKAA1 Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 Protein Coding SAT1 Spermidine/Spermine N1-Acetyltransferase 1 Protein Coding NF2 Neurofibromin 2 Protein Coding YAP1 Yes1 Associated Transcriptional Regulator Protein Coding FTH1 Ferritin Heavy Chain 1 Protein Coding TF Transferrin Protein Coding TFRC Transferrin Receptor Protein Coding FTL Ferritin Light Chain Protein Coding CYBB Cytochrome B-245 Beta Chain Protein Coding GSS Glutathione Synthetase Protein Coding CP Ceruloplasmin Protein Coding PRNP Prion Protein Protein Coding SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding SLC40A1 Solute Carrier Family 40 Member 1 Protein Coding STEAP3 STEAP3 Metalloreductase Protein Coding ACSL1 Acyl-CoA Synthetase Long Chain Family Member 1 Protein -
Genomes Assembly, Gene Finding, Annotation & Gene
GENOMES ASSEMBLY, GENE FINDING, ANNOTATION & GENE ONTOLOGY Tore Samuelsson, March 2013 Craig Venter Francis Collins James Watson Human genome sequencing Human genome sequencing Shotgun sequencing Original DNA is broken into a collection of fragments The ends of each fragment (drawn in green) are sequenced ~100 million reads (shotgun sequences) required to assemble human genome! Shotgun sequencing The sequence reads are assembled together based on sequence similarity Sequence assembly 1) Overlap detection Because of sequencing errors we need to make use of methods that takes gaps and mismatches into account 2) Fragment layout 3) Deciding consensus Sequence assembly - fragment layout Greedy assemblers - The first assembly programs followed a simple but effective strategy in which the assembler greedily joins together the reads that are most similar to each other. An example is shown in figure, where the assembler joins, in order, reads 1 and 2 (overlap = 200 bp), then reads 3 and 4 (overlap = 150 bp), then reads 2 and 3 (overlap = 50 bp) thereby creating a single contig from the four reads provided in the input. One disadvantage of the simple greedy approach is that because local information is considered at each step, the assembler can be easily confused by complex repeats, leading to mis-assemblies. Greedy assembly of four reads Sequence assembly would have been a lot easier if not for the presence of REPEATS actual genome architecture misassembly Sequence assembly - fragment layout Using graph theory Sequence assembly - fragment layout Contigs Sequence assembly merge sequence reads to contigs Contig reads Scaffolding Scaffolds - collection of ordered contigs with approximately known distances between them reads clone approx.