Nuclear Genome
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
2020 Program Book
PROGRAM BOOK Note that TAGC was cancelled and held online with a different schedule and program. This document serves as a record of the original program designed for the in-person meeting. April 22–26, 2020 Gaylord National Resort & Convention Center Metro Washington, DC TABLE OF CONTENTS About the GSA ........................................................................................................................................................ 3 Conference Organizers ...........................................................................................................................................4 General Information ...............................................................................................................................................7 Mobile App ....................................................................................................................................................7 Registration, Badges, and Pre-ordered T-shirts .............................................................................................7 Oral Presenters: Speaker Ready Room - Camellia 4.......................................................................................7 Poster Sessions and Exhibits - Prince George’s Exhibition Hall ......................................................................7 GSA Central - Booth 520 ................................................................................................................................8 Internet Access ..............................................................................................................................................8 -
Role and Regulation of the P53-Homolog P73 in the Transformation of Normal Human Fibroblasts
Role and regulation of the p53-homolog p73 in the transformation of normal human fibroblasts Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Lars Hofmann aus Aschaffenburg Würzburg 2007 Eingereicht am Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Dr. Martin J. Müller Gutachter: Prof. Dr. Michael P. Schön Gutachter : Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt und keine anderen als die angegebenen Hilfsmittel und Quellen verwendet habe. Diese Arbeit wurde weder in gleicher noch in ähnlicher Form in einem anderen Prüfungsverfahren vorgelegt. Ich habe früher, außer den mit dem Zulassungsgesuch urkundlichen Graden, keine weiteren akademischen Grade erworben und zu erwerben gesucht. Würzburg, Lars Hofmann Content SUMMARY ................................................................................................................ IV ZUSAMMENFASSUNG ............................................................................................. V 1. INTRODUCTION ................................................................................................. 1 1.1. Molecular basics of cancer .......................................................................................... 1 1.2. Early research on tumorigenesis ................................................................................. 3 1.3. Developing -
Genome-Wide CRISPR-Cas9 Screens Reveal Loss of Redundancy Between PKMYT1 and WEE1 in Glioblastoma Stem-Like Cells
Article Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells Graphical Abstract Authors Chad M. Toledo, Yu Ding, Pia Hoellerbauer, ..., Bruce E. Clurman, James M. Olson, Patrick J. Paddison Correspondence [email protected] (J.M.O.), [email protected] (P.J.P.) In Brief Patient-derived glioblastoma stem-like cells (GSCs) can be grown in conditions that preserve patient tumor signatures and their tumor initiating capacity. Toledo et al. use these conditions to perform genome-wide CRISPR-Cas9 lethality screens in both GSCs and non- transformed NSCs, revealing PKMYT1 as a candidate GSC-lethal gene. Highlights d CRISPR-Cas9 lethality screens performed in patient brain- tumor stem-like cells d PKMYT1 is identified in GSCs, but not NSCs, as essential for facilitating mitosis d PKMYT1 and WEE1 act redundantly in NSCs, where their inhibition is synthetic lethal d PKMYT1 and WEE1 redundancy can be broken by over- activation of EGFR and AKT Toledo et al., 2015, Cell Reports 13, 2425–2439 December 22, 2015 ª2015 The Authors http://dx.doi.org/10.1016/j.celrep.2015.11.021 Cell Reports Article Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells Chad M. Toledo,1,2,14 Yu Ding,1,14 Pia Hoellerbauer,1,2 Ryan J. Davis,1,2,3 Ryan Basom,4 Emily J. Girard,3 Eunjee Lee,5 Philip Corrin,1 Traver Hart,6,7 Hamid Bolouri,1 Jerry Davison,4 Qing Zhang,4 Justin Hardcastle,1 Bruce J. Aronow,8 Christopher L. -
Identifying the Link Between Non-Coding Regulatory Rnas and Phenotypic Severity in a Zebrafish Model of Gmppb Dystroglycanopathy
The University of Maine DigitalCommons@UMaine Honors College Spring 5-2020 Identifying the Link Between Non-Coding Regulatory RNAs and Phenotypic Severity in a Zebrafish Model of gmppb Dystroglycanopathy Grace Smith Follow this and additional works at: https://digitalcommons.library.umaine.edu/honors Part of the Genetics Commons, Molecular Biology Commons, and the Musculoskeletal Diseases Commons This Honors Thesis is brought to you for free and open access by DigitalCommons@UMaine. It has been accepted for inclusion in Honors College by an authorized administrator of DigitalCommons@UMaine. For more information, please contact [email protected]. IDENTIFYING THE LINK BETWEEN NON-CODING REGULATORY RNAS AND PHENOTYPIC SEVERITY IN A ZEBRAFISH MODEL OF GMPPB DYSTROGLYCANOPATHY by Grace Smith A Thesis Submitted in Partial Fulfillment of the Requirements for a Degree with Honors (Molecular & Cellular Biology) The Honors College University of Maine May 2020 Advisory Committee: Benjamin King, Assistant Professor of Bioinformatics, Advisor Clarissa Henry, Associate Professor of Biological Sciences Melissa Ladenheim, Associate Dean of the Honors College Sally Molloy, Assistant Professor of Genomics and NSFA-Honors Preceptor of Genomics Kristy Townsend, Associate Professor of Neurobiology ABSTRACT Muscular Dystrophy (MD) is characterized by varying severity and time-of-onset by individuals afflicted with the same forms of MD, a phenomenon that is not well understood. MD affects 250,000 individuals in the United States and is characterized by mutations in the dystroglycan complex. gmppb encodes an enzyme that glycosylates dystroglycan, making it functionally active; thus, mutations in gmppb cause dystroglycanopathic MD1. The zebrafish (Danio rerio) is a powerful vertebrate model for musculoskeletal development and disease. -
Ep 2327796 A1
(19) & (11) EP 2 327 796 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 01.06.2011 Bulletin 2011/22 C12Q 1/68 (2006.01) (21) Application number: 10184813.3 (22) Date of filing: 09.06.2004 (84) Designated Contracting States: • Spira, Avrum AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Newton, Massachusetts 02465 (US) HU IE IT LI LU MC NL PL PT RO SE SI SK TR (74) Representative: Brown, David Leslie (30) Priority: 10.06.2003 US 477218 P Haseltine Lake LLP Redcliff Quay (62) Document number(s) of the earlier application(s) in 120 Redcliff Street accordance with Art. 76 EPC: Bristol 04776438.6 / 1 633 892 BS1 6HU (GB) (71) Applicant: THE TRUSTEES OF BOSTON Remarks: UNIVERSITY •This application was filed on 30-09-2010 as a Boston, MA 02218 (US) divisional application to the application mentioned under INID code 62. (72) Inventors: •Claims filed after the date of filing of the application/ • Brody, Jerome S. after the date of receipt of the divisional application Newton, Massachusetts 02458 (US) (Rule 68(4) EPC). (54) Detection methods for disorders of the lung (57) The present invention is directed to prognostic vides a minimally invasive sample procurement method and diagnostic methods to assess lung disease risk in combination with the gene expression-based tools for caused by airway pollutants by analyzing expression of the diagnosis and prognosis of diseases of the lung, par- one or more genes belonging to the airway transcriptome ticularly diagnosis and prognosis of lung cancer provided herein. -
Facteur De Risque Génétique Aux Maladies Inflammatoires De L’Intestin Et Modulateur D’Inflammation
Université de Montréal MAST3 : facteur de risque génétique aux maladies inflammatoires de l’intestin et modulateur d’inflammation par Catherine Labbé Département de sciences biomédicales Faculté de médecine Thèse présentée à la Faculté de médecine en vue de l’obtention du grade de doctorat en sciences biomédicales 5 août, 2011 © Catherine Labbé, 2011 Université de Montréal Faculté de médecine Cette thèse intitulée : MAST3 : facteur de risque génétique aux maladies inflammatoires de l’intestin et modulateur d’inflammation Présentée par : Catherine Labbé a été évaluée par un jury composé des personnes suivantes : Daniel Sinnett, président-rapporteur John D. Rioux, directeur de recherche Zoha Kibar, membre du jury Yohan Bossé, examinateur externe Gaëtan Mayer, représentant du doyen de la FES i Résumé La maladie de Crohn (MC) et la colite ulcéreuse (CU) sont des maladies inflammatoires chroniques du tube digestif qu’on regroupe sous le terme maladies inflammatoires de l’intestin (MII). Les mécanismes moléculaires menant au développement des MII ne sont pas entièrement connus, mais des études génétiques et fonctionnelles ont permis de mettre en évidence des interactions entre des prédispositions génétiques et des facteurs environnementaux - notamment la flore intestinale – qui contribuent au développement d’une dérégulation de la réponse immunitaire menant à l’inflammation de la muqueuse intestinale. Des études d’association pangénomiques et ciblées ont permis d’identifier plusieurs gènes de susceptibilité aux MII mais les estimations de la contribution de ces gènes à l’héritabilité suggèrent que plusieurs gènes restent à découvrir. Certains d’entre eux peuvent se trouver dans les régions identifiées par des études de liaison génétique. -
Transcriptome-Wide Association Study Identifies New Susceptibility Genes
Li et al. Translational Psychiatry (2021) 11:306 https://doi.org/10.1038/s41398-021-01411-w Translational Psychiatry ARTICLE Open Access Transcriptome-wide association study identifies new susceptibility genes and pathways for depression Xiaoyan Li1,2,XiSu3,4, Jiewei Liu1, Huijuan Li1,MingLi 1,5, the 23andMe Research Team, Wenqiang Li3,4 and Xiong-Jian Luo 1,5,6 Abstract Depression is the most prevalent mental disorder with substantial morbidity and mortality. Although genome-wide association studies (GWASs) have identified multiple risk variants for depression, due to the complicated gene regulatory mechanisms and complexity of linkage disequilibrium (LD), the biological mechanisms by which the risk variants exert their effects on depression remain largely unknown. Here, we perform a transcriptome-wide association study (TWAS) of depression by integrating GWAS summary statistics from 807,553 individuals (246,363 depression cases and 561,190 controls) and summary-level gene-expression data (from the dorsolateral prefrontal cortex (DLPFC) of 1003 individuals). We identified 53 transcriptome-wide significant (TWS) risk genes for depression, of which 23 genes were not implicated in risk loci of the original GWAS. Seven out of 53 risk genes (B3GALTL, FADS1, TCTEX1D1, XPNPEP3, ZMAT2, ZNF501 and ZNF502) showed TWS associations with depression in two independent brain expression quantitative loci (eQTL) datasets, suggesting that these genes may represent promising candidates. We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each fi 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; locus. Finally, pathway enrichment analysis revealed biologically pathways relevant to depression. Our study identi ed new depression risk genes whose expression dysregulation may play a role in depression. -
Corporate Medical Policy
Corporate Medical Policy Genetic Testing for Duchenne, Becker, Facioscapulohumeral, Limb- Girdle Muscular Dystrophies AHS – M2074 File Name: genetic_testing_for_duchenne_becker_facioscapulohumeral_limb_girdle_muscular_dystrophies Origination: 01/01/2019 Last CAP Review: 07/2021 Next CAP Review: 07/2022 Last Review: 07/2021 Description of Procedure or Service Muscular dystrophies, genetic conditions characterized by progressive muscle atrophy, can be caused by several genetic mutations. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are due to mutations to the dystrophin gene on the X chromosome (Darras, 2020a). Facioscapulohumeral muscular dystrophy (FSHD) occurs due to a contraction of the polymorphic macrosatellite repeat D4Z4 on chromosome 4q35 (Darras, 2020b). Duchenne muscular dystrophy (DMD), the more severe of the dystrophin-related muscular dystrophies, typically presents in males during their toddler years. Patients with DMD rarely survive beyond their thirties due to respiratory insufficiency or cardiomyopathy. Unlike DMD, Becker muscular dystrophy (BMD) is less severe and typically presents in the teen years or adulthood; moreover, patients with BMD usually survive beyond thirty years of age (Darras, 2018a, 2020a). In Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant disorder, the contraction of the macrosatellite repeat D4Z4 results in an inappropriate expression of the DUX4 (double homeobox protein 4) gene, which alters chromatin structure. FSHD has also been linked to DNA hypomethylation. Symptoms include muscle weakness in the face, arms, legs, abdomen, and scapula with a variable age of onset; however, 90% of patients are affected by the age of 20. Disease progression is slower than DMD with a normal or near-normal life span (Darras, 2018b, 2020b). The limb-girdle muscular dystrophies (LGMDs) are a group of more than 30 rare hereditary progressive neuromuscular disorders (Murphy & Straub, 2015) characterized by predominantly proximal distribution of weakness in the pelvic and shoulder girdles. -
Using Massively Parallel Sequencing to Determine the Genetic Basis of Leigh Syndrome, the Most Common Mitochondrial Disorder Affecting Children
Using Massively Parallel Sequencing to determine the genetic basis of Leigh Syndrome, the most common mitochondrial disorder affecting children Nicole Janet Lake ORCID ID 0000-0003-4103-6387 Doctor of Philosophy January 2018 Department of Paediatrics Faculty of Medicine, Dentistry and Health Sciences University of Melbourne Submitted in total fulfilment of the requirements of the degree of Doctor of Philosophy Abstract Mitochondrial diseases are debilitating illnesses caused by mutations that impair mitochondrial energy generation. The most common clinical presentation of mitochondrial disease in children is Leigh syndrome. This neurodegenerative disorder can be caused by mutations in more than 85 genes, encoded by both nuclear and mitochondrial DNA (mtDNA). When this PhD commenced, massively parallel sequencing for genetic diagnosis of Leigh syndrome was transitioning into the clinic, however its diagnostic utility in a clinical setting was unknown. Furthermore, a significant number of Leigh syndrome patients remained without a genetic diagnosis, indicating that further research was required to expand our understanding of the genetic basis of disease. To identify the maximum diagnostic yield of massively parallel sequencing in patients with Leigh syndrome, and to provide insight into the genetic basis of disease, unsolved patients from a historical Leigh syndrome cohort were studied. This cohort is comprised of 67 clinically- ascertained patients diagnosed with Leigh or Leigh-like syndrome according to stringent criteria. DNA from all 33 patients lacking a genetic diagnosis underwent whole exome sequencing, with parallel sequencing of the mtDNA. A targeted analysis of 2273 genes was performed, which included known and candidate mitochondrial disease genes, and differential diagnosis genes underlying distinct disorders with phenotypic overlap. -
Mutations in GMPPA Cause a Glycosylation Disorder Characterized by Intellectual Disability and Autonomic Dysfunction
REPORT Mutations in GMPPA Cause a Glycosylation Disorder Characterized by Intellectual Disability and Autonomic Dysfunction Katrin Koehler,1,24 Meera Malik,2,24 Saqib Mahmood,3 Sebastian Gießelmann,2 Christian Beetz,4 J. Christopher Hennings,2 Antje K. Huebner,2 Ammi Grahn,5 Janine Reunert,6 Gudrun Nu¨rnberg,7 Holger Thiele,7 Janine Altmu¨ller,7 Peter Nu¨rnberg,7,8,9 Rizwan Mumtaz,2 Dusica Babovic-Vuksanovic,10 Lina Basel-Vanagaite,11,12,13 Guntram Borck,14 Ju¨rgen Bra¨mswig,6 Reinhard Mu¨hlenberg,15 Pierre Sarda,16 Alma Sikiric,17 Kwame Anyane-Yeboa,18 Avraham Zeharia,12,19 Arsalan Ahmad,20 Christine Coubes,16 Yoshinao Wada,21 Thorsten Marquardt,6 Dieter Vanderschaeghe,22,23 Emile Van Schaftingen,5 Ingo Kurth,2 Angela Huebner,1,* and Christian A. Hu¨bner2,* In guanosine diphosphate (GDP)-mannose pyrophosphorylase A (GMPPA), we identified a homozygous nonsense mutation that segre- gated with achalasia and alacrima, delayed developmental milestones, and gait abnormalities in a consanguineous Pakistani pedigree. Mutations in GMPPA were subsequently found in ten additional individuals from eight independent families affected by the combina- tion of achalasia, alacrima, and neurological deficits. This autosomal-recessive disorder shows many similarities with triple A syndrome, which is characterized by achalasia, alacrima, and variable neurological deficits in combination with adrenal insufficiency. GMPPA is a largely uncharacterized homolog of GMPPB. GMPPB catalyzes the formation of GDP-mannose, which is an essential precursor of glycan moieties of glycoproteins and glycolipids and is associated with congenital and limb-girdle muscular dystrophies with hypoglycosyla- tion of a-dystroglycan. Surprisingly, GDP-mannose pyrophosphorylase activity was unchanged and GDP-mannose levels were strongly increased in lymphoblasts of individuals with GMPPA mutations. -
GMPPA Defects Cause a Neuromuscular Disorder with Α- Dystroglycan Hyperglycosylation
GMPPA defects cause a neuromuscular disorder with α- dystroglycan hyperglycosylation Patricia Franzka, … , Julia von Maltzahn, Christian A. Hübner J Clin Invest. 2021. https://doi.org/10.1172/JCI139076. Research In-Press Preview Muscle biology Graphical abstract Find the latest version: https://jci.me/139076/pdf GMPPA defects cause a neuromuscular disorder with α- dystroglycan hyperglycosylation Authors: Patricia Franzka1, Henriette Henze2†, M. Juliane Jung2†, Svenja Caren Schüler2, Sonnhild Mittag3, Karina Biskup4, Lutz Liebmann1, Takfarinas Kentache5, José Morales6, Braulio Martínez7, Istvan Katona8, Tanja Herrmann1, Antje-Kathrin Huebner1, J. Christopher Hennings1, Susann Groth2, Lennart Gresing1, Rüdiger Horstkorte8, Thorsten Marquardt9, Joachim Weis8, Christoph Kaether2, Osvaldo M. Mutchinick6, Alessandro Ori2, Otmar Huber3, Veronique Blanchard4, Julia von Maltzahn2, Christian A. Hübner1* Affiliations: 1Institute of Human Genetics, University Hospital Jena, Friedrich Schiller University, Jena, Germany 2Leibniz-Institute on Aging - Fritz-Lipmann-Institute, Jena, Germany 3Department of Biochemistry II, University Hospital Jena, Friedrich Schiller University, Jena, Germany 4Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Berlin, Germany 5Welbio and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium 6Department of Genetics, Instituto Nacional