DOCSLIB.ORG

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes Published OnlineFirst April 1, 2020; DOI: 10.1158/2159-8290.CD-19-1030 RESEARCH ARTICLE Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes Matthew Clarke1, Alan Mackay1, Britta Ismer2,3,4, Jessica C. Pickles5, Ruth G. Tatevossian6, Scott Newman7, Tejus A. Bale8, Iris Stoler9, Elisa Izquierdo1, Sara Temelso1, Diana M. Carvalho1, Valeria Molinari1, Anna Burford1, Louise Howell1, Alex Virasami5, Amy R. Fairchild5, Aimee Avery5, Jane Chalker5, Mark Kristiansen5, Kelly Haupfear6, James D. Dalton6, Wilda Orisme6, Ji Wen6, Michael Hubank10, Kathreena M. Kurian11, Catherine Rowe11, Mellissa Maybury12,13,14, Stephen Crosier15, Jeffrey Knipstein16, Ulrich Schüller17,18, Uwe Kordes18, David E. Kram19, Matija Snuderl20, Leslie Bridges21, Andrew J. Martin22, Lawrence J. Doey23, Safa Al-Sarraj23, Christopher Chandler24, Bassel Zebian24, Claire Cairns24, Rachael Natrajan25, Jessica K.R. Boult26, Simon P. Robinson26, Martin Sill2, Ira J. Dunkel27, Stephen W. Gilheeney27, Marc K. Rosenblum8, Debbie Hughes10, Paula Z. Proszek10, Tobey J. Macdonald28, Matthias Preusser29, Christine Haberler29,30, Irene Slavc31, Roger Packer32, Ho-Keung Ng33, Shani Caspi34, Mara Popović35, Barbara Faganel Kotnik36, Matthew D. Wood37, Lissa Baird38, Monika Ashok Davare39, David A. Solomon40,41, Thale Kristin Olsen42, Petter Brandal43, Michael Farrell44, Jane B. Cryan44, Michael Capra45, Michael Karremann46, Jens Schittenhelm47, Martin U. Schuhmann48, Martin Ebinger49, Winand N.M. Dinjens50, Kornelius Kerl51, Simone Hettmer52, Torsten Pietsch53, Felipe Andreiuolo53, Pablo Hernáiz Driever54, Andrey Korshunov55, Lotte Hiddingh2, Barbara C. Worst2,4,56, Dominik Sturm2,4,56, Marc Zuckermann2,4, Olaf Witt2,4,56, Tabitha Bloom57, Clare Mitchell57, Evelina Miele58, Giovanna Stefania Colafati59, Francesca Diomedi-Camassei60, Simon Bailey15, Andrew S. Moore12,13,14, Timothy E.G. Hassall13,61,62, Stephen P. Lowis11, Maria Tsoli63,64, Mark J. Cowley63,64, David S. Ziegler63,64, Matthias A. Karajannis27, Kristian Aquilina65, Darren R. Hargrave66, Fernando Carceller67,68, Lynley V. Marshall67,68, Andreas von Deimling55,69, Christof M. Kramm70, Stefan M. Pfister2,4,56, Felix Sahm54,69, Suzanne J. Baker71, Angela Mastronuzzi72, Andrea Carai73, Maria Vinci58, David Capper9,74, Sergey Popov1,75, David W. Ellison6, Thomas S. Jacques5, David T.W. Jones2,4, and Chris Jones1 1Division of Molecular Pathology, Institute of Cancer Research, London, College Hospital NHS Trust, London, United Kingdom. 24Department of Neu- United Kingdom. 2German Cancer Research Center (DKFZ), Heidelberg, rosurgery, Kings College Hospital NHS Trust, London, United Kingdom. 25The Germany. 3Faculty of Biosciences, Heidelberg University, Heidelberg, Ger- Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer many. 4Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Ger- Research, London, United Kingdom. 26Division of Radiotherapy and Imag- many. 5UCL Great Ormond Street Institute of Child Health, London, United ing, The Institute of Cancer Research, London, United Kingdom. 27Depart- Kingdom. 6Department of Neuropathology, St. Jude Children’s Research ment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New Hospital, Memphis, Tennessee. 7Department of Computational Biology, St. York. 28Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Jude Children’s Research Hospital, Memphis, Tennessee. 8Department of Emory University School of Medicine, Atlanta, Georgia. 29Comprehensive Neuropathology, Memorial Sloan-Kettering Cancer Center, New York, New Cancer Center, Medical University of Vienna, Vienna, Austria. 30Institute of York. 9Charité Universitätsmedizin Berlin, corporate member of Freie Uni- Neurology, Medical University of Vienna, Vienna, Austria. 31Department of versität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Department of Neuropathology, Berlin, Germany. 10Molecular Diagnostics, Austria. 32Center for Neuroscience and Behavioural Medicine, Children’s Royal Marsden Hospital NHS Trust, Sutton, United Kingdom. 11Brain Tumour National Medical Center, Washington, DC. 33Department of Anatomical and Research Centre, University of Bristol, Bristol, United Kingdom. 12The Uni- Cellular Pathology, The Chinese University of Hong Kong, China. 34Cancer versity of Queensland Diamantina Institute, The University of Queensland, Research Center, Sheba Medical Center, Tel Aviv, Israel. 35Faculty of Medi- Woolloongabba, Australia. 13Oncology Service, Queensland Children’s Hos- cine, University of Ljubljana, Ljubljana, Slovenia. 36Department of Hema- pital, Brisbane, Australia. 14Child Health Research Centre, The University of tology and Oncology, University Children’s Hospital, Ljubljana, Slovenia. Queensland, South Brisbane, Australia. 15Newcastle Hospitals NHS Foun- 37Department of Pathology, Oregon Health & Science University, Portland, dation Trust, Newcastle, United Kingdom. 16Division of Pediatric Hematol- Oregon. 38Department of Neurosurgery, Oregon Health & Science Univer- ogy/Oncology/BMT, Medical College of Wisconsin, Milwaukee, Wisconsin. sity, Portland, Oregon. 39Department of Pediatrics, Oregon Health & Sci- 17Department of Neuropathology, University Hospital Hamburg-Eppendorf, ence University, Portland, Oregon. 40Department of Pathology, University and Research Institute Children’s Cancer Center, Hamburg, Germany. 18Pedi- of California, San Francisco, California. 41Clinical Cancer Genomics Labora- atric Hematology and Oncology, University Hospital Hamburg-Eppendorf, tory, University of California, San Francisco, California. 42Department of Hamburg, Germany. 19Section of Pediatric Hematology-Oncology, Wake Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden. Forest School of Medicine, Winston-Salem, North Carolina. 20Department 43Department of Oncology, Oslo University Hospital, Oslo, Norway. 44Depart- of Neuropathology, NYU Langone Health, New York, New York. 21Depart- ment of Histopathology, Beaumont Hospital, Dublin, Ireland. 45Paediatric ment of Neuropathology, St George’s Hospital NHS Trust, London, United Oncology, Our Lady’s Children’s Hospital, Dublin, Ireland. 46Department of Kingdom. 22Department of Neurosurgery, St George’s Hospital NHS Trust, Pediatrics, University Medical Center Mannheim, Medical Faculty Mannheim, London, United Kingdom. 23Department of Clinical Neuropathology, Kings Heidelberg University, Mannheim, Germany. 47Institute of Pathology and 942 | CANCER DISCOVERY JULY 2020 AACRJournals.org Downloaded from cancerdiscovery.aacrjournals.org on September 25, 2021. © 2020 American Association for Cancer Research. Published OnlineFirst April 1, 2020; DOI: 10.1158/2159-8290.CD-19-1030 Neuropathology, University Hospital Tübingen, Germany. 48Department of Cancer Research Center (DKFZ), Heidelberg, Germany. 70Division of Pediatric Neurosurgery, University Hospital Tübingen, Germany. 49Department of Hematology and Oncology, University Medical Centre Göttingen, Germany. Pediatric Hematology and Oncology, University Hospital Tübingen, Germany. 71Department of Neurobiology, St. Jude Children’s Research Hospital, Mem- 50Department of Pathology, Erasmus Medical Center, Rotterdam, the Neth- phis, Tennessee. 72Neuro-oncology Unit, Department of Onco-haematology, erlands. 51Department of Pediatric Hematology and Oncology, University Cell and Gene Therapy, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy. Hospital Muenster, Germany. 52Department of Pediatric Hematology and 73Oncological Neurosurgery Unit, Department of Neuroscience and Neurore- Oncology, University Hospital Freiburg, Germany. 53Institute of Neuropathol- habilitation, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy. 74German ogy, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Bonn, Germany. 54Department of Paediatric Haematology/Oncology Charité Center (DKFZ), Heidelberg, Germany. 75Department of Pathology, University Universitätsmedizin, Berlin, Germany. 55Department of Neuropathology, Uni- of Wales Hospital NHS Trust, Cardiff, United Kingdom. 56 versity Hospital Heidelberg, Germany. Department of Pediatric Oncology, Note: Supplementary data for this article are available at Cancer Discovery Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Online (http://cancerdiscovery.aacrjournals.org/). Heidelberg, Germany. 57BRAIN UK, University of Southampton, Southamp- ton, United Kingdom. 58Department of Onco-haematology, Cell and Gene M. Clarke, A. Mackay, and B. Ismer contributed equally to this article. Therapy, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy. 59Oncological Corresponding Authors: Chris Jones, The Institute of Cancer Research, Neuroradiology Unit, Department of Diagnostic Imaging, Bambino Gesù Chil- 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 5NG, United Kingdom. dren’s Hospital-IRCCS, Rome, Italy. 60Department of Laboratories - Pathol- Phone: 4420-872-24416; Fax: 4420-8722-4321; E-mail: chris.jones@icr. ogy Unit, Bambino Gesù Children’s Hospital-IRCCS, Rome, Italy. 61Institute ac.uk; David T.W. Jones, Hopp Children’s Cancer Center Heidelberg (KiTZ) for Molecular Bioscience, The University of Queensland, St Lucia, Australia. and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 62School of Biomedical Sciences, Faculty of Health, Queensland
Load more

Recommended publications
  • Analysis of Trans Esnps Infers Regulatory Network Architecture
    Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation.
    [Show full text]
  • The Contribution of CLIP2 Haploinsufficiency to the Clinical
    REPORT The Contribution of CLIP2 Haploinsufficiency to the Clinical Manifestations of the Williams-Beuren Syndrome Geert Vandeweyer,1 Nathalie Van der Aa,1 Edwin Reyniers,1 and R. Frank Kooy1,* Williams-Beuren syndrome is a rare contiguous gene syndrome, characterized by intellectual disability, facial dysmorphisms, connec- tive-tissue abnormalities, cardiac defects, structural brain abnormalities, and transient infantile hypercalcemia. Genes lying telomeric to RFC2, including CLIP2, GTF2I and GTF2IRD1, are currently thought to be the most likely major contributors to the typical Williams syndrome cognitive profile, characterized by a better-than-expected auditory rote-memory ability, a relative sparing of language capa- bilities, and a severe visual-spatial constructive impairment. Atypical deletions in the region have helped to establish genotype-pheno- type correlations. So far, however, hardly any deletions affecting only a single gene in the disease region have been described. We present here two healthy siblings with a pure, hemizygous deletion of CLIP2. A putative role in the cognitive and behavioral abnormalities seen in Williams-Beuren patients has been suggested for this gene on the basis of observations in a knock-out mouse model. The presented siblings did not show any of the clinical features associated with the syndrome. Cognitive testing showed an average IQ for both and no indication of the Williams syndrome cognitive profile. This shows that CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome, nor does it lead to the Williams syndrome cognitive profile. Although contri- bution of CLIP2 to the phenotype cannot be excluded when it is deleted in combination with other genes, our results support the hypothesis that GTF2IRD1 and GTF2I are the main genes causing the cognitive defects associated with Williams-Beuren syndrome.
    [Show full text]
  • In This Table Protein Name, Uniprot Code, Gene Name P-Value
    Supplementary Table S1: In this table protein name, uniprot code, gene name p-value and Fold change (FC) for each comparison are shown, for 299 of the 301 significantly regulated proteins found in both comparisons (p-value<0.01, fold change (FC) >+/-0.37) ALS versus control and FTLD-U versus control. Two uncharacterized proteins have been excluded from this list Protein name Uniprot Gene name p value FC FTLD-U p value FC ALS FTLD-U ALS Cytochrome b-c1 complex P14927 UQCRB 1.534E-03 -1.591E+00 6.005E-04 -1.639E+00 subunit 7 NADH dehydrogenase O95182 NDUFA7 4.127E-04 -9.471E-01 3.467E-05 -1.643E+00 [ubiquinone] 1 alpha subcomplex subunit 7 NADH dehydrogenase O43678 NDUFA2 3.230E-04 -9.145E-01 2.113E-04 -1.450E+00 [ubiquinone] 1 alpha subcomplex subunit 2 NADH dehydrogenase O43920 NDUFS5 1.769E-04 -8.829E-01 3.235E-05 -1.007E+00 [ubiquinone] iron-sulfur protein 5 ARF GTPase-activating A0A0C4DGN6 GIT1 1.306E-03 -8.810E-01 1.115E-03 -7.228E-01 protein GIT1 Methylglutaconyl-CoA Q13825 AUH 6.097E-04 -7.666E-01 5.619E-06 -1.178E+00 hydratase, mitochondrial ADP/ATP translocase 1 P12235 SLC25A4 6.068E-03 -6.095E-01 3.595E-04 -1.011E+00 MIC J3QTA6 CHCHD6 1.090E-04 -5.913E-01 2.124E-03 -5.948E-01 MIC J3QTA6 CHCHD6 1.090E-04 -5.913E-01 2.124E-03 -5.948E-01 Protein kinase C and casein Q9BY11 PACSIN1 3.837E-03 -5.863E-01 3.680E-06 -1.824E+00 kinase substrate in neurons protein 1 Tubulin polymerization- O94811 TPPP 6.466E-03 -5.755E-01 6.943E-06 -1.169E+00 promoting protein MIC C9JRZ6 CHCHD3 2.912E-02 -6.187E-01 2.195E-03 -9.781E-01 Mitochondrial 2-
    [Show full text]
  • Transcriptome Network of the Papillary Thyroid Carcinoma Radiation Marker
    Selmansberger et al. Radiation Oncology (2020) 15:182 https://doi.org/10.1186/s13014-020-01620-5 RESEARCH Open Access Transcriptome network of the papillary thyroid carcinoma radiation marker CLIP2 Martin Selmansberger1, Agata Michna1, Herbert Braselmann1, Ines Höfig2, Kenji Schorpp3, Peter Weber1, Natasa Anastasov2, Horst Zitzelsberger1,4,5, Julia Hess1,4,5 and Kristian Unger1,4,5* Abstract Background: We present a functional gene association network of the CLIP2 gene, generated by de-novo reconstruction from transcriptomic microarray data. CLIP2 was previously identified as a potential marker for radiation induced papillary thyroid carcinoma (PTC) of young patients in the aftermath of the Chernobyl reactor accident. Considering the rising thyroid cancer incidence rates in western societies, potentially related to medical radiation exposure, the functional characterization of CLIP2 is of relevance and contributes to the knowledge about radiation-induced thyroid malignancies. Methods: We generated a transcriptomic mRNA expression data set from a CLIP2-perturbed thyroid cancer cell line (TPC-1) with induced CLIP2 mRNA overexpression and siRNA knockdown, respectively, followed by gene-association network reconstruction using the partial correlation-based approach GeneNet. Furthermore, we investigated different approaches for prioritizing differentially expressed genes for network reconstruction and compared the resulting networks with existing functional interaction networks from the Reactome, Biogrid and STRING databases. The derived CLIP2 interaction partners were validated on transcript and protein level. Results: The best reconstructed network with regard to selection parameters contained a set of 20 genes in the 1st neighborhood of CLIP2 and suggests involvement of CLIP2 in the biological processes DNA repair/maintenance, chromosomal instability, promotion of proliferation and metastasis.
    [Show full text]
  • CLIP2 As Radiation Biomarker in Papillary Thyroid Carcinoma
    Oncogene (2015) 34, 3917–3925 © 2015 Macmillan Publishers Limited All rights reserved 0950-9232/15 www.nature.com/onc ORIGINAL ARTICLE CLIP2 as radiation biomarker in papillary thyroid carcinoma M Selmansberger1, A Feuchtinger2, L Zurnadzhy3, A Michna1, JC Kaiser4, M Abend5, A Brenner6, T Bogdanova3, A Walch2, K Unger1,7, H Zitzelsberger1,7 and J Hess1,7 A substantial increase in papillary thyroid carcinoma (PTC) among children exposed to the radioiodine fallout has been one of the main consequences of the Chernobyl reactor accident. Recently, the investigation of PTCs from a cohort of young patients exposed to the post-Chernobyl radioiodine fallout at very young age and a matched nonexposed control group revealed a radiation-specific DNA copy number gain on chromosomal band 7q11.23 and the radiation-associated mRNA overexpression of CLIP2. In this study, we investigated the potential role of CLIP2 as a radiation marker to be used for the individual classification of PTCs into CLIP2- positive and -negative cases—a prerequisite for the integration of CLIP2 into epidemiological modelling of the risk of radiation- induced PTC. We were able to validate the radiation-associated CLIP2 overexpression at the protein level by immunohistochemistry (IHC) followed by relative quantification using digital image analysis software (P = 0.0149). Furthermore, we developed a standardized workflow for the determination of CLIP2-positive and -negative cases that combines visual CLIP2 IHC scoring and CLIP2 genomic copy number status. In addition to the discovery cohort (n = 33), two independent validation cohorts of PTCs (n = 115) were investigated. High sensitivity and specificity rates for all three investigated cohorts were obtained, demonstrating robustness of the developed workflow.
    [Show full text]
  • Agricultural University of Athens
    ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική
    [Show full text]
  • European Sea Bass Genome and Its Variation Provide Insights Into
    European sea bass genome and its variation provide insights into adaptation to euryhalinity and speciation Mbaye Tine, Heiner Kuhl, Pierre-Alexandre Gagnaire, Bruno Louro, Erick Desmarais, Rute S.T. Martins, Jochen Hecht, Florian Knaust, Khalid Belkhir, Sven Klages, et al. To cite this version: Mbaye Tine, Heiner Kuhl, Pierre-Alexandre Gagnaire, Bruno Louro, Erick Desmarais, et al.. European sea bass genome and its variation provide insights into adaptation to euryhalinity and speciation. Na- ture Communications, Nature Publishing Group, 2014, 5 (1), 10.1038/ncomms6770. hal-01922671 HAL Id: hal-01922671 https://hal.archives-ouvertes.fr/hal-01922671 Submitted on 5 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ARTICLE Received 15 May 2014 | Accepted 5 Nov 2014 | Published 23 Dec 2014 DOI: 10.1038/ncomms6770 OPEN European sea bass genome and its variation provide insights into adaptation to euryhalinity and speciation Mbaye Tine1,2,*, Heiner Kuhl2,*, Pierre-Alexandre Gagnaire3,4,*, Bruno Louro5, Erick Desmarais3, Rute S.T. Martins5, Jochen Hecht2,6, Florian Knaust2, Khalid Belkhir3, Sven Klages2, Roland Dieterich1, Kurt Stueber1, Francesc Piferrer7, Bruno Guinand3, Nicolas Bierne3,4, Filip A.M. Volckaert8, Luca Bargelloni9, Deborah M.
    [Show full text]
  • Phenotype Informatics
    Freie Universit¨atBerlin Department of Mathematics and Computer Science Phenotype informatics: Network approaches towards understanding the diseasome Sebastian Kohler¨ Submitted on: 12th September 2012 Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) am Fachbereich Mathematik und Informatik der Freien Universitat¨ Berlin ii 1. Gutachter Prof. Dr. Martin Vingron 2. Gutachter: Prof. Dr. Peter N. Robinson 3. Gutachter: Christopher J. Mungall, Ph.D. Tag der Disputation: 16.05.2013 Preface This thesis presents research work on novel computational approaches to investigate and characterise the association between genes and pheno- typic abnormalities. It demonstrates methods for organisation, integra- tion, and mining of phenotype data in the field of genetics, with special application to human genetics. Here I will describe the parts of this the- sis that have been published in peer-reviewed journals. Often in modern science different people from different institutions contribute to research projects. The same is true for this thesis, and thus I will itemise who was responsible for specific sub-projects. In chapter 2, a new method for associating genes to phenotypes by means of protein-protein-interaction networks is described. I present a strategy to organise disease data and show how this can be used to link diseases to the corresponding genes. I show that global network distance measure in interaction networks of proteins is well suited for investigat- ing genotype-phenotype associations. This work has been published in 2008 in the American Journal of Human Genetics. My contribution here was to plan the project, implement the software, and finally test and evaluate the method on human genetics data; the implementation part was done in close collaboration with Sebastian Bauer.
    [Show full text]
  • Williams Syndrome
    Williams syndrome Description Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems. People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder. Young children with Williams syndrome have distinctive facial features including a broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips. Many affected people have dental problems such as teeth that are small, widely spaced, crooked, or missing. In older children and adults, the face appears longer and more gaunt. A form of cardiovascular disease called supravalvular aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvular aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Other problems with the heart and blood vessels, including high blood pressure (hypertension), have also been reported in people with Williams syndrome. Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin.
    [Show full text]
  • Gain of Chromosome Band 7Q11 in Papillary Thyroid Carcinomas of Young Patients Is Associated with Exposure to Low-Dose Irradiation
    Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation Julia Heßa, Gerry Thomasb, Herbert Braselmanna, Verena Bauera, Tatjana Bogdanovac, Johannes Wienbergd, Horst Zitzelsbergera, and Kristian Ungerb,1 aResearch Unit of Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany; bHuman Cancer Studies Group, Department of Surgery and Cancer, Hammersmith Hospital, London W12 0HS, United Kingdom; cInstitute of Endocrinology and Metabolism, Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine; and dDepartment Biologie II, Anthropologie und Humangenetik, Ludwig-Maximilians-University, 82152 Martinsried, Germany Edited* by Janet D. Rowley, University of Chicago, Chicago, IL, and approved April 26, 2011 (received for review November 21, 2010) The main consequence of the Chernobyl accident has been an in the development of radiation-associated PTC that appropriate increase in papillary thyroid carcinomas (PTCs) in those exposed to tumor, sex, and age-matched cohorts with exposed cases and radioactive fallout as young children. Our aim was to identify nonexposed individuals for comparison are used. This approach genomic alterations that are associated with exposure to radiation. minimizes variability in the study that results particularly with We used array comparative genomic hybridization to analyze a respect to age at diagnosis. Studies of early Chernobyl-related main (n = 52) and a validation cohort (n = 28) of PTC from patients tumors by several groups found that a very high proportion aged <25 y at operation and matched for age at diagnosis and showed RET rearrangements, predominantly RET/PTC3 (3–6). residency. Both cohorts consisted of patients exposed and not ex- It was speculated that this rearrangement might be a marker posed to radioiodine fallout.
    [Show full text]
  • The Pennsylvania State University Schreyer Honors College
    THE PENNSYLVANIA STATE UNIVERSITY SCHREYER HONORS COLLEGE DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY EXAMINING DROSOPHILA MELANOGASTER WING SIZE UPON TISSUE SPECIFIC RNAI-INDUCED KNOCKDOWN OF CANDIDATE GENE REGIONS OF NEURODEVELOPMENTAL DISORDERS AVIK MONI SARKER FALL 2019 A thesis submitted in partial fulfillment of the requirements for a baccalaureate degrees in Biochemistry and Molecular Biology and Statistics with honors in Biochemistry and Molecular Biology Reviewed and approved* by the following: Santhosh Girirajan Associate Professor of Genomics Thesis Supervisor and Honors Advisor David Gilmour Professor of Molecular and Cell Biology Faculty Reader * Signatures are on file in the Schreyer Honors College. i ABSTRACT In humans, deletions and duplications in the genome known as rare copy number variants (CNVs) are known to be associated with neurodevelopmental disorders, such as autism, intellectual disability, and schizophrenia. While specific genes, both in these regions and elsewhere in the genome, are known to contribute to nervous tissue development, these genes could also have implications in general (not necessarily neuronal) tissue development. To explore this possibility, this study utilized the tissue specific RNAi knockdown of homologs of these genes in wing pouch tissue of Drosophila melanogaster to evaluate the effects on wing area. The homologs of 79 genes, categorized in 10 CNV regions or core neurodevelopmental gene categories, were studied in a high throughput manner. The results of this study indicate that 23 genes possibly contribute to the development of non-neuronal tissue in both male and female flies; however, further testing on additional lines would increase confidence in these conclusions. ii TABLE OF CONTENTS LIST OF FIGURES ....................................................................................................
    [Show full text]
  • Mouse Clip2 Knockout Project (CRISPR/Cas9)
    https://www.alphaknockout.com Mouse Clip2 Knockout Project (CRISPR/Cas9) Objective: To create a Clip2 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Clip2 gene (NCBI Reference Sequence: NM_009990 ; Ensembl: ENSMUSG00000063146 ) is located on Mouse chromosome 5. 17 exons are identified, with the ATG start codon in exon 2 and the TGA stop codon in exon 17 (Transcript: ENSMUST00000100647). Exon 3~7 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous and heterozygous for disruptions in this gene display growth deficiency, brain abnormalities and hippocampal dysfunction and deficits in motor coordination. Exon 3 starts from about 3.98% of the coding region. Exon 3~7 covers 38.14% of the coding region. The size of effective KO region: ~9147 bp. The KO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 3 4 5 6 7 17 Legends Exon of mouse Clip2 Knockout region Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 3 is aligned with itself to determine if there are tandem repeats. Tandem repeats are found in the dot plot matrix. The gRNA site is selected outside of these tandem repeats. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section downstream of Exon 7 is aligned with itself to determine if there are tandem repeats.
    [Show full text]