September 1997 Volume 24

Total Page:16

File Type:pdf, Size:1020Kb

September 1997 Volume 24 Volume 1 - Number 1 May - September 1997 Volume 24 - Number 6 June 2020 Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Scope The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal in open access, devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. It is made for and by: clinicians and researchers in cytogenetics, molecular biology, oncology, haematology, and pathology. One main scope of the Atlas is to conjugate the scientific information provided by cytogenetics/molecular genetics to the clinical setting (diagnostics, prognostics and therapeutic design), another is to provide an encyclopedic knowledge in cancer genetics. The Atlas deals with cancer research and genomics. It is at the crossroads of research, virtual medical university (university and post-university e-learning), and telemedicine. It contributes to "meta-medicine", this mediation, using information technology, between the increasing amount of knowledge and the individual, having to use the information. Towards a personalized medicine of cancer. It presents structured review articles ("cards") on: 1- Genes, 2- Leukemias, 3- Solid tumors, 4- Cancer-prone diseases, and also 5- "Deep insights": more traditional review articles on the above subjects and on surrounding topics. It also present 6- Case reports in hematology and 7- Educational items in the various related topics for students in Medicine and in Sciences. The Atlas of Genetics and Cytogenetics in Oncology and Haematology does not publish research articles. See also: http://documents.irevues.inist.fr/bitstream/handle/2042/56067/Scope.pdf Editorial correspondance Jean-Loup Huret, MD, PhD, [email protected] Editor, Editorial Board and Publisher See:http://documents.irevues.inist.fr/bitstream/handle/2042/48485/Editor-editorial-board-and-publisher.pdf The Atlas of Genetics and Cytogenetics in Oncology and Haematology is published 12 times a year by ARMGHM, a non profit organisation, and by the INstitute for Scientific and Technical Information of the French National Center for Scientific Research (INIST-CNRS) since 2008. The Atlas is hosted by INIST-CNRS (http://www.inist.fr) Staff: Vanessa Le Berre Philippe Dessen is the Database Directorof the on-line version (Gustave Roussy Institute – Villejuif – France). Publisher Contact: INIST-CNRS Mailing Address: Catherine Morel, 2,Allée du Parc de Brabois, CS 10130, 54519 Vandoeuvre-lès-Nancy France. Email Address:[email protected] Articles of the ATLAS are free in PDF format, and metadata are available on the web in Dublin Core XML format and freely harvestable.A Digital object identifier (DOI®), recorded at the International Agency CrossRefhttp://www.crossref.org/ is assigned to each article. http://AtlasGeneticsOncology.org © ATLAS - ISSN 1768-3262 The PDF version of the Atlas of Genetics and Cytogenetics in Oncology and Haematology is a reissue of the original articles published in collaboration with the Institute for Scientific and Technical Information (INstitut de l’Information Scientifique et Technique - INIST) of the French National Center for Scientific Research (CNRS) on its electronic publishing platform I-Revues. Online and PDF versions of the Atlas of Genetics and Cytogenetics in Oncology and Haematology are hosted by INIST-CNRS. Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Editors-in-Chief Jesús María Hernández Rivas (Salamanca, Spain) Paola Dal Cin (Boston, Massachusetts) Jean-Loup Huret (Poitiers, France) Hematology Section Editor Ana E. Rodríguez, Teresa Gonzalez (Salamanca, Spain) Bone Tumors Section Editor Judith Bovee (Leiden, Netherlands) Head and Neck Tumors Section Editor Cécile Badoual (Paris, France) Urinary Tumors Section Editor Paola Dal Cin (Boston, Massachusetts) Pediatric Tumors Section Editor Frederic G. Barr (Bethesda, Maryland) Cancer Prone Diseases Section Editor Gaia Roversi (Milano, Italy) Cell Cycle Section Editor João Agostinho Machado-Neto (São Paulo, Brazil) DNA Repair Section Editor Godefridus Peters (Amsterdam, Netherlands) Epigenetics Section Editor Roberto Piergentili (Rome, Italy) Hematopoeisis Section Editor Olga Weinberg (Boston, Massachusetts) Hormones and Growth factors Section Editor Gajanan V. Sherbet (Newcastle upon Tyne, UK) Mitosis Section Editor Patrizia Lavia (Rome, Italy) Oxidative stress Section Editor Thierry Soussi (Stockholm, Sweden/Paris, France) WNT pathway Section Editor Alessandro Beghini (Milano, Italy) B-cell activation Section Editors Anette Gjörloff Wingren, Barnabas Nyesiga (Malmö, Sweden) Board Members Sreeparna Banerjee Department of Biological Sciences, Middle East Technical University, Ankara, Turkey; [email protected] Alessandro Beghini Department of Health Sciences, University of Milan, Italy; [email protected] Judith Bovée 2300 RC Leiden, The Netherlands; [email protected] Antonio Cuneo Dipartimento di ScienzeMediche, Sezione di Ematologia e Reumatologia Via Aldo Moro 8, 44124 - Ferrara, Italy; [email protected] Paola Dal Cin Department of Pathology, Brigham, Women's Hospital, 75 Francis Street, Boston, MA 02115, USA; [email protected] IRBA, Departement Effets Biologiques des Rayonnements, Laboratoire de Dosimetrie Biologique des Irradiations, Dewoitine C212, 91223 François Desangles Bretigny-sur-Orge, France; [email protected] Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, Roosevelt Dr. Oxford, OX37BN, UK Enric Domingo [email protected] Ayse Elif Erson- Department of Biological Sciences, Middle East Technical University, Ankara, Turkey; [email protected] Bensan Ad Geurts van Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, 6500 HB Nijmegen, Kessel The Netherlands; [email protected] Department of Pediatrics and Adolescent Medicine, St. Anna Children's Hospital, Medical University Vienna, Children's Cancer Research Oskar A. Haas Institute Vienna, Vienna, Austria. [email protected] Anne Hagemeijer Center for Human Genetics, University Hospital Leuven and KU Leuven, Leuven, Belgium; [email protected] Department of Pathology, The Ohio State University, 129 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210, USA; Nyla Heerema [email protected] Sakari Knuutila Hartmann Institute and HUSLab, University of Helsinki, Department of Pathology, Helsinki, Finland; [email protected] Lidia Larizza Lab Centro di Ricerche e TecnologieBiomedicheIRCCS-IstitutoAuxologico Italiano Milano, Italy; l.larizza@auxologico Department of Human, Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms, Cell Cultures, Braunschweig, Roderick Mc Leod Germany; [email protected] Cristina Mecucci Hematology University of Perugia, University Hospital S.Mariadella Misericordia, Perugia, Italy; [email protected] Department of Clinical Genetics, University and Regional Laboratories, Lund University, SE-221 85 Lund, Sweden; Fredrik Mertens [email protected] Konstantin Miller Institute of Human Genetics, Hannover Medical School, 30623 Hannover, Germany; [email protected] Department of Clinical Genetics, University and Regional Laboratories, Lund University, SE-221 85 Lund, Sweden; Felix Mitelman [email protected] Hossain Mossafa Laboratoire CERBA, 95066 Cergy-Pontoise cedex 9, France; [email protected] Department of Human, Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms, Cell Cultures, Braunschweig, Stefan Nagel Germany; [email protected] Florence Pedeutour Laboratory of Solid Tumors Genetics, Nice University Hospital, CNRSUMR 7284/INSERMU1081, France; [email protected] Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 250, Memphis, Tennessee 38105- Susana Raimondi 3678, USA; [email protected] Clelia Tiziana Department of Biology, University of Bari, Bari, Italy; [email protected] Storlazzi Sabine Strehl CCRI, Children's Cancer Research Institute, St. Anna Kinderkrebsforschunge.V., Vienna, Austria; [email protected] Nancy Uhrhammer Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France; [email protected] Dan L. Van Dyke Mayo Clinic Cytogenetics Laboratory, 200 First St SW, Rochester MN 55905, USA; [email protected] Roberta Vanni Universita di Cagliari, Dipartimento di ScienzeBiomediche(DiSB), CittadellaUniversitaria, 09042 Monserrato (CA) - Italy; [email protected] Atlas Genet Cytogenet Oncol Haematol. 2020; 24(6) Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Volume 24, Number 6, June 2020 Table of contents Gene Section HTR4 (5-hydroxytryptamine receptor 4) 224 Rafig Gurbanov, Hazel Karadag BIRC7 (baculoviral IAP repeat containing 7) 234 Dhiego Botelho Rigato, Paola Cristina Branco , Catarina Sofia Mateus Reis Silva, João Agostinho Machado-Neto, Letícia Veras Costa-Lotufo, Paula Christine Jimenez Leukaemia Section del(5q) in acute lymphoblastic leukemia (ALL) 248 Adriana Zamecnikova, Soad al Bahar t(14;19)(q11;q13) TRA/NECTIN2 253 Jean Loup Huret t(14;19)(q32;q13) IGH/Various Partners 255 Jean Loup Huret Case Report Section B-cell acute lymphoblastic leukemia with t(2;9)(p11;p13) involving the immunoglobulin kappa locus (IGK) and PAX-5 259 Robert K McCall, Paula
Recommended publications
  • Mechanical Forces Induce an Asthma Gene Signature in Healthy Airway Epithelial Cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T
    www.nature.com/scientificreports OPEN Mechanical forces induce an asthma gene signature in healthy airway epithelial cells Ayşe Kılıç1,10, Asher Ameli1,2,10, Jin-Ah Park3,10, Alvin T. Kho4, Kelan Tantisira1, Marc Santolini 1,5, Feixiong Cheng6,7,8, Jennifer A. Mitchel3, Maureen McGill3, Michael J. O’Sullivan3, Margherita De Marzio1,3, Amitabh Sharma1, Scott H. Randell9, Jefrey M. Drazen3, Jefrey J. Fredberg3 & Scott T. Weiss1,3* Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufcient to induce infammatory, late repair, and fbrotic pathways. Remarkably, this molecular profle of non-asthmatic cells after compression recapitulated the profle of asthmatic cells before compression. Together, these results show that even in the absence of any infammatory stimulus, mechanical compression alone is sufcient to induce an asthma-like molecular signature. Bronchial epithelial cells (BECs) form a physical barrier that protects pulmonary airways from inhaled irritants and invading pathogens1,2. Moreover, environmental stimuli such as allergens, pollutants and viruses can induce constriction of the airways3 and thereby expose the bronchial epithelium to compressive mechanical stress. In BECs, this compressive stress induces structural, biophysical, as well as molecular changes4,5, that interact with nearby mesenchyme6 to cause epithelial layer unjamming1, shedding of soluble factors, production of matrix proteins, and activation matrix modifying enzymes, which then act to coordinate infammatory and remodeling processes4,7–10.
    [Show full text]
  • Genome-Wide Copy Number Variant Analysis For
    An et al. BMC Medical Genomics (2016) 9:2 DOI 10.1186/s12920-015-0163-4 RESEARCH ARTICLE Open Access Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population Yu An1,2,4, Wenyuan Duan3, Guoying Huang4, Xiaoli Chen5,LiLi5, Chenxia Nie6, Jia Hou4, Yonghao Gui4, Yiming Wu1, Feng Zhang2, Yiping Shen7, Bailin Wu1,4,7* and Hongyan Wang8* Abstract Background: Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. Methods: We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Results: Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD.
    [Show full text]
  • Characterization of Chronic Lymphocytic Leukemia by Acgh/MLPA
    UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS DEPARTAMENTO DE BIOLOGIA VEGETAL Characterization of Chronic Lymphocytic Leukemia by aCGH/MLPA Diana Cristina Antunes Candeias Adão Mestrado em Biologia Molecular e Genética Dissertação orientada por: Professora Doutora Isabel Maria Marques Carreira Professor Doutor Manuel Carmo Gomes 2018 Agradecimentos Começo por agradecer ao CIMAGO e à ACIMAGO por todo o apoio prestado no âmbito do desenvolvimento deste trabalho, tanto a nível logístico como financeiro. Agradeço também ao Laboratório de Citogenética e Genómica e ao Laboratório de Oncologia e Hematologia da FMUC, pelo fornecimento dos equipamentos e bens necessários à realização deste projeto. À Professora Doutora Isabel Marques Carreira, muito obrigada por me permitir desenvolver o meu projeto de tese de mestrado no Laboratório de Citogenética e Genómica da FMUC e por orientar este trabalho. Agradeço tudo o que me ensinou, o apoio e, acima de tudo, o exemplo que é como profissional na área da Genética Humana, que em muito contribuiu para o meu desenvolvimento e crescimento a nível académico e profissional. Ao Professor Doutor Manuel Carmo Gomes, pela sempre célere e incondicional orientação durante este ano. Mostrou-se sempre disponível para responder às minhas dúvidas e questões, e por isso demonstro o meu agradecimento. À Professora Doutora Ana Bela Sarmento Ribeiro, pela proposta que me apresentou para trabalhar no âmbito da Leucemia Linfocítica Crónica, pelo apoio nas correções necessárias, e pela possibilidade que me deu de realizar alguns passos do meu trabalho nas instalações do Laboratório de Oncologia e Hematologia da FMUC. Ao Miguel Pires, por todos os ensinamentos ao nível do trabalho laboratorial, pela enorme disponibilidade e apoio na realização desta tese, bem como pela amizade e conselhos que me deu.
    [Show full text]
  • Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders
    177 Arch Neuropsychitry 2020;57:177−191 RESEARCH ARTICLE https://doi.org/10.29399/npa.24890 Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders Hakan GÜRKAN1 , Emine İkbal ATLI1 , Engin ATLI1 , Leyla BOZATLI2 , Mengühan ARAZ ALTAY2 , Sinem YALÇINTEPE1 , Yasemin ÖZEN1 , Damla EKER1 , Çisem AKURUT1 , Selma DEMİR1 , Işık GÖRKER2 1Faculty of Medicine, Department of Medical Genetics, Edirne, Trakya University, Edirne, Turkey 2Faculty of Medicine, Department of Child and Adolescent Psychiatry, Trakya University, Edirne, Turkey ABSTRACT Introduction: Aneuploids, copy number variations (CNVs), and single in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown nucleotide variants in specific genes are the main genetic causes of significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients developmental delay (DD) and intellectual disability disorder (IDD). were reported. In 6 patients, one or more pathogenic CNVs were These genetic changes can be detected using chromosome analysis, determined. Therefore, the diagnostic efficiency of CMA was found to chromosomal microarray (CMA), and next-generation DNA sequencing be 31.7% (39/123). techniques. Therefore; In this study, we aimed to investigate the Conclusion: Today, genetic analysis is still not part of the routine in the importance of CMA in determining the genomic etiology of unexplained evaluation of IDD patients who present to psychiatry clinics. A genetic DD and IDD in 123 patients. diagnosis from CMA can eliminate genetic question marks and thus Method: For 123 patients, chromosome analysis, DNA fragment analysis alter the clinical management of patients. Approximately one-third and microarray were performed. Conventional G-band karyotype of the positive CMA findings are clinically intervenable.
    [Show full text]
  • Patient-Derived Organoids and Orthotopic Xenografts of Primary and Recurrent Gliomas Represent Relevant Patient Avatars for Precision Oncology
    Henry Ford Health System Henry Ford Health System Scholarly Commons Neurosurgery Articles Neurosurgery 12-1-2020 Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology Anna Golebiewska Ann-Christin Hau Anaïs Oudin Daniel Stieber Yahaya A. Yabo See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/neurosurgery_articles Authors Anna Golebiewska, Ann-Christin Hau, Anaïs Oudin, Daniel Stieber, Yahaya A. Yabo, Virginie Baus, Vanessa Barthelemy, Eliane Klein, Sébastien Bougnaud, Olivier Keunen, May Wantz, Alessandro Michelucci, Virginie Neirinckx, Arnaud Muller, Tony Kaoma, Petr V. Nazarov, Francisco Azuaje, Alfonso De Falco, Ben Flies, Lorraine Richart, Suresh Poovathingal, Thais Arns, Kamil Grzyb, Andreas Mock, Christel Herold-Mende, Anne Steino, Dennis Brown, Patrick May, Hrvoje Miletic, Tathiane M. Malta, Houtan Noushmehr, Yong-Jun Kwon, Winnie Jahn, Barbara Klink, Georgette Tanner, Lucy F. Stead, Michel Mittelbronn, Alexander Skupin, Frank Hertel, Rolf Bjerkvig, and Simone P. Niclou Acta Neuropathologica (2020) 140:919–949 https://doi.org/10.1007/s00401-020-02226-7 ORIGINAL PAPER Patient‑derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology Anna Golebiewska1 · Ann‑Christin Hau1 · Anaïs Oudin1 · Daniel Stieber1,2 · Yahaya A. Yabo1,3 · Virginie Baus1 · Vanessa Barthelemy1 · Eliane Klein1 · Sébastien Bougnaud1 · Olivier Keunen1,4 · May Wantz1 · Alessandro Michelucci1,5,6 · Virginie Neirinckx1 · Arnaud Muller4 · Tony Kaoma4 · Petr V. Nazarov4 · Francisco Azuaje4 · Alfonso De Falco2,3,7 · Ben Flies2 · Lorraine Richart3,7,8,9 · Suresh Poovathingal6 · Thais Arns6 · Kamil Grzyb6 · Andreas Mock10,11,12,13 · Christel Herold‑Mende10 · Anne Steino14,15 · Dennis Brown14,15 · Patrick May6 · Hrvoje Miletic16,17 · Tathiane M.
    [Show full text]
  • Genetic Analysis of 400 Patients Refines Understanding And
    BASIC RESEARCH www.jasn.org Genetic Analysis of 400 Patients Refines Understanding and Implicates a New Gene in Atypical Hemolytic Uremic Syndrome Fengxiao Bu,1,2 Yuzhou Zhang,2 Kai Wang,3 Nicolo Ghiringhelli Borsa,2 Michael B. Jones,2 Amanda O. Taylor,2 Erika Takanami,2 Nicole C. Meyer,2 Kathy Frees,2 Christie P. Thomas,4 Carla Nester,2,4,5 and Richard J.H. Smith2,4,5 1Medical Genetics Center, Southwest Hospital, Chongqing, China; and 2Molecular Otolaryngology and Renal Research Laboratories, 3College of Public Health, 4Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, and 5Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa ABSTRACT Background Genetic variation in complement genes is a predisposing factor for atypical hemolytic uremic syndrome (aHUS), a life-threatening thrombotic microangiopathy, however interpreting the effects of genetic variants is challenging and often ambiguous. Methods We analyzed 93 complement and coagulation genes in 400 patients with aHUS, using as controls 600 healthy individuals from Iowa and 63,345 non-Finnish European individuals from the Genome Aggre- gation Database. After adjusting for population stratification, we then applied the Fisher exact, modified Poisson exact, and optimal unified sequence kernel association tests to assess gene-based variant burden. We also applied a sliding-window analysis to define the frequency range over which variant burden was significant. Results We found that patients with aHUS are enriched for ultrarare coding variants in the CFH, C3, CD46, CFI, DGKE,andVTN genes. The majority of the significance is contributed by variants with a minor allele frequency of ,0.1%.
    [Show full text]
  • Structural Variant Selection for High-Altitude Adaptation Using Single-Molecule 2 Long-Read Sequencing
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.27.436702; this version posted March 27, 2021. 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 Structural variant selection for high-altitude adaptation using single-molecule 2 long-read sequencing 3 Jinlong Shi1,2,4*, Zhilong Jia1,2,3*, Xiaojing Zhao2*, Jinxiu Sun4*, Fan Liang5*, Minsung Park5*, Chenghui Zhao1, 4 Xiaoreng Wang2, Qi Chen4, Xinyu Song2,3, Kang Yu1, Qian Jia2, Depeng Wang5, Yuhui Xiao5, Yinzhe Liu5, Shijing 5 Wu1, Qin Zhong2, Jue Wu2, Saijia Cui2, Xiaochen Bo6, Zhenzhou Wu7, Manolis Kellis8,9, Kunlun He1,2# 6 1. Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information 7 Technology, Chinese PLA General Hospital, Beijing, China. 8 2. Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Chinese PLA General Hospital, Beijing, 9 China. 10 3. Research Center of Medical Artificial Intelligence, Chinese PLA General Hospital, Beijing, China. 11 4. Research Center of Medical Big Data, Chinese PLA General Hospital, Beijing, China. 12 5. GrandOmics Biosciences Inc, Beijing, China. 13 6. Beijing Institute of Radiation Medicine, Beijing, China. 14 7. BioMind Inc, Beijing, China. 15 8. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, 16 MA, USA. 17 9. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 18 *These authors contributed equally to this work. 19 #Corresponding author: [email protected] 20 21 Abstract: (150 words) 22 Structural variants (SVs) can be important drivers of human adaptation with strong effects, but previous studies 23 have focused primarily on common variants with weak effects.
    [Show full text]
  • The Pdx1 Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet Β Cell
    Page 1 of 125 Diabetes The Pdx1 bound Swi/Snf chromatin remodeling complex regulates pancreatic progenitor cell proliferation and mature islet β cell function Jason M. Spaeth1,2, Jin-Hua Liu1, Daniel Peters3, Min Guo1, Anna B. Osipovich1, Fardin Mohammadi3, Nilotpal Roy4, Anil Bhushan4, Mark A. Magnuson1, Matthias Hebrok4, Christopher V. E. Wright3, Roland Stein1,5 1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 2 Present address: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 3 Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 4 Diabetes Center, Department of Medicine, UCSF, San Francisco, California 5 Corresponding author: [email protected]; (615)322-7026 1 Diabetes Publish Ahead of Print, published online June 14, 2019 Diabetes Page 2 of 125 Abstract Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β cell function are controlled by the ATP-dependent Swi/Snf chromatin remodeling coregulatory complex that physically associates with Pdx1, a diabetes- linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, was necessary to compromise adult islet β cell activity, which included whole animal glucose intolerance, hyperglycemia and impaired insulin secretion. Notably, lineage-tracing analysis revealed Swi/Snf-deficient β cells lost the ability to produce the mRNAs for insulin and other key metabolic genes without effecting the expression of many essential islet-enriched transcription factors.
    [Show full text]
  • Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential
    RESEARCH ARTICLE Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential Blair R. McCallie1,3*, Jason C. Parks1,3, Alyssa L. Patton1, Darren K. Griffin3, William B. Schoolcraft2, Mandy G. Katz-Jaffe1,2 1 National Foundation for Fertility Research, Lone Tree, Colorado, 80124, United States of America, 2 Colorado Center for Reproductive Medicine, Lone Tree, Colorado, 80124, United States of America, 3 School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom * [email protected] Abstract a11111 DNA methylation is a key epigenetic mechanism responsible for gene regulation, chromatin remodeling, and genome stability, playing a fundamental role during embryonic develop- ment. The aim of this study was to determine if these epigenetic marks are associated with chromosomal aneuploidy in human blastocysts. Surplus, cryopreserved blastocysts that were donated to research with IRB consent were chosen with varying chromosomal aneu- OPEN ACCESS ploidies and respective implantation potential: monosomies and trisomies 7, 11, 15, 21, and Citation: McCallie BR, Parks JC, Patton AL, Griffin 22. DNA methylation analysis was performed using the Illumina Infinium HumanMethyla- DK, Schoolcraft WB, Katz-Jaffe MG (2016) tion450 BeadChip (~485,000 CpG sites). The methylation profiles of these human blasto- Hypomethylation and Genetic Instability in Monosomy cysts were found to be similar across all samples, independent of chromosome constitution; Blastocysts May Contribute to Decreased Implantation Potential. PLoS ONE 11(7): e0159507. however, more detailed examination identified significant hypomethylation in the chromo- doi:10.1371/journal.pone.0159507 some involved in the monosomy. Real-time PCR was also performed to determine if down- Editor: Christine Wrenzycki, Justus-Liebig- stream messenger RNA (mRNA) was affected for genes on the monosomy chromosome.
    [Show full text]
  • The 2Q37-Deletion Syndrome: an Update of the Clinical Spectrum Including Overweight, Brachydactyly and Behavioural Features in 14 New Patients
    European Journal of Human Genetics (2013) 21, 602–612 & 2013 Macmillan Publishers Limited All rights reserved 1018-4813/13 www.nature.com/ejhg ARTICLE The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients Camille Leroy1,2,3, Emilie Landais1,2,4, Sylvain Briault5, Albert David6, Olivier Tassy7, Nicolas Gruchy8, Bruno Delobel9, Marie-Jose´ Gre´goire10, Bruno Leheup3,11, Laurence Taine12, Didier Lacombe12, Marie-Ange Delrue12, Annick Toutain13, Agathe Paubel13, Francine Mugneret14, Christel Thauvin-Robinet3,15, Ste´phanie Arpin13, Cedric Le Caignec6, Philippe Jonveaux3,10, Myle`ne Beri10, Nathalie Leporrier8, Jacques Motte16, Caroline Fiquet17,18, Olivier Brichet16, Monique Mozelle-Nivoix1,3, Pascal Sabouraud16, Nathalie Golovkine19, Nathalie Bednarek20, Dominique Gaillard1,2,3 and Martine Doco-Fenzy*,1,2,3,18 The 2q37 locus is one of the most commonly deleted subtelomeric regions. Such a deletion has been identified in 4100 patients by telomeric fluorescence in situ hybridization (FISH) analysis and, less frequently, by array-based comparative genomic hybridization (array-CGH). A recognizable ‘2q37-deletion syndrome’ or Albright’s hereditary osteodystrophy-like syndrome has been previously described. To better map the deletion and further refine this deletional syndrome, we formed a collaboration with the Association of French Language Cytogeneticists to collect 14 new intellectually deficient patients with a distal or interstitial 2q37 deletion characterized by FISH and array-CGH. Patients exhibited facial dysmorphism (13/14) and brachydactyly (10/14), associated with behavioural problems, autism or autism spectrum disorders of varying severity and overweight or obesity. The deletions in these 14 new patients measured from 2.6 to 8.8 Mb.
    [Show full text]
  • (Adrenomedullin 2) Suppresses the Growth of Glioblastoma And
    Published OnlineFirst December 9, 2020; DOI: 10.1158/1535-7163.MCT-20-0619 MOLECULAR CANCER THERAPEUTICS | SMALL MOLECULE THERAPEUTICS Inhibition of Intermedin (Adrenomedullin 2) Suppresses the Growth of Glioblastoma and Increases the Antitumor Activity of Temozolomide A C Luping Huang1, Denian Wang2, Zhongxue Feng1, Huan Zhao1, Fei Xiao3, Yong’gang Wei4, Heng Zhang5, Hongyu Li6, Lingmiao Kong1, Min Li1, Fei Liu4, Haili Zhang4, and Wei Zhang1 ABSTRACT ◥ Glioblastoma multiforme (GBM; grade IV glioma) is the by promoting filopodia formation, which is dependent on most malignant type of primary brain tumor and is character- ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also ized by rapid proliferation and invasive growth. Intermedin promoted GBM cell proliferation. In addition, IMD enhanced (IMD)isanendogenouspeptidebelonging to the calcitonin mitochondrial function and hypoxia-induced responses in gene-related peptide family and has been reported to play an GBM cells. Treatment with anti-IMD monoclonal antibodies important role in cell survival and invasiveness in several not only inhibited tumor growth in both ectopic and orthotopic types of cancers. In this study, we found that the expression models of GBM but also significantly enhanced the antitumor level of IMD was positively related to the malignancy grade of activity of temozolomide. Our study may provide novel insights gliomas. The highest expression of IMD was found in GBM, into the mechanism of GBM cell invasion and proliferation and indicating that IMD may play an important role in glioma provide an effective strategy to improve the therapeutic effect of malignancy. IMD increased the invasive ability of glioma cells GBM treatments. Introduction radiotherapy, and chemotherapy, but the outcomes are often poor.
    [Show full text]
  • A Role for Bivalent Genes in Epithelial to Mesenchymal Transition
    A Role for Bivalent Genes in Epithelial to Mesenchymal Transition Francisco Sadras (B.Sc, Hns) Thesis submitted for the degree of Doctor of Philosophy Faculty of Sciences School of Biological Sciences Department of Molecular & Cellular Biology Affiliated with Gene Regulation Laboratory Centre for Cancer Biology IMVS, SA Pathology April 2017 Contents Abstract ...................................................................................................................................... 5 Declaration ................................................................................................................................. 8 Preface........................................................................................................................................ 9 Acknowledgments.................................................................................................................... 10 List of Figures .......................................................................................................................... 12 List of Tables ........................................................................................................................... 13 Abbreviations ........................................................................................................................... 14 Chapter 1 Introduction ........................................................................................................ 16 1.1 Preamble ...................................................................................................................
    [Show full text]