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Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases.
Marcogliese, Paul C; Deal, Samantha L; Andrews, Jonathan; Harnish, J Michael; Bhavana, V Hemanjani; Graves, Hillary K; Jangam, Sharayu; Luo, Xi; Liu, Ning; Bei, Danqing; Chao, Yu-Hsin; Hull, Brooke; Lee, Pei-Tseng; Pan, Hongling; Bhadane, Pradnya; Huang, Mei-Chu; Longley, Colleen M; Chao, Hsiao-Tuan; Chung, Hyung-Lok; Haelterman, Nele A; Kanca, Oguz; Manivannan, Sathiya N; Rossetti, Linda Z; German, Ryan J; Gerard, Amanda; Schwaibold, Eva Maria Christina; Fehr, Sarah; Guerrini, Renzo; Vetro, Annalisa; England, Eleina; Murali, Chaya N; Barakat, Tahsin Stefan; van Dooren, Marieke F; Wilke, Martina; van Slegtenhorst, Marjon; Lesca, Gaetan; Sabatier, Isabelle; Chatron, Nicolas; Brownstein, Catherine A; Madden, Jill A; Agrawal, Pankaj B; Keren, Boris; Courtin, Thomas; Perrin, Laurence; Brugger, Melanie; Roser, Timo; Leiz, Steffen; Mau-Them, Frederic Tran; Delanne, Julian; Sukarova-Angelovska, Elena.
Afiliação
  • Marcogliese PC; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Deal SL; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Program in Developmental Biology, BCM, Houston, TX 77030, USA.
  • Andrews J; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Harnish JM; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Bhavana VH; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Graves HK; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Jangam S; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Luo X; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Department of Pediatrics, Division of Hematology/Oncology, BCM, Houston, TX 77030, USA.
  • Liu N; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Baylor Genetics Laboratories, Houston, TX 77021, USA.
  • Bei D; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Chao YH; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Hull B; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Lee PT; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Pan H; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Bhadane P; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Huang MC; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Longley CM; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Program in Developmental Biology, BCM, Houston, TX 77030, USA.
  • Chao HT; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Department of Pediatrics, Division of Neurology and Developmental Neuroscience, BCM, Hous
  • Chung HL; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA; Howard Hughes Medical Institute, Houston, TX 77030, USA.
  • Haelterman NA; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Kanca O; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Manivannan SN; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Rossetti LZ; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA.
  • German RJ; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital (TCH), Houston, TX 77030, USA.
  • Gerard A; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; TCH, Houston, TX 77030, USA.
  • Schwaibold EMC; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
  • Fehr S; Praxis für Humangenetik Tübingen, Tübingen, Germany.
  • Guerrini R; Neuroscience Department, Children's Hospital Meyer-University of Florence, Florence, Italy.
  • Vetro A; Neuroscience Department, Children's Hospital Meyer-University of Florence, Florence, Italy.
  • England E; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Murali CN; Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; TCH, Houston, TX 77030, USA.
  • Barakat TS; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
  • van Dooren MF; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
  • Wilke M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
  • van Slegtenhorst M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
  • Lesca G; Department of Medical Genetics, Lyon University Hospital, Université Claude Bernard Lyon 1, Lyon, France; Institut NeuroMyoGène, CNRS UMR 5310 - INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France.
  • Sabatier I; Department of Pediatric Neurology, Lyon University Hospitals, Lyon, France.
  • Chatron N; Department of Medical Genetics, Lyon University Hospital, Université Claude Bernard Lyon 1, Lyon, France; Institut NeuroMyoGène, CNRS UMR 5310 - INSERM U1217, Université Claude Bernard Lyon 1, Lyon, France.
  • Brownstein CA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Madden JA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA.
  • Agrawal PB; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Division of Newborn Medicine, Boston Childr
  • Keren B; Genetic Department, Pitié-Salpêtrière Hospital, APHP.Sorbonne Université, Paris 75013, France.
  • Courtin T; Genetic Department, Pitié-Salpêtrière Hospital, APHP.Sorbonne Université, Paris 75013, France.
  • Perrin L; Genetic Department, Robert Debré Hospital, APHP.Nord-Université de Paris, Paris 75019, France.
  • Brugger M; Institute of Human Genetics, Technical University Munich, Munich, Germany.
  • Roser T; Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Lindwurmstraße 4, 80337 Munich, Germany.
  • Leiz S; Department of Pediatrics and Adolescent Medicine, Hospital Dritter Orden, Munich, Germany.
  • Mau-Them FT; INSERM U1231, LNC UMR1231 GAD, Burgundy University, 21000 Dijon, France; Laboratoire de Génétique, Innovation en Diagnostic Génomique des Maladies Rares UF6254, Plateau Technique de Biologie, CHU Dijon, 14 Rue Paul Gaffarel, BP 77908, 21079 Dijon, France.
  • Delanne J; INSERM U1231, LNC UMR1231 GAD, Burgundy University, 21000 Dijon, France.
  • Sukarova-Angelovska E; Department of Endocrinology and Genetics, University Clinic for Children's Diseases, Medical Faculty, University Sv. Kiril i Metodij, Skopje, Republic of Macedonia.
Cell Rep ; 38(11): 110517, 2022 03 15.
Article em En | MEDLINE | ID: mdl-35294868
ABSTRACT
Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through "humanization" rescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Receptores de Glicina / Drosophila / Transtornos do Neurodesenvolvimento / Transtorno do Espectro Autista Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Receptores de Glicina / Drosophila / Transtornos do Neurodesenvolvimento / Transtorno do Espectro Autista Idioma: En Ano de publicação: 2022 Tipo de documento: Article