Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders.

CpG Islands / genetics DNA Methylation / genetics DNA, Intergenic Epigenesis, Genetic Humans Neurodevelopmental Disorders / diagnosis Syndrome
DNA methylation clinical diagnostics episignatures neurodevelopmental syndromes

Journal

Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429

Informations de publication

Date de publication:
11 2022
Historique:
revised: 30 06 2022
received: 06 12 2021
accepted: 27 07 2022
pubmed: 30 7 2022
medline: 14 10 2022
entrez: 29 7 2022
Statut: ppublish

Résumé

An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.

Identifiants

DOI: 10.1002/humu.24446 PMID: 35904121
pubmed: 35904121
doi: 10.1002/humu.24446
doi:

Substances chimiques

DNA, Intergenic 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1609-1628

Subventions

Organisme : NICHD NIH HHS
ID : K08 HD086250
Pays : United States

Informations de copyright

© 2022 Wiley Periodicals LLC.

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Auteurs

Michael A Levy (MA)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.

Raissa Relator (R)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.

Haley McConkey (H)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.

Erinija Pranckeviciene (E)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.

Jennifer Kerkhof (J)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.

Mouna Barat-Houari (M)

Autoinflammatory and Rare Diseases Unit, Medical Genetic Department for Rare Diseases and Personalized Medicine, CHU Montpellier, Montpellier, France.

Sara Bargiacchi (S)

Medical Genetics Unit, "A. Meyer" Children Hospital of Florence, Florence, Italy.

Elisa Biamino (E)

Department of Pediatrics, University of Turin, Turin, Italy.

María Palomares Bralo (M)

Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.

Gerarda Cappuccio (G)

Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
ORCID: 0000-0003-3934-2342

Andrea Ciolfi (A)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Angus Clarke (A)

Cardiff University School of Medicine, Cardiff, UK.
ORCID: 0000-0002-1200-9286

Barbara R DuPont (BR)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Mariet W Elting (MW)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Laurence Faivre (L)

INSERM-Université de Bourgogne UMR1231 GAD, Génétique Des Anomalies du Développement, FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Centre de Référence Maladies Rares, Anomalies du Développement et Syndromes Malformatifs, Centre de Génétique, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.

Timothy Fee (T)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Marco Ferilli (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Robin S Fletcher (RS)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Florian Cherick (F)

Genetic Medical Center, CHU Clermont Ferrand, France.
Montpellier University, Reference Center for Rare Disease, Medical Genetic Department for Rare Disease and Personalize Medicine, CHU Montpellier, Montpellier, France.

Aidin Foroutan (A)

Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

Michael J Friez (MJ)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Cristina Gervasini (C)

Division of Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
ORCID: 0000-0002-1165-7935

Sadegheh Haghshenas (S)

Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

Benjamin A Hilton (BA)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Zandra Jenkins (Z)

Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
ORCID: 0000-0003-4628-9789

Simranpreet Kaur (S)

Brain and Mitochondrial Research Group, Murdoch Children s Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.

Suzanne Lewis (S)

BC Children's and Women's Hospital and Department of Medical Genetics, Faculty of Medicine, University of British Columbia.

Raymond J Louie (RJ)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Silvia Maitz (S)

Clinical Pediatric Genetics Unit, Pediatrics Clinics, MBBM Foundation, Hospital San Gerardo, Monza, Italy.

Donatella Milani (D)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Angela T Morgan (AT)

Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.

Renske Oegema (R)

Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Elsebet Østergaard (E)

Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Nathalie R Pallares (NR)

Autoinflammatory and Rare Diseases Unit, Medical Genetic Department for Rare Diseases and Personalized Medicine, CHU Montpellier, Montpellier, France.

Maria Piccione (M)

Medical Genetics Unit Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

Astrid S Plomp (AS)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Cathryn Poulton (C)

Undiagnosed Diseases Program, Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.

Jack Reilly (J)

Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

Rocio Rius (R)

Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
Department of Paediatrics, University of Melbourne, Melbourne, Australia.

Stephen Robertson (S)

Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
ORCID: 0000-0002-5181-7809

Kathleen Rooney (K)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

Justine Rousseau (J)

CHU Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.

Gijs W E Santen (GWE)

Department of Clinical Genetics, LUMC, Leiden, The Netherlands.
ORCID: 0000-0003-1959-3267

Fernando Santos-Simarro (F)

Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.

Josephine Schijns (J)

Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Gabriella M Squeo (GM)

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.

Miya St John (MS)

Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.

Christel Thauvin-Robinet (C)

INSERM-Université de Bourgogne UMR1231 GAD, Génétique Des Anomalies du Développement, FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Centre de Référence Maladies Rares, Anomalies du Développement et Syndromes Malformatifs, Centre de Génétique, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.
Unité Fonctionnelle d'Innovation Diagnostique des Maladies Rares, FHU-TRANSLAD, France Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon Bourgogne, CHU Dijon Bourgogne, Dijon, France.
Centre de Référence Déficiences Intellectuelles de Causes Rares, Hôpital D'Enfants, CHU Dijon Bourgogne, Dijon, France.

Giovanna Traficante (G)

Medical Genetics Unit, "A. Meyer" Children Hospital of Florence, Florence, Italy.

Pleuntje J van der Sluijs (PJ)

Department of Clinical Genetics, LUMC, Leiden, The Netherlands.

Samantha A Vergano (SA)

Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, Virginia, USA.
Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, USA.

Niels Vos (N)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Kellie K Walden (KK)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Dimitar Azmanov (D)

Department of Diagnostic Genomics, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Australia.

Tugce B Balci (TB)

Department of Pediatrics, Division of Medical Genetics, Western University, London, Ontario, Canada.
Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre and Children's Health Research Institute, London, Ontario, Canada.

Siddharth Banka (S)

Division of Evolution, Infection & Genomics, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, United Kingdom.

Jozef Gecz (J)

School of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, Australia.
South Australian Health and Medical Research Institute, Adelaide, Australia.
ORCID: 0000-0002-7884-6861

Peter Henneman (P)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Jennifer A Lee (JA)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Marcel M A M Mannens (MMAM)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Tony Roscioli (T)

Neuroscience Research Australia (NeuRA), Sydney, Australia.
Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.
New South Wales Health Pathology Randwick Genomics, Prince of Wales Hospital, Sydney, Australia.
Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, Australia.

Victoria Siu (V)

Department of Pediatrics, Division of Medical Genetics, Western University, London, Ontario, Canada.
Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre and Children's Health Research Institute, London, Ontario, Canada.

David J Amor (DJ)

Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.

Gareth Baynam (G)

Undiagnosed Diseases Program, Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Undiagnosed Diseases Program, Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Division of Paediatrics and Telethon Kids Institute, Faculty of Health and Medical Sciences, Perth, Australia.

Eric G Bend (EG)

PreventionGenetics, Marshfield, Wisconsin, USA.

Kym Boycott (K)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
ORCID: 0000-0003-4186-8052

Nicola Brunetti-Pierri (N)

Department of Translational Medicine, Federico II University of Naples, Naples, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
ORCID: 0000-0002-6895-8819

Philippe M Campeau (PM)

CHU Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada.
ORCID: 0000-0001-9713-7107

Dominique Campion (D)

INSERM U1245, Faculté de Médecine, Rouen, France.

John Christodoulou (J)

Brain and Mitochondrial Research Group, Murdoch Children s Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
ORCID: 0000-0002-8431-0641

David Dyment (D)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

Natacha Esber (N)

KAT6A Foundation, New York, New York, USA.

Jill A Fahrner (JA)

Departments of Genetic Medicine and Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.

Mark D Fleming (MD)

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
ORCID: 0000-0003-0948-4024

David Genevieve (D)

Montpellier University, Reference Center for Rare Disease, Medical Genetic Department for Rare Disease and Personalize Medicine, CHU Montpellier, Montpellier, France.

Delphine Heron (D)

AP-HP, Département de Génétique Médicale, Groupe Hospitalier Pitié Salpétrière, Paris, France.

Thomas Husson (T)

Department of Genetics and Reference Center for Developmental Disorders, Normandie Université, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.

Kristin D Kernohan (KD)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Canada.

Alisdair McNeill (A)

Department of Neuroscience, University of Sheffield, UK, and Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.

Leonie A Menke (LA)

Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Giuseppe Merla (G)

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.

Paolo Prontera (P)

Medical Genetics Unit, University of Perugia Hospital SM della Misericordia, Perugia, Italy.

Cheryl Rockman-Greenberg (C)

Department of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba and Program in Genetics and Metabolism, Shared Health MB, Winnipeg, Manitoba, Canada.

Charles Schwartz (C)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Steven A Skinner (SA)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Roger E Stevenson (RE)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Marie Vincent (M)

Service de génétique Médicale, CHU Nantes, Nantes, France.
Institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.

Antonio Vitobello (A)

INSERM-Université de Bourgogne UMR1231 GAD, Génétique Des Anomalies du Développement, FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Unité Fonctionnelle d'Innovation Diagnostique des Maladies Rares, FHU-TRANSLAD, France Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalier Universitaire Dijon Bourgogne, CHU Dijon Bourgogne, Dijon, France.

Marco Tartaglia (M)

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
ORCID: 0000-0001-7736-9672

Marielle Alders (M)

Amsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.

Matthew L Tedder (ML)

Greenwood Genetic Center, Greenwood, South Carolina, USA.

Bekim Sadikovic (B)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada.
Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
ORCID: 0000-0001-6363-0016

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Classifications MeSH

Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › Functional correlation of genome-wide DNA...
Recherchemedicale.com › Phénomènes génétiques › Méthylation de l'ADN › Functional correlation of genome-wide DNA...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › ADN intergénique › Functional correlation of genome-wide DNA...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Functional correlation of genome-wide DNA...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Functional correlation of genome-wide DNA...
Recherchemedicale.com › Troubles mentaux › Troubles du développement neurologique › Functional correlation of genome-wide DNA...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Maladie › Syndrome › Functional correlation of genome-wide DNA...