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

Michael Levy; Raissa Relator; Haley Mcconkey; Erinija Pranckeviciene; Jennifer Kerkhof; Mouna Barat-Houari; Sara Bargiacchi; Elisa Biamino; María Palomares Bralo; Gerarda Cappuccio; Andrea Ciolfi; Angus Clarke; Barbara Dupont; Mariet Elting; Laurence Faivre; Timothy Fee; Marco Ferilli; Robin Fletcher; Florian Cherick; Aidin Foroutan; Michael Friez; Cristina Gervasini; Sadegheh Haghshenas; Benjamin Hilton; Zandra Jenkins; Simranpreet Kaur; Suzanne Lewis; Raymond Louie; Silvia Maitz; Donatella Milani; Angela Morgan; Renske Oegema; Elsebet Østergaard; Nathalie Pallares; Maria Piccione; Astrid Plomp; Cathryn Poulton; Jack Reilly; Rocio Rius; Stephen Robertson; Kathleen Rooney; Justine Rousseau; Gijs Santen; Fernando Santos-Simarro; Josephine Schijns; Gabriella Squeo; Miya St John; Christel Thauvin-Robinet; Giovanna Traficante; Pleuntje van der Sluijs; Samantha Vergano; Niels Vos; Kellie Walden; Dimitar Azmanov; Tugce Balci; Siddharth Banka; Jozef Gecz; Peter Henneman; Jennifer Lee; Marcel Mannens; Tony Roscioli; Victoria Siu; David Amor; Gareth Baynam; Eric Bend; Kym Boycott; Nicola Brunetti-Pierri; Philippe Campeau; Dominique Campion; John Christodoulou; David Dyment; Natacha Esber; Jill Fahrner; Mark Fleming; David Genevieve; Delphine Heron; Thomas Husson; Kristin Kernohan; Alisdair Mcneill; Leonie Menke; Giuseppe Merla; Paolo Prontera; Cheryl Rockman-Greenberg; Charles Schwartz; Steven Skinner; Roger Stevenson; Marie Vincent; Antonio Vitobello; Marco Tartaglia; Marielle Alders; Matthew Tedder; Bekim Sadikovic

doi:10.1002/humu.24446

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

Journal article

Open access

Peer reviewed

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

Michael Levy, Raissa Relator, Haley Mcconkey, Erinija Pranckeviciene, Jennifer Kerkhof, Mouna Barat-Houari, Sara Bargiacchi, Elisa Biamino, María Palomares Bralo, Gerarda Cappuccio, …

Human Mutation, Vol.43(11), pp.1609-1628

21/08/2022

DOI: https://doi.org/10.1002/humu.24446

PMID: 35904121

Abstract

DNA methylation

clinical diagnostics

episignatures

neurodevelopmental syndromes

CpG Islands

DNA Methylation

DNA, Intergenic

Epigenesis, Genetic

Humans

Neurodevelopmental Disorders

Syndrome

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.

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Title: Functional correlation of genome‐wide DNA methylation profiles in genetic neurodevelopmental disorders
Creators - without role: Michael Levy - London Health Sciences Centre
Raissa Relator - London Health Sciences Centre
Haley Mcconkey - London Health Sciences Centre
Erinija Pranckeviciene - London Health Sciences Centre
Jennifer Kerkhof - London Health Sciences Centre
Mouna Barat-Houari - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Sara Bargiacchi - Meyer Children's Hospital
Elisa Biamino - University of Turin
María Palomares Bralo
Gerarda Cappuccio - University of Naples Federico II
Andrea Ciolfi - Bambino Gesù Children's Hospital
Angus Clarke - Cardiff University
Barbara Dupont - Greenwood Genetic Center
Mariet Elting - University of Amsterdam
Laurence Faivre - Université de Bourgogne
Timothy Fee - Greenwood Genetic Center
Marco Ferilli - Bambino Gesù Children's Hospital
Robin Fletcher - Greenwood Genetic Center
Florian Cherick - Centre Hospitalier Universitaire de Clermont-Ferrand
Aidin Foroutan - Western University
Michael Friez - Greenwood Genetic Center
Cristina Gervasini - University of Milan
Sadegheh Haghshenas - Western University
Benjamin Hilton - Greenwood Genetic Center
Zandra Jenkins - University of Otago
Simranpreet Kaur - Murdoch Children's Research Institute
Suzanne Lewis - University of British Columbia
Raymond Louie - Greenwood Genetic Center
Silvia Maitz - Azienda Ospedaliera San Gerardo
Donatella Milani - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Angela Morgan - University of Melbourne
Renske Oegema - University Medical Center Utrecht
Elsebet Østergaard - Copenhagen University Hospital
Nathalie Pallares
Maria Piccione - University of Palermo
Astrid Plomp - University of Amsterdam
Cathryn Poulton - King Edward Memorial Hospital
Jack Reilly - Western University
Rocio Rius - Murdoch Children's Research Institute
Stephen Robertson - University of Otago
Kathleen Rooney - London Health Sciences Centre
Justine Rousseau - Université de Montréal
Gijs Santen
Fernando Santos-Simarro - Hospital Universitario La Paz
Josephine Schijns - University of Amsterdam
Gabriella Squeo - University of Naples Federico II
Miya St John - Murdoch Children's Research Institute
Christel Thauvin-Robinet - Université de Bourgogne
Giovanna Traficante - Meyer Children's Hospital
Pleuntje van der Sluijs - Leiden University Medical Center
Samantha Vergano
Niels Vos - University of Amsterdam
Kellie Walden - Greenwood Genetic Center
Dimitar Azmanov - Pathwest Laboratory Medicine
Tugce Balci - Western University
Siddharth Banka - St Mary's Hospital
Jozef Gecz - University of Adelaide
Peter Henneman - Amsterdam University Medical Centers
Jennifer Lee - Greenwood Genetic Center
Marcel Mannens - University of Amsterdam
Tony Roscioli - Neuroscience Research Australia
Victoria Siu - Western University
David Amor - Murdoch Children's Research Institute
Gareth Baynam - King Edward Memorial Hospital
Eric Bend
Kym Boycott - University of Ottawa
Nicola Brunetti-Pierri - University of Naples Federico II
Philippe Campeau - Université de Montréal
Dominique Campion - Inserm
John Christodoulou - University of Melbourne
David Dyment - University of Ottawa
Natacha Esber
Jill Fahrner - Johns Hopkins University
Mark Fleming - Boston Children's Hospital
David Genevieve - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Delphine Heron - Assistance Publique – Hôpitaux de Paris
Thomas Husson - Inserm
Kristin Kernohan - Newborn Screening Ontario
Alisdair Mcneill - University of Sheffield
Leonie Menke - University of Amsterdam
Giuseppe Merla - Casa Sollievo della Sofferenza
Paolo Prontera - University of Perugia
Cheryl Rockman-Greenberg - University of Manitoba
Charles Schwartz - Greenwood Genetic Center
Steven Skinner - Greenwood Genetic Center
Roger Stevenson - Greenwood Genetic Center
Marie Vincent - Institut du Thorax
Antonio Vitobello - Université de Bourgogne
Marco Tartaglia - Istituti di Ricovero e Cura a Carattere Scientifico
Marielle Alders - Amsterdam University Medical Centers
Matthew Tedder - Greenwood Genetic Center
Bekim Sadikovic - Western University
Publication Details: Human Mutation, Vol.43(11), pp.1609-1628
Identifiers: 9940909509311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: hal-04521828