6533b870fe1ef96bd12cf2f2
RESEARCH PRODUCT
Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders
Michael A. LevyRaissa RelatorHaley McconkeyErinija PranckevicieneJennifer KerkhofMouna Barat‐houariSara BargiacchiElisa BiaminoMaría Palomares BraloGerarda CappuccioAndrea CiolfiAngus ClarkeBarbara R. DupontMariet W. EltingLaurence FaivreTimothy FeeMarco FerilliRobin S. FletcherFlorian CherickAidin ForoutanMichael J. FriezCristina GervasiniSadegheh HaghshenasBenjamin A. HiltonZandra JenkinsSimranpreet KaurSuzanne LewisRaymond J. LouieSilvia MaitzDonatella MilaniAngela T. MorganRenske OegemaElsebet ØStergaardNathalie R. PallaresMaria PiccioneAstrid S. PlompCathryn PoultonJack ReillyRocio RiusStephen RobertsonKathleen RooneyJustine RousseauGijs W. E. SantenFernando Santos‐simarroJosephine SchijnsGabriella Maria SqueoMiya St JohnChristel Thauvin‐robinetGiovanna TraficantePleuntje J. Van Der SluijsSamantha A. VerganoNiels VosKellie K. WaldenDimitar AzmanovTugce B. BalciSiddharth BankaJozef GeczPeter HennemanJennifer A. LeeMarcel M. A. M. MannensTony RoscioliVictoria SiuDavid J. AmorGareth BaynamEric G. BendKym BoycottNicola Brunetti‐pierriPhilippe M. CampeauDominique CampionJohn ChristodoulouDavid DymentNatacha EsberJill A. FahrnerMark D. FlemingDavid GenevieveDelphine HeronThomas HussonKristin D. KernohanAlisdair McneillLeonie A. MenkeGiuseppe MerlaPaolo PronteraCheryl Rockman‐greenbergCharles SchwartzSteven A. SkinnerRoger E. StevensonMarie VincentAntonio VitobelloMarco TartagliaMarielle AldersMatthew L. TedderBekim Sadikovicsubject
DNA methylationclinical diagnostics.SyndromeDNA methylation clinical diagnostics episignatures neurodevelopmental syndromesneurodevelopmental syndromesEpigenesis GeneticNeurodevelopmental DisordersGeneticsHumansCpG IslandsDNA IntergenicepisignaturesEpisignatureGenetics (clinical)clinical diagnosticsdescription
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 amongst 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. This article is protected by copyright. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-11-01 |