- Interactions between Folate, Other B Vitamins, DNA Methylation, and Neurodevelopmental Disorders

2010 ◽  
pp. 334-379
Keyword(s):  
Dna Methylation ◽  
Neurodevelopmental Disorders ◽  
B Vitamins

scholarly journals Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

2021 ◽  
Vol 108 (6) ◽  
pp. 1161-1163
Author(s):  
Erfan Aref-Eshghi ◽  
Jennifer Kerkhof ◽  
Victor P. Pedro ◽  
Groupe DI France ◽  
Mouna Barat-Houari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurodevelopmental Disorders

scholarly journals Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

2020 ◽  
Vol 106 (3) ◽  
pp. 356-370 ◽  
Author(s):  
Erfan Aref-Eshghi ◽  
Jennifer Kerkhof ◽  
Victor P. Pedro ◽  
Mouna Barat-Houari ◽  
Nathalie Ruiz-Pallares ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurodevelopmental Disorders

scholarly journals DNMT3A haploinsufficiency results in behavioral deficits and global epigenomic dysregulation shared across neurodevelopmental disorders

2020 ◽  
Author(s):  
Diana L. Christian ◽  
Dennis Y. Wu ◽  
Jenna R. Martin ◽  
J. Russell Moore ◽  
Yiran R. Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rett Syndrome ◽  
Neurodevelopmental Disorders ◽  
Dna Methyltransferase ◽  
Behavioral Alterations ◽  
Protein Activity ◽  
Neurodevelopmental Disease ◽  
Convergence Point ◽  
Nervous System Function ◽  
Syndrome Protein

SummaryMutations in DNA methyltransferase 3A (DNMT3A) have been detected in autism and related disorders, but how these mutations disrupt nervous system function is unknown. Here we define the effects of neurodevelopmental disease-associated DNMT3A mutations. We show that diverse mutations affect different aspects of protein activity yet lead to shared deficiencies in neuronal DNA methylation. Heterozygous DNMT3A knockout mice mimicking DNMT3A disruption in disease display growth and behavioral alterations consistent with human phenotypes. Strikingly, in these mice we detect global disruption of neuron-enriched non-CG DNA methylation, a binding site for the Rett syndrome protein MeCP2. Loss of this methylation leads to enhancer and gene dysregulation that overlaps with models of Rett syndrome and autism. These findings define effects of DNMT3A haploinsufficiency in the brain and uncover disruption of the non-CG methylation pathway as a convergence point across neurodevelopmental disorders.

scholarly journals Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome

2021 ◽  
Vol 22 (16) ◽  
pp. 8611
Author(s):  
Kathleen Rooney ◽  
Michael A. Levy ◽  
Sadegheh Haghshenas ◽  
Jennifer Kerkhof ◽  
Daniela Rogaia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Neurodevelopmental Disorders ◽  
Clinical Presentation ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Mild Intellectual Disability ◽  
Genomic Disorder ◽  
22Q11.2 Deletion ◽  
Chromatin Remodelers ◽  
Genome Wide

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.

scholarly journals DNA methylation variant, B-vitamins intake and longitudinal change in body mass index

2018 ◽  
Vol 43 (3) ◽  
pp. 468-474
Author(s):  
Xiang Li ◽  
Tiange Wang ◽  
Min Zhao ◽  
Tao Huang ◽  
Dianjianyi Sun ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
B Vitamins ◽  
Longitudinal Change

Plasma B vitamins and LINE-1 DNA methylation in leukocytes of patients with a history of colorectal adenomas

2012 ◽  
Vol 57 (4) ◽  
pp. 698-708 ◽  
Author(s):  
Audrey Y. Jung ◽  
Akke Botma ◽  
Carolien Lute ◽  
Henk J. Blom ◽  
Per M. Ueland ◽  
...  
Keyword(s):  
Dna Methylation ◽  
B Vitamins ◽  
Colorectal Adenomas ◽  
History Of

scholarly journals Comethyl: A network-based methylome approach to investigate the multivariate nature of health and disease

2021 ◽  
Author(s):  
Charles E. Mordaunt ◽  
Julia S. Mouat ◽  
Rebecca J. Schmidt ◽  
Janine M. LaSalle
Keyword(s):  
Dna Methylation ◽  
Health Disparities ◽  
Neurodevelopmental Disorders ◽  
Association Studies ◽  
Health Sciences ◽  
Autism Spectrum ◽  
Associate Professor ◽  
System Level ◽  
Genome Wide Association Studies ◽  
Medical Microbiology

AbstractHealth outcomes are frequently shaped by difficult to dissect inter-relationships between biological, behavioral, social, and environmental factors. DNA methylation patterns reflect such multi-variate intersections, providing a rich source of novel biomarkers and insight into disease etiologies. Recent advances in whole-genome bisulfite sequencing (WGBS) enable investigation of DNA methylation over all genomic CpGs, but existing bioinformatic approaches lack accessible system-level tools. Here, we develop the R package Comethyl, for weighted gene correlation network analysis (WGCNA) of user-defined genomic regions that generates modules of comethylated regions, which are then tested for correlations with sample traits. First, regions are defined by CpG genomic location or regulatory annotation and filtered based on CpG count, sequencing depth, and variability. Next, correlation networks are used to find modules of interconnected nodes using methylation values within the selected regions. Each module containing multiple comethylated regions is reduced in complexity to a single eigennode value, which is then tested for correlations with experimental metadata. Comethyl has the ability to cover the noncoding regulatory regions of the genome with high relevance to interpretation of genome-wide association studies and integration with other types of epigenomic data. We demonstrate the utility of Comethyl on a dataset of male cord blood samples from newborns later diagnosed with autism spectrum disorder (ASD) versus typical development. Comethyl successfully identified an ASD-associated module containing gene regions with brain glial functions. Comethyl is expected to be useful in uncovering the multi-variate nature of health disparities for a variety of common disorders. Comethyl is available at github.com/cemordaunt/comethyl.Description of the AuthorsCharles E. Mordaunt, Ph.D. developed Comethyl while a postdoctoral fellow in the department of Medical Microbiology and Immunology at UC Davis. He is currently a Computational Biologist at GSK.Julia S. Mouat is a doctoral student in the Integrative Genetics and Genomics graduate group at UC Davis with interests in health disparities and intergenerational epigenetic risk factors for autism spectrum disorders.Rebecca J. Schmidt, Ph.D. is an Associate Professor of Public Health Sciences at UC Davis, with expertise in the use of epigenetics in epidemiology and neurodevelopmental disorders.Janine M. LaSalle, Ph.D. is a Professor of Medical Microbiology and Immunology, Co-Director of the Perinatal Origins of Disparities Center, and Deputy Director of the Environmental Health Sciences Center at UC Davis, with expertise in epigenomics and neurodevelopmental disorders.

DNA methylation analysis for screening and diagnostic testing in neurodevelopmental disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 785-795 ◽  
Author(s):  
David E. Godler ◽  
David J. Amor
Keyword(s):  
Dna Methylation ◽  
Neurodevelopmental Disorders ◽  
Diagnostic Testing ◽  
Direct Analysis ◽  
Analytical Sensitivity ◽  
Methylation Analysis ◽  
Genome Wide ◽  
Long Read ◽  
Indirect Analysis ◽  
Low Coverage

Abstract DNA methylation (mDNA) plays an important role in the pathogenesis of neurodevelopmental disorders (NDDs), however its use in diagnostic testing has been largely restricted to a handful of methods for locus-specific analysis in monogenic syndromes. Recent studies employing genome-wide methylation analysis (GWMA) have explored utility of a single array-based test to detect methylation changes in probands negative by exome sequencing, and to diagnose different monogenic NDDs with defined epigenetic signatures. While this may be a more efficient approach, several significant barriers remain. These include non-uniform and low coverage of regulatory regions that may have CG-rich sequences, and lower analytical sensitivity as compared with locus-specific analyses that may result in methylation mosaicism not being detected. A major challenge associated with the above technologies, regardless of whether the analysis is locus specific or genome wide, is the technical bias introduced by indirect analysis of methylation. This review summarizes evidence from the most recent studies in this field and discusses future directions, including direct analysis of methylation using long-read technologies and detection of 5-methylcytosine (5-mC or total mDNA) and 5-hydroxymethylacytosine (5-hmC) as biomarkers of NDDs.

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