A5054098582- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
- Autism Spectrum Disorder Research
- Cancer-related gene regulation
- Congenital heart defects research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Acute Myeloid Leukemia Research
- BRCA gene mutations in cancer
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- Reproductive Health and Technologies
- Genetic Mapping and Diversity in Plants and Animals
- Pancreatic and Hepatic Oncology Research
- Cytokine Signaling Pathways and Interactions
- Glioma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Cancer-related molecular mechanisms research
McMaster University
2015-2024
Hamilton Health Sciences
2019-2024
Hamilton Regional Laboratory Medicine Program
2019-2024
Health Sciences Centre
2022-2023
St. Joseph’s Healthcare Hamilton
2022
Hospital for Sick Children
2009-2017
Institut thématique Génétique, génomique et bioinformatique
2013
University College London
2013
University of Toronto
2013
Great Ormond Street Hospital
2013
DNA methylation, an important type of epigenetic modification in humans, participates crucial cellular processes, such as embryonic development, X-inactivation, genomic imprinting and chromosome stability. Several platforms have been developed to study genome-wide methylation. Many investigators the field chosen Illumina Infinium HumanMethylation microarray for its ability reliably assess methylation following sodium bisulfite conversion. Here, we analyzed profiles 489 adult males 357...
Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder that affects girls due primarily to mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). The majority of RTT patients carry missense and nonsense leading hypomorphic MECP2, while null complete absence functional are rare. MECP2 an X-linked subject random X-chromosome inactivation resulting mosaic expression mutant MECP2. lack human brain tissue motivates need for alternative cellular models study RTT. Here...
Abstract Sotos syndrome (SS) represents an important human model system for the study of epigenetic regulation; it is overgrowth/intellectual disability caused by mutations in a histone methyltransferase, NSD1 . As layered modifications are often interdependent, we propose that pathogenic have genome-wide impact on most stable mark, DNA methylation (DNAm). By interrogating DNAm SS patients, identify genome-wide, highly significant +/− -specific signature differentiates from controls, benign...
Epigenetic dysregulation has emerged as a recurring mechanism in the etiology of neurodevelopmental disorders. Two such disorders, CHARGE and Kabuki syndromes, result from loss function mutations chromodomain helicase DNA-binding protein 7 (CHD7LOF) lysine (K) methyltransferase 2D (KMT2DLOF), respectively. Although these two syndromes are clinically distinct, there is significant phenotypic overlap. We therefore expected that epigenetically driven developmental pathways regulated by CHD7...
Imprinted genes are critical for normal human growth and neurodevelopment. They characterized by differentially methylated regions (DMRs) of DNA that confer parent origin-specific transcription. We developed a new strategy to identify imprinted gene-associated DMRs. Using genome-wide methylation profiling sodium bisulfite modified from tissues biparental origin, candidate DMRs were identified selecting CpGs with levels consistent putative allelic differential methylation. In parallel, the...
Abstract Background A number of neurodevelopmental syndromes are caused by mutations in genes encoding proteins that normally function epigenetic regulation. Identification alterations occurring these disorders could shed light on molecular pathways relevant to neurodevelopment. Results Using a genome-wide approach, we identified with significant loss DNA methylation blood males intellectual disability and the X-linked KDM5C gene, histone H3 lysine 4 demethylase, comparison age/sex matched...
Neonates with birthweights below the tenth percentile for gestational age are considered small (SGA). Such infants have an increased risk perinatal mortality and morbidity as well lifetime adult onset disorders. Low birth weight is etiologically heterogeneous may result from maternal, fetal, placental environmental factors. However, molecular determinants of human SGA not elucidated. We proposed that fetal growth potential could be negatively impacted by epigenetic dysregulation specific...
Background Epigenetic variants have been shown in recent studies to be important contributors the pathogenesis of systemic lupus erythematosus (SLE). Here, we report a 2-step study discovery followed by replication identify DNA methylation alterations associated with SLE Chinese population. Using genome-wide microarray, Illumina Infinium HumanMethylation450 BeadChip, compared levels CpG sites extracted from white blood cells 12 female patients and 10 healthy controls. Results We identified...
We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to CGG-repeat expansion mutation (∼450 repeats) 5′ intron ZNF713. This expanded allele showed hypermethylation adjacent CpG island reduced ZNF713 expression observed proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried unmethylated premutation (85 repeats). length polymorphism control samples (five 22 In second unrelated family, three...
AbstractIn this study, we verified the accuracy of two array methods—methylated DNA immunoprecipitation coupled with CpG island microarrays (MeDIP-CGI-arrays) and sodium bisulfite conversion based (BC-arrays)—in predicting regional methylation levels as measured by pyrosequencing converted (BC-pyrosequencing). To test these methods used Agilent Human Illumina HumanMethylation27 respectively, compared microarray outputs to data from targeted BC-pyrosequencing assays several genomic regions...
Aim: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the euchromatic histone lysine methyltransferase 1 gene, EHMT1, due to either submicroscopic 9q34.3 deletion or pathogenic EHMT1 variant. KS characterized intellectual disability, autistic-like features, heart defects, hypotonia and distinctive facial features. Here, we aimed (1) identify unique DNA methylation signature in patients with KS, (2) demonstrate efficacy predicting pathogenicity...
Molecular biomarkers, such as IDH1/IDH2 mutations and 1p19q co-deletion, are included in the histopathological clinical criteria currently used to diagnose classify gliomas. mutation is a common feature of gliomas associated with glioma-CpG island methylator phenotype (CIMP). Aberrant genomic methylation patterns can also be extrapolate information about copy number variation tumor. This project’s goal was assess feasibility DNA array for simultaneous detection glioma biomarkers more...
Molecular variants including single nucleotide (SNVs), copy number (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection little genomic input material. They are gaining popularity laboratories, where sample volumes limited, variant allele fractions may present. However, data on reproducibility between laboratories is limited. Using a ring study, we evaluated performance 7 Ontario sequencing panels. All analysed...
The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring to optimize testing for neurotrophic receptor tyrosine kinase (NTRK) fusions in laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) NTRK1, NTRK2, or NTRK3 fusions. Each laboratory received 12 formalin-fixed, paraffin-embedded tumor samples with unique and two control non-NTRK fusion (one ALK one ROS1). Laboratories validated protocols NGS detection. Panels included Oncomine Comprehensive...