A5021052973- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Congenital heart defects research
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Genomics and Chromatin Dynamics
- Cardiovascular Effects of Exercise
- Genetic factors in colorectal cancer
- Williams Syndrome Research
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Metabolism and Genetic Disorders
- Health Systems, Economic Evaluations, Quality of Life
- Biomedical Text Mining and Ontologies
- Neonatal Respiratory Health Research
- Neuroscience of respiration and sleep
- Genetic Associations and Epidemiology
- BRCA gene mutations in cancer
- Viral Infections and Immunology Research
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Migraine and Headache Studies
- Congenital Diaphragmatic Hernia Studies
Children's Hospital of Eastern Ontario
2016-2025
University of Ottawa
2009-2024
Agricultural Research Institute of Ontario
2019-2023
McGill University
2023
Ottawa Hospital
2023
University College London
2022
SickKids Foundation
2022
Institute for Clinical Evaluative Sciences
2022
Hospital for Sick Children
2022
Great Ormond Street Hospital
2022
We have investigated the functional significance of conserved sequences within 9p21.3 risk locus for coronary artery disease (CAD) and determined relationship to expression ANRIL whole genome gene expression.We demonstrate that a sequence has enhancer activity variant significantly increases reporter in primary aortic smooth muscle cells. Whole blood RNA short variants was increased by 2.2-fold whereas long decreased 1.2-fold healthy subjects homozygous allele. Expression levels were...
Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular has a signature genetic theme. Hypertrophic are largely understood diseases sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing complex diverse architecture. To clarify this, systematic curation evidence to establish relationship with DCM was conducted.
<h3>Background:</h3> Rare diseases often present in the first days and weeks of life may require complex management setting a neonatal intensive care unit (NICU). Exhaustive consultations traditional genetic or metabolic investigations are costly fail to arrive at final diagnosis when no recognizable syndrome is suspected. For this pilot project, we assessed feasibility next-generation sequencing as tool improve rare newborns NICU. <h3>Methods:</h3> We retrospectively identified...
Dlx homeobox genes of vertebrates are generally arranged as three bigene clusters on distinct chromosomes. The Dlx1/Dlx2 , Dlx5/Dlx6 and Dlx3/Dlx7 likely originate from duplications an ancestral gene pair. Overlaps in expression often observed between the different clusters. To determine if overlaps a result conservation enhancer sequences paralogous clusters, we compared Dlx1/2 intergenic regions human, mouse, zebrafish, two pufferfish, Spheroides nephelus Takifugu rubripes . Conservation...
ClinVar provides open access to variant classifications shared from many clinical laboratories. Although most are consistent across laboratories, classification differences exist. To facilitate resolution of on a large scale, laboratories were encouraged reassess outlier variants with medically significant (MSDs). Outliers identified by first comparing submissions 41 detect MSDs between the (650 variants). Next, filtered for ≥3 (244 variants), which 87.6% (213 variants) had majority...
Abstract Background As the availability of genomic testing grows, variant interpretation will increasingly be performed by generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. Methods We analyse evidence inheritance patterns, allelic requirement, disease mechanism and disease-relevant classes 65 ClinGen-curated ICC gene-disease pairs. present this...
<h3>Background</h3> A homozygous loss-of-function mutation p.(Arg316Gln) in the <i>fat mass and obesity-associated</i> (<i>FTO</i>) gene, which encodes for an iron 2-oxoglutarate-dependent oxygenase, was previously identified a large family nine affected individuals present with lethal syndrome characterised by growth retardation multiple malformations. To date, no other pathogenic <i>FTO</i> has been as cause of congenital <h3>Methods</h3> We investigated 21-month-old girl who presented...
Background: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise clinical validity previously new putative HCM genes. Methods: The gene curation framework was used...
ALPK3 encodes the protein alpha-kinase 3, an essential cardiac-enriched atypical a-kinase that inserts in nuclear envelope and sarcomere M-band of cardiac myocytes, functioning to aid myosin-mediated force buffering proteostasis. Previously, bi-allelic loss-of-function variants have been reported causative a severe paediatric phenotype including hypertrophic (HCM) dilated cardiomyopathy (DCM). Very few heterozygous carries these cases express any phenotype. However, recently studies HCM. In...
Coenzyme Q10 (CoQ10) is an important electron carrier and antioxidant. The COQ7 enzyme catalyzes the hydroxylation of 5-demethoxyubiquinone-10 (DMQ10), second-to-last step in CoQ10 biosynthesis pathway. We report a consanguineous family presenting with hereditary motor neuropathy associated homozygous c.1A > G p.? variant abnormal biosynthesis.Affected members underwent clinical assessments that included nerve conduction testing, histologic analysis, MRI. Pathogenicity was assessed cultured...
The duplication-degeneration-complementation (DDC) model predicts that subfunctionalization of duplicated genes is a common mechanism for their preservation. additional Hox complexes teleost fish constitute good system in which to test this hypothesis. Zebrafish have two hoxbcomplexes, with hoxb5 genes, hoxb5a and hoxb5b,the expression patterns suggest an ancestral gene. We characterized conserved non-coding elements (CNEs)near the zebrafish genes. One CNE, J3, only retained locus, whereas...
Background: The cardiomyopathies are classically categorized as hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular (ARVC), each have a signature genetic theme. HCM ARVC largely understood diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning more than 10 gene ontologies been implicated in DCM, representing complex diverse architecture. To clarify this, systematic curation evidence to establish the relationship with DCM was...
Nablus mask-like facial syndrome (NMLFS) has many distinctive phenotypic features, particularly tight glistening skin with reduced expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, several individuals NMLFS have been reported to a microdeletion of 8q21.3q22.1, demonstrated by microarray analysis. The minimal overlapping region is 93.98-96.22 Mb (hg19). Here we present...
We present the investigation and management of a premature, hypotensive neonate born after pregnancy complicated by anhydramnios to highlight impact early informed for rare kidney disease. Vasopressin was used successfully treat refractory hypotension anuria in at 27 weeks gestation. Next generation sequencing targeted panel genes then performed parents. Subsequently, two compound heterozygous deletions leading frameshift mutations were identified angiotensin 1-converting enzyme gene ACE;...
<h3>Background:</h3> Genome-wide sequencing has emerged as a promising strategy for the timely diagnosis of rare diseases, but it is not yet available clinical test performed in Canadian diagnostic laboratories. We describe protocol evaluating 2-year pilot project, Sequencing Ontario, to offer high-quality genome-wide Canada. <h3>Methods:</h3> The Ontario was codesigned by Ministry Health, Hospital Sick Children Toronto and Children’s Eastern Ottawa. Enrolment prospective cohort patients...
As availability of genomic testing grows, variant interpretation will increasingly be performed by generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including as secondary findings.
With the exponential reduction of cost next-generation sequencing (NGS), it is no longer generation data but analysis and interpretation massive amounts that are seen as key challenges for effective integration these technologies into clinical practice. Clinical geneticists, informaticians, scientists from 17 countries gathered 12th International Symposium on Mutation in Genome at Fairmont Chateau Lake Louise (Canada) to discuss technological advances applications NGS consider possible...
Abstract: Background: Epilepsy is a common neurological condition that shows marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available epilepsy as licensed test Ontario, Canada. Eligible patient samples sent out country commercial laboratories, which incurs significant cost to public healthcare...