A5089342260- Congenital Heart Disease Studies
- Congenital heart defects research
- Pulmonary Hypertension Research and Treatments
- Genomics and Rare Diseases
- PARP inhibition in cancer therapy
- Chemotherapy-induced cardiotoxicity and mitigation
- Cancer Treatment and Pharmacology
- Cardiomyopathy and Myosin Studies
- Genetic Associations and Epidemiology
- Cardiovascular Function and Risk Factors
- Cancer Genomics and Diagnostics
- Antiplatelet Therapy and Cardiovascular Diseases
- Genomic variations and chromosomal abnormalities
- Viral Infections and Immunology Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Heparin-Induced Thrombocytopenia and Thrombosis
- Cardiac Valve Diseases and Treatments
- Ethics in Clinical Research
- Ethics and Legal Issues in Pediatric Healthcare
- NF-κB Signaling Pathways
- Venous Thromboembolism Diagnosis and Management
- Ethics in medical practice
- Colorectal Cancer Treatments and Studies
- Peroxisome Proliferator-Activated Receptors
- Angiogenesis and VEGF in Cancer
University of Toronto
2013-2020
Hospital for Sick Children
2012-2020
SickKids Foundation
2013-2020
University of Windsor
2011
Lifeline Hospital
2009-2010
Congenital heart defects (CHDs) are the most common birth defect worldwide and a leading cause of neonatal mortality. Nonsyndromic atrioventricular septal (AVSDs) an important subtype CHDs for which genetic architecture is poorly understood. We performed exome sequencing in 13 parent-offspring trios 112 unrelated individuals with nonsyndromic AVSDs identified five rare missense variants (two arose de novo) highly conserved gene NR2F2, very significant enrichment (p = 7.7 × 10−7) compared to...
Abstract Motivation: The prioritization and identification of disease-causing mutations is one the most significant challenges in medical genomics. Currently available methods address this problem for non-synonymous single nucleotide variants (SNVs) variation promoters/enhancers; however, recent research has implicated synonymous (silent) exonic a number disorders. Results: We have curated 33 such from literature developed Silent Variant Analyzer (SilVA), machine-learning approach to...
Background For clinical genetic testing of cardiomyopathy (CMP), current guidelines do not address which gene panels to use: targeted specific a CMP phenotype or expanded (panCMP) that include genes associated with multiple phenotypic subtypes. Aim Our objective was assess the utility versus panCMP panel in pediatric CMPs. Methods 151 patients primary hypertrophic ( n = 66), dilated 64), restrictive 8), left‐ventricular non‐compaction 13) who underwent at single centre were included. PanCMP...
PurposeThe genetic etiology of atrioventricular septal defect (AVSD) is unknown in 40% cases. Conventional sequencing and arrays have identified the only a minority nonsyndromic individuals with AVSD.MethodsWhole-exome was performed 81 unrelated probands AVSD to identify potentially causal variants comprehensive set 112 genes strong biological relevance AVSD.ResultsA significant enrichment rare damaging gene set, compared controls (odds ratio (OR): 1.52; 95% confidence interval (CI):...
Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging.This study sought to develop a and genetic prediction model for in childhood cancer survivors.We performed exome sequencing 289 survivors at least 3 years from exposure. In nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), 106 control preserved >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency...
Consenting minors for genetics research and biobanking involves ethical social challenges. We examined factors influencing participation rates in a population-based biorepository childhood heart disease.Individuals were prospectively enrolled across 7 centers Ontario by using standardized consent form. Individuals approached the donation of blood/saliva (DNA), tissue, skin from affected individual future genomics stem cell research. Consent compared between pediatric adult patients affecting...
The chromosomal region 9p21 has been reported to be associated with myocardial infarction, coronary artery disease (CAD), diabetes, and many other related multifactorial diseases in humans. Although the genome-wide association studies have identified a limited number of single-nucleotide polymorphisms (SNPs) at for CAD risk, role flanking SNPs not studied so far. Therefore, present work, we respect that previously rs10757278 rs2383207 among Indian subjects found (n = 414) along age-...
We sought to determine the frequency of genetic variations in Troponin T (TNNT2) gene and its association Indian cardiomyopathy patients. Sequencing entire TNNT2 162 hypertrophic (HCM) patients, along with 179 healthy controls, revealed a total 15 variants. These included an A28V missense mutation, novel single-nucleotide polymorphism (SNP) (g.7239;G→A) predicted disturb splicing significantly, three SNPs, rs3729547 (C→T), rs3729843 (G→A), rs3729842 which were high linkage disequilibrium, 5...
Given the growing use of whole-exome sequencing (WES) for clinical diagnostics complex human disorders, we evaluated coverage clinically relevant cardiac genes on WES and factors influencing uniformity depth exonic regions.Two hundred thirteen DNA samples were exome sequenced via Illumina HiSeq using different versions Agilent SureSelect capture kit. 50 further analyzed including 31 from American College Medical Genetics (ACMG) list reporting incidental findings 19 associated with congenital...
Distal and proximal colon cancers have been recognized as two different disease types in human population. The environmental factors involved the pathogenesis of distal tumors also differ. main objective this study was to determine if obesity-augmented colonic differ from each other they are located regions axis. Zucker obese rats were injected with azoxymethane (AOM) 10 mg/kg body weight/week for 2 weeks. appeared within 20 highest proportion colon, number declined towards splenic flexure....
Congenital heart disease (CHD) is a complex disorder with multifactorial etiology and high heritability. We used whole exome sequencing to identify novel variants associated familial CHD. Methods: CHD patients were enrolled in prospective biobank registry (n=2800). Whole was performed 12 affected members LV outflow tract defects 7 non-affected from 5 families using Illumina Hi-Seq 2000, Agilent SureSelect Human All Exon v.2 Kit for sequence capture. Results: Sequence alignment the reference...
Introduction: Thrombosis is an important and widespread post-operative complication of pediatric cardiac surgery. Prophylaxis intraoperative anticoagulation in this context obtained by using heparin which requires a bond with antithrombin to achieve anticoagulant effect. We sought identify SNPs associated blood levels, response thrombosis risk patients undergoing surgery cardiopulmonary bypass (CPB). Methods: A total 625 operations CPB 383 were reviewed. Ninety-six on 53 genes the...