Michael J. Szego
A5085672675- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- BRCA gene mutations in cancer
- Autism Spectrum Disorder Research
- Ethics in Clinical Research
- Ethics in medical practice
- Genetics and Neurodevelopmental Disorders
- Retinoids in leukemia and cellular processes
- CRISPR and Genetic Engineering
- Palliative Care and End-of-Life Issues
- Congenital heart defects research
- Ethics and Legal Issues in Pediatric Healthcare
- Biomedical Ethics and Regulation
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Pluripotent Stem Cells Research
- Health and Medical Research Impacts
- Prenatal Screening and Diagnostics
- Renal and related cancers
- Health Systems, Economic Evaluations, Quality of Life
- Retinal Development and Disorders
- Kruppel-like factors research
- Melanoma and MAPK Pathways
- Genetics, Bioinformatics, and Biomedical Research
- Wnt/β-catenin signaling in development and cancer
University of Toronto
2016-2025
Unity Health Toronto
2019-2024
Public Health Ontario
2017-2024
Hospital for Sick Children
2003-2018
St. Michael's Hospital
2013-2018
St Joseph's Health Centre
2013-2018
SickKids Foundation
2003-2018
University Health Network
2007-2018
Toronto Western Hospital
2007
Jackson Laboratory
2003
PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard care often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly inconclusive. Whole-genome (WGS) provides comprehensive platform that has the potential to streamline genetic assessments, but there are limited comparative data guide its clinical use.MethodsWe prospectively recruited 103 patients from non-genetic...
Abstract The standard of care for first-tier clinical investigation the aetiology congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching smaller insertion–deletions (indels) single-nucleotide variant (SNV) mutations. Whole-genome (WGS) has potential to capture all classes genetic variation in one experiment; however, diagnostic yield mutation detection WGS...
The cost of whole genome sequencing is dropping rapidly. There has been a great deal enthusiasm about the potential for this technological advance to transform clinical care. Given interest and significant investment in genomics, seems an ideal time consider what evidence tells us benefits harms, particularly context health care policy. scale pace adoption powerful new technology should be driven by need, evidence, commitment put patients at centre
<h3>Objective</h3> To better understand the consequences of returning whole genome sequencing (WGS) results in paediatrics and facilitate its evidence-based clinical implementation, we studied parents9 experiences with WGS their preferences for return adult-onset secondary variants (SVs)—medically actionable genomic unrelated to child9s current medical condition that predict disease. <h3>Methods</h3> We conducted qualitative interviews parents whose children were undergoing as part SickKids...
<h3>BACKGROUND:</h3> The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers. <h3>METHODS:</h3> Volunteers were screened for eligibility provided informed consent open sharing. Using blood DNA, we performed all possible classes DNA variants. A genetic counsellor explained implication results to each participant....
Natural antisense transcripts (NATs) are a class of genes whose role in controlling gene expression is becoming more and relevant. We describe the identification eight novel mouse NATs associated with transcription factors (Pax6, Pax2, Six3, Six6, Otx2, Crx, Rax Vax2) that play an important eye development function. These newly identified overlap mature processed mRNAs or primary unprocessed transcript their corresponding sense genes, predicted to represent either protein coding non-coding...
Purpose: To estimate the proportion of molecular genetic diagnoses in a real-world, phenotypically heterogeneous patient cohort that are amenable to antisense oligonucleotide (ASO) treatment. Methods: We retrospectively applied N=1 Collaborative's VARIANT (Variant Assessments towards Eligibility for Antisense Oligonucleotide Treatment) guidelines all diagnostic variants found by clinical genome-wide sequencing at single pediatric hospital 532 patients over 6-year period. Variants were...
Background Whole blood is currently the most common DNA source for whole-genome sequencing (WGS), but studies requiring non-invasive collection, self-collection, greater sample stability or additional tissue references, saliva buccal samples may be preferred. However, relative quality of data and accuracy genetic variant detection from blood-derived, saliva-derived buccal-derived need to thoroughly investigated. Methods Matched blood, four unrelated individuals were used compare metrics...
Induced pluripotent stem cells (iPSC) derived from healthy individuals are important controls for disease-modeling studies. Here we apply precision health to create a high-quality resource of control iPSCs. Footprint-free lines were reprogrammed four volunteers the Personal Genome Project Canada (PGPC). Multilineage-directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users demonstrated versatility by generating kidney organoids, T...
Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in photoreceptors (PRs) mouse models inherited PR degeneration (IPD). To examine role Edn2 mutant survival, we generated Edn2(-/-) mice carrying homozygous Pde6b(rd1) alleles or Tg(RHO P347S) transgene. In background, survival 110% Pde6b(rd1/rd1) at post-natal (PN) day 15, and 60% PN40. contrast, was not retinal explants ; mice. This finding, together with systemic abnormalities mice, suggested that PRs background resulted least...
Inherited photoreceptor degenerations (IPDs), a group of incurable progressive blinding diseases, are caused by mutations in more than 200 genes, but little is known about the molecular pathogenesis (PR) death. Increased retinal expression STAT3 has been observed response to many insults, including IPDs, role this increase PR death unknown. Here, we show that Stat3 increased PRs Tg(RHO P347S) and Prph2(rds) (/+) mouse models IPD activated tyrosine phosphorylation. PR-specific deletion...
We report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and spectrum mildly dysmorphic features. Karyotype was normal all foetuses (46, XX) comparative genomic hybridization microarray analysis detected pathogenic copy number variants. Whole-exome sequencing genome-wide homozygosity...
DNA microarrays are a powerful technology that can provide wealth of gene expression data for disease studies, drug development, and wide scope other investigations. Because the large volume inherent variability microarray data, many new statistical methods have been developed evaluating significance observed differences in expression. However, until now little attention has given to characterization dispersion data.Here we examine obtained from 682 Affymetrix GeneChips with 22 different...
Children with rare and common diseases now undergo whole genome sequencing (WGS) in clinical research contexts. Parents sometimes request access to their child's raw genomic data, pursue own analyses or for onward sharing health professionals researchers. These requests raise legal, ethical, practical issues parents alike. The advent of widespread WGS pediatrics occurs a context where privacy data protection law remains focused on giving individuals control-oriented rights respect personal...
In March of this year, G3: Genes | Genomes Genetics published an early online version a manuscript by Landry et al. documenting the genome sequence HeLa cell line ([Landry 2013][1]). It prompted commentary in New York Times Rebecca Skloot ([Skloot 2013][2]), who is well
The presenilin proteins (PS1 and PS2) with their partners (NCT, Aph1, Pen2) are the major components of high molecular weight γ-secretase complex which facilitates intramembraneous cleavage various type 1 transmembrane proteins, including amyloid-β precursor protein (APP) Notch receptor. Additional may be involved in regulation its activity specificity. A recent investigation indicated that Crumbs is a negative regulator signaling act by repressing γ/ε-secretase Drosophila [Herranz, H.,...
Background: In Ontario, Canada, patients who lack decision-making capacity and have no family or friends to act as substitute decision-makers currently rely on the Office of Public Guardian Trustee consent long-term care (nursing home) placement, but they legal representative for other placement decisions. Objectives: We highlight current gap in legislation difficult transition cases involving unrepresented provide a novel framework ought assist with making these decisions how be made....