Daniele Merico
A5072404345- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Biomedical Text Mining and Ontologies
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Prenatal Screening and Diagnostics
- Genomics and Chromatin Dynamics
- NF-κB Signaling Pathways
- Blood disorders and treatments
- Cancer-related Molecular Pathways
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
Hospital for Sick Children
2016-2025
SickKids Foundation
2016-2025
Rapt Therapeutics (United States)
2023-2025
Ontario Genomics
2012-2023
Great Ormond Street Hospital
2015-2023
University College London
2015-2023
Genomics (United Kingdom)
2013-2019
University Health Network
2017-2018
University of Toronto
2008-2018
MaRS
2018
Background Gene-set enrichment analysis is a useful technique to help functionally characterize large gene lists, such as the results of expression experiments. This finds coherent gene-sets, pathways, that are statistically over-represented in given list. Ideally, number resulting sets smaller than genes list, thus simplifying interpretation. However, increasing and redundancy gene-sets used by many current software works against this ideal. Principal Findings To overcome gene-set...
To facilitate precision medicine and whole-genome annotation, we developed a machine-learning technique that scores how strongly genetic variants affect RNA splicing, whose alteration contributes to many diseases. Analysis of more than 650,000 intronic exonic revealed widespread patterns mutation-driven aberrant splicing. Intronic disease mutations are 30 nucleotides from any splice site alter splicing nine times as often common variants, missense have the least impact on protein function...
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed excess genic deletions duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) increase subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD intellectual disability (odds ratio 12.62, 2.7 10(-15), ∼3% subjects). Pathogenic CNVs, often showing variable expressivity,...
Recurrent glioblastoma multiforme (GBM) is incurable with current therapies. Biallelic mismatch repair deficiency (bMMRD) a highly penetrant childhood cancer syndrome often resulting in GBM characterized by high mutational burden. Evidence suggests that mutation and neoantigen loads are associated response to immune checkpoint inhibition.We performed exome sequencing prediction on 37 bMMRD cancers compared them adult brain neoplasms. Neoantigen was responsive from multiple tissues. Two...
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...
Autism Spectrum Disorder (ASD) demonstrates high heritability and familial clustering, yet the genetic causes remain only partially understood as a result of extensive clinical genomic heterogeneity. Whole-genome sequencing (WGS) shows promise tool for identifying ASD risk genes well unreported mutations in known loci, but an assessment its full utility group has not been performed. We used WGS to examine 32 families with detect de novo or rare inherited variants predicted be deleterious...
The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study.To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group children ASD determine the diagnostic yield these sample typical developmental pediatric clinic.The consisted 258 consecutively ascertained unrelated who underwent detailed assessments define morphology scores based on presence major congenital...
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...
To uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) secondary high-grade (sHGG).We retrospectively identified patients with sHGG from a population-based cohort 886 PLGG long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed analysis entire cohort. Clinical outcome data genetically distinct subgroups obtained.sHGG was observed in 2.9% PLGGs (26 patients). Patients had high frequency nonsilent...
De novo mutations (DNMs) are important in Autism Spectrum Disorder (ASD), but so far analyses have mainly been on the ~1.5% of genome encoding genes. Here, we performed whole sequencing (WGS) 200 ASD parent-child trios and characterized germline somatic DNMs. We confirmed that majority DNMs (75.6%) originated from father, these increased significantly with paternal age only (p=4.2×10-10). However, when clustered (those within 20kb) were found ASD, not did they mostly originate mother...
Abstract Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted identify etiology among NDDs, but this is the first genome-wide CNV analysis autism spectrum disorder (ASD), attention deficit hyperactivity (ADHD), schizophrenia (SCZ), obsessive-compulsive (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ,...
The identification of rare inherited and de novo copy number variations (CNVs) in human subjects has proven a productive approach to highlight risk genes for autism spectrum disorder (ASD). A variety microarrays are available detect CNVs, including single-nucleotide polymorphism (SNP) arrays comparative genomic hybridization (CGH) arrays. Here, we examine cohort 696 unrelated ASD cases using high-resolution one-million feature CGH microarray, the majority which were previously genotyped with...
Structural genetic changes, especially copy number variants (CNVs), represent a major source of variation contributing to human disease. Tetralogy Fallot (TOF) is the most common form cyanotic congenital heart disease, but date little known about role CNVs in etiology TOF. Using high-resolution genome-wide microarrays and stringent calling methods, we investigated rare prospectively recruited cohort 433 unrelated adults with TOF and/or pulmonary atresia at single centre. We excluded those...
Rare copy number variants (CNVs) disrupting ASTN2 or both and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, its paralog ASTN1, key roles glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 ASTN1 (1q25.2) for exonic CNVs clinical microarray data from...