Edward J. Higginbotham
A5053983678- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Prenatal Screening and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Immunodeficiency and Autoimmune Disorders
- Hippo pathway signaling and YAP/TAZ
- Metabolism and Genetic Disorders
- Cystic Fibrosis Research Advances
- Nuclear Structure and Function
- Cerebral Palsy and Movement Disorders
- Epilepsy research and treatment
- Pluripotent Stem Cells Research
- Health, Environment, Cognitive Aging
- Neurogenetic and Muscular Disorders Research
Hospital for Sick Children
2017-2024
SickKids Foundation
2019-2024
University of Toronto
2019
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,...
PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side the body affected. Our earlier study unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) 9.6% participants. Here, we examined prevalence types CNVs specifically hemiplegic CP.MethodsWe genotyped 97 unrelated probands their parents. We compared to those 10,851 population controls, order identify (<0.1% frequency) that might be CP. also sequenced...
Abstract We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health cognition a community sample 7100 unrelated children youth European or East Asian ancestry (Spit for Science). Clinically significant susceptibility CNVs were present 3.9% participants associated with elevated scores on continuous measure attention-deficit/hyperactivity disorder (ADHD) (P = 5.0 × 10−3), longer response inhibition (a cognitive...
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...
Rare or de novo structural variation, primarily in the form of copy number variants, is detected 5%–10% autism spectrum disorder (ASD) families. While complex variants involving duplications can generally be using microarray short-read genome sequencing (GS), these methods frequently fail to characterize breakpoints at nucleotide resolution, requiring additional molecular for validation and fine-mapping. Here, we use Oxford Nanopore Technologies PromethION long-read GS genomic rearrangements...
Copy number variants (CNVs) are recognized as a crucial genetic cause of neurodevelopmental disorders (NDDs). Chromosomal microarray analysis (CMA), the first-tier diagnostic test for individuals with NDDs, has been utilized to detect CNVs in clinical practice, but most reports still from populations European ancestry. To contribute more worldwide genomics data, we investigated etiology 410 Han Chinese patients NDDs (151 autism and 259 unexplained intellectual disability (ID) developmental...
Abstract Oligogenic inheritance of autism spectrum disorder (ASD) has been supported by several studies. However, little is known about how the risk variants interact and converge on causative neurobiological pathways. We identified in an ASD proband deleterious compound heterozygous missense Reelin ( RELN ) gene, a de novo splicing variant Cav3.2 calcium channel CACNA1H gene. Here, using iPSC-derived neural progenitor cells (NPCs) heterologous expression system, we show that leads to...
In more than one-third of primary immunodeficiency (PID) patients, extensive genetic analysis including whole-exome sequencing (WES) fails to identify the defect. Whole-genome (WGS) is able detect variants missed by other genomics platforms, enabling molecular diagnosis otherwise unresolved cases. Here, we report two siblings, offspring consanguineous parents, who experienced similar severe events encompassing early onset colitis, lymphoproliferation, and hypogammaglobulinemia, typical...
Copy number variants (CNVs) represent major etiologic factors in rare genetic diseases. Current clinical CNV interpretation workflows require extensive back-and-forth with multiple tools and databases. This increases complexity time burden, potentially resulting missed diagnoses. We present the Suite for Interpretation Prioritization (SCIP), a software package of CNVs detected by whole-genome sequencing (WGS). The SCIP Visualization Module near-instantaneously displays all information...
Abstract Fully understanding the genetic factors involved in Autism Spectrum Disorder (ASD) requires whole-genome sequencing (WGS), which theoretically allows detection of all types variants. With aim generating an unprecedented resource for resolving genomic architecture underlying ASD, we analyzed genome sequences and phenotypic data from 5,100 individuals with ASD 6,212 additional parents siblings (total n=11,312) Speaks MSSNG Project, as well other WGS cohorts. autism phenotyping were...
Abstract We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health, cognitive biomarkers a community sample 7,100 unrelated European, East Asian children youth (Spit for Science). Diagnoses health disorders were found 17.5% participants 27.6% scored highest 10% on either or both ADHD OCD trait measures. Clinically relevant CNVs present 3.9% associated with elevated scores continuous measure ( p =5.0×10 −3 ),...