Bhooma Thiruvahindrapuram
A5035343631- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Genetic Associations and Epidemiology
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Cystic Fibrosis Research Advances
- SARS-CoV-2 and COVID-19 Research
- Congenital Heart Disease Studies
- Genetic Neurodegenerative Diseases
- Immunodeficiency and Autoimmune Disorders
- Neurogenetic and Muscular Disorders Research
- COVID-19 Clinical Research Studies
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Microbial infections and disease research
- Coronary Artery Anomalies
Hospital for Sick Children
2016-2025
SickKids Foundation
2016-2025
Great Ormond Street Hospital
2019-2025
University College London
2019-2025
University of Toronto
2014-2020
University Health Network
2018
Genomics (United Kingdom)
2013-2018
National University of Sciences and Technology
2018
Shifa Tameer-e-Millat University
2018
Shifa International Hospital
2018
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,...
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...
A high-resolution analysis of copy number variation in patients with ADHD reveals new gene associations, few de novo mutations, and overlap genes implicated other disorders such as autism.
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...
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...
Inherited variation contributes to autism About one-quarter of genetic variants that are associated with spectrum disorder (ASD) due de novo mutations in protein-coding genes. Brandler et al. wanted determine whether changes noncoding regions the genome autism. They applied whole-genome sequencing ∼2600 families at least one affected child. Children ASD had inherited structural from their father. Regulatory some specific genes were disrupted among multiple families, supporting idea a...
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...
The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible clustering and localization of glycine GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated genetic risk neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia epilepsy including neuroligins (NLGN2, NLGN4), neurexins (NRXN1, NRXN2, NRXN3) collybistin (ARHGEF9)....
Abstract Cerebral palsy (CP) represents a group of non-progressive clinically heterogeneous disorders that are characterized by motor impairment and early age onset, frequently accompanied co-morbidities. The cause CP has historically been attributed to environmental stressors resulting in brain damage. While genetic risk factors also implicated, guidelines for diagnostic assessment do not recommend routine testing. Given numerous reports aetiologic copy number variations (CNVs) other...
Autism spectrum disorder (ASD) is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert protein tag premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction iPSCs allowed production excitatory neurons, mutant proteins were not detectable. RNA...
Abstract Roifman Syndrome is a rare congenital disorder characterized by growth retardation, cognitive delay, spondyloepiphyseal dysplasia and antibody deficiency. Here we utilize whole-genome sequencing of patients to reveal compound heterozygous variants that disrupt highly conserved positions the RNU4ATAC small nuclear RNA gene, minor spliceosome component essential for intron splicing. Targeted confirms allele segregation in six cases from four unrelated families. have been recently...