A5011782728- Genomics and Rare Diseases
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- CAR-T cell therapy research
- Parkinson's Disease Mechanisms and Treatments
- COVID-19 Clinical Research Studies
- Genomics and Phylogenetic Studies
- Phagocytosis and Immune Regulation
- Alzheimer's disease research and treatments
- Autism Spectrum Disorder Research
- Cellular Mechanics and Interactions
- Tracheal and airway disorders
- Congenital Heart Disease Studies
- Molecular Biology Techniques and Applications
- Cardiac electrophysiology and arrhythmias
- Cancer Immunotherapy and Biomarkers
- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
- RNA regulation and disease
- Biotechnology and Related Fields
- Legionella and Acanthamoeba research
Mohammed Bin Rashid University of Medicine and Health Sciences
2021-2025
Bharathidasan University
2022
Indian Institute of Technology Madras
2017-2019
Abstract Microtubule-associated protein tau ( MAPT ) aggregates in neurons, astrocytes and oligodendrocytes a number of neurodegenerative diseases, including progressive supranuclear palsy (PSP). Tau is target therapy the strategy includes either elimination pathological or reducing expression, thus amount made to prevent its aggregation. Disease-associated affects brain regions sequential manner that cell-to-cell spreading. Involvement glial cells show interpreted as taking up misfolded...
Abstract Background In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the underpinning ASD, particularly from point view ‘brain to behaviour’ pathogenic mechanisms, remains largely unknown. Methods We undertook study investigate patterns spatiotemporal and cell type expression ASD-implicated by integrating large-scale brain single-cell transcriptomes (> million cells) de novo...
Pangenomes represent a significant shift from relying on single reference sequence to robust set of assemblies. Arab populations remain significantly underrepresented; hence, we present the first Pangenome Reference (APR) utilizing 53 individuals diverse ethnicities. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads 65.46X Hi-C yielded contiguous haplotype-phased de novo assemblies exceptional quality, with an average N50 124.28...
Summary Pangenomes represent a significant shift from relying on single reference sequence to robust set of assemblies, Arab populations remain significantly underrepresented; hence, we present the first Pangenome Reference (APR) utilizing 53 individuals diverse ethnicities. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads 65.46X Hi-C yielded contiguous haplotype-phased de novo assemblies exceptional quality, with an average N50...
The advent of long-read sequencing offers a new assessment method detecting genomic structural variation (SV) in numerous rare genetic diseases. For autism spectrum disorders (ASD) cases where pathogenic variants fail to be found the protein-coding genic regions along chromosomes, we proposed scalable workflow characterize risk factor SVs impacting non-coding elements genome. We applied whole-genome on an Emirati family having three children with ASD using long and short-read technology. A...
Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation GCIs unclear, particular whether abnormal aggregates result from the elevation endogenous expression MSA or ingested neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role developing GCI pathology. Here, total cell body, nucleus, and area density SNCA TPPP...
Progressive supranuclear palsy (PSP) is a main form of idiopathic tauopathy characterized neuropathologically by subcortical neurofibrillary tangles in neurons, oligodendroglial coiled bodies, and tufted astrocytes, which follow sequential distribution the human brain. Mitochondrial dysfunction thought to be contributor many neurodegenerative diseases, but its role PSP at cellular level remains incompletely understood. To address this, we performed cell-specific morphometric analysis...
The genomic representation of populations across the globe is critical to ensuring a comprehensive and equitable human reference. Constructing pangenome graph reference for different best approach addressing local diversities. Although major initiatives continents are underway construct references, field lacks necessary toolsets tertiary analysis characterize telomere-to-telomere (T2T) assemblies complexity haplotypes. PanScan bioinformatics software package developed analysis. It includes...
Rare post-zygotic mutations in the brain are now known to contribute several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due limited availability of tissue, most studies rely on estimates mosaicism from peripheral samples. In this study, we undertook whole exome sequencing tissue 26 ASD donors Harvard Brain Tissue Resource Center (HBTRC) and ascertained presence germline categorized as pathological, those impacting ASD-implicated genes. Although...
Misfolded α-synuclein (α-syn) is believed to contribute neurodegeneration in Lewy body disease (LBD) based on considerable evidence including a gene-dosage effect observed relation point mutations and multiplication of SNCA familial Parkinson's disease. A contradictory concept proposes early loss the physiological α-syn as major driver neurodegeneration. There paucity data transcripts various immunoreactive cytopathologies. Here, total cell body, nuclear, cytoplasmic area density neurons...
Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics an ethnically underrepresented homogenous population Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male female ratio 2.2:1.0 rare CNVs. To candidate within gene constraint metrics [i.e.,...
Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated severe comorbidities are significantly upregulated in bronchoalveolar lavage fluid cases. FCGR3B consistently demarcated MoAM subset different...
Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are rare with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts NDD CA patients to identify de novo CNVs candidate genes associated both phenotypes. We analyzed clinical microarray CNV data from 10,620 3176 cases annotated using Horizon platform GenomeArc Analytics applied rigorous downstream analysis evaluate overlapping CNVs. Out 13,796...
Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely variants in five children with diseases. We present evidence for disease-causing autosomal recessive range disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet-Biedl Syndrome...
Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several have been identified, yet full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook first detailed genotype phenotype characterization of DMD Bangladeshi population. We investigated spectrum gene 36 DMD-suspected participants using an economically affordable diagnostic strategy...
Telomerase, particularly its main subunit, the reverse transcriptase, TERT, prevents DNA erosion during eukaryotic chromosomal replication, but also has poorly understood non-canonical functions. Here, in model social amoeba Dictyostelium discoideum, we show that protein encoded by tert telomerase-like motifs, and regulates, non-canonically, important developmental processes. Expression levels of wild-type (WT) were biphasic, peaking at 8 12 h post-starvation, aligning with events, such as...
Brugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence clinically relevant mutations and to identify developmental cell types that are associated BrS etiology, we collected 733 represented by 16 sodium, calcium, potassium channels, regulatory structural genes related BrS. Among mutations, 266 unique singletons 88 recurrent. We observed an over-representation (∼80%) in SCN5A gene also identified several candidate...
Abstract Purpose Our study assesses the Horizon model, a novel CNV classification tool developed in line with American College of Medical Genetics (ACMG) guidelines, to enhance pathogenicity CNVs. Methods utilizes ranking-based algorithm, incorporating multiple proprietary databases and variant inheritance models as per ACMG standards. The model’s effectiveness was verified through Area Under Curve (AUC) analyses on three datasets comprising 696 pathogenic inherited or de novo variants,...
We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. construct comorbid disease-associated gene list multiple databases literature resources. Next, we identify type where are upregulated. further characterize identified enrichment analysis. detect upregulation of restricted to severe validate our findings in silico, vivo, vitro cellular models. For complete details on use execution this...
Abstract Telomerase, particularly its main subunit, the reverse transcriptase, TERT, prevents DNA erosion during eukaryotic chromosomal replication, but also has poorly understood non-canonical functions. Here, in model social amoeba Dictyostelium discoideum, we show that protein encoded by tert telomerase-like motifs and regulates, non-canonically, important developmental processes. Expression levels of wild-type (WT) were biphasic, peaking at 8 12 h post-starvation, aligning with events,...