Browsing by Author "Mohamed, Nesrin"

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A draft UAE-based Arab pangenome reference.
(2025-07-24) Nassir, Nasna; Almarri, Mohamed A; Kumail, Muhammad; Mohamed, Nesrin; Balan, Bipin; Hanif, Shehzad; AlObathani, Maryam; Jamalalail, Bassam; Elsokary, Hanan; Kondaramage, Dasuki; Shiyas, Suhana; Kosaji, Noor; Satsangi, Dharana; Suwaidi, Hanan Al; Albanna, Ammar; S Du Plessis, Stefan; Khansaheb, Hamda Hassan; Alsheikh-Ali, Alawi; Uddin, Mohammed
Pangenomes provide a robust and comprehensive portrayal of genetic diversity in humans, but Arab populations remain underrepresented. We present a preliminary UAE-based Arab Pangenome Reference (UPR) utilizing 53 individuals of diverse Arab ethnicities residing in the United Arab Emirates. We assembled nuclear and mitochondrial pangenomes using 35.27X high-fidelity long reads, 54.22X ultralong reads and 65.46X Hi-C reads. This approach yielded contiguous haplotype-phased de novo assemblies of exceptional quality, with an average N50 of 124.28 Mb. We discovered 111.96 million base pairs of previously uncharacterized euchromatic sequences absent from existing human pangenomes, the T2T-CHM13 and GRCh38 reference human genomes, and other public datasets. Moreover, we identified 8.94 million population-specific small variants and 235,195 structural variants within the Arab pangenome, not present in linear and pangenome references and public datasets. We detected 883 gene duplications, including the TATA-binding protein gene TAF11L5, which was uniquely duplicated across all Arab populations and that included 15.06% of genes associated with recessive diseases. By exploring the mitochondrial pangenome, we identified 1,436 bp of previously unreported sequences. Our study provides a valuable resource for future genetic research and genomic medicine initiatives in Arab population and other population with similar genetic backgrounds.
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort.
(2024-09-26) Mohamed, Nesrin; Satsangi, Dharana; Hanif, Shehzad; Tambi, Richa; Nassir, Nasna; Uddin, Mohammed
Purpose: The genetic underpinning of neurodevelopmental disorders (NDDs) in diverse ethnic populations, especially those with high rates of consanguinity, remains largely unexplored. Here, we aim to elucidate genomic insight from 576 well-phenotyped and highly consanguineous (16%) NDD cohort.
Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease
(2023) Tambi, Richa; Bente, Zehra; Nandkishore, Sharon; Sharafat, Shermin; Kader, Faiza; Nassir, Nasna; Mohamed, Nesrin; Ahmed, Awab; Abdel Hameid, Reem; Alasrawi, Samah; Alsheikh-Ali, Alawi; Uddin, Mohammed; Berdiev, Bakhrom K
Abstract: Congenital heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. To catalog the putative candidate CHD risk genes, we collected 16,349 variants [single-nucleotide variants (SNVs) and Indels] impacting 8,308 genes in 3,166 CHD cases for a comprehensive meta-analysis. Using American College of Medical Genetics (ACMG) guidelines, we excluded the 0.1% of benign/likely benign variants and the resulting dataset consisted of 83% predicted loss of function variants and 17% missense variants. Seventeen percent were de novo variants. A stepwise analysis identified 90 variant-enriched CHD genes, of which six (GPATCH1, NYNRIN, TCLD2, CEP95, MAP3K19, and TTC36) were novel candidate CHD genes. Single-cell transcriptome cluster reconstruction analysis on six CHD tissues and four controls revealed upregulation of the top 10 frequently mutated genes primarily in cardiomyocytes. NOTCH1 (highest number of variants) and MYH6 (highest number of recurrent variants) expression was elevated in endocardial cells and cardiomyocytes, respectively, and 60% of these gene variants were associated with tetralogy of Fallot and coarctation of the aorta, respectively. Pseudobulk analysis using the single-cell transcriptome revealed significant (P < 0.05) upregulation of both NOTCH1 (endocardial cells) and MYH6 (cardiomyocytes) in the control heart data. We observed nine different subpopulations of CHD heart cardiomyocytes of which only four were observed in the control heart. This is the first comprehensive meta-analysis combining genomics and CHD single-cell transcriptomics, identifying the most frequently mutated CHD genes, and demonstrating CHD gene heterogeneity, suggesting that multiple genes contribute to the phenotypic heterogeneity of CHD. Cardiomyocytes and endocardial cells are identified as major CHD-related cell types.