Biology subjects

Sakr, M.

Publications and source records attributed to Sakr, M..

3 recordsLinked to original sources

bioRxiv2026

EGP1K: Whole-Genome Sequencing of 1,024 Egyptians Characterizes Population Structure and Genetic Diversity

Middle Eastern and North African populations remain underrepresented in genomic databases, comprising less than 1% of genome-wide association study participants despite representing approximately 6% of the global population. Here we present the Egypt Genome Project (EGP1K), in which we performed whole-genome sequencing on 1,024 unrelated Egyptian individuals originating from 21 of Egypts 27 governorates, recruited through eight clinical and research centers across Upper and Lower Egypt. We identified over 51.3 million variants, of which 17.1 million (33.4%) were absent from dbSNP. Allele frequency comparisons across 6.5 million shared variants showed the strongest concordance with Middle Eastern populations ({tau} = 0.977). Principal component analysis and ADMIXTURE modeling at K = 7 revealed that Egyptians share a dominant ancestry component (71.8%) with Middle Eastern populations and carry a smaller Egyptian-enriched component (18.5%) that distinguishes them from neighboring groups. Runs of homozygosity varied substantially across subregions, with Upper Egypt showing the highest burden, paralleling elevated consanguinity rates. Carrier frequency analysis identified MEFV (Familial Mediterranean Fever) at 9.1% as the most prevalent pathogenic carrier state; when adjusted for the national consanguinity rate, MEFV carrier status alone projects approximately 6,600 affected births per year. HLA class I typing identified allele frequencies placing Egyptians within the Levantine-Eastern Mediterranean cluster, providing baseline immunogenetic data currently absent from international databases. Analysis of polygenic risk score distributions revealed substantial differences in threshold-based risk stratification between Egyptians and European reference populations. When the Europeanderived 90th percentile threshold was applied, 83.3% of Egyptians were assigned to high-risk strata for stroke, 76.4% for chronic kidney disease, and 72.8% for gout, compared to the intended 10% high-risk proportion. These distributional shifts were observed across several cardiometabolic traits (Cohens d = 1.55-1.61), while other traits showed closer cross-population concordance, indicating that the degree of threshold miscalibration varies by trait. Together, these findings establish EGP1K as a genomic reference for Egypt and indicate that European-derived risk stratification thresholds may not be directly transferable to the Egyptian population, supporting the need for population-specific calibration of polygenic risk scores.

genomics↗

bioRxiv2024

A Novel GelMA-OrnMA Electrically Conductive Bioink for Developing Engineered Neural Tissues

Electrical conductivity is a crucial requirement of matrices for developing engineered neural tissues. A conductive matrix not only supports cell growth but also provides potential to stimulate the cells. However, electrically conductive matrices often require inclusion of synthetic polymers, nanomaterials and large number of ionic species. While enhancing electrical conductivity, often properties like transparency, mechanical stiffness and biocompatibility are compromised which can render the resulting matrices partially suitable for neural tissue engineering. Further, the byproducts of matrix degradation can have unforeseen influences. Therefore, electrically active matrices are required which provide a suitable combination of electrical conductivity, mechanical properties and biocompatibility. In this work, a novel biomaterial is described which results in optically transparent, electrically conductive and highly biocompatible matrices along with ability to match the native neural tissue stiffness. Using gelatin methacryloyl (GelMA) as base hydrogel, we covalently incorporated zwitterionic functional groups to obtain a composite matrix. The zwitterion moieties were derived from Ornithine by synthesizing ornithine methacryloyl (OrnMA) and blending with GelMA inks. Through systematic characterization we demonstrated the suitability of GelMA-OrnMA hydrogels in providing mechanical stiffness matching the native neural tissues, supporting proliferation of human astrocytes in 3D culture and electrical conductivity in the range required for electrically active cell types like astrocytes. Owing to their electrical conductivity, these matrices also influenced the growth of astrocytes which manifested as significant changes in their organization and morphology. These findings suggest that GelMA-OrnMA has immense potential as a bioink for developing engineered neural tissues.

bioengineering↗

bioRxiv2023

TREM2 is downregulated by HSV1 in microglia and involved in antiviral defense in the brain

Immunological control of viral infection in the brain is essential for immediate protection, but also for long-term maintenance of brain integrity. As the primary resident immune cell of the brain, microglia protect against viral infections through key macrophage functions, including release of the antiviral type I interferons (IFN-I) and clearance of infected cells. Microglia express the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), which can bind viral DNA leading to signaling through stimulator of interferon genes (STING), and downstream immune activation. Here we report that herpes simplex virus (HSV) 1 infection of microglia leads to activation of IFN-I genes and pro-inflammatory cytokines. However, HSV1 also down-regulated expression of a subset of genes, including genes in the pathway engaged by the microglial receptor triggering receptor expressed on myeloid cells-2 (TREM2). Knockdown experiments revealed that TREM2 is important for viral activation of cGAS-STING signaling in microglia, induction of IFN-I, and phagocytosis of HSV1 infected neurons. Consequently, TREM2 depletion increased susceptibility to HSV1 infection in human microglia-neuron co-cultures and mice in vivo. Mechanistically, we show that TREM2 is essential for phosphorylation of STING, and downstream activation of the IFN-inducing transcription factor IRF3. We conclude that TREM2 is a novel component of the antiviral immune response in microglia, crucial for immediate host defense against HSV1 in the brain. Since both TREM2 loss-of-function mutations and HSV1 serological status are linked to development of Alzheime[r]s disease (AD), this work opens the question whether defects in TREM2 could predispose to impaired viral clearance and post-infection pathological neurological changes.

immunology↗