The relationship between genetic variations and susceptibility to infection provides insight into the pathogenesis of diseases caused by infections, illustrating host–pathogen interactions, informing preventive measures, and offering a novel therapeutic approach.
This cross-sectional study was conducted at Baghdad Medical City Hospital from April 2024 to October 2024 and involved 100 subjects referred to the laboratory for confirmatory diagnosis. Bacterial isolates were identified using routine phenotypic and biochemical tests. DNA was extracted from participants and used to genotype the rs231775 single-nucleotide polymorphism (SNP) using TaqMan® SNP Genotyping Assays; the serum levels of interleukin-7 (IL-7) were also determined for the studied groups.
A total of 32 patients were infected with Acinetobacter baumannii, and 68 were controls. No statistically significant difference was noted between the blood group and the infection status (p = 0.109). The results indicated a highly statistically significant association between genotype AA and the occurrence of disease (p = 0.003) and an extremely significant association between genotype GG and the occurrence of disease (p < 0.001), respectively. The results indicated that individuals with the AA genotype had lower odds (odds ratio (OR) = 0.217) of having the disease, as did those with the AG genotype (OR = 0.80). However, the presence of the GG genotype GG exhibited higher odds in patients compared to the controls (OR = 5.439). Serum levels of IL-7 differed significantly between patients and controls (p < 0.001) and between the three genotype groups in patients (p = 0.029).
Individuals with genotypes AA and AG are characterized by protective attributes against infection with Acinetobacter baumannii, while those having the genotype GG are more prone to infection with this bacterium. Furthermore, an association between specific genotypes and serum levels of IL-7 can hint at the possible role of genetic polymorphism in modulating immune response in relation to bacterial infection.
Developmental language disorders (DLDs) are common neurodevelopmental conditions, affecting approximately 7–10% of children, with significant impacts on communication, academic achievement, and social integration. While genetic factors are known contributors, the underlying genomic architecture and biological pathways remain incompletely understood. This analysis explores key genomic biomarkers of DLD and investigates their functional interactions.
We conducted an integrative genomic analysis combining multiple data-driven approaches. Using the Open Targets platform, we compiled a set of genes associated with DLD-related phenotypes (based on evidence scores ≥0.3) and constructed a gene-phenotype network to visualize these associations. Protein-protein interaction mapping of the identified genes was performed using the STRING database to uncover interaction clusters and shared pathways. We then analyzed sequence and structural relationships among the encoded proteins, including pairwise sequence homology (BLAST alignments), 3D structural modeling, and multimeric interaction prediction using AlphaFold 3.
Our analysis identified 89 genes linked to 14 DLD-related phenotypic terms, with strong clustering around delayed speech. Several genes (e.g., GRN, MAPT, FOXP2, FOXP1, AP4E1) showed particularly high-confidence associations. Structural analysis of encoded proteins revealed unexpected similarity between functionally related but sequence-divergent pairs (e.g., WDR45 and GNB1). AlphaFold 3 modeling predicted a potential interaction between DCDC2 and KIAA0319, suggesting a plausible structural mechanism for their co-involvement in dyslexia.
DLDs emerge from diverse genetic contributors but converge on shared neurodevelopmental pathways. Structural modeling enhances genomic insights by uncovering hidden relationships and candidate interactions, paving the way for more precise genetic screening and functional studies in language disorders.
Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age and are frequently associated with impaired fertility, reproductive dysfunction, and pregnancy complications. Arterial hypertension (AH) is another prevalent chronic condition in women, while increasing epidemiological evidence demonstrates the existence of a bidirectional relationship between UFs and AH. However, the genetic mechanisms underlying this association remain unclear. We hypothesized that UF-associated loci identified in genome-wide association studies (GWAS) may contribute to AH susceptibility.
Genomic DNA from 606 hospitalized patients with UFs (n = 178 with comorbid AH; n = 428 AH-free) underwent allele-specific PCR amplification targeting 17 common GWAS-derived polymorphisms.
The rs1812266 (LOC105375949) locus was associated with a reduced risk of AH (odds ratio (OR) = 0.74; p = 0.028). Model-based multivariate dimensionality reduction (MB-MDR) analysis revealed significant gene–gene interactions (pperm ≤ 0.05) involving UF loci and AH risk, including five key variants (rs66998222, LOC102723323; rs2456181, ZNF346; rs1812266, LOC105375949; rs10929757, GREB1; rs7986407, FOXO1) appearing in multiple models. Notably, rs66998222 was observed in five models, suggesting this residue possesses a central role. For gene–environment interactions, five variants, rs66998222, LOC102723323; rs1812266, LOC105375949; rs10929757, GREB1; rs2456181, ZNF346; rs2553772, LOC105376626, appeared in multiple models, with the smoking × rs66998222 interaction being central to five models. These six risk variants subsequently underwent systematic functional annotation to characterize the potential associated biological roles. Bioinformatics analysis indicated that single nucleotide polymorphisms (SNPs) associated with oxidative stress, renin–angiotensin–aldosterone system (RAAS) function, tissue fibrosis, angiogenesis, and smooth muscle cell remodeling are common mechanisms in both UFs and AH. Cis-eQTL genes and transcription factor (TF)-linked biological processes mediate these mechanisms. Validation using the Cardiovascular Disease Knowledge Portal confirmed the relevance of several SNPs to blood pressure traits.
To our knowledge, this is the first study to explore the genetic overlap between UFs and AH, providing novel molecular evidence for shared pathophysiological pathways. Our findings support the concept of a common genetic predisposition underlying both conditions and may inform new directions for integrated reproductive and cardiovascular health strategies.
Leigh syndrome (LS), first reported in 1951, is the most common primary mitochondrial disease. The overarching term, Leigh Syndrome Spectrum (LSS) was proposed by a ClinGen Expert Panel to encompass the wide continuum of neurodegenerative and non-neurologic manifestations which were associated with classic LS and Leigh-Like Syndrome (LLS). Notably, LSS typically presents developmental regression or delay by two years of age, with about 20% of cases presenting as late-/adult-onset forms after 2 years. Historically defined by clinical, biochemical, and neuropathological findings, the genetic basis of LSS has been elucidated through the use of Sanger and next-generation sequencing (NGS), resulting in the discovery of over 120 causative genes. Moreover, LSS can be caused by mutations in both nuclear-encoded genes and mitochondrial DNA (mtDNA), with overlapping clinical characteristics that occur at similar frequencies. This review aims to summarize the clinical and onset characteristics of LSS, genetic testing-aided diagnosis criteria, and the development of treatments. Furthermore, this review organizes the years since the first reports of gene and mutation discoveries into four consecutive eras: Clinical-Biochemical Era (1990–1999), Early Genomics Era (2000–2009), NGS Revolution Era (2010–2019), and Modern Era (2020–Present). Thus, using this framework, this review chronicles the evolution of LSS molecular genetics and treatment development, highlighting the shift from supportive care to targeted therapies driven by modern technologies. Cornerstone experimental models, such as the Ndufs4 -/-knockout mouse and patient-derived induced pluripotent stem cells (iPSCs), have facilitated mechanistic studies and drug repurposing screens, including the identification of sildenafil as a potential therapeutic agent, which has led to medical improvements in patients. Current advances in gene editing, including mitochondrial single-base editors such as eTd-mtABE and mitoBEs, are enabling gene therapy with precise introduction and correction of LS-causing variants in rat and mouse models. On the preventative front, Mitochondrial Replacement Therapy (MRT), guided by precise maternal mtDNA genotyping, has been successfully applied in clinical practice, allowing mothers carrying LSS-causing mtDNA variants to have healthy babies free of the LS manifestation. Collectively, these advances in gene discovery, genetic diagnosis, sophisticated disease modeling, rapid screening of small molecule drugs, precise gene editing for gene therapy, and innovative treatment strategies, such as MRT, are ushering in an era of precision medicine for LSS.
DNA double-strand breaks (DSB) represent one of the most severe forms of genomic damage. Thus, cells have evolved a complex network of DSB repair pathways, including homologous recombination, classical and alternative end joining, and single-strand annealing, which are tightly regulated by genetic and epigenetic factors. The selection and efficiency of these pathways influence genome integrity, oncogenesis, and therapeutic response. This comprehensive review synthesizes recent findings on the genetic regulation of DSB repair, with emphasis on pathway-specific regulators, chromatin context, and post-translational modifications. Moreover, this review integrates primary research from mammalian systems, including CRISPR-based studies, proteomics, and imaging, with a focus on publications from 2020 to 2025. We discuss the role of key players, such as MRE11–RAD50–NBS1 (MRN), ataxia telangiectasia mutated (ATM), mediator tumor suppressor p53-binding protein 1 (53BP1), breast cancer type 1 susceptibility protein (BRCA1), anti-silencing function 1 (ASF1), ring finger protein (RNF)8/168, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and RAD51 recombinase (RAD51), in orchestrating the associated pathway choice. Epigenetic modifications, RNA-mediated mechanisms, and chromatin remodeling dynamically influence the efficiency and fidelity of repair. Particular attention is provided to emerging regulators, including thyroid hormone receptor interactor 13 (TRIP13), ubiquitin-like with plant homeodomain (PHD) and RING finger domains 1 (UHRF1), Shieldin, and polymerase theta. This review highlights novel insights into transcription-associated DSB repair, the interplay of replication stress with repair pathway engagement, and context-dependent synthetic lethality. We also examine implications for cancer biology, including therapy resistance and biomarker development. Ultimately, understanding the genetic regulation of DSB repair pathways can provide critical insights into genome stability maintenance and reveal new therapeutic opportunities in cancer. Future work should focus on pathway crosstalk, phase-specific regulation, and integrating repair modulation into personalized medicine.