Front Genet [JOURNAL]
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200 papers
Metabolomic and transcriptomic analyses reveal the mechanisms underlying seed dormancy release.
Wang H, Zhong D, Wang F … +5 more , Zheng S, Sun X, Pang Y, Yuan Y, Tang X
Front Genet · 2026 · PMID 42146266 · Full text
, a perennial vine with high pharmaceutical value, exhibits seed dormancy under natural conditions that severely restricts artificial propagation and industrial-scale cultivation. This study aims to systematically invest...
, a perennial vine with high pharmaceutical value, exhibits seed dormancy under natural conditions that severely restricts artificial propagation and industrial-scale cultivation. This study aims to systematically investigate the physiological and molecular mechanisms underlying temperature-stratification-induced (25 °C/4 °C) dormancy release in seeds, providing a scientific basis for optimizing seed propagation protocols. In this study, ultraviolet spectrophotometry (UV) was employed to monitor the dynamic variations in soluble sugars, starch, soluble protein content, and enzymatic activities (including phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), and glucose-6-phosphate dehydrogenase (G6PDH)) during temperature stratification (25 °C/4 °C) of seeds. Additionally, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and RNA-seq were integrated to systematically characterize the phytohormone metabolic profiles and molecular biological mechanisms underlying seed stratification. The results demonstrated that alternating temperatures of 25 °C/4 °C effectively broke seed dormancy. During the dormancy release process, seeds consumed soluble proteins and starch, while starch-degrading genes ( and ) were significantly upregulated to drive starch conversion into soluble sugars. Meanwhile, PGI activity exhibited a marked decrease, while MDH and G6PDH activities showed overall upward trends. At the hormone metabolism level, downregulation of and upregulation of synergistically reduced ABA levels, while upregulation of and promoted GA biosynthesis; downregulation of protein-encoding genes relieved GA signal suppression, collectively forming the "ABA decline-GA rise" hormonal balance shift that drives seed germination. Simultaneously, JA biosynthesis genes and were upregulated, leading to OPDA accumulation, but OPDA was not converted into JA. Furthermore, the upregulation of the negative regulator blocked JA signal transduction, thereby relieving JA-mediated inhibition of germination. This study reveals the molecular mechanisms underlying 25 °C/4 °C temperature-stratification-mediated dormancy release in seeds through integrated physiological, metabolic, and transcriptional analyses.
Mating portfolio and neutral mechanisms are primary causes of genet-ramet frequencies and spatial distributions in smooth cordgrass () along salt marsh tidal gradients.
Tomasula J, Caslin S, Wimp GM … +1 more , Hamilton MB
Front Genet · 2026 · PMID 42146265 · Full text
Partially clonal plants are common and often act as ecological foundation species. Patterns of clonal genotypes (genets) and their vegetative modules (ramets) in natural populations remain poorly documented. Knowledge ga...
Partially clonal plants are common and often act as ecological foundation species. Patterns of clonal genotypes (genets) and their vegetative modules (ramets) in natural populations remain poorly documented. Knowledge gaps in ecological genetics include if environmental variation promotes or limits ramet production, and if random mechanisms or natural selection mainly shape variation in the frequency distributions and spatial organization of ramets and genets. We used genetic markers to measure genet and ramet patterns of , a foundation plant species in North American Atlantic coastal salt marshes, along its natural gradient of tidal inundation and interspecific competition. In ten patches in a natural salt marsh, we sampled 935 stems on 1 m grid transects spanning natural environmental gradients. Samples were genotyped with ten microsatellite loci that provided high exclusion probabilities. Genotypes showed 223 multilocus lineage genets (MLLs) genets that were unique to patches (except a single MLL) and excess homozygosity consistent with biparental mating among relatives or as much as 50% selfing. Patches showed low to no genetic differentiation and there was no isolation by distance within nor between patches. Distributions of ramets per genet were consistent with random sampling with replacement that was heterogeneous among patches, except three MLLs from two patches with high ramet counts. Spatial patterns of ramets within MLLs exhibited intermediate aggregation and interspersion consistent with vegetative expansion by rhizomes. Genotype frequencies, ramet and genet spatial patterns, and distributions of ramets per genet were overall consistent with life history (mating portfolio, vegetative growth by rhizomes) and neutral sampling mechanisms. The three MLLs with high ramet counts could be explained by a range of neutral mechanisms such as patch disturbance history or priority effects, while adaptation to environmental gradients of a few meters is unlikely since these MLLs spanned large areas. As ecosystems dominated by partially clonal species experience a myriad of anthropogenic impacts, our results support wider recognition of combined sexual and vegetative mating portfolios in foundation plant species and improved quantification of clonal patterns on landscapes to better understand and predict ecological genetic variation.
Correction: Case Report: Novel mutations in two patients with -related intellectual disability highlighting the importance of genetic counseling.
Cao H, He T, Wang J … +3 more , Zhou C, Wei X, Zhang X
Front Genet · 2026 · PMID 42137247 · Full text
[This corrects the article DOI: 10.3389/fgene.2025.1669849.].
[This corrects the article DOI: 10.3389/fgene.2025.1669849.].
Non-death loss and GenAI: ethical reflections on griefbots of the living.
Manevich A, Haber Y
Front Genet · 2026 · PMID 42137246 · Full text
The rapid integration of artificial intelligence into loss and bereavement marks a paradigmatic shift in the way humans maintain the relationship with the dead. Rather than relying primarily on memory, individuals may no...
The rapid integration of artificial intelligence into loss and bereavement marks a paradigmatic shift in the way humans maintain the relationship with the dead. Rather than relying primarily on memory, individuals may now engage with algorithmic entities that simulate the deceased by drawing on personal data to reproduce patterns of language, voice, and behavior. Although such technologies may respond to the enduring human need for ongoing dialogue with the deceased, they raise significant questions about the boundaries between life and death, as well as about their potential impact on the grieving process. To date, scholarly attention has focused almost exclusively on bereavement following death. However, it is reasonable to anticipate that these applications will soon extend to forms of loss that do not result from death, particularly situations in which individuals grieve loved ones who remain alive. Introducing the concept of a , a digital representation based on the individual's premorbid personality, this article examines the ethical implications of such developments in advance of their wider adoption. The analysis proceeds through the prism of Beauchamp and Childress's four principles of biomedical ethics, with dementia serving as an illustrative case, given its unique convergence of physical presence and progressive psychological absence. Finally, we propose the ALIVE model (Autonomy & Consent, Living Presence, Intended Benefit, Vigilance Against Harm, Equity & Accountability) as a preliminary framework for ethical evaluation and decision-making in AI-mediated non-death loss contexts, a conceptual foundation rather than a fully elaborated model, with operationalization left to future empirical and normative inquiry.
RUNX1-mediated repression of miR-24 promotes hepatic stellate cell activation and liver fibrosis by targeting the ALK4/Smad3 signaling pathway.
Wang Z, Song M, Zhao Y … +4 more , Li J, Xia L, Wang F, Yang C
Front Genet · 2026 · PMID 42137245 · Full text
BACKGROUND: Epigenetic mechanisms, including microRNAs (miRNAs), are increasingly recognized as crucial regulators of organ fibrosis. In this study, we investigated the role of miR-24 in hepatic stellate cell (HSC) activ...
BACKGROUND: Epigenetic mechanisms, including microRNAs (miRNAs), are increasingly recognized as crucial regulators of organ fibrosis. In this study, we investigated the role of miR-24 in hepatic stellate cell (HSC) activation and liver fibrosis. METHODS: miR-24 expression was analyzed in carbon tetrachloride (CCl)-induced liver fibrosis and activated HSCs using quantitative real-time PCR (qRT-PCR). Gain- and loss-of-function experiments of miR-24 were performed . Western blotting, qRT-PCR, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, luciferase reporter assays, bioinformatics analysis, and chromatin immunoprecipitation PCR (ChIP-PCR) were performed to examine the molecular mechanisms of miR-24. Serum miR-24 levels were measured in patients with liver cirrhosis and further analyzed by subgroup. RESULTS: We observed significant downregulation of miR-24 in CCl-induced liver fibrosis and activated HSCs. Functional assays showed that miR-24 overexpression markedly inhibited HSC activation and migration, whereas miR-24 inhibition had the opposite effects. Mechanistically, ALK4 was identified as a direct target of miR-24: miR-24 bound the 3'UTR of ALK4 mRNA, thereby suppressing Smad3 phosphorylation and downstream fibrosis-associated signaling pathways. Furthermore, the transcription factor RUNX1 was induced during HSC activation, and it transcriptionally repressed miR-24 expression. Clinically, serum miR-24 levels were significantly lower in patients with liver cirrhosis than in healthy controls and were negatively correlated with Child-Pugh grade. CONCLUSION: Our findings suggest that the RUNX1/miR-24/ALK4 axis plays a crucial role in HSC activation and migration. miR-24 may serve as a biomarker for liver fibrosis screening, representing a potential therapeutic target for anti-fibrotic intervention.
Genetic metrics decode diversity: complexity of infection, parasite connectivity, and transmission intensity in Mainland Tanzania's diverse regions.
Pereus D, Fola AA, Bakari C … +20 more , Seth MD, DeFeo R, Lyimo BM, Mandara CI, Madebe RA, Mbata D, Popkin-Hall ZR, Moshi R, Mbwambo RB, Mbwambo D, Aaron S, Lusasi A, Lazaro S, Giesbrecht DJ, Kulohoma B, Juliano JJ, Bailey JA, Juma G, Mobegi VA, Ishengoma DS
Front Genet · 2026 · PMID 42137244 · Full text
INTRODUCTION: Recent evidence indicates that an increasing number of endemic countries have deployed and are using genomic surveillance to determine and monitor the trends and patterns of malaria transmission. This study...
INTRODUCTION: Recent evidence indicates that an increasing number of endemic countries have deployed and are using genomic surveillance to determine and monitor the trends and patterns of malaria transmission. This study aimed to evaluate and identify the most informative genetic metrics for establishing and monitoring the genetic diversity of and its correlation with malaria transmission intensities in Mainland Tanzania. METHODS: A cross-sectional survey of symptomatic patients was conducted in 100 health facilities from February to July 2021 and covered 10 regions categorized into four strata based on transmission intensity. Parasite samples (n = 12,875) were collected as dried blood spots, and all samples with positive test by rapid diagnostic tests (n = 7,199) were sequenced using molecular inversion probes. We targeted 1,832 single nucleotide polymorphisms distributed across the 14 chromosomes. Raw sequence data were analyzed using MIPTools and the final dataset was used to estimate different genetic metrics. RESULTS: The countrywide mean complexity of infection (COI) was 1.5, with 1,878 (59.6%) of parasite samples being monoclonal. The mean COI was significantly higher in high and moderate transmission strata (p < 0.001) compared to low and very low transmission strata. The odds of polyclonal infections were significantly lower in moderate, low, and very low strata compared to the high transmission stratum (p < 0.001). Parasite genetic differentiation among regions was very low, with fixation index ( ) values of 0-0.006. Countrywide parasite populations indicated weak genetic relatedness with pairwise identity by descent (IBD < 0.1). Few pairs (1.8%) met the thresholds of IBD ≥ 50%, and among these, the average pairs of parasites sharing ≥50% IBD were 0.89 and 0.98 for those sharing ≥90%. Discriminant analysis of principal components (DAPC) revealed overlapping parasite population clusters, suggesting genetic similarity among them. DISCUSSION: The study revealed high complexity and polyclonality, particularly in regions with high transmission intensities. The significant association between COI, polyclonality, and transmission intensity suggests these metrics can be integrated within the current malaria surveillance system and may be useful in assessing trends and patterns of malaria transmission. Further validation is needed to link these measures with the current control strategies and evaluate their use in determining the impact of different malaria interventions in Mainland Tanzania.
X chromosome inactivation, X-linked disorders, and cancer.
Salas-Labadía C, Pérez-Vera P, Gómez-Chávez F … +4 more , Pérez Baena X, Martínez Anaya D, Colín Rubio J, Navarrete-Meneses MDP
Front Genet · 2026 · PMID 42137243 · Full text
X chromosome inactivation is an essential process that compensates for gene dosage differences between men and women. During early embryogenesis, one of the two X chromosomes in females is randomly selected for transcrip...
X chromosome inactivation is an essential process that compensates for gene dosage differences between men and women. During early embryogenesis, one of the two X chromosomes in females is randomly selected for transcriptional silencing, inactivating either the maternal or paternal chromosome. This process makes the functional genetic information in females equivalent to a single X chromosome, as in males. Usually, X inactivation occurs in approximately 50% of maternal and 50% of paternal X chromosomes. However, deviations from this ratio can occur, resulting in skewed X inactivation. In women carrying pathogenic variants on the X chromosome-thus presenting X-linked syndromes-such skewing can lead to a wide range of phenotypic manifestations, making X inactivation an important subject of study. Moreover, several X-linked syndromes have been associated with an increased risk of various types of cancer. This risk is influenced not only by specific pathogenic variants but also by mechanisms such as defective X inactivation, which has itself been linked to tumor development. This review compiles both historical and recent findings on X inactivation and its relationship with cancer. It provides an updated overview of the X chromosome inactivation mechanism, a summary of X-linked disorders associated with cancer risk, a discussion of X chromosome involvement in tumorigenesis, an examination of cancer-related genes on the X chromosome, and information on sexual dimorphism in cancer.
Genetics-guided screening and biological validation identify zeylenol as a promising EGFR inhibitor in glioma.
Pan L, Li Y, Chen L … +8 more , Yang W, Gao H, Hou Y, Liu S, Zhao Z, Wang X, Chen H, Wang D
Front Genet · 2026 · PMID 42130808 · Full text
INTRODUCTION: To overcome the high attrition rates in glioma drug discovery, this study established a systematic "Genetics-to-Drug" pipeline aimed at identifying potential therapeutic targets for glioma through causal in...
INTRODUCTION: To overcome the high attrition rates in glioma drug discovery, this study established a systematic "Genetics-to-Drug" pipeline aimed at identifying potential therapeutic targets for glioma through causal inference and discovering potent natural inhibitors. METHODS: We initiated the study with a drug-target Mendelian Randomization (MR) analysis, leveraging quantitative trait loci (QTL) and large-scale genome-wide association studies (GWAS) data for all glioma, glioblastoma (GBM), and non-GBM subtypes. Based on the identified targets, we performed a virtual screening of 17,931 ZINC15 compounds utilizing LibDock, absorption, distribution, metabolism, and excretion (ADME) profiling, toxicity prediction by komputer assisted technology (TOPKAT), CDOCKER, and molecular dynamics (MD) simulations. The binding affinity of selected candidates was confirmed via biolayer interferometry (BLI), and the therapeutic efficacy of the identified small molecules were biologically validated through assays on glioma cells. RESULTS: The druggable MR screening of 140 genes identified EGFR as a key causal target across all glioma subtypes (GBM, non-GBM, and all glioma). Through a series of computer-aided techniques, two promising lead compounds, tremulacin (ZINC000004098458) and zeylenol (ZINC000229763735), were prioritized. Subsequent BLI assays validated a direct physical interaction between zeylenol and EGFR, and biological validation demonstrated that zeylenol treatment significantly suppressed GBM cell proliferation and migration while promoting apoptosis, supporting its therapeutic potential as a novel EGFR inhibitor. DISCUSSION: This study identifies EGFR as a causally relevant therapeutic target in glioma and highlights tremulacin and zeylenol as promising natural EGFR inhibitors, warranting further preclinical development of these compounds as novel glioma therapeutics.
Application of integrated nested Laplace approximation to identify hot spots of methylation heterogeneity in healthy individuals from the MAMELI cohort.
Nardi T, Dariol E, Matsagani R … +5 more , Zojaji D, Gustincich S, Pandolfini L, Biganzoli E, Bollati V
Front Genet · 2026 · PMID 42130807 · Full text
DNA methylation is an epigenetic regulator of gene expression and cell identity, which can be shaped by both physiological and pathological factors, including environmental exposure. The identification of sites with high...
DNA methylation is an epigenetic regulator of gene expression and cell identity, which can be shaped by both physiological and pathological factors, including environmental exposure. The identification of sites with high methylation variability can be computationally challenging, especially in large-scale studies. To address this, we propose a framework based on the integrated nested Laplace approximation (INLA) to model methylation with Bayesian generalized linear mixed models (GLMMs), accounting for subject covariates, genomic annotations, and cell composition. To validate the methodology, we sequenced 158 healthy subjects with nanopore and analyzed a panel of 13 genes related to inflammation and stress response. We identified a set of hypervariable CpG sites whose genomic context and methylation levels were consistent with a regulatory role, making them potential candidates for epigenomic association studies. In our comparison, INLA results were concordant with those obtained with MCMC-based methods, with runtimes shorter by orders of magnitude. The computational efficiency of the framework allows for fast exploratory data analysis, model testing, and iterative prototyping, making it viable for large-scale studies that otherwise would be computationally prohibitive.
21 novel pathogenic variants identified in a cohort of 77 Chinese families with osteogenesis imperfecta.
Zhao B, Zheng C, Liu Z … +5 more , Zhou S, Tao S, Ren X, Liu Y, Zhao X
Front Genet · 2026 · PMID 42130806 · Full text
OBJECTIVE: Osteogenesis imperfecta (OI) is a group of connective tissue disorders with significantly clinical and genetic heterogeneity, which is characterized by low bone mineral density, recurrent fractures and skeleta...
OBJECTIVE: Osteogenesis imperfecta (OI) is a group of connective tissue disorders with significantly clinical and genetic heterogeneity, which is characterized by low bone mineral density, recurrent fractures and skeletal deformities. This study aimed to conduct clinical and genetic analyses in a Chinese OI cohort to expand the spectrum of pathogenic variants and provide evidence for precise genetic counseling and prenatal genetic diagnosis. METHODS: A total of 77 Chinese families with clinically suspected OI were enrolled in this study. Clinical assessments at enrollment included physical examinations, X-ray imaging, and bone mineral density testing. Whole exome sequencing (WES) combined with Sanger sequencing was used to detect candidate pathogenic variants. Variant pathogenicity was evaluated via bioinformatics analysis and familial co-segregation analysis. In this OI cohort, the spectra of pathogenic variants, clinical phenotypes, and genotype-phenotype correlations were analyzed. RESULTS: A 100% detection rate for pathogenic variants was achieved in the 77 families, with 79 variants identified in total. Among the 79 variants, 21 (26.6%) were novel variants founded across six OI-associated genes. Interestingly, apart from the correlation between different pathogenic genes and clinical phenotypes, we also discovered that the severity and phenotype of patients associated with the location of pathogenic variants within the type I collagen domain, exhibiting an aggravating trend from the amino terminus to the carboxyl terminus. CONCLUSION: Based on previous studies of large OI cohorts, we expanded the spectrum of pathogenic variants by identifying 21 novel ones. Meanwhile, we discovered that the location of pathogenic variants, particularly missense variants, in type I procollagen is correlated with the clinical manifestations and severity of patients. These findings will provide important evidence for the precise diagnosis and genetic counseling of the disease.
Single cell and single nucleus RNA sequencing in liver tissues: applications and prospects in model and non-model organisms.
Feng X, Feng Y, Raza SHA … +2 more , Ma Y, Deng H
Front Genet · 2026 · PMID 42125272 · Full text
The liver serves as a central metabolic hub, essential for homeostasis, detoxification, and immunity. Recent advances in single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq) have fundamentally transfor...
The liver serves as a central metabolic hub, essential for homeostasis, detoxification, and immunity. Recent advances in single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq) have fundamentally transformed our capacity to resolve the cellular architecture and functional states of this complex organ. This review comprehensively examines the pivotal applications and expanding potential of these high-resolution transcriptomic technologies in hepatic research, encompassing both established model organisms and emerging non-model species. In human and classical models such as mice and zebrafish, scRNA-seq and snRNA-seq have been critical for delineating developmental trajectories, deciphering the molecular logic of metabolic zonation, and uncovering the precise cellular dynamics and intercellular communication networks that drive diseases like non-alcoholic fatty liver disease (NAFLD), fibrosis, and hepatocellular carcinoma. Beyond these systems, pioneering work in species such as cattle, pigs, tree shrews, and reptiles is now providing unique insights into evolutionary adaptations, specialized physiologies, and comparative disease mechanisms. By synthesizing findings across this broad biological spectrum, we illustrate how single-cell transcriptomics is refining the core principles of liver biology while simultaneously revealing species-specific divergences. Looking ahead, the continued maturation and application of these technologies are poised to yield deeper comparative pathophysiological understanding and accelerate the development of targeted diagnostic and therapeutic strategies for liver diseases in both human and veterinary contexts.
Long noncoding RNAs, microRNAs, and circular RNAs landscape in hypertensive disorders of pregnancy: progress, challenges, and perspectives.
Xu T, Yu X, Ji B … +3 more , Zhang Y, Tong R, Gao Q
Front Genet · 2026 · PMID 42125271 · Full text
Hypertensive disorders of pregnancy (HDP) are a major public health problem that increase morbidity and mortality in many mothers and newborn infants and are considered a significant clinical and economic burden worldwid...
Hypertensive disorders of pregnancy (HDP) are a major public health problem that increase morbidity and mortality in many mothers and newborn infants and are considered a significant clinical and economic burden worldwide. The precise pathogenesis of HDP is not yet fully understood, but as the disease progresses, noncoding RNAs (ncRNAs) such as long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) play abnormal regulatory roles. These ncRNAs function in complex regulatory networks and regulate key biological processes such as cell proliferation, invasion, migration, and apoptosis. Special attention is given to their molecular targets, associated signaling pathways, and the underlying mechanisms of regulatory imbalances. By integrating recent findings and identifying gaps in the main knowledge, this article aims to provide valuable insights into ncRNAs in HDP and to guide therapeutic strategies for this maternal-fetal condition. This will help to establish a profile in this important area of knowledge concerning the clinical management of pregnant women and encourage further research.
Leveraging Hamiltonian neural flow for robust single-cell multi-omics integration: application to Alzheimer's disease.
Huang Z, Kong W, Wang S
Front Genet · 2026 · PMID 42110915 · Full text
Alzheimer's disease (AD) progression involves complex molecular interactions across multiple biological layers, yet integrating high-dimensional single-cell multi-omics data remains computationally challenging. While Gra...
Alzheimer's disease (AD) progression involves complex molecular interactions across multiple biological layers, yet integrating high-dimensional single-cell multi-omics data remains computationally challenging. While Graph Convolutional Networks (GCNs) effectively model cell-gene interaction topologies, they face three critical limitations: over-smoothing in deep architectures, instability under data perturbations, and lack of mechanistic interpretability-obstacles that impede clinical translation. The Hamiltonian Graph Convolutional Network (HGCN), a physics-inspired framework integrating symplectic dynamics with graph-based learning, is proposed in this study, which incorporates energy-conserving Hamiltonian mechanics to address these limitations through: (1) geometric constraints that prevent over-smoothing, (2) stable gradient propagation via symplectic integration, and (3) interpretable phase space representations of cellular states. To validate the effectiveness of the HGCN model, it was evaluated on three single-cell multi-omics datasets: an AD prefrontal cortex dataset, and peripheral blood benchmarks. Meanwhile, differential analysis emerged as the most effective feature extraction strategy in the evaluated experimental setting through systematic preprocessing comparisons. On the AD composite classification task requiring simultaneous prediction of cell type and disease state, HGCN achieved 92.28% accuracy and 0.9228 F1-score, significantly outperforming baseline GCN (88.59% accuracy, 0.8860 F1-score). Phase space visualization revealed biologically meaningful patterns: Inhibitory neurons exhibited heterogeneous subtype structures, while disease states showed symmetric geometric organization suggesting cell-type-invariant pathological mechanisms. Robustness experiments on citation networks demonstrated superior resilience to both feature and structural perturbations compared to standard GCN, with performance advantages increasing under higher perturbation intensities. These results establish HGCN as a robust, interpretable framework for multi-omics integration in complex disease analysis, with potential applications in precision medicine.
Sex-specific variations in subgingival microbiome of elderly patients with moderate periodontitis: an exploratory study.
Zhao YQ, Kuang BF, Dusenge MA … +3 more , Liu Q, Zhang FY, Zhou YH
Front Genet · 2026 · PMID 42110914 · Full text
INTRODUCTION: Periodontitis, a leading cause of alveolar bone destruction and tooth loss, is associated with oral microbiota dysbiosis and shows higher susceptibility in males than in females. This study investigated sex...
INTRODUCTION: Periodontitis, a leading cause of alveolar bone destruction and tooth loss, is associated with oral microbiota dysbiosis and shows higher susceptibility in males than in females. This study investigated sex-specific variations in the subgingival microbiome of elderly patients with moderate periodontitis. METHODS: Subgingival plaque samples were collected from 25 patients with moderate periodontitis (8 males, 17 females; aged 50-73 years). The microbial composition was analyzed using 16S rRNA gene sequencing (V3-V4 region). Functional prediction was conducted utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: Males exhibited higher Chao1 diversity, and beta diversity analysis revealed sex-based clustering. Wilcoxon rank-sum tests and LEfSe analysis identified was enriched in females. KEGG analysis predicted a trend of enrichment of Immune system and Metabolic pathways in females. CONCLUSION: This exploratory study observed sex-specific subgingival microbiome variations of elderly patients with moderate periodontitis. Females exhibited specific enrichment of , which may be associated with predicted Immune system and Metabolic pathways. These findings suggest that sex-specific microbiome differences may be a relevant biological variable in future periodontitis research, and their potential link to alveolar bone loss deserves further exploration.
Clinical outcomes of preimplantation genetic testing for structural rearrangements in couples with chromosomal inversions: a retrospective analysis.
Li Y, Keqie Y, Peng C … +11 more , Chen H, Ren J, Yang H, Liu Z, Fan W, Luo S, Zhang X, Hu T, Liu S, Chen X, Zhou F
Front Genet · 2026 · PMID 42110913 · Full text
Chromosomal inversion is one of the common types of chromosomal structural rearrangements. For couples with chromosomal inversions, the appropriate recommendations for preimplantation genetic testing (PGT) remain a subje...
Chromosomal inversion is one of the common types of chromosomal structural rearrangements. For couples with chromosomal inversions, the appropriate recommendations for preimplantation genetic testing (PGT) remain a subject of ongoing debate. This study retrospectively included couples who underwent PGT between January 2019 and December 2024. All included couples were classified into subgroups based on karyotyping analysis: PGT-INV (chromosomal inversion), PGT-PV (chromosomal polymorphic variation), PGT-A (normal karyotype), and PGT-SR (other balanced chromosomal rearrangements). The euploid rate of biopsied blastocysts did not differ significantly among the PGT-INV, PGT-PV, and PGT-A groups ( > 0.05); however, a statistically significant difference was observed between the PGT-SR group and each of the other three groups ( < 0.001). The aneuploidy rate in couples with female inversion was significantly higher than that in couples with male inversion ( = 0.046). Meanwhile, the proportion of aneuploid blastocysts associated with rearrangement was significantly higher in pericentric (38.94%) compared to paracentric inversions (23.60%) ( = 0.022). With the inverted fragment size increased, the proportion of aneuploid blastocysts associated with rearranged chromosomes increased accordingly and exhibited a linear trend ( < 0.05). In conclusion, the overall euploid rate of blastocysts in couples with chromosomal inversion showed no statistically significant difference compared to those with normal karyotype and chromosomal polymorphic variation; however, the carrier gender and the size of the inverted fragment are influencing factors for the abnormality rate associated with homologous rearranged chromosomes. Genetic counseling is strongly recommended for couples carrying chromosomal inversions.
Development and research trends of stay-green biology in legumes: a bibliometric and visual analysis over three decades.
Yadav SPS, Adhikari U, Myers JR … +1 more , Wallace LT
Front Genet · 2026 · PMID 42110912 · Full text
BACKGROUND: The stay-green trait, which manifests as a delayed leaf senescence in plants, is increasingly viewed as a valuable target for improving crop resilience, quality and yield stability. While most of the progress...
BACKGROUND: The stay-green trait, which manifests as a delayed leaf senescence in plants, is increasingly viewed as a valuable target for improving crop resilience, quality and yield stability. While most of the progress in this area has been made in cereals, research in legumes remains less consolidated, despite their importance for nutrition and sustainable agriculture. METHODS: Bibliometric and structured literature reviews were combined to examine the evolution, thematic structure, and research frontiers of stay-green research in legumes over the past 3 decades. Using the Web of Science Core Collection and Dimensions database, 157 relevant articles published between 1993 and 2025 were identified following PRISMA guidelines and analyzed using VOSviewer and the Bibliometrix R framework to assess publication trends, collaboration networks, thematic evolution, and to classify reported stay-green phenotypes into functional and non-functional categories. RESULTS: The results show a steady rise in publications with a growth rate of 8.6% per year, involving 883 authors across 96 journals, and a strong pattern of international collaboration. Most publications were original research articles, with only 11 review articles, indicating a lack of integrative work in this field. Foundational work by Thomas and colleagues remains highly influential, while recent studies increasingly emphasize molecular genetics and functional analyses in soybean, common bean, pea, and other grain legumes. The keyword analysis highlighted five main research hotspots: drought tolerance, molecular regulation of senescence, photosynthesis related mechanisms, trait mapping and genomics, and pathological stay-green syndromes. Research emphasis has shifted from descriptive physiology toward molecular breeding applications, with increasing focus on distinguishing functional from non-functional stay-green. CONCLUSION: This is the first comprehensive study to apply bibliometric approaches to analyze the trends and research frontiers of stay-green traits in legumes, offering valuable insights and reference points for advancing future research and breeding applications.
Clinical variant interpretation comparing two saturation genome editing-based functional studies for .
Shin JH, Park KS, Kim YG … +3 more , Jang MA, Jang JH, Kim JW
Front Genet · 2026 · PMID 42110911 · Full text
BACKGROUND: Two saturation genome editing (SGE) studies for using haploid human HAP1 cells and mouse embryonic stem cells, respectively, demonstrated contradictory functional results in 16.9% (1,052/6,208) of the varian...
BACKGROUND: Two saturation genome editing (SGE) studies for using haploid human HAP1 cells and mouse embryonic stem cells, respectively, demonstrated contradictory functional results in 16.9% (1,052/6,208) of the variants. We performed clinical variant interpretation and tried to address the discordance by comparing two studies combined with 24 years of clinicopathological data collected at a single institution. METHODS: Retrospectively, we collected data from patients with variants evaluated in the SGE studies. The variants were reassessed according to the ClinGen guidelines and/or multifactorial likelihood analysis. For variants with concordant SGE functional results, either PS3 or BS3 was assigned. Major error rates were compared for variants with discordant results. RESULTS: Among the 88 variants from 526 patients, 13, including three potentially hypomorphic variants, showed discordant results. Major error rates were lower for HAP1-SGE dataset, but without statistical significance. Among the 75 variants with concordant results, 28 and 47 were assigned PS3 and BS3, respectively. Consequently, 93.1% (27/29) of the variants of uncertain significance were reclassified as likely pathogenic (n = 3) or likely benign (n = 24). CONCLUSION: Concordant SGE results are clinically useful for variant reclassification. When discordant results are present, functional evidence should not be assigned, but HAP1-SGE dataset is suggested to be more consistent with patient-specific data. Further segregation analysis and long-term follow-up are needed to resolve discordant cases.
Causal effects of maternal BMI on pregnancy outcomes: a Mendelian randomisation study investigating the mediating role of blood counts.
Flatley C, Wang G, Hatton A … +3 more , Nguyen KM, Hwang LD, Warrington NM
Front Genet · 2026 · PMID 42110910 · Full text
BACKGROUND: Pregnancy requires a delicate balance between the maternal immune system and inflammatory responses. Elevated maternal body mass index (BMI) significantly compromises the immune system and increases systemic...
BACKGROUND: Pregnancy requires a delicate balance between the maternal immune system and inflammatory responses. Elevated maternal body mass index (BMI) significantly compromises the immune system and increases systemic inflammation. High maternal BMI is associated with adverse pregnancy outcomes, including an increased risk of both pre-eclampsia and preterm birth, which may be mediated through immune-related blood cell changes. METHODS: This study used Mendelian randomisation (MR) to investigate the causal relationship between maternal BMI and pregnancy outcomes, including birth weight, placental weight, gestational duration, and pre-eclampsia. We applied two-step MR to assess whether immune-related blood counts, such as neutrophils, lymphocytes, and platelets, mediate these relationships. Single-nucleotide polymorphism (SNP) effect estimates for maternal BMI and pregnancy outcomes were sourced from publicly available genome-wide association studies (GWASs), with pregnancy outcomes partitioned into maternal genetic effects to proxy genetic effects on the intrauterine environment. RESULTS: We found that elevated maternal BMI causally increased placental weight (β = 0.164 standard deviation (SD) increase in placental weight per SD increase in maternal BMI, = 2.92 × 10) and the risk of pre-eclampsia (OR 1.75, = 6.3 × 10). The effect of maternal BMI on placental weight was larger than its effect on birth weight. Mediation analysis found no evidence of the involvement of immune-related blood counts in these relationships. CONCLUSION: Maternal BMI has a significant impact on pregnancy outcomes, particularly by increasing placental weight and the risk of pre-eclampsia. These findings highlight BMI-driven placental adaptations as key contributors to pregnancy complications.
Decoding thalassemia and sickle cell disease: advances in molecular technologies for comprehensive variant detection.
Foord E, Sairafi D, Berg M … +5 more , Westerling S, Adigun T, Uzunel M, Papasavva T, Uhlin M
Front Genet · 2026 · PMID 42100348 · Full text
Thalassemia and sickle cell disease are inherited hemoglobinopathies caused by pathogenic variants in the globin genes and represent a major global health burden. Despite major advances in screening and diagnostics, chal...
Thalassemia and sickle cell disease are inherited hemoglobinopathies caused by pathogenic variants in the globin genes and represent a major global health burden. Despite major advances in screening and diagnostics, challenges persist due to extensive genetic heterogeneity and complex genotype-phenotype relationships. Conventional workflows typically combine hematologic and biochemical analyses with targeted DNA-based testing. However, traditional molecular approaches are often sequential and labor-intensive, with limited capacity to detect the full spectrum of pathogenic variation. Advances in next-generation sequencing (NGS) now enables integrated and comprehensive strategies to support hemoglobinopathy diagnostics and screening follow-up. Currently available NGS-based platforms allow simultaneous detection of diverse variant classes, including sequence variants and copy number alterations, across multiple disease-relevant genes, including genetic modifiers that may influence disease severity. This review summarizes the genetic basis of thalassemia and sickle cell disease and compiles traditional and emerging molecular testing methodologies. It further discusses the strengths, limitations and utility of NGS-based platforms, and considers their role in shaping future screening and diagnostic workflows for hemoglobinopathies.
Prevalence of GSTM1 and GSTT1 null polymorphisms in an admixed healthy Venezuelan population: implications for pharmacogenetic baselines.
Fernández-Mestre M, Salazar-Alcalá E, De Sanctis JB … +4 more , Moreno D, Garmendia JV, Regalado-Gutiérrez O, Peña MJ
Front Genet · 2026 · PMID 42100347 · Full text
INTRODUCTION: The Glutathione S-Transferase (GST) family consists of enzymes with widely studied genetic polymorphisms. Current documentation of GST variant distribution across Venezuelan regions is fragmented. This stud...
INTRODUCTION: The Glutathione S-Transferase (GST) family consists of enzymes with widely studied genetic polymorphisms. Current documentation of GST variant distribution across Venezuelan regions is fragmented. This study aims to determine the prevalence of GSTM1 and GSTT1 null genotypes in a healthy urban Venezuelan group and to compare these frequencies with regional and global reference data. METHODS: A cross-sectional descriptive study was conducted on 300 healthy unrelated individuals. Genotyping was performed via multiplex PCR, and frequencies were calculated based on the presence or absence of specific amplicons. RESULTS: The frequencies of the GSTM1 and GSTT1 null genotypes were 38.67% and 32.67%, respectively. The "double null" genotype was observed in 6.00% of the sample, representing a relevant ethnogeographic heterogeneity. DISCUSSION: Comparative analysis revealed a divergence from reported data for ancestral Amerindian groups and an allelic distribution pattern reflecting a tri-hybrid genetic architecture intermediate between West African and Southern European references. These findings establish an updated genetic baseline for this urban cohort, highlighting a distinct genotypic distribution within the Venezuelan population. This study underscores the degree of population stratification in the region and provides a descriptive framework for future toxicogenomic research and personalized medicine applications.
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