Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
Core genome analysis reveals novel drug and vaccine targets in multidrug-resistant Citrobacter koseri.
Ashraf Z, Arshad F, Shakeel SN … +7 more , Rahman FU, Fawy KF, Altwaim SA, Alasmari SM, Ali A, Khan MU, Shah M
Mol Genet Genomics · 2025 Dec · PMID 41460334 · Publisher ↗
Citrobacter koseri is a Gram-negative, multidrug-resistant bacterium linked to severe infections in immunocompromised individuals and neonates. It is especially linked to sepsis and meningitis, which often lead to CNS ab...
Citrobacter koseri is a Gram-negative, multidrug-resistant bacterium linked to severe infections in immunocompromised individuals and neonates. It is especially linked to sepsis and meningitis, which often lead to CNS abscesses in newborns. Most infections happen randomly, but some are passed down from parent to child. There have also been reports of hospital-acquired outbreaks in neonatal care units. Even though diagnostic and treatment methods have improved, the death rate is still high. About one in three affected babies dies, and almost half of them suffer long-term neurological damage. As antibiotic resistance becomes more common, there is a growing need to look into new ways to treat diseases, such as vaccines and new drug targets. In order to address this issue, a thorough in-silico methodology integrating subtractive proteomics and reverse vaccinology was employed to pinpoint potential therapeutic targets from the core proteome. Five multi-epitope vaccine constructs were created using B- and T-cell epitopes from prioritized proteins, based on epitope prediction. Physicochemical and docking analysis identified constructs V1 and V5 as having strong binding affinities to Toll-like receptors TLR4 and TLR2, respectively. Furthermore, MD simulations validated the structural stability of docked complexes. In-silico immune simulations revealed that the constructs might induce robust immune responses. Additionally, potential drug target proteins were subjected to druggability analysis. This study presents a promising computational framework for combating C. koseri, though experimental and animal model validations are necessary to confirm the findings of this study.
Genomic insights into date palm (Phoenix dactylifera) diversity through molecular marker prospectives.
Detroja A, Ibrahim M, Koradiya J … +4 more , Bhatt TC, Bhimani A, Sanghvi G, Bishoyi AK
Mol Genet Genomics · 2025 Dec · PMID 41457197 · Publisher ↗
Date palm (Phoenix dactylifera L.) is a vital fruit crop of North Africa, the Middle East, and South Asia, serving as both a staple food and a source of income. With more than 5,000 cultivars reported worldwide but only...
Date palm (Phoenix dactylifera L.) is a vital fruit crop of North Africa, the Middle East, and South Asia, serving as both a staple food and a source of income. With more than 5,000 cultivars reported worldwide but only a few being commercially exploited, preserving and understanding genetic diversity is essential for sustainable production, crop improvement, and food security. This review provides a critical synthesis of recent progress in assessing date palm diversity using molecular markers and omics-based approaches. Molecular markers are effective tools, such as RAPD, ISSR, SSR, AFLP, and SCoT, have been effectively applied for cultivar identification, phylogenetic studies, and diversity assessment. For example, SSR markers enabling precise fingerprinting of different cultivars across North Africa and the Middle East, and ISSRs reveal high polymorphism in Tunisian genotypes. this article integrates molecular marker studies with advances from genomics and transcriptomics, highlighting novel insights into stress tolerance, fruit quality traits, and genetic structuring of male and female populations. The nobility of this study lies in comparing marker systems and emphasizing their relative strengths, limitations, and complementary applications in biodiversity studies. Additionally, bibliometric and patent landscape analyses were incorporated to map global research trends and innovation patterns, emphasizing the growing relevance of date palm genomics. In conclusion, molecular markers, when combined with modern genomics and transcriptomics, offer powerful tools for characterizing diversity, guiding conservation strategies, and accelerating marker-assisted breeding. This integrative approach supports the Sustainable Development Goal 2 (Zero Hunger) by advancing genetic improvement and sustainable cultivation of date palm.
The first case of Branchio-oto-renal (BOR) syndrome caused by a deep intronic variant in EYA1.
Lorans M, Skipper KA, Nielsen TØ … +6 more , Drue SO, Nielsen CK, Thorup CV, Nørholt SE, Thøstesen LM, Gregersen PA
Mol Genet Genomics · 2025 Dec · PMID 41457110 · Publisher ↗
The aim of this study was to identify the genetic cause of Branchio-oto-renal (BOR) syndrome using whole genome sequencing (WGS) in a previously unsolved case. We describe a novel, deep intronic variant in EYA1 that segr...
The aim of this study was to identify the genetic cause of Branchio-oto-renal (BOR) syndrome using whole genome sequencing (WGS) in a previously unsolved case. We describe a novel, deep intronic variant in EYA1 that segregates with BOR syndrome in three generations in a Danish family. According to the prediction algorithm, SpliceAI, the variant creates a cryptic splice donor site in intron 7, resulting in inclusion of a pseudo-exon. We functionally assessed the intronic variant using an in-vitro splicing assay confirming a spliceogenic effect. The abnormally spliced EYA1 transcript is expected to undergo nonsense mediated decay resulting in haploinsufficiency. In conclusion, we identified the genetic cause of BOR syndrome in the family. To the best of our knowledge, this is the first report of a causative deep intronic variant in BOR syndrome. Our results demonstrate the clinical utility of WGS in cases with highly specific phenotypes.
Improving variant interpretation and diagnosis in Koolen-de Vries syndrome through a curated genotype-phenotype repository.
Huang H, Geng J, Long Y … +11 more , Xiong W, Wang X, Wang C, Zhang Q, Tang T, Chen Y, Zhao Y, Cheng J, Lu Y, Bu F, Yuan H
Mol Genet Genomics · 2025 Dec · PMID 41457108 · Publisher ↗
Neurodevelopmental disorders (NDDs) exhibit complex genotype-phenotype associations that frequently result in inconclusive variant interpretations, contributing to suboptimal diagnostic yields (~ 40%). Koolen-de Vries sy...
Neurodevelopmental disorders (NDDs) exhibit complex genotype-phenotype associations that frequently result in inconclusive variant interpretations, contributing to suboptimal diagnostic yields (~ 40%). Koolen-de Vries syndrome (KdVS), an autosomal dominant NDD caused by KANSL1 haploinsufficiency, exemplifies this diagnostic challenge with its multisystem manifestations and lack of systematic genotype-phenotype associations. To address this gap, we constructed a comprehensive KdVS genotype-phenotype repository by systematically integrating all molecularly confirmed cases from global literature. Comprehensive phenotypic analysis revealed that core KdVS features include developmental delay/intellectual disability, characteristic craniofacial dysmorphism, hypotonia, and multisystem abnormalities. Phenotypic association analysis identified 249 significant correlations, demonstrating that KdVS clinical manifestations are highly interconnected rather than representing isolated features, such as the association between strabismus and hydrocephalus (OR = 14.26). Application of this repository to screen a Chinese rare disease cohort identified 53 KANSL1 variants. Among these, one de novo nonsense variant (NM_001193466.2: c.902T > G, p.Leu301Ter) was classified as pathogenic in a Chinese boy with classic KdVS features. The remaining 52 variants were categorized as variants of uncertain significance (VUS), approximately half of which were absent from gnomAD databases. Each VUS was comprehensively annotated with detailed clinical profiles to facilitate phenotype-driven reinterpretation. In conclusion, this study establishes KdVS as a highly interconnected multisystem disorder and demonstrates that deep phenotypic association analysis enhanced genetic diagnosis. This disease-specific repository approach provides a scalable framework for improving molecular diagnostics across rare NDDs.
Twin pairs discordant for incident coronary artery disease reveal epigenetic and transcriptomic differences by gene region.
Skovgaard AC, Thinggaard M, Hjelmborg JV … +4 more , Nejad AM, Beck HC, Tan Q, Soerensen M
Mol Genet Genomics · 2025 Dec · PMID 41381984 · Full text
Cardiovascular diseases are the leading causes of mortality globally, of which coronary artery disease (CAD) is the most frequent. Several epigenomics and transcriptomics studies of CAD have been conducted, however, only...
Cardiovascular diseases are the leading causes of mortality globally, of which coronary artery disease (CAD) is the most frequent. Several epigenomics and transcriptomics studies of CAD have been conducted, however, only a few studies have utilized the statically powerful discordant twin pair design, which reduces the confounding introduced by genetics. Finally, no study has investigated the link between the DNA methylation position and gene expression levels. The present study aims at filling this knowledge gap, to present novel biomarkers of CAD. We investigated 44 Danish twin pairs that were discordant for incident CAD, for whom, both genome-wide DNA methylation (CpG) and gene expression (probe) data were available. We identified CpGs and probes, which were more different within the twin pairs than expected by change, and investigated these by Cox regression analysis. CpGs and probes belonging to the same gene were divided into groups based on their directions of effect, and these genes were investigated by gene set enrichment and interaction network analyses. Overall, we found that CAD co-twins showed DNA methylation patterns leading to up-regulated gene expression; especially with demethylation of promoters and methylation of gene bodies, compared to their non-CAD co-twin. Generally, we found that the largest biological group of up-regulated pathways related to immune-inflammation processes, whereas down-regulated pathways related to muscle system biology, among others. Hence, the present study uncovers a specific pattern between DNA methylation position and gene expression levels relating to CAD, pointing to a need for additional studies. However, such multi-omics designs are surprisingly rare.
Complete mitochondrial genome of Hypoclinemus mentalis and phylogenetic analysis of the order Pleuronectiformes.
Sun CH, Xu Y, Zhan YJ … +3 more , Ma X, Chen XD, Lu CH
Mol Genet Genomics · 2025 Dec · PMID 41381976 · Publisher ↗
We sequenced the mitochondrial genome of the freshwater flatfish Hypoclinemus mentalis, analyzed its structural characteristics, and constructed a phylogenetic tree for the order Pleuronectiformes based on sequence data...
We sequenced the mitochondrial genome of the freshwater flatfish Hypoclinemus mentalis, analyzed its structural characteristics, and constructed a phylogenetic tree for the order Pleuronectiformes based on sequence data of 13 protein-coding genes (PCGs) to elucidate the mitochondrial genome characteristics of H. mentalis and its phylogenetic position in Pleuronectiformes. The mitochondrial genome of H. mentalis is 16,802 bp in length and encodes 13 PCGs, two rRNA genes, 22 tRNA genes, and one non-coding region. Its base composition shows AT preference (A + T content 56.4%). The PCG nad6 and eight tRNA genes (trnQ, trnA, trnN, trnC, trnY, trnS2, trnE, and trnP) are located on the light strand, whereas the remaining 28 genes are located on the heavy strand. Among the 22 tRNAs, the secondary structure of trnS1 lacks the dihydrouridine arm, whereas the remaining tRNAs form a typical clover secondary structure. In the phylogenetic tree, H. mentalis clustered well with three other species of the family Achiridae. In the order Pleuronectiformes, monophyletic issues existed in three families (Cynoglossidae, Soleidae, and Pleuronectidae) and five genera (Ancylopsetta, Arnoglossus, Citharichthys, Cynoglossus, and Etropus). Our findings elucidate the structural characteristics of the complete mitochondrial genome of H. mentalis and its phylogenetic position and provide key molecular evidence for understanding the taxonomic relationships of this species within Pleuronectiformes.
ATR&RNASEL germline variants: novel findings in a case of familial cancer.
Biswas S, Vihol D, Manekar S … +1 more , Bakshi S
Mol Genet Genomics · 2025 Dec · PMID 41381960 · Publisher ↗
In familial cancer the genetic etiology can play a significant role in the cancer onset. This study aims to explore the genetic predisposition to familial cancer by analysing germline variants in Indian family across gen...
In familial cancer the genetic etiology can play a significant role in the cancer onset. This study aims to explore the genetic predisposition to familial cancer by analysing germline variants in Indian family across generations through whole exome sequencing (WES). Given the limited genetic data from Indian populations and the under representation in the global data, this research seeks to identify genetic variants from India that may contribute to cancer risk. The detection of such constitutional genetic variants in both symptomatic and asymptomatic individuals, can facilitate risk assessment and personalized management strategies for future generations. We report findings from whole exome sequencing for the proband with right breast fibroadenoma and a strong family history of breast cancer, colon cancer and uterine cancer in her mother and maternal grandmother, niece, and paternal grandmother respectively. Sanger sequencing was implemented in the proband and her asymptomatic father to validate the presence of any inherited genetic variants, previously reported in other ethnic groups however being reported for the first time in Indian Population. We report two germline variants ATR c.2320dup and RNASEL c.1029G > A. The variant effect predictor analysis in the proband revealed two pathogenic variants rs1800566 and rs1799983of the NQO3 c.559 C > T (p. Pro187Ser) and NOS3c.894T > G (p. Asp298Glu) genes. The main findings were evaluated for pathogenicity using various mutation score prediction tools, followed by an in-silico analysis of protein structural and functional changes, which revealed alterations in protein domains impacting DNA damage repair and antiviral pathways. Identifying the novel germline variants in the ATR and RNASEL genes within an Indian familial cancer case, underscores the critical role of comprehensive genetic screening in early detection and risk management of hereditary cancers. Our findings emphasize the importance of integrating genomic analyses for personalized medicine approaches, to better assess familial cancer risk and guide early intervention strategies. Our findings will pave the way for functional validation of these variants through in vitro and in vivo studies evaluating RNA and protein expression. We demonstrate importance of expanding genetic studies to diverse populations, which could enhance risk stratification and inform targeted therapeutic developments.
Unveiling crosstalk between abiotic and biotic stress responses in soybean (Glycine max) using integrative RNA-Seq meta-analysis.
Pathak AK, Narang J, Kumar A
Mol Genet Genomics · 2025 Dec · PMID 41381957 · Publisher ↗
Soybean (Glycine max) is a critical world crop, highly valued for its high protein and oil content. However, its yield is increasingly threatened by varied abiotic and biotic stresses. Biotic and abiotic stresses often s...
Soybean (Glycine max) is a critical world crop, highly valued for its high protein and oil content. However, its yield is increasingly threatened by varied abiotic and biotic stresses. Biotic and abiotic stresses often show antagonistic or synergistic cross-talk, whereby one stress may induce cross-tolerance or cross-susceptibility to another stress. Therefore, investigating the molecular interactions for the identification of key hub genes is essential for development of multistress resilient soybean crop. The current research conducts an extensive meta-analysis of available RNA-Seq data to identify conserved transcriptional responses to major stress conditions. 903 and 1,136 meta-differentially expressed genes (meta-DEGS) were found under abiotic (drought, heat, cold, salt) and biotic (aphids, mites, rust, viruses) stresses, respectively, with 28 genes regulated across both types of stresses. Central to the stress response was co-upregulation of protein kinases and NAC transcription factors, regulation of redox buffers and programmed cell death. Abiotic stresses initiate a proteostasis-centred response, involving elevated protein folding, degradation, and ribosome biogenesis, and repression of energy-expensive pathways like photosynthesis. Contrarily, biotic stress triggers immune responses through upregulation of defence and signalling genes, while suppressing circadian function and growth. Furthermore, network analysis, promoter motif discovery and miRNA profiling revealed key hub genes, such as Bystin, BING4, Nucleolar Protein 6, DOF transcription factors, miR171, and miR172. Briefly, in this research we identified putative converging genes of soybean where abiotic and biotic stresses signalling cross-talk. Candidate miRNAs, DOF and NAC transcription factors, HSP chaperones, and ERAD- and ribosome-related genes as for stress resilience in soybean were identified. This systems-level understanding provides promising targets for functional validation and afterwards developing climate-resilient and pathogen-tolerant soybean cultivars through targeted genetic and breeding strategies.
The degradation of extended protein isoforms points to a misfiring translation initiation process.
Tress ML
Mol Genet Genomics · 2025 Dec · PMID 41381938 · Publisher ↗
There is ever increasing evidence for significant amounts of translation upstream of known AUG start codons in protein coding genes. Some of this translation is from upstream open reading frames (ORFs) that are unconnect...
There is ever increasing evidence for significant amounts of translation upstream of known AUG start codons in protein coding genes. Some of this translation is from upstream open reading frames (ORFs) that are unconnected to the main coding exons, but upstream initiation codons that are in-frame with coding exons can produce N-terminally extended protein isoforms. N-terminal extensions have much more proteomics support than the shorter proteins predicted to be produced from upstream ORFs. The upstream regions that produce N-terminal extensions have certain characteristics in common. They are highly GC-rich, most of the predicted start codons are non-AUG, and most do not conserve their reading frames beyond simians. The extended isoforms themselves are found significantly more frequently in dysregulated cells than in normal tissues. Approximately one in seven of these N-terminal extensions are upstream of signal peptides and would almost certainly block their recognition by the signal recognition particle. As a result, N-terminally extended isoforms containing exposed, hydrophobic signal peptides would be expected to accumulate in the cytoplasm. However, this analysis finds that those N-terminal extensions that would block signal recognition are practically not detected at the protein level even though the transcripts that would produce these extensions are found as expected in ribosome profiling experiments. This is a clear indication that these mislocated proteins are degraded after translation. Theprobable degradation of these extended proteins strongly suggests that their translation is a side effect of inefficient translation initiation.
Genome wide dissection and haplotype analysis to identify candidate loci for harvest index under spot blotch in bread wheat.
Singh GM, Bhati PK, Vishwakarma MK … +4 more , Ladejobi F, Mishra VK, Sharma S, Joshi AK
Mol Genet Genomics · 2025 Dec · PMID 41381936 · Publisher ↗
Harvest index (HI), a key yield-related trait in wheat, is influenced by genetic, phenological, environmental, and stress factors. In the Indo-Gangetic Plains (IGP) of India, spot blotch (SB) poses a major biotic stress,...
Harvest index (HI), a key yield-related trait in wheat, is influenced by genetic, phenological, environmental, and stress factors. In the Indo-Gangetic Plains (IGP) of India, spot blotch (SB) poses a major biotic stress, reducing grain yield by affecting photosynthesis and HI. Identifying stable wheat genotypes and genomic regions controlling these traits are essential for developing resilient wheat for the IGP. We evaluated 1500 elite wheat lines in four environments at IGP, including SB and disease-free (DF) conditions. On average, in the SB condition HI (%) reduced by 4.3% compared to its DF environment. Genome-wide association studies identified important SNPs:1A_494392059, 1A_495192503, 2A_32931719, 3B_10249157, 3B_10644041, 3B_6127880, 5B_538548049, 6A_96651968, 7A_49592941 and 7D_326728664, and a favourable haplotype TTGTCG (n = 303), which showed higher average HI (39.75%) under SB conditions. Additionally, most of candidate genes associated with the identified SNPs were involved in senescence and disease resistance. Stability analysis using AMMI and genotype selection index identified a set of genotypes with consistently high and stable HI under both SB and DF conditions. Further, genotypes with favourable alleles at all these identified significant MTAs, and stable genotypes identified for HI shared common genetic contributors, including the SR50 gene and prominent wheat varieties such as KACHU, PASTOR, and PRL. These genetic backgrounds play a pivotal role in conferring both disease resistance and yield stability, highlighting their importance in wheat breeding programs for IGP. Further, Genomic predictions using genome-wide markers demonstrated moderate predictive accuracy, ranging from 0.22 to 0.39, with higher accuracy observed under SB conditions. The stable genotypes and genomic regions identified in this study could serve as important resources and knowledge for developing resilient genotypes adapted to the IGP.
On the role of dcm and vsr in Escherichia coli adaptive mutation.
Minda R, Ramchandani J, Bindal G … +4 more , Rath D, Kodgire P, Makde RD, Bhattacharjee S
Mol Genet Genomics · 2025 Dec · PMID 41381922 · Publisher ↗
Microorganisms rapidly adapt to non-lethal stress through mutations, a process central to microbial evolution. In this study, we investigate the molecular mechanism of adaptive mutagenesis in the bacterial strain Escheri...
Microorganisms rapidly adapt to non-lethal stress through mutations, a process central to microbial evolution. In this study, we investigate the molecular mechanism of adaptive mutagenesis in the bacterial strain Escherichia coli K-12 harboring a frameshift lac mutation. A non-random mutational spectrum, featuring a prominent - 1 bp deletion hot-spot is an intriguing unsolved phenomenon seen in the revertants of starving cells of this strain. The very-short-patch mismatch repair, a stationary-phase specific DNA repair pathway, has been hypothesized to create this hot-spot. To test this, we independently inactivated two main players of this pathway: dcm involved in DNA cytosine methylation and vsr encoding a sequence-specific DNA repair endonuclease. Contrary to the prediction of our hypothesis, the stationary-phase mutational spectra of Δdcm and Δvsr strains were indistinguishable from that of the wild-type strain, i.e., the frequency of mutations at the hot-spot remained unchanged. Unexpectedly, both Δdcm and Δvsr strains showed a two-fold increase in stationary-phase reversion frequency with respect to the wild-type strain. This result differed from an earlier finding where simultaneous deletion of both genes had no effect. We conclude that the adaptive mutation hot-spot is not caused by very-short-patch mismatch repair. Instead, our data suggest that dcm and vsr independently influence adaptive mutagenesis rate, possibly through previously unrecognized 'moonlighting' functions. Future work will aim to uncover the mechanism behind this unique adaptive mutational spectrum, advancing our understanding of stress-induced mutagenesis.
RBM7 suppresses mitochondrial dysfunction and ferroptosis by destabilizing FBXL16 mRNA to enhance Temozolomide resistance in glioblastoma.
Liu N, Cui Y, Li J … +5 more , Li S, Tu Y, Huo J, Zhang T, Zhen H
Mol Genet Genomics · 2025 Dec · PMID 41381783 · Publisher ↗
Temozolomide (TMZ) resistance is a major cause of treatment failure in glioblastoma (GBM). This study investigates the role and mechanism of the RNA-binding protein RNA-binding motif protein 7 (RBM7) and F-box and leucin...
Temozolomide (TMZ) resistance is a major cause of treatment failure in glioblastoma (GBM). This study investigates the role and mechanism of the RNA-binding protein RNA-binding motif protein 7 (RBM7) and F-box and leucine-rich repeat protein 16 (FBXL16) in TMZ resistance in GBM, focusing on mitochondrial dysfunction and ferroptosis. TMZ-resistant GBM cell lines (TR/U87) were established through gradient induction. Cell viability and proliferation were assessed using the Cell Counting Kit-8 assay and colony formation assays. Western blot analysis and immunohistochemistry were performed to measure FBXL16, activating transcription factor 4, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha protein expression. Transwell assays evaluated TR/U87 cell migration and invasion. Co-immunoprecipitation and RNA immunoprecipitation assays verified the interaction between RBM7 and FBXL16. An actinomycin D assay analyzed FBXL16 mRNA stability. Flow cytometry was used to detect reactive oxygen species, iron levels, and apoptosis. A nude mouse xenograft model was used to validate in vivo effects. RBM7 was highly expressed in TMZ-resistant cells. Knockdown of RBM7 suppressed TR/U87 cell proliferation and migration, induced mitochondrial structural damage, and triggered ferroptosis. Mechanistically, RBM7 interacted with FBXL16 and reduced its mRNA stability. FBXL16 knockdown reversed RBM7 deficiency-induced ferroptosis and chemosensitivity. In vivo experiments confirmed that RBM7 knockdown combined with TMZ significantly inhibited tumor growth. RBM7 promotes TMZ resistance by suppressing mitochondrial dysfunction and ferroptosis through destabilization of FBXL16. Targeting the RBM7-FBXL16 axis may represent a novel strategy to overcome GBM chemoresistance.
Paternal transgenerational epigenetic effects: high fat diet induced obesity alters miRNA expression in F1 and F2 C57BL/6 male mice.
Satir-Basaran G, Rassoulzadegan M, Cumaoglu A
Mol Genet Genomics · 2025 Dec · PMID 41351773 · Publisher ↗
Paternal obesity affects offspring’s metabolic health. Genetic and environmental factors lead to metabolic dysfunction and obesity, a condition affecting future generations worldwide. The reasons for this condition’s tra...
Paternal obesity affects offspring’s metabolic health. Genetic and environmental factors lead to metabolic dysfunction and obesity, a condition affecting future generations worldwide. The reasons for this condition’s transgenerational transmission are important. The mechanisms of RNA-mediated heritability remain unclear, and there is limited knowledge about the effects of paternal exposure. Recent studies indicate that microRNAs (miRNAs) regulate metabolic processes that alter or maintain metabolic homeostasis and energy balance in obesity. Considering the increase in global obesity rates, this study aimed to investigate the impact of paternal influence on metabolic health through the epigenetic mechanism in normal diet (ND) fed F1 and F2 offspring of high fat diet (HFD) induced C57BL/6 male mice. Paternal obesity can transmit epigenetic changes in germ cells to subsequent generations, causing adipose tissue remodeling in offspring. To investigate the effects of HFD exposure in epididymal adipose tissue of male mouse offspring, miRNA expression levels were determined by qRT-PCR and protein levels by western blotting. In addition, paternal HFD exposure had significantly increased the expression of adipogenic proteins involved in lipid metabolism in epididymal adipose tissue. Expression levels of miR-199a-5p significantly increased in offspring. This study emphasizes the significance of paternal miRNAs in transmitting diet-induced phenotypes and metabolic adaptations to offspring. The results imply that metabolic disorders in fathers may be heritable and that lifestyle may serve as molecular biomarkers for epigenetic changes in the development and subsequent health of offspring.
Bioinformatics and artificial intelligence in genomic data analysis: current advances and future directions.
Olawade DB, Kade A, Egbon E … +4 more , Usman SO, Fapohunda O, Ijiwade J, Ogbonna CE
Mol Genet Genomics · 2025 Dec · PMID 41348251 · Publisher ↗
The exponential growth of genomic data from next-generation sequencing technologies has created an urgent need for advanced computational approaches that can efficiently process, integrate, and interpret complex multi-di...
The exponential growth of genomic data from next-generation sequencing technologies has created an urgent need for advanced computational approaches that can efficiently process, integrate, and interpret complex multi-dimensional biological information. This comprehensive review examines how artificial intelligence (AI), particularly machine learning and deep learning, is transforming genomic data analysis and addressing critical limitations of traditional bioinformatics methods. A thorough literature search was conducted across PubMed, Scopus, and Google Scholar databases, targeting peer-reviewed studies published between 2010 and 2024. This review addresses a critical knowledge gap by synthesizing current AI applications across the genomic analysis pipeline, from variant calling to multi-omics integration and personalized medicine, whilst critically evaluating emerging technologies including explainable AI and federated learning. AI methods have significantly improved accuracy in variant calling, gene expression profiling, and disease risk prediction. Key findings demonstrate that deep learning models achieve superior performance in complex pattern recognition, whilst explainable AI addresses the "black box" problem essential for clinical adoption. Federated learning enables privacy-preserving collaborative research across institutions. However, significant challenges remain, including data standardization, computational costs, algorithm interpretability, and ethical considerations surrounding privacy and algorithmic bias. Future directions include quantum computing integration and AI-enhanced CRISPR technologies. This review concludes that whilst AI represents a transformative force in genomic research, successful clinical translation requires addressing current technical and ethical challenges through interdisciplinary collaboration, robust validation frameworks, and responsible implementation strategies prioritizing patient safety and data security.
Resveratrol mitigates diabetes-induced cardiac dysfunction via SIRT1/PPAR-α/PGC-1 pathway.
Fu R, Hao J
Mol Genet Genomics · 2025 Dec · PMID 41348235 · Publisher ↗
Diabetic cardiomyopathy (DCM) significantly contributes to cardiovascular complications in diabetes. This study investigated the protective effects of Resveratrol (RES) in combination with evidence-based nursing on DCM a...
Diabetic cardiomyopathy (DCM) significantly contributes to cardiovascular complications in diabetes. This study investigated the protective effects of Resveratrol (RES) in combination with evidence-based nursing on DCM and the underlying molecular mechanisms. Eighty elderly patients with type 2 diabetes mellitus (T2DM) and DCM were randomly assigned to a control group or an RES group. The RES group received RES (800 mg/day) along with evidence-based nursing, while the control group received a placebo with nursing care for six months. Clinical indicators, including glucose and lipid metabolism, lactate dehydrogenase (LDH) activity, inflammatory markers, and cardiac function parameters, were evaluated. Additionally, T2DM rat models were used to examine oxidative stress, cells proliferation, fats accumulation, mitochondrial dysfunction, apoptosis and autophagy, while high glucose (HG)-induced H9C2 myocardial cells were used to investigate cellular mechanisms involving the SIRT1/PPAR-α/PGC-1 pathway. RES combined with evidence-based nursing improved glucose and lipid metabolism, reduced LDH activity, decreased inflammatory markers (TNF-α, IL-6), and enhanced cardiac function in T2DM patients with DCM. In rats, RES restored left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) while reducing myocardial apoptosis with lower Bax and cleaved caspase-3 levels and higher Bcl-2 expression, reduced fibrosis and fat accumulation. Additionally, RES alleviated oxidative stress by decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, suppressed myocardial apoptosis, improved mitochondrial function while increasing ATP and superoxide dismutase (SOD) activity as well as enhancing autophagy. SIRT1 inhibitor (EX527) injections in rats reversed the beneficial effects of RES. In HG-treated H9C2 cells, RES improved cell viability, reduced apoptosis, alleviated oxidative stress and enhanced autophagy. RES ameliorates DCM through SIRT1/PPAR-α/PGC-1 signaling pathway in rats and improves efficacy of elderly DM patients in combination with evidence-based care.
Weakened invasion of severe fever with thrombocytopenia syndrome bunyavirus beneficial to its immune escape by multi-site mutation of glycoprotein.
Wang L, Wang J, Zhang J … +6 more , Wang X, Cao W, Yang L, Wu Y, Li B, Qiao Y
Mol Genet Genomics · 2025 Nov · PMID 41273444 · Publisher ↗
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) which results in a high mortality rate and poses a public health t...
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) which results in a high mortality rate and poses a public health threat. Gene variation of SFTSV is one of the major forces driving its persistence and widespread prevalence. However, how genetic variations affect virus invasion is not yet fully understood. In this study, we evaluated the adaptive advantage of three stable high-frequency substitutions D170N, I323V, and K619R located on the envelope glycoprotein of SFTSV based on 1041 M segments of their genomes. The result demonstrated that single mutation of D170N, or K619R reduced infectivity of mutant. However, the combined presence of both D170N, and K619R mutation enhanced infectivity of mutants. Structure model and SPR assay studies indicated that the substitution at the 170 site reduced the binding affinity between Gn glycoprotein and host C-C motif chemokine receptor 2 (CCR2). Additionally, neutralization assay showed I323/K619R mutant exhibited completely resistance to neutralizing antibodies pressure. This study reveals that SFTSV balances its entry ability by gene variation of different loci on its glycoprotein via a trade-off between Gn and Gc. In addition, a weakened invasion strategy facilitated by site mutations benefits its immune evasion. The findings provide mechanistic insights into its prevalence, thereby enabling early warnings for potential future outbreaks.
Detection of three novel loci involved in reduced seed-shattering behaviour of an aus rice cultivar, Oryza sativa Kasalath.
Shionari N, Yamaguchi Y, Takama N … +9 more , Oka Y, Takenaka Y, Matsubara N, Inoue C, Htun TM, Tsujimura Y, Numaguchi K, Ishii T, Ishikawa R
Mol Genet Genomics · 2025 Nov · PMID 41258559 · Publisher ↗
Reduced seed shattering is a key yield-improving trait selected during the domestication of the Asian rice, Oryza sativa, from its wild ancestor, O. rufipogon. Three quantitative trait loci, qSH1, sh4, and qSH3, are repo...
Reduced seed shattering is a key yield-improving trait selected during the domestication of the Asian rice, Oryza sativa, from its wild ancestor, O. rufipogon. Three quantitative trait loci, qSH1, sh4, and qSH3, are reported to be involved in the reduced seed-shattering behaviour of cultivated rice. Genotyping surveys of these loci have shown that the sh4 mutation is conserved in all cultivars, whereas the qSH1 mutation is only observed in some japonica cultivars. Furthermore, the qSH3 mutation is observed in indica and japonica cultivars; however, aus cultivars carry a functional allele of wild rice at qSH3, indicating there may be distinct genetic mechanisms in aus for its reduced seed-shattering behaviour independently of qSH1 and qSH3. Through genetic analysis of the segregating populations between an aus cultivar, Kasalath, and wild rice introgression lines carrying the domesticated allele at sh4, we detected three loci associated with the reduced seed-shattering behaviour of Kasalath. Subsequent progeny tests validated their effects on this trait. These findings indicate that there are common and distinct genetic loci governing seed-shattering reduction in rice cultivars, providing novel insights into the complex process of rice domestication. This knowledge may help improve breeding strategies to optimise yield through targeted genetic selection.
Stable genetic loci orchestrate redox networks and grain traits in polyploid wheat (Triticum aestivum L.) under combined salinity and drought stress.
Alwutayd KM, Shami A, Alqudah AM … +1 more , Thabet SG
Mol Genet Genomics · 2025 Nov · PMID 41258517 · Publisher ↗
Combined drought and secondary salinization threaten wheat production in arid and semi-arid regions. While trans- and inter-generational patterns of enhanced tolerance have been reported, their genomic underpinnings rema...
Combined drought and secondary salinization threaten wheat production in arid and semi-arid regions. While trans- and inter-generational patterns of enhanced tolerance have been reported, their genomic underpinnings remain unclear. Here, we combined multi-environment phenotyping across three successive generations with high-density (90K) single nucleotide polymorphism (SNP) genotyping of 111 bread wheat accessions to map loci associated with performance under recurrent drought–salinity. Multi-trait, multi-generation genome-wide association analyses identified five genomic regions on chromosomes 1B, 2A, 2B, 6B, and 7A that were repeatedly associated with grain-yield stability, antioxidant capacity, and water-use efficiency. Gene annotations within these regions highlight plausible mechanisms including flavonoid-directed reactive oxygen species (ROS) scavenging, organellar RNA processing, proteostasis and hormone signaling, sucrose partitioning, and Ca2⁺-linked signaling, which transmit rapid stress signals to the cell cycle. Nevertheless, the repeatedly detected regions and their lead SNPs provide practical markers for breeding (e.g., KASP assays) and entry points for functional validation. Future work should fine-map these intervals and test causative roles through near-isogenic lines, genome editing, expression and metabolite profiling, and transgenerational designs.
Correction: Testis-specific serine/threonine kinase 3 regulates the size of sperm reservoir in Anopheles stephensi.
Meghwanshi KK, Choudhary C, Rohilla P … +3 more , Dixit R, Saxena V, Shukla JN
Mol Genet Genomics · 2025 Nov · PMID 41258262 · Publisher ↗
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Retraction Note: HEATR3 involved in the cell proliferation, metastasis and cell cycle development of bladder cancer acts as a tumor suppressor.
Dou X, Ma X, Meng W … +5 more , Zhang W, Yang S, Niu F, Xiong Y, Jin T
Mol Genet Genomics · 2025 Nov · PMID 41238913 · Publisher ↗
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