Genes

10 pages, 1074 KB

Open AccessCase Report

A Rare Case of Childhood Glaucoma Resulting from Anterior Segment Dysgenesis Associated with a Homozygous Mutation in the CPAMD8 Gene

by Nevyana Veleva-Krasteva, Kiril Genov, Kunka Kamenarova, Yoanna Kaneva, Kalina Mihova, Stanislava Kostova, Radka Kaneva and Alexander Oscar

Genes 2026, 17(4), 494; https://doi.org/10.3390/genes17040494 - 21 Apr 2026

Viewed by 276

Abstract

The term “childhood glaucoma” summarizes a heterogeneous group of diseases characterized by elevated intraocular pressure and associated optic nerve damage. Secondary glaucoma may develop based on non-acquired ocular anomalies, the most common of which are anterior segment dysgeneses. We present a rare case [...] Read more.

The term “childhood glaucoma” summarizes a heterogeneous group of diseases characterized by elevated intraocular pressure and associated optic nerve damage. Secondary glaucoma may develop based on non-acquired ocular anomalies, the most common of which are anterior segment dysgeneses. We present a rare case of infantile childhood glaucoma resulting from anterior segment dysgenesis due to a homozygous mutation c.1881delG, p.(Arg627Serfs*6), leading to loss of function in the CPAMD8 gene. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

► Show Figures

Figure 1

11 pages, 1147 KB

Open AccessArticle

Genetic Characterization and Statistical Interpretation of 16 STR Markers in South-West Bulgaria: Implications for Forensic Identification and Kinship Analysis

by Vera Djeliova, Bogdan Mirchev, Ekaterina Angelova, Milka Mileva, Dimo Krastev, Atanas Hristov, Yanko Kolev and Aleksandar Apostolov

Genes 2026, 17(4), 493; https://doi.org/10.3390/genes17040493 - 21 Apr 2026

Viewed by 244

Abstract

Background/Objectives: The widespread adoption of short tandem repeat (STR) marker technology in genetic analysis has led to the collection of substantial STR data from diverse populations. Allele-frequency data provide robust forensic utility and support accurate likelihood ratio calculations, highlighting the importance of regional [...] Read more.

Background/Objectives: The widespread adoption of short tandem repeat (STR) marker technology in genetic analysis has led to the collection of substantial STR data from diverse populations. Allele-frequency data provide robust forensic utility and support accurate likelihood ratio calculations, highlighting the importance of regional databases. Methods: The presented study aimed to determine the allelic frequencies and statistical parameters for 16 autosomal genetic STR markers included in the NGM Detect^TM PCR Amplification Kit in a population sample of 220 unrelated individuals from the South-West region of the Republic of Bulgaria. Results: We found that the most polymorphic and informative marker for the Bulgarian population in the southwestern region is SE33, with the next most informative markers being D1S1656, D12S391, D18S51, and FGA. In contrast, D22S1045, D16S539, and D2S441 showed comparatively lower genetic variability and informativeness. At the same time, no deviations from the Hardy–Weinberg equilibrium were observed for the 16 loci studied. Conclusions: This work not only enriches knowledge of the genetic diversity of the Bulgarian population but also provides the Bulgarian and international justice systems with an objective, scientifically sound basis for expert decision-making. Full article

(This article belongs to the Special Issue Advances and Challenges in Forensic Genetics)

► Show Figures

Graphical abstract

30 pages, 702 KB

Open AccessReview

Genetic Identification of Human Skeletal Remains in Forensic Context: A Review

by Laura Cainé, Madalena Henriques, Adelina Rohovska, Bárbara Sousa, Heloísa Afonso Costa, Helena Correia Dias, Joana Rodrigues, Magda Franco, Olena Mukan, Rui Nascimento, Vânia Mofreita and António Amorim

Genes 2026, 17(4), 492; https://doi.org/10.3390/genes17040492 - 21 Apr 2026

Viewed by 386

Abstract

Background/Objectives: Genetic identification of human skeletal remains plays a pivotal role in forensic investigations when other traditional or primary methods are not appropriate. Decomposition, storage and environmental conditions often leave the skeletal structure as the only basis for identification. This review synthesizes current [...] Read more.

Background/Objectives: Genetic identification of human skeletal remains plays a pivotal role in forensic investigations when other traditional or primary methods are not appropriate. Decomposition, storage and environmental conditions often leave the skeletal structure as the only basis for identification. This review synthesizes current methodologies and technological advances in damaged DNA extraction and analysis, emphasizing the forensic relevance of skeletal remains for genetic identification. Methods: A comprehensive literature analysis highlights the basis of genetic identification; sampling that considers intrinsic and extrinsic factors influencing the DNA yield and its quality; pre-treatment methods; extraction protocols that are suitable for its sensitivity; genetic marker panels that allow for human identification; and statistical evaluation and analysis of the results. The last chapter demonstrates the real-world impact of genetic identification on historical cases, underscoring its broader significance in legal, humanitarian, and socio-historical contexts, supporting a critical evaluation of best practices, methodological robustness, and ethical considerations within the field. Results: Teeth, femur and the petrous portion of temporal bone are the main samples used for genetic analysis. STR profiling and mitochondrial DNA are the gold standard markers for skeletal human identification. Minimally destructive protocols that enhance a high DNA yield are chosen, with silica-based methods being highlighted in the extraction protocols. Next-Generation Sequencing techniques have also improved analytical outcomes, by enabling high-throughput data generation, increased coverage depth, nucleotide-level sequence data, and high-level multiplexing of genetic targets. Conclusions: This review provides a comprehensive framework for researchers and practitioners seeking to optimize genetic identification workflows in forensic sciences and bioarcheology. These methodological advances have significantly increased identification success rates, especially in cases involving degraded or limited skeletal remains. Reviews such as this one help us to identify methodological gaps, ethical concerns, and future research directions, thereby establishing best practices when working with highly degraded skeletal material, supporting more reliable, standardized, and legally defensible applications of genetic identification in forensic, archeological, and humanitarian contexts. Full article

(This article belongs to the Special Issue Forensic DNA Profiling: PCR Techniques and Innovations)

► Show Figures

Figure 1

26 pages, 81486 KB

Open AccessArticle

Landscape of Gene Essentiality in Cancer Cell Death Pathways

by Shangjia Li, Zhimo Zhu, Chen Yang, Nuo Sun, Lijun Cheng and Lang Li

Genes 2026, 17(4), 491; https://doi.org/10.3390/genes17040491 - 21 Apr 2026

Viewed by 319

Abstract

Background/Objectives: Regulated cell death (RCD), a process that relies on a series of molecular mechanisms, can be targeted to eliminate superfluous, irreversibly damaged, and potentially harmful cells. In this research, we want to better understand how the cell death pathway contributes to cancer [...] Read more.

Background/Objectives: Regulated cell death (RCD), a process that relies on a series of molecular mechanisms, can be targeted to eliminate superfluous, irreversibly damaged, and potentially harmful cells. In this research, we want to better understand how the cell death pathway contributes to cancer therapy. Methods: We studied 1150 cancer cells in the Dependency Map (DepMap) database for 12 distinct cell death pathways and assessed their gene essentialities. Genes which are essential in 90% or more of cancer cell lines are called always essential, or partial essential if falling into (10%, 90%), or rare essential if they are essential in less than 10% of cancer cell lines. Results: Overall, among these 12 cell death pathways, 23, 47, and 549 genes were classified as always essential, partial essential, and rare essential, respectively. In two cell death pathways, Parthanatos, and Pyroptosis, all genes were rare essential. Among the other ten cell death pathways, Apoptosis, Autosis, Necroptosis, Efferocytosis, Ferroptosis, Mitotic cell death, Autophagy, Lysosome-dependent cell death, MPT-driven necrosis and Immunogenic, there are (10, 1, 13, 6, 3, 9, 11, 1, 1, 0) partial essential genes, and (2, 0, 3, 1, 1, 13, 4, 0, 0, 1) always essential genes. Conclusions: These cell death pathway essential genes could be viable targets for therapeutic drug development for cancer therapies. Full article

(This article belongs to the Special Issue Selected Papers from the International Conference on Intelligent Biology and Medicine (ICIBM 2025))

► Show Figures

Figure 1

17 pages, 2811 KB

Open AccessArticle

Genetic Diversity and Phylogenetic Relationships Among Accessions of Pediomelum tenuiflorum (Pursh) A.N. Egan

by Cynthia O. Anukege, Mark Schoenbeck and P. Roxanne Kellar

Genes 2026, 17(4), 490; https://doi.org/10.3390/genes17040490 - 20 Apr 2026

Viewed by 367

Abstract

Background: Differentiating plant species is complex, complicated by morphological similarities that confound species’ delineation. For hundreds of years, researchers have used herbarium specimens to study plant morphology, and over the last forty years, these samples have also served as material for molecular phylogenetic [...] Read more.

Background: Differentiating plant species is complex, complicated by morphological similarities that confound species’ delineation. For hundreds of years, researchers have used herbarium specimens to study plant morphology, and over the last forty years, these samples have also served as material for molecular phylogenetic research. Taxonomists have alternately split and combined morphotypes of Pediomelum tenuiflorum for two centuries. With samples of P. tenuiflorum from across its distribution, this research aimed to (1) infer a robust phylogeny using molecular data, i.e., gene sequences from chloroplast and nuclear genomes; (2) assess genetic diversity using molecular markers, specifically Inter Simple Sequence Repeats (ISSRs); (3) provide evidence to support the taxonomic placement and possible splitting of P. tenuiflorum; and (4) identify consistent morphological characteristics using a correlation matrix to distinguish among the morphotypes. Results: Striking morphological differences among the individuals of P. tenuiflorum from across the species’ distribution resulted in more than two morphotypes. Phylogenetic data suggest hybridization is occurring among genetically and morphologically distinct members of P. tenuiflorum and with other species in the genus Pediomelum, whereas ISSR results indicate detectable genetic variation but do not resolve discrete clusters. This study reports the first ISSR markers used to assess genetic diversity in Pediomelum species. Conclusions: Morphological and genetic variation exist across individuals of P. tenuiflorum but not in monophyletic groups that support splitting the morphotypes into multiple species. Future investigations into chromosome numbers might reveal polyploidization in the lineage, and phylogenies estimated from low-copy nuclear genes could elucidate hybridization pathways. Full article

(This article belongs to the Special Issue Genetic and Morphological Diversity in Plants)

► Show Figures

Figure 1

20 pages, 6122 KB

Open AccessArticle

Genome-Wide Identification of the IDD Gene Family in Soybean (Glycine max) and Their Expression Profiles in Response to Drought, Salt Stress, and Different Photoperiod Conditions

by Rouxing Li, Zixiang Ning, Zhihui Dong, Jian Xi, Chenjie Shi, Xianlian Chen, Qingyuan He, Shaochuang Chuang, Xue Yang and Yingjie Shu

Genes 2026, 17(4), 489; https://doi.org/10.3390/genes17040489 - 20 Apr 2026

Viewed by 258

Abstract

Background: INDETERMINATE DOMAIN proteins (IDDs) are a plant-specific transcription factor family, and members of this family play crucial roles in regulating growth and development as well as environmental adaptation. However, a comprehensive analysis of the IDD family in soybean [Glycine max (L.) [...] Read more.

Background: INDETERMINATE DOMAIN proteins (IDDs) are a plant-specific transcription factor family, and members of this family play crucial roles in regulating growth and development as well as environmental adaptation. However, a comprehensive analysis of the IDD family in soybean [Glycine max (L.) Merrill] is limited. Methods and Results: A total of 27 GmIDD genes were identified in the soybean genome, unevenly distributed across 14 chromosomes, and their encoded proteins all harbor a conserved INDETERMINATE (ID) domain with two Cys2His2 (C2H2) and two Cys2HisCys (C2HC) zinc finger motifs. Phylogenetic analysis classified these GmIDD genes into three subgroups. Soybean GmIDD genes exhibit high homology with their Arabidopsis thaliana IDD counterparts. Cis-acting element analysis indicated that the promoters of GmIDD genes are enriched in light-responsive elements (such as Box4), hormone-responsive elements (such as ABRE and AuxRR-core), and abiotic stress-responsive elements (such as MBS and LTR). The qRT-PCR results showed that GmIDD3/5/14/22/26 were upregulated under salt stress, while GmIDD8/9/10/12/16/17/19/20/23/24/25/27 were obviously downregulated during treatment. Under drought stress, the expression levels of GmIDD4/6/7/10/14/16/19/22/24/25/26/27 were upregulated during the treatment. The expression levels of GmIDD1/2/3/4/12/14/15/16/17/18/22/23/25/26 were induced by short-day conditions, whereas GmIDD9/13/19/21 were induced by long-day conditions in soybean leaves. Conclusions: This study provides a theoretical basis for further understanding the functions of the soybean IDD gene family in abiotic stress tolerance and photoperiod adaptability. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

12 pages, 1080 KB

Open AccessArticle

Dual-Caspase-Mediated Apoptosis Underlies Peritoneal Cell-Free DNA Release After PD-Related Peritonitis

by Grazia Maria Virzì, Sabrina Milan Manani, Matteo Marcello, Angelo Porrovecchio, Claudio Ronco and Monica Zanella

Genes 2026, 17(4), 488; https://doi.org/10.3390/genes17040488 - 19 Apr 2026

Viewed by 366

Abstract

Background/Objectives: Cell-free DNA (cfDNA) is released into the circulation during inflammation-driven cellular injury and regulated cell death. Elevated cfDNA concentrations have been reported in several clinical settings, including chronic kidney disease, hemodialysis, and peritoneal dialysis (PD). We previously demonstrated that PD-related peritonitis [...] Read more.

Background/Objectives: Cell-free DNA (cfDNA) is released into the circulation during inflammation-driven cellular injury and regulated cell death. Elevated cfDNA concentrations have been reported in several clinical settings, including chronic kidney disease, hemodialysis, and peritoneal dialysis (PD). We previously demonstrated that PD-related peritonitis induces an increase in circulating cfDNA; however, the mechanisms underlying cfDNA generation remained unclear. This study aimed (i) to confirm peritoneal cfDNA variation following peritonitis in PD patients, and (ii) to elucidate the apoptotic pathways responsible for cfDNA release. Methods: Fifty-four PD patients were enrolled and stratified into the following groups: Group A—no history of peritonitis (n = 25); Group B—remote peritonitis > 3 months prior (n = 21); Group C—recent peritonitis < 3 months prior (n = 8). cfDNA was quantified by qPCR. Apoptosis was assessed qualitatively by DNA laddering and quantitatively using ELISA assays for Caspase-3, Caspase-8 and Caspase-9. Results: cfDNA levels were significantly higher in patients with recent peritonitis compared to both other groups (p < 0.01). DNA laddering showed enhanced nucleosomal fragmentation, consistent with apoptosis. Caspase-3 concentrations were markedly increased in recent peritonitis (<3 months) and significantly correlated with cfDNA levels (ρ = 0.511, p < 0.01). Both Caspase-8 and Caspase-9 correlated with Caspase-3 (ρ = 0.57 and ρ = 0.47, respectively), indicating engagement of both extrinsic and intrinsic apoptotic pathways. Conclusions: In conclusion, peritoneal cfDNA in PD patients with peritonitis originates primarily from apoptosis and reflects dual-pathway caspase activation. cfDNA and Caspase-3 progressively decline with longer time elapsed from peritonitis, supporting their potential use as biomarkers for inflammatory activity and membrane recovery. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

► Show Figures

Figure 1

14 pages, 2359 KB

Open AccessArticle

Effect of DNA Methylation Modulators on UV Damage Formation and Repair

by Kyle Jones, Rishav Rajbhandari and Wentao Li

Genes 2026, 17(4), 487; https://doi.org/10.3390/genes17040487 - 19 Apr 2026

Viewed by 424

Abstract

Background/Objectives: DNA methylation is a key epigenetic modification involved in regulating many cellular processes, including gene expression and the maintenance of genome stability. Ultraviolet (UV) radiation induces DNA damage in the form of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] and cyclobutane pyrimidine dimers (CPDs), which [...] Read more.

Background/Objectives: DNA methylation is a key epigenetic modification involved in regulating many cellular processes, including gene expression and the maintenance of genome stability. Ultraviolet (UV) radiation induces DNA damage in the form of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] and cyclobutane pyrimidine dimers (CPDs), which can lead to mutations if not efficiently repaired. While cytosine methylation has been implicated in influencing UV-induced DNA damage formation, the effect of DNA methylation modulators such as S-adenosyl-L-methionine (SAM) and RG108 on UV damage formation and repair remains unclear. Methods: Here, using immunoslot blot assays, we investigated the effects of SAM and RG108 on UV-induced DNA damage formation and repair in human lymphoblastoid cells. Results: We found that SAM, but not RG108, rapidly suppresses the formation of both (6-4)PP and CPD, with detectable effects within minutes of exposure. Although SAM pretreatment was associated with modestly accelerated early (6-4)PP repair, this effect was accompanied by substantially lower initial damage levels. When cells were treated with SAM or RG108 immediately after UV irradiation to ensure equivalent initial damage burden, no significant differences in repair were observed for either lesion type, demonstrating that the accelerated early (6-4)PP repair reflects reduced lesion burden rather than increased intrinsic nucleotide excision repair (NER). Global 5-methylcytosine (5mC) levels remained stable following SAM or RG108 treatment and during UV damage repair, suggesting that these effects occur independently of global alterations in DNA methylation. Conclusions: Together, our findings reveal that SAM modulates UV damage susceptibility at the level of lesion formation without altering repair, highlighting a previously unrecognized role for DNA methylation modulators in regulating genome stability. Full article

(This article belongs to the Special Issue DNA Repair, Genomic Instability and Cancer)

► Show Figures

Figure 1

23 pages, 16003 KB

Open AccessArticle

An Integrative Network Analysis Framework for Identifying Altered Glycosylation Pathways Associated with Autism Spectrum Disorder

by Anup Mammen Oommen, Marie Morel, Stephen Cunningham, Cathal Seoighe and Lokesh Joshi

Genes 2026, 17(4), 486; https://doi.org/10.3390/genes17040486 - 19 Apr 2026

Viewed by 462

Abstract

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by heterogeneous behavioral symptoms and systemic comorbidities, including immune and gastrointestinal dysfunctions. Emerging studies suggest that glycosylation—a fundamental post-translational modification regulating cellular communication and immune responses—may play a role in ASD [...] Read more.

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by heterogeneous behavioral symptoms and systemic comorbidities, including immune and gastrointestinal dysfunctions. Emerging studies suggest that glycosylation—a fundamental post-translational modification regulating cellular communication and immune responses—may play a role in ASD pathophysiology, yet its contribution remains underexplored. Methods: In this study, we developed an integrative transcriptomic and network analysis framework to investigate glycosylation-related gene expression changes and their functional associations in ASD. Using publicly available datasets from bulk and single-cell RNA sequencing of brain and blood tissues, we focused on four prior-knowledge gene subsets: glycogenes, extracellular matrix glycoproteins, immune response genes, and autism risk genes. Results: Differential expression and pathway enrichment analyses revealed consistent dysregulation of glycosylation pathways, including mucin-type O-glycan biosynthesis, glycosaminoglycan metabolism, GPI-anchor formation, and sialylation, across ASD tissues. These transcriptional changes were functionally linked to altered immune signaling (e.g., IL-17, Toll-like receptor, and complement pathways) and synaptic development pathways, forming a distinct glyco-immune axis. Network analysis identified key glycogenes such as GALNT10, NEU1, LMAN2L, and CHST1 as central molecular nodes, interacting with immune and neuronal regulators. Linkage disequilibrium analysis further revealed ASD-associated SNPs influencing the expression of these glycogenes in both blood and brain tissues. Conclusions: Together, these findings support a model in which disrupted glycosylation contributes to ASD pathophysiology by mediating immune dysregulation and altered neuronal connectivity. This study offers a systems-level framework to understand the molecular complexity of ASD and highlights glycogenes as potential biomarkers and targets for future therapeutic exploration. Full article

(This article belongs to the Special Issue Autism: Genetics, Environment, Pathogenesis, and Treatment)

► Show Figures

Figure 1

13 pages, 3028 KB

Open AccessArticle

A Novel Col4a5-G814fs Knock-In Mouse Model Reveals Phenotypic Heterogeneity Among Truncating COL4A5 Mutations in X-Linked Alport Syndrome

by Yingqi Lin, Lei Sun, Mengying Li, Xinyu Kuang, Xiuli Gong, Qin Cai, Yanwen Chen, Miao Xu, Wenyan Huang and Fanyi Zeng

Genes 2026, 17(4), 485; https://doi.org/10.3390/genes17040485 - 19 Apr 2026

Viewed by 382

Abstract

Background/Objectives: X-linked Alport syndrome (XLAS) arises from pathogenic variants in COL4A5. Truncating variants are generally classified as severe, but whether clinically meaningful heterogeneity exists within this group remains unclear. This study aimed to establish a novel Col4a5 knock-in mouse model based [...] Read more.

Background/Objectives: X-linked Alport syndrome (XLAS) arises from pathogenic variants in COL4A5. Truncating variants are generally classified as severe, but whether clinically meaningful heterogeneity exists within this group remains unclear. This study aimed to establish a novel Col4a5 knock-in mouse model based on a clinical variant and to determine whether truncating mutation position influences disease severity. Methods: A de novo COL4A5 frameshift variant, c.2440delG, was identified in a patient with severe early-onset XLAS. A Col4a5-G814fs knock-in mouse was generated by CRISPR/Cas9 on the C57BL/6J inbred mouse strain background and compared with the established Col4a5-G5X nonsense model using survival analysis, serial functional measurements, kidney histopathology, transmission electron microscopy, and RNA sequencing. Results: The Col4a5-G814fs knock-in mouse was successfully generated and showed loss of glomerular α5(IV) collagen chain expression. Compared with G5X mice, G814fs mice exhibited shorter survival (median 141 vs. 161.5 days, p = 0.0004), earlier onset of proteinuria, and more severe kidney functional decline. By 16 weeks, G814fs mice also showed more severe glomerular basement membrane abnormalities and more extensive glomerulosclerosis. RNA sequencing revealed a shared inflammatory gene signature in both models, together with selective upregulation of genes related to the PPAR signaling pathway and fatty acid metabolism in G814fs kidneys. Conclusions: This study reports a novel de novo COL4A5 frameshift variant and establishes the first Col4a5-G814fs knock-in mouse model. Direct comparison with the G5X model shows that distinct truncating COL4A5 mutations can be associated with substantially different disease severity, providing a useful platform for future mechanistic and therapeutic studies in XLAS. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

► Show Figures

Figure 1

10 pages, 845 KB

Open AccessReview

Could Metabolism-Related Long Non-Coding RNAs Be More Conserved than Their Brain-Related Counterparts?

by Laurent Metzinger and Valérie Metzinger-Le Meuth

Genes 2026, 17(4), 484; https://doi.org/10.3390/genes17040484 - 18 Apr 2026

Viewed by 293

Abstract

The human genome produces a large repertoire of non-coding RNAs (ncRNAs) with important regulatory roles in development, physiology, and most of diseases. Among these, long non-coding RNAs (lncRNAs) have emerged as key modulators of gene expression, chromatin organization, and cellular homeostasis, despite displaying [...] Read more.

The human genome produces a large repertoire of non-coding RNAs (ncRNAs) with important regulatory roles in development, physiology, and most of diseases. Among these, long non-coding RNAs (lncRNAs) have emerged as key modulators of gene expression, chromatin organization, and cellular homeostasis, despite displaying remarkably low primary-sequence conservation across species. This apparent evolutionary paradox questions the limitations of predicting biological function based on conservation, particularly across different biological domains. Here, we examine current evidence on lncRNA evolution, with a focus on their roles in metabolic regulation compared with neurobiological processes. We hypothesize that lncRNAs involved in ancient and conserved pathways such as metabolism may be under stronger evolutionary constraint than those associated with higher-order, species-specific traits, although available data support a more nuanced interpretation. Functional importance often correlates poorly with linear sequence conservation and instead appears to depend on higher-level features, including RNA secondary or tertiary structure, genomic context, regulatory architecture, and interactions with conserved molecular partners. We propose a systematic comparative framework to empirically assess conservation among metabolism- and neuro-associated lncRNAs using phylogenetic, syntenic, structural, and expression-based metrics. Finally, we discuss the therapeutic implications of lncRNA biology, highlighting how a deeper understanding of their evolutionary and mechanistic properties may inform the development of more precise and effective RNA-targeting strategies. Together, these insights underscore the non-coding transcriptome as a critical frontier for both fundamental biology and precision medicine. Full article

(This article belongs to the Special Issue Reviews in RNA: Mechanisms and Roles)

► Show Figures

Figure 1

13 pages, 1151 KB

Open AccessArticle

STAG1: Bridging the Gap Between Cohesin Complex and Epigenetic Machinery

by Tiziano Palazzotti, Giulia Bruna Marchetti, Rosa Maria Alfano, Ilaria Bestetti, Palma Finelli and Donatella Milani

Genes 2026, 17(4), 483; https://doi.org/10.3390/genes17040483 - 18 Apr 2026

Viewed by 293

Abstract

Background: The STAG1 gene has been related to a poorly known form of intellectual disability, known as Intellectual Developmental Disorder, Autosomal Dominant 47 (MRD47). Functionally, MRD47 is part of the Cohesinopathies, a small family of rare genetic disorders caused by defective cohesin [...] Read more.

Background: The STAG1 gene has been related to a poorly known form of intellectual disability, known as Intellectual Developmental Disorder, Autosomal Dominant 47 (MRD47). Functionally, MRD47 is part of the Cohesinopathies, a small family of rare genetic disorders caused by defective cohesin complex, whose activity is essential for sister chromatid cohesion and therefore for chromatin organization. Chromatin state modulation is an entangled process finely modulated by a large number of actors that, if altered, give rise to the so-called Chromatinopathies. The clinical and biological overlap among these families of conditions on one hand poses significant challenges during diagnostic definition, and, on the other, may help delineate more accurate management guidelines. Methods: Starting from the report of a novel pathogenic variant in the STAG1 gene, we performed a retrospective clinical and molecular review of all previously reported patients affected by this rare disorder. Once clinical and photographic data of all published patients were collected, we used Face2Gene deep learning technology to analyze STAG1 facial phenotype, comparing it to both Chromatinopathy and Cohesinopathy profiles. Results: Our clinical and molecular re-evaluation of reported cases confirms MRD47 as a mainly neurodevelopmental disorder. Through artificial intelligence technology, we were able to first create the gestaltic profile of MRD47. Face2Gene analyses of this composite phenotype, although limited by the tool’s analysis modalities, demonstrates the strong overlap of STAG1 disorder with Chromatinopathies. Conclusions: The present literature review, together with gestaltic analyses of the STAG1-related phenotype, underscores the strong resemblance of MRD47 to epigenetic machinery disorders. The present case brings to light once more the biological and phenotypical entanglement of Cohesinopathies and Chromatinopathies, hinting at STAG1 as the joining chain. Full article

(This article belongs to the Collection Genetics and Genomics of Rare Disorders)

► Show Figures

Figure 1

14 pages, 6851 KB

Open AccessArticle

Identification of a High-Yield and Low-Cadmium-Accumulating Rice Cultivar by LAMP-Based Gn1a-i Screening and Physiological Evaluation

by Xiyi Chen, Shangdu Zhang, Yaoxian Chin, Mingshi Lao, Guibo Zhang, Fengtao Yu, Linfeng Cheng and Yonghang Tian

Genes 2026, 17(4), 482; https://doi.org/10.3390/genes17040482 - 18 Apr 2026

Viewed by 261

Abstract

Background/Objectives: With the acceleration of global industrialization and continuous population growth, the world is increasingly confronted with the dual challenges of food insecurity and cultivated land contamination. The screening and breeding of rice varieties with superior agronomic traits and low heavy metal accumulation [...] Read more.

Background/Objectives: With the acceleration of global industrialization and continuous population growth, the world is increasingly confronted with the dual challenges of food insecurity and cultivated land contamination. The screening and breeding of rice varieties with superior agronomic traits and low heavy metal accumulation have therefore become important strategies for ensuring food safety and sustainable agricultural production. Methods: In this study, rice varieties carrying the Gn1a-i gene and exhibiting specific cadmium (Cd) accumulation characteristics were screened using a combination of molecular marker detection and cadmium accumulation evaluation. Specific loop-mediated isothermal amplification (LAMP) primers targeting the Gn1a-i gene were designed and combined with a lateral flow dipstick (LFD) assay to enable rapid genetic screening of rice varieties. A six-day hydroponic experiment under cadmium stress was conducted across three temperature ranges (15–20 °C, 22–27 °C, and 30–35 °C), and cadmium accumulation in different plant organs (roots, stem sheath, and leaves) was analyzed. Results: Seven varieties carrying the Gn1a-i gene, including Xiangwanxian 12, were identified among ten tested rice varieties. Xiangwanxian 12 was subsequently selected for further evaluation, with the high-cadmium-accumulating variety Yuzhenxiang used as a control. At 144 h, the total Cd content in the measured organs of Xiangwanxian 12 was 9.6%, 4.0%, and 23.2% lower than that of Yuzhenxiang under low, medium, and high temperatures, respectively (one-tailed t-test, p < 0.01 for all three temperatures). Conclusions: The integration of LAMP-based genotyping and physiological evaluation provides a novel and reliable strategy for identifying low-Cd rice germplasm. Xiangwanxian 12, which carries the Gn1a-i allele and exhibits consistently lower Cd accumulation than Yuzhenxiang, suggests potential as a candidate for breeding high-yield, low-Cd rice cultivars. Full article

(This article belongs to the Special Issue Research on Genetics and Breeding of Rice)

► Show Figures

Figure 1

16 pages, 2108 KB

Open AccessArticle

Infantile-Onset Glutaric Acidemia Type I with Mild Hepatopathy: Clinical, Biochemical, and Molecular Characterization of an Iranian Pediatric Cohort

by Zahra Beyzaei, Bita Geramizadeh, Seyed Mohsen Dehghani, Sorour Inaloo and Ralf Weiskirchen

Genes 2026, 17(4), 481; https://doi.org/10.3390/genes17040481 - 18 Apr 2026

Viewed by 223

Abstract

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study [...] Read more.

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype–phenotype correlations. Methods: We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. Results: All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. Conclusions: This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype–phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. Full article

(This article belongs to the Special Issue Diagnosis, Management and Therapy of Rare Diseases)

► Show Figures

Figure 1

20 pages, 2839 KB

Open AccessArticle

NuRepress: Inferring Transcriptional Repressors from Phased Nucleosome Architecture

by Qianming Xiang and Binbin Lai

Genes 2026, 17(4), 480; https://doi.org/10.3390/genes17040480 - 18 Apr 2026

Viewed by 331

Abstract

Background: The systematic identification of transcriptional repressors remains challenging, as current inference frameworks are predominantly optimized for accessible chromatin, leaving regulatory signals embedded within repressive domains undercharacterized. Methods: Here, we present NuRepress, a computational framework that predicts candidate transcriptional repressors by integrating repressive [...] Read more.

Background: The systematic identification of transcriptional repressors remains challenging, as current inference frameworks are predominantly optimized for accessible chromatin, leaving regulatory signals embedded within repressive domains undercharacterized. Methods: Here, we present NuRepress, a computational framework that predicts candidate transcriptional repressors by integrating repressive chromatin architecture, functional signatures, and transcriptional outcomes. NuRepress first identifies well-phased nucleosome arrays within repressive chromatin. These arrays are treated as discrete structural units that capture characteristic local chromatin organization associated with regulatory activity. Since distinct Tn5 cut signal patterns often imply divergent regulatory functions, the framework stratifies these arrays into potential functional subtypes. By synthesizing the quantified repressive efficacy of each subtype with spatial motif enrichment and observed transcriptional dynamics, NuRepress systematically prioritizes and ranks candidate repressors. Results: Our analysis indicated that well-phased nucleosome arrays exhibited accessibility-defined organizational patterns with distinct repressive efficacies, and that these patterns were also observed across species, suggesting that the structural principles captured by NuRepress might extend beyond one specific biological system. Positional motif analysis revealed that distinct TFs exhibited different spatial preferences relative to well-phased nucleosome arrays, suggesting scale-specific preferences for their interactions with these organized chromatin structures. When applied to pancreatic cancer progression, NuRepress identified changes in nucleosome organization associated with stage-specific transcriptional remodeling, highlighting candidate repressors of key oncogenic drivers. Conclusions: NuRepress establishes a structure-aware strategy for repressor inference that extends regulatory genomics beyond accessibility-centered paradigms. By linking well-phased nucleosome organization to transcriptional outcomes, it provides a principled framework for dissecting transcriptional repression across diverse biological settings. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

16 pages, 5290 KB

Open AccessArticle

Genome-Wide Identification and Tissue-Specific Expression Analysis of the FtAQP Gene Family in Tartary Buckwheat (Fagopyrum tataricum)

by Wenxuan Chu, Zhikun Li, Ziyi Zhang, Yutong Zhu, Yan Zeng, Ruigang Wu and Xing Wang

Genes 2026, 17(4), 479; https://doi.org/10.3390/genes17040479 - 17 Apr 2026

Viewed by 347

Abstract

Background: Tartary buckwheat (Fagopyrum tataricum) serves as an excellent model for studying plant water adaptation mechanisms due to its exceptional drought tolerance. While aquaporins (AQPs) mediate the transmembrane transport of water and solutes in plants, their fine-tuned regulatory networks underlying stress [...] Read more.

Background: Tartary buckwheat (Fagopyrum tataricum) serves as an excellent model for studying plant water adaptation mechanisms due to its exceptional drought tolerance. While aquaporins (AQPs) mediate the transmembrane transport of water and solutes in plants, their fine-tuned regulatory networks underlying stress resilience in Tartary buckwheat remain largely elusive. Methods: Here, we combined bioinformatics and transcriptomics to systematically identify 30 highly conserved FtAQP genes at the genome-wide level. Results: Cross-validated by qRT-PCR, our analysis revealed their distinct expression patterns across different organs. Based on our transcriptomic data, we hypothesize that FtAQP family members potentially participate in a coordinated whole-plant water management network through differential spatiotemporal expression. Specifically, the robust transcription of FtAQP8, FtAQP12, and FtAQP28 in roots is associated with the initial water uptake process. As water undergoes long-distance transport, the synergistic upregulation of FtAQP13, FtAQP17, FtAQP20, and FtAQP29 in the stem suggests a potential role in facilitating critical lateral water flow. Furthermore, during reproductive development, FtAQP27 exhibits extreme tissue specificity in floral organs, implying its possible involvement in maintaining local osmotic homeostasis. Furthermore, the promoter regions of FtAQPs are highly enriched with cis-acting elements responsive to light, abscisic acid (ABA), and cold stress, suggesting they are intimately regulated by a coupling of endogenous phytohormones and environmental cues. Conclusions: Ultimately, this study provides valuable insights into the potential molecular basis of multidimensional water regulation in Tartary buckwheat, and identifies candidate genetic targets for improving water use efficiency in dryland agriculture through the precise manipulation of aquaporins. Collectively, while these observational findings provide valuable predictive models, future in vivo experimental validations are required to confirm their exact biological functions. Full article

(This article belongs to the Topic Genetic Engineering in Agriculture, 2nd Edition)

► Show Figures

Figure 1

14 pages, 252 KB

Open AccessArticle

Maternal RFC1 Gene Polymorphisms and Neural Tube Defects: A Case–Control Study in Ethiopia

by Hasset Tamirat Molla, Dawd Gashu, Barbara Stoecker and Winyoo Chowanadisai

Genes 2026, 17(4), 478; https://doi.org/10.3390/genes17040478 - 17 Apr 2026

Viewed by 318

Abstract

Background: Etiologies of neural tube defects (NTDs) are multifactorial. Genetic, epigenetic and environmental factors may contribute to their reported variation in prevalence across the globe. Ethiopia has among the highest reported NTD prevalence globally, making investigation of genetic determinants in this high-risk population [...] Read more.

Background: Etiologies of neural tube defects (NTDs) are multifactorial. Genetic, epigenetic and environmental factors may contribute to their reported variation in prevalence across the globe. Ethiopia has among the highest reported NTD prevalence globally, making investigation of genetic determinants in this high-risk population particularly important for advancing the understanding of NTD etiology. Genes involved in folate metabolism, such as the reduced folate carrier 1 (RFC1), have been investigated for the potential associations with NTDs, but findings throughout the literature remain inconsistent and inconclusive. Objective: The aim of this study was to determine an association of RFC-1 polymorphism at rs1131596 and rs1051266 loci (functional variants previously implicated in folate transport efficiency and NTD susceptibility) among mothers with the occurrence of NTDs in their offspring in Ethiopia. Methods: A case–control study involving 250 mothers (187 controls and 63 cases) of children with or without NTDs was conducted in Addis Ababa, Ethiopia from April 2022, to September 2024. A total of 250 maternal whole blood samples were systematically collected and subjected to genetic analysis at loci rs1131596 and rs1051266 by polymerase chain reaction (PCR) and Sanger sequencing. Results: Detection of heterozygous (TC) and homozygous (CC) genotypes for SNP rs1131596 (−43T>C) in the RFC1 gene was 27.2%, with heterozygous (TC) comprising 10.4% and homozygous (CC) 16.8%. In contrast, for the rs1051266 (80A>G), the prevalence of the AG polymorphism was 28% while the GG polymorphism was 16.4%, resulting in a cumulative prevalence of 44.4%. The presence of maternal RFC-1 polymorphism at these two locations were not associated with significantly (p = 0.601 & p = 0.225 respectively) higher odds for NTD births. Conclusions: This study did not reveal significant association between maternal RFC1 gene polymorphisms and NTD-affected births. Comprehensive whole-genome sequencing of affected off-spring is essential to identify specific mutations or polymorphisms that may individually or collaboratively affect the risk of NTDs in the Ethiopian context. Full article

(This article belongs to the Special Issue Genetic Insights into Pediatric Neurological Disorders: From Mechanisms to Therapies)

28 pages, 626 KB

Open AccessReview

The Epigenetic Landscape and Exposome of Non-Melanoma Skin Cancer: Mechanisms, Biomarkers, and Therapeutic Perspectives

by Adrian Albulescu, Alina Fudulu, Iulia Virginia Constantin (Iancu), Adriana Plesa, Irina Huica and Anca Botezatu

Genes 2026, 17(4), 477; https://doi.org/10.3390/genes17040477 - 17 Apr 2026

Viewed by 303

Abstract

Accounting for over 1.2 million new diagnoses worldwide in 2022, non-melanoma skin cancer (NMSC) represents the most common human cancer, predominantly manifesting as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). NMSC serves as a powerful natural model for studying how environmental [...] Read more.

Accounting for over 1.2 million new diagnoses worldwide in 2022, non-melanoma skin cancer (NMSC) represents the most common human cancer, predominantly manifesting as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). NMSC serves as a powerful natural model for studying how environmental exposure, the exposome, reprograms the epigenome to drive carcinogenesis. Chronic ultraviolet radiation (UVR), the dominant risk factor, induces DNA damage and inflammation that dysregulate epigenetic enzymes (e.g., DNMTs, HDACs). These effects are layered with perturbations from β-HPV infection and cutaneous dysbiosis, altering DNA methylation, histone modifications, and non-coding RNA and miRNA expression in a multistep carcinogenic process. This review synthesizes the central role of epigenetic regulation as the critical interface between genetic susceptibility and cumulative exposome factors in NMSC pathogenesis. We integrate how UVR, HPV, and inflammation converge to remodel the keratinocyte epigenome. Finally, we evaluate the translational potential of this knowledge for refined risk stratification through epigenetic biomarkers and discuss emerging therapeutic strategies, including epidrugs, that target these dysregulated pathways for advanced NMSC management. Full article

(This article belongs to the Special Issue Epigenetic Regulation in Tumors)

► Show Figures

Figure 1

13 pages, 2363 KB

Open AccessArticle

Toxoplasma gondii GRA12 Inhibits the NF-ΚB Signaling Pathway by Targeting P65 and the IKK Complex

by Meiling Ou, Xiaowen Fang, Ying Yuan, Zhizhuo Huang, Boren Bai, Xiuying Hou, Yongjun Li, Chunxia Jing and Guang Yang

Genes 2026, 17(4), 476; https://doi.org/10.3390/genes17040476 - 17 Apr 2026

Viewed by 305

Abstract

Background: The NF-κB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by [...] Read more.

Background: The NF-κB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by employing sophisticated immune evasion strategies. Dense granule (GRA) proteins are essential for the survival and pathogenesis of T. gondii. Methods: In this study, plasmid transfection, cell culture, luciferase reporter assay, quantitative PCR, and western blot were employed to identify T. gondii GRA proteins that regulate the NF-κB pathway. Results: We demonstrate that GRA12, a specific GRA protein, significantly inhibits NF-κB promoter activity and the transcriptional expression of key cytokines, including IL-6, IL-12, TNF-α, and IFN-β. Western blot analysis further revealed that GRA12 suppresses the activation of the IKK complex and p65. Moreover, GRA12 prevents the nuclear translocation of p65. Conclusions: Our findings demonstrate that GRA12 is involved in immune evasion by inhibiting the NF-κB pathway, thereby facilitating T. gondii dissemination and infection. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

14 pages, 562 KB

Open AccessArticle

Extracellular Matrix Signalling and Injury Susceptibility: ACAN and FMOD Variants in Sports-Related Musculoskeletal Injuries

by Agata Rzeszutko-Bełzowska and Agata Leońska-Duniec

Genes 2026, 17(4), 475; https://doi.org/10.3390/genes17040475 - 17 Apr 2026

Viewed by 177

Abstract

Background/Objectives: Musculoskeletal soft-tissue injuries are common among physically active individuals and arise from complex interactions between environmental and biological factors. Genetic variation in genes involved in extracellular matrix (ECM) organization may contribute to individual susceptibility to such injuries. This study investigated whether [...] Read more.

Background/Objectives: Musculoskeletal soft-tissue injuries are common among physically active individuals and arise from complex interactions between environmental and biological factors. Genetic variation in genes involved in extracellular matrix (ECM) organization may contribute to individual susceptibility to such injuries. This study investigated whether polymorphisms in aggrecan (ACAN, rs2351491 and rs1042631) and fibromodulin (FMOD, rs7543148) genes are associated with susceptibility to sports-related injuries. Methods: The study included 335 physically active Caucasians, comprising 202 participants with a history of non-contact sports-related musculoskeletal injuries and 133 uninjured controls. Genotyping was performed using real-time polymerase chain reaction. Results: No significant associations were observed between the analyzed polymorphisms and overall injury occurrence after correction for multiple comparisons. A nominal association was observed for ACAN rs2351491 in the overall injury comparison under the overdominant model (p = 0.0457), where CT heterozygotes were more frequent among injured participants. The ACAN rs1042631 variant showed nominal associations with anterior cruciate ligament (ACL) injury under the codominant (p = 0.0179), recessive (p = 0.0243), and overdominant (p = 0.0346) models, with the TT genotype associated with lower odds of ACL injury under the recessive model (OR = 0.15, 95% CI: 0.02–1.22). No significant associations were observed for FMOD rs7543148 or for haplotype analysis of ACAN variants. Conclusions: No robust associations were identified between the investigated variants and susceptibility to musculoskeletal soft-tissue injury after correction for multiple testing. Nominal signals observed for ACAN variants, particularly in ACL-focused analyses, warrant further investigation but should be interpreted cautiously and confirmed in larger, independent cohorts. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

► Show Figures

Figure 1

24 pages, 614 KB

Open AccessReview

Epigenetic and Neurogenomic Mechanisms Linking Physical Activity to Brain Plasticity and Cognitive Function

by Agata Leońska-Duniec

Genes 2026, 17(4), 474; https://doi.org/10.3390/genes17040474 - 17 Apr 2026

Viewed by 620

Abstract

Background/Objectives: Physical activity is one of the most powerful lifestyle factors influencing brain health, with growing evidence supporting its role in promoting neuroplasticity, cognitive function, and resilience to age-related neurological decline. Recent studies indicate that these effects are mediated by coordinated molecular [...] Read more.

Background/Objectives: Physical activity is one of the most powerful lifestyle factors influencing brain health, with growing evidence supporting its role in promoting neuroplasticity, cognitive function, and resilience to age-related neurological decline. Recent studies indicate that these effects are mediated by coordinated molecular responses involving epigenetics, activity-dependent gene expression, metabolic adaptation, and inter-organ communication pathways. This narrative review synthesizes current knowledge from experimental and clinical studies on the neurogenomic and epigenetic mechanisms underlying exercise-induced brain plasticity. Methods: Literature searches were conducted in PubMed, Scopus, Web of Science, and Google Scholar to identify studies examining neurogenomic and epigenetic mechanisms underlying neuroplasticity and cognitive adaptations in response to exercise, with an emphasis on mechanistic and translational evidence. Results: Available evidence, derived predominantly from animal studies and supported by more limited, often indirect human data, indicates that physical activity induces epigenetic modifications, including changes in DNA methylation, histone modifications, and microRNA expression, which contribute to lasting changes in exercise-responsive genes involved in brain plasticity. These adaptations include the upregulation of key neuroplasticity-related mediators that support neurogenesis, synaptic plasticity, angiogenesis, and metabolic adaptation, alongside the downregulation of pathways linked to neuroinflammation, oxidative stress, and apoptotic signalling. Conclusions: Integrating neurogenomics with systems biology approaches offers promising opportunities to better understand how physical activity influences brain plasticity throughout life. These insights may support the development of personalized exercise medicine to improve cognitive health and reduce the risk of neurodegenerative disorders. Full article

(This article belongs to the Special Issue Feature Papers in "Neurogenetics and Neurogenomics": 2026)

► Show Figures

Figure 1

20 pages, 3387 KB

Open AccessArticle

The Genome-Wide Identification and Expression Profiling of the HSF Gene Family in Ganoderma lucidum Under Temperature Stress

by Jinyu Hu, Yihong Li, Shaohua Wu, Liwei Liu, Jiawei Zhou, Wei Li, Rui Zhang, Zongsuo Liang, Dongfeng Yang and Zongqi Yang

Genes 2026, 17(4), 473; https://doi.org/10.3390/genes17040473 - 17 Apr 2026

Viewed by 363

Abstract

Objective: In this study, the heat shock transcription factor (HSF) gene family in Ganoderma lucidum was systematically characterized. Using genomic and transcriptomic data, we identified HSF family members and investigated their expression patterns under temperature stress and their potential regulatory roles in triterpenoid [...] Read more.

Objective: In this study, the heat shock transcription factor (HSF) gene family in Ganoderma lucidum was systematically characterized. Using genomic and transcriptomic data, we identified HSF family members and investigated their expression patterns under temperature stress and their potential regulatory roles in triterpenoid biosynthesis. Methods: A genome-wide identification of HSF genes in G. lucidum was performed using bioinformatic approaches. A phylogenetic tree was constructed, and conserved motifs, gene structures, and protein tertiary structures were predicted. The relative expression levels of HSF genes and key mevalonate (MVA) pathway enzyme genes were examined by a quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in mycelia subjected to temperature stress. Total triterpenoid content in fermented mycelia under temperature stress was determined using the vanillin–glacial acetic acid method. Results: Eight HSF family members (GlHSF1–GlHSF8) were identified in G. lucidum. Phylogenetic analysis revealed that GlHSF proteins were closely related to PoHSF from Pleurotus ostreatus. Transcriptomic analysis showed that HSF genes exhibited relatively high expression levels during the mature stage while being barely expressed during the mycelial stage. Under heat stress (42 °C), most GlHSF genes peaked at 18 h, with GlHSF2 showing the most pronounced response (approximately 13-fold upregulation). Downstream MVA pathway genes, including IDI, PMK, and MVD, were significantly upregulated at 24 h, whereas the upstream rate-limiting enzyme gene HMGR was continuously suppressed. Despite HMGR suppression, total triterpenoid content did not decrease significantly, likely due to the activation of downstream genes. Under cold stress (14 °C), the expression of most GlHSF and MVA pathway genes decreased, accompanied by a significant reduction in total triterpenoid content. Conclusions: The HSF gene family was identified in the G. lucidum genome. Based on expression analysis, GlHSF2 showed the strongest response under heat stress, and its expression peak was correlated with the sequential activation of downstream genes in the MVA pathway. This suggests that GlHSF2 acts as a potential key regulatory node, differentially regulating upstream and downstream MVA pathway genes to influence triterpenoid biosynthesis under heat stress. These findings provide a theoretical basis for future research on the biological functions of GlHSF homeostasis. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

8 pages, 214 KB

Open AccessArticle

Enrichment of Rare Variants in Nuclear-Encoded Mitochondrial Metabolism Genes in Patients with Early-Onset or Familial Parkinson’s Disease

by Gaber Bergant, Vesna M. van Midden, Polina Tsygankova, Dorian Laslo, Valentino Rački, Dejan Georgiev, Eliša Papić, Marija Branković, Milena Janković, Marina Svetel, Nataša Teran, Natasa Dragasević Misković, Igor Petrović, Aleš Maver, Ivana Novaković, Zvezdan Pirtošek, Martin Rakuša, Vladimira Vuletić and Borut Peterlin

Genes 2026, 17(4), 472; https://doi.org/10.3390/genes17040472 - 17 Apr 2026

Viewed by 310

Abstract

Introduction: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset [...] Read more.

Introduction: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset and familial PD. Methods: We performed a retrospective analysis on 248 early-onset and familial PD patients and 1622 control individuals. We assessed both pathway-level and gene-level burden of germline rare variants detected using exome sequencing in 467 nuclear genes related to mitochondrial metabolism. Results: Gene-set mutation burden analysis indicated an increased burden in genes associated with mtDNA maintenance. In addition, gene-level analysis identified a possible association between PD and rare variant burden in 14 mitochondrial metabolism-related genes under dominant or recessive inheritance models. Conclusions: Our findings support a potential contribution of rare germline variants affecting mitochondrial metabolism to the susceptibility in early-onset and familial PD. Full article

(This article belongs to the Special Issue Genetics and Treatment in Neurodegenerative Diseases)

19 pages, 6929 KB

Open AccessArticle

Genomic Signatures of Somatic Mutation and Selection Shape Distinct Clonal Lineages in Bougainvillea × buttiana ‘Miss Manila’ Bud Sport

by Hongyan Meng, Qun Zhou, Duchao Chen, Bayan Huang, Mingqiong Zheng and Wanqi Zhang

Genes 2026, 17(4), 471; https://doi.org/10.3390/genes17040471 - 17 Apr 2026

Viewed by 320

Abstract

Background/Objectives: Bud sports (somatic mutations) offer a quick way to develop new bougainvillea varieties by altering specific traits while keeping the desirable genetic background of the original cultivar. However, we still lack a comprehensive understanding of their genomic architecture and the molecular [...] Read more.

Background/Objectives: Bud sports (somatic mutations) offer a quick way to develop new bougainvillea varieties by altering specific traits while keeping the desirable genetic background of the original cultivar. However, we still lack a comprehensive understanding of their genomic architecture and the molecular mechanisms behind their formation. This study aimed to characterize the population genomic characteristics of bud sports derived from the commercial variety Bougainvillea × buttiana ‘Miss Manila’. Methods: We employed genotyping by sequencing (GBS) on 39 accessions, including 27 bud sports and 12 conventional varieties. Population genomic analyses, such as principal component analysis (PCA), phylogenetic reconstruction, ADMIXTURE, and diversity statistics (π, He, Tajima’s D), were performed on 64,810 high-quality SNPs. Genome-wide scans for differentiation (FST) and selective sweeps (XP-CLR) were also conducted. Results: Bud sports showed significantly lower genetic diversity (π and He) than conventional varieties, which matches their clonal origin. PCA, phylogenetic, and ADMIXTURE analyses (optimal K = 4) revealed clear genetic differentiation and distinct population structures between the two groups. The bud sport population possessed fewer private alleles and a less negative Tajima’s D value. Genomic scans identified regions under selection in bud sports, with functional annotation pointed to genes involved in ubiquitin-mediated proteolysis and RNA transport. Notably, Bou_119143 (UDP-rhamnose rhamnosyltransferase 1) showed a high mutation frequency specifically in bud sports. Conclusions: We provide the first population-genomic evidence that bud sports of ‘Miss Manila’ are genetically distinct clonal lineages, shaped by somatic mutation and selection. These findings support bud sports as efficient sources for germplasm innovation. The identified genomic regions and candidate genes lay a foundation for future marker-assisted selection and molecular breeding in bougainvillea. Full article

(This article belongs to the Topic Genetic Breeding and Biotechnology of Garden Plants)

► Show Figures

Figure 1

16 pages, 1742 KB

Open AccessArticle

Integrated Insights into Drought Tolerance Mechanism of the Autotetraploid from Gossypium herbaceum by Transcriptome and Physiological Analyses

by Lili Feng, Lexiang Wang, Jiamin Li, Xianglong Li, Erhua Rong and Yuxiang Wu

Genes 2026, 17(4), 470; https://doi.org/10.3390/genes17040470 - 17 Apr 2026

Viewed by 351

Abstract

Background: Information on the autopolyploid of Gossypium herbaceum remains limited until now. Previously, the autotetraploid of G. herbaceum was successfully generated via colchicine-induced chromosome doubling from the diploid cultivar ‘Hongxing’ in our lab. Methods: To investigate the drought stress response mechanism of this [...] Read more.

Background: Information on the autopolyploid of Gossypium herbaceum remains limited until now. Previously, the autotetraploid of G. herbaceum was successfully generated via colchicine-induced chromosome doubling from the diploid cultivar ‘Hongxing’ in our lab. Methods: To investigate the drought stress response mechanism of this tetraploid, the autotetraploid S4 was used as the experimental material. The plants were subjected to drought stress during the flowering stage, followed by measurements of physiological and biochemical indicators and transcriptomic sequencing analysis. Results: Under drought stress, MDA content increased, and cell membranes sustained oxidative damage. Photosynthetic parameters, such as net photosynthetic rate (Pn), were significantly suppressed, while the activity of osmotic regulators and key antioxidant enzymes increased significantly. After rehydration, all of the above physiological indicators showed varying degrees of recovery. Transcriptome analysis revealed that, when comparing the treatment group with the control group, a total of 5530 differentially expressed genes (DEGs) were identified, with 2714 up-regulated and 2816 down-regulated. Furthermore, this study investigated the drought resistance mechanism involving the interaction between the MAPK signaling pathway and other metabolic pathways in the autotetraploid. Nine drought-resistant genes, including MAPK3, bHLH47, GaRbohD, RIBA1, PIP1-3, RCA1, RbohD, CYP707A and HSP70, were selected and analyzed using real-time quantitative PCR; the results were generally consistent with the transcriptomic data. Conclusions: These findings substantially enhance our understanding of the molecular mechanisms underlying drought responses in autotetraploids. This novel autotetraploid genotype expands the available cotton germplasm resources and is expected to hold significant value for research on polyploidy evolution. Full article

(This article belongs to the Special Issue Abiotic Stress in Crop: Molecular Genetics and Genomics)

► Show Figures

Figure 1

21 pages, 5207 KB

Open AccessArticle

Genome-Wide Identification of the PME Gene Family in Plum and Its Potential Roles in Fruit Texture Formation

by Longji Li, Yu Wang, Siyu Li, Yuan Wang, Menghan Wu, Yanke Geng, Gaopu Zhu, Danfeng Bai, Shaobin Yang, Fangdong Li, Taishan Li and Gaigai Du

Genes 2026, 17(4), 469; https://doi.org/10.3390/genes17040469 - 16 Apr 2026

Viewed by 249

Abstract

Background: Fruit texture is a major component of plum quality, affecting both consumer acceptance and postharvest behavior. Pectin methylesterases (PMEs) play important roles in cell-wall pectin modification and are therefore likely to contribute to plum fruit texture development and ripening-associated softening. However, the [...] Read more.

Background: Fruit texture is a major component of plum quality, affecting both consumer acceptance and postharvest behavior. Pectin methylesterases (PMEs) play important roles in cell-wall pectin modification and are therefore likely to contribute to plum fruit texture development and ripening-associated softening. However, the PME gene family has not yet been comprehensively investigated in plum (Prunus salicina L.). Methods: In the present study, a chromosome-level plum genome was used to survey this gene family at the whole-genome scale. Phylogenetic relationships, chromosomal positions, exon–intron organization, conserved motifs, domain architectures, gene duplication, and cis-elements were analyzed. Four flesh texture traits were measured in 55 plum accessions to characterize texture variation and select two representative cultivars with contrasting flesh textures for further molecular analysis. Based on the clustering results, ‘WSCL’ and ‘FR’ were selected for expression profiling during fruit development and subsequent correlation analysis with texture traits. Results: A total of 46 PsPME genes were identified. Phylogenetic analysis classified them into four major subgroups. Structural analyses indicated an overall conserved family framework, although noticeable variation was retained among individual members. Dispersed duplication made the largest contribution to family expansion, and most duplicated pairs appeared to have evolved under purifying selection. Correlation analysis showed that PsPME20, PsPME22, and PsPME25 were significantly negatively correlated with flesh firmness, while PsPME20 was additionally linked to flesh compactness and flesh fragility. Conclusions: Overall, this study clarifies the structural and evolutionary characteristics of the PsPME family and identifies candidate genes that may contribute to texture differences in plum, offering a basis for future functional studies and breeding programs. Full article

(This article belongs to the Section Plant Genetics and Genomics)

► Show Figures

Figure 1

10 pages, 546 KB

Open AccessArticle

Population-Specific Mutational Spectrum of Autosomal Recessive Nonsyndromic Hearing Loss in Croatian Roma: Implications for Clinical Genetics

by Iva Kutija Fučkar, Matea Zajc Petranović, Irena Martinović Klarić, Marijana Peričić Salihović and Lovorka Barać Lauc

Genes 2026, 17(4), 468; https://doi.org/10.3390/genes17040468 - 16 Apr 2026

Viewed by 285

Abstract

Background/Objectives: Hearing impairment is a highly prevalent sensory disorder resulting from a variety of causes. A high proportion of autosomal recessive non-syndromic hearing impairment is linked to the GJB2 (OMIM 121011) gene which encodes for a gap junction protein, connexin-26. Alterations of genes [...] Read more.

Background/Objectives: Hearing impairment is a highly prevalent sensory disorder resulting from a variety of causes. A high proportion of autosomal recessive non-syndromic hearing impairment is linked to the GJB2 (OMIM 121011) gene which encodes for a gap junction protein, connexin-26. Alterations of genes that encode for connexins can lead to changes in cell ion content and cause hearing impairment. Methods: GJB2 gene polymorphisms (c.71G>A, p.Trp24*rs104894396; c.457G>A, p.Val153Ile, rs111033186; c.380G>A, p.Arg127His, rs111033196; c.109G>A, p.Val37Ile, rs72474224; and c.269T>C, p.Leu90Pro, rs80338945) were analyzed in the Roma population of Croatia. Loci were genotyped using the KASP method. Results: Altered alleles were detected on the loci c.71G>A, c.457G>A and c.380G>A and statistically significant differences in allele frequencies were noticed. Furthermore, in comparison to worldwide populations, the Roma population also shows statistically significant difference in allele frequency of these loci. Conclusions: This study reveals marked genetic differentiation among Croatian Roma particularly with respect to the c.71G>A variant. Characterizing such population-specific mutational heterogeneity is crucial for the accurate prevention, diagnosis, and clinical management of autosomal recessive nonsyndromic hearing loss. Full article

(This article belongs to the Special Issue Unraveling the Genetic Tapestry of Human Populations: New Insights from Population Genetics and Identification in Anthropology)

► Show Figures

Figure 1

19 pages, 1493 KB

Open AccessReview

Precision Medicine Through Network Language: Integrating Clinical Insight and Data Expertise

by Maria Concetta Palumbo, Lorenzo Farina and Manuela Petti

Genes 2026, 17(4), 467; https://doi.org/10.3390/genes17040467 - 16 Apr 2026

Viewed by 431

Abstract

Precision medicine is facing a critical transition driven by the growing complexity of biological data and the insufficient ability of current models to translate such data into clinically meaningful information. Linear, single-gene approaches are no longer adequate to explain the multifactorial nature of [...] Read more.

Precision medicine is facing a critical transition driven by the growing complexity of biological data and the insufficient ability of current models to translate such data into clinically meaningful information. Linear, single-gene approaches are no longer adequate to explain the multifactorial nature of most modern diseases, whose phenotypes emerge from combinations of genetic, molecular, and environmental factors. Network-based precision medicine addresses this by providing a systemic framework capable of integrating heterogeneous omics data, interactomes, and clinical information to identify disease modules and novel therapeutic opportunities. The distinct novelty of this review is its focus on the potential of “network language” as the primary driver for realizing precision medicine through professional collaboration. We argue that networks are not merely tools that achieve precision “per se”; rather, their transformative power lies in their ability to serve as a shared and interpretable interface grounded in network theory. By offering this common conceptual ground, the paradigm bridges the deep cultural and methodological gaps between clinicians and data analysts, enabling effective cooperation between figures with fundamentally different, and often divergent, backgrounds. Practical tools—such as biological network analysis and Molecular Tumor Boards—demonstrate how computational modeling and clinical expertise can be successfully combined to generate actionable insights. Ultimately, network-based precision medicine represents a decisive step toward reconstructing the patient’s complexity and promoting a genuinely personalized clinical approach in which quantitative analysis and medical reasoning act synergistically through multidisciplinary integration. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Complex Traits)

► Show Figures

Figure 1

16 pages, 1641 KB

Open AccessArticle

Multi-Omics Mendelian Randomization and Clinical Validation Implicate NLRP6 as a Candidate Autophagy-Related Gene in Systemic Lupus Erythematosus

by Daan Nie, Jianguo Yin, Wei Tu, Kecheng Huang, Jing Wan, Yikai Yu, Bei Wang, Yu Chen, Shengyan Lin and Zhipeng Zeng

Genes 2026, 17(4), 466; https://doi.org/10.3390/genes17040466 - 16 Apr 2026

Viewed by 371

Abstract

Background/Objectives: Autophagy plays a role in systemic lupus erythematosus (SLE) pathogenesis. Nevertheless, the specific genetic determinants underpinning this process remain poorly characterized. Summary data-based Mendelian randomization (SMR) analysis was therefore utilized to pinpoint autophagy-related genes associated with SLE risk. Methods: We analyzed [...] Read more.

Background/Objectives: Autophagy plays a role in systemic lupus erythematosus (SLE) pathogenesis. Nevertheless, the specific genetic determinants underpinning this process remain poorly characterized. Summary data-based Mendelian randomization (SMR) analysis was therefore utilized to pinpoint autophagy-related genes associated with SLE risk. Methods: We analyzed 700 autophagy-related genes, integrating methylation quantitative trait loci (mQTL), expression QTL (eQTL) from blood and relevant tissue, and protein QTL (pQTL) data with genome-wide association studies (GWAS) data on SLE from the IEU dataset (discovery). GWAS data from FinnGen and the GWAS Catalog were used as replication datasets. Colocalization analysis identified shared genetic variants. Blood samples from 10 healthy control and 20 SLE patients were collected and analyzed for the expression of candidate genes. Results: Our SMR analysis identified suggestive associations between NLRP6 expression (OR = 0.528, 95%CI = 0.291–0.96) and p27Kip1 protein abundance (OR = 0.269, 95%CI = 0.08–0.904) with SLE susceptibility in the discovery cohort, supported by colocalization evidence. Additionally, we found that the methylation of the NLRP6 promoter (cg06432119) was significantly increased, while NLRP6 expression and p27Kip1 level were significantly decreased in SLE patients compared to controls. Furthermore, NLRP6 mRNA expression was significantly negatively correlated with the SLE severity (SLEDAI-2000). Conclusions: These findings not only prioritized candidate genes via SMR analysis but also provided evidence of epigenetic dysregulation of NLRP6 and its correlation with disease activity in SLE, thereby offering novel insights into the underlying mechanisms. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

24 pages, 21078 KB

Open AccessArticle

Neuronal Ceroid Lipofuscinosis-like Disorder in a Dachshund with Sequence Variants in Lysosome-Related Genes

by Joan R. Coates, Kristen Keyes, Rebecca E. H. Whiting, Juri Kuroki, Brandie Morgan-Jack, Tendai Mhlanga-Mutangadura, Keiichi Kuroki and Martin L. Katz

Genes 2026, 17(4), 465; https://doi.org/10.3390/genes17040465 - 15 Apr 2026

Viewed by 307

Abstract

Background/Objectives: Among the most common hereditary neurodegenerative disorders in people are the neuronal ceroid lipofuscinoses (NCLs), a subgroup of lysosomal storage disorders. For most cases of NCL, the genes containing the causative variants have been identified. NCLs also occur in dogs, and in [...] Read more.

Background/Objectives: Among the most common hereditary neurodegenerative disorders in people are the neuronal ceroid lipofuscinoses (NCLs), a subgroup of lysosomal storage disorders. For most cases of NCL, the genes containing the causative variants have been identified. NCLs also occur in dogs, and in most instances variants responsible for the canine NCLs occur in genes orthologous to those associated with the human disorders. An adult miniature Dachshund presented with clinical signs consistent with NCL. Studies were undertaken to determine whether the disease phenotype supported the classification of the disease as an NCL and to identify potential causal DNA sequence variants. Methods: The proband underwent complete neurological and ophthalmological examinations followed by euthanasia. Tissues were examined for NCL-like pathology. Whole genome sequence analysis (WGS) was performed. Results: The clinical signs and tissue pathology were consistent with those of NCL disease, although with some features distinct from previously described forms of canine NCL. The proband was uniquely homozygous for variants in five genes associated with lysosomal function, four of which have not previously been associated with the NCLs. Conclusions: The proband suffered from a novel NCL-like disorder. Determining whether one or a combination of more than one of the five potentially causal DNA sequence variants was responsible for the disease will require evaluation of additional cases. Full article

(This article belongs to the Section Animal Genetics and Genomics)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genes, Volume 17, Issue 4 (April 2026) – 135 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI