Genes

26 pages, 850 KB

Open AccessReview

The Enhancement of Fungal Disease Resistance in Major Staple Crops Using CRISPR-Cas Technology

by Zagipa Sapakhova, Rakhim Kanat, Dias Daurov, Ainash Daurova, Malika Shamekova and Kabyl Zhambakin

Genes 2025, 16(11), 1263; https://doi.org/10.3390/genes16111263 (registering DOI) - 26 Oct 2025

Abstract

Fungal pathogens represent a major constraint to global agricultural productivity, causing a wide range of plant diseases that severely affect staple crops such as cereals, legumes, and vegetables. These infections result in substantial yield losses, deterioration of grain and produce quality, and significant [...] Read more.

Fungal pathogens represent a major constraint to global agricultural productivity, causing a wide range of plant diseases that severely affect staple crops such as cereals, legumes, and vegetables. These infections result in substantial yield losses, deterioration of grain and produce quality, and significant economic impacts across the entire agri-food sector. Among phytopathogens, fungi are considered the most destructive, causing a wide range of diseases such as powdery mildew, rusts, fusarium head blight, smut, leaf spot, rots, late blight, and other fungal pathogens. Traditional plant protection methods do not always provide long-term effectiveness and environmental safety, which requires the introduction of innovative approaches to creating sustainable varieties. CRISPR-Cas technology opens up new opportunities for targeted genome editing, allowing the modification or silencing of susceptibility genes and thus increasing plant resistance to fungal infections. This review presents current achievements and prospects for the application of CRISPR-Cas technology to increase the resistance of major agricultural crops to fungal diseases. The implementation of these approaches contributes to the creation of highly productive and resistant varieties, which is crucial for ensuring food security in the context of climate change. Full article

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

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15 pages, 6232 KB

Open AccessArticle

Characterization of LTR Retrotransposon Reverse Transcriptase in Tamarix chinensis L. and Activity Analysis Under Salt and Alkali Stresses

by Long Wang, Bo Li, Yuqian Wang, Shiji Wang, Meichun Zhang, Mengyao Li, Tong Zheng and Hongyan Wang

Genes 2025, 16(11), 1262; https://doi.org/10.3390/genes16111262 (registering DOI) - 26 Oct 2025

Abstract

Transposable elements (TEs) are major components of plant genomes and play crucial roles in adaptive genome evolution and stress tolerance. Under abiotic stress, activated TEs can generate abundant genetic variation and regulate the expression of stress-responsive genes. As a pioneer species in desert [...] Read more.

Transposable elements (TEs) are major components of plant genomes and play crucial roles in adaptive genome evolution and stress tolerance. Under abiotic stress, activated TEs can generate abundant genetic variation and regulate the expression of stress-responsive genes. As a pioneer species in desert and saline–alkali environments, Tamarix chinensis L. has been little studied with respect to the abundance and evolutionary relationships of its LTR retrotransposons, particularly their activation patterns under salt and alkali stresses. This study aimed to investigate the characteristics of the reverse transcriptase (RT) domain of LTR retrotransposons in T. chinensis and to determine their patterns of activation in response to salt and alkali stresses. A total of 629 Ty1-copia and 607 Ty3-gypsy RT nucleotide sequences, which displayed high AT/GC ratios and evidence of stop codon insertions, were identified in T. chinensis by amplicon sequencing. Among these, 211 Ty1-copia and 117 Ty3-gypsy RT sequences with potential transpositional activity each contained distinct domains, suggesting a high degree of conservation. Phylogenetic analysis revealed that the RT sequences of T. chinensis are closely related to those of mangrove, wild potato, and Ipomoea, and may have undergone horizontal transfer. Expression analysis showed that 634 and 181 RT sequences were activated under salt and alkali stresses, respectively, with the majority belonging to salt-induced Ty1-copia families. Compared with the control group, under salt and alkali stresses, the cTy1-copia elements (Ty1-copia with amplificated from cDNA of T. chinensis, the same below) with dominant abundance were mainly concentrated in the Angela subfamily, while the cTy3-gypsy elements induced by alkali stress were primarily distributed in the Tekay and Reina subfamilies. Furthermore, four cTy1-copia and five cTy3-gypsy were identified as candidate key LTR retrotransposons responsive to salt and alkali stresses. Overall, this study provides new insights into the epigenetic mechanisms underlying the adaptation of T. chinensis to saline and alkali stresses and offers a theoretical basis for its potential applications in saline–alkali land reclamation. Full article

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

13 pages, 800 KB

Open AccessArticle

Towards Personalized Chemotherapy in Gastrointestinal Cancers: Prospective Analysis of Pharmacogenetic Variants in a Russian Cohort

by Denis Fedorinov, Vladimir Lyadov, Marina Lyadova, Sherzod Abdullaev, Anastasia Kachanova, Rustam Heydarov, Igor Shashkov, Sergey Surzhikov, Vladimir Mikhailovich and Dmitry Sychev

Genes 2025, 16(11), 1261; https://doi.org/10.3390/genes16111261 (registering DOI) - 25 Oct 2025

Abstract

Background/Objectives: Pharmacogenetic variability plays a crucial role in determining both the efficacy and toxicity of chemotherapy for gastrointestinal cancers. However, data on allele frequencies and their clinical relevance in Russian populations remain scarce. Methods: We conducted a prospective observational study of [...] Read more.

Background/Objectives: Pharmacogenetic variability plays a crucial role in determining both the efficacy and toxicity of chemotherapy for gastrointestinal cancers. However, data on allele frequencies and their clinical relevance in Russian populations remain scarce. Methods: We conducted a prospective observational study of 412 patients with gastrointestinal malignancies between 2020 and 2023. Pharmacogenetic testing was performed prior to the initiation of chemotherapy using real-time allele-specific PCR and microarray hybridization technology. Polymorphisms in the DPYD, UGT1A1, CYP2C8, CYP3A5, GSTP1, ERCC1, XPC, CDA, MTHFR, TYMS, and SLC31A1 genes were analyzed. Results: The frequency of most variants was consistent with those reported in European populations, reflecting the ethnic proximity of the studied cohort. Several clinically relevant variants were identified: DPYD rs2297595 occurred more frequently than in European cohorts, and UGT1A1 rs8175347 was observed at a higher prevalence, underscoring the potential risk of irinotecan-related neutropenia and diarrhea. CYP2C8 rs10509681 was present at frequencies comparable to European populations and is associated with an increased risk of taxane-induced peripheral neuropathy. Other markers (GSTP1, ERCC1, CDA, SLC31A1, MTHFR, TYMS) demonstrated variable associations with chemotherapy efficacy and toxicity, consistent with findings from previous international studies. Conclusions: This study provides the first comprehensive description of pharmacogenetic polymorphisms in a Russian cohort of patients with gastrointestinal cancers. Our findings confirm the clinical importance of DPYD and UGT1A1 testing and highlight additional variants of potential interest. Full article

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

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10 pages, 881 KB

Open AccessArticle

Examining the Concordance of Detection of Hereditary Cancer Gene Variants Between Blood, Tumour, and Normal Tissue in Patients with High-Grade Serous Ovarian Carcinoma

by L. Mui, J. Kerkhof, C. M. McLachlin, K. Panabaker, J. McGee, B. Sadikovic and E. A. Goebel

Genes 2025, 16(11), 1260; https://doi.org/10.3390/genes16111260 (registering DOI) - 25 Oct 2025

Abstract

Background/Objectives: Access to genetic counselling and BRCA1/2 germline testing is standard of care for patients with high-grade serous ovarian carcinoma (HGSOC). While tumour testing reliably detects pathogenic variants in hereditary cancer genes, it cannot distinguish somatic from germline variants. Concurrent testing of non-cancerous [...] Read more.

Background/Objectives: Access to genetic counselling and BRCA1/2 germline testing is standard of care for patients with high-grade serous ovarian carcinoma (HGSOC). While tumour testing reliably detects pathogenic variants in hereditary cancer genes, it cannot distinguish somatic from germline variants. Concurrent testing of non-cancerous (normal) tissue obtained during surgery may improve triage for germline testing and clinical genetics referral. This study evaluated the concordance of inherited variant detection among tumour, normal tissue, and blood to determine whether archived normal tissue can reliably identify germline pathogenic variants. Methods: Patients with HGSOC who had a pathogenic variant identified by targeted Next Generation Sequencing (NGS) tumour testing and underwent germline hereditary cancer gene panel (HCP) testing between April 2019 and November 2020 were included. HCP testing was performed on formalin-fixed, paraffin-embedded normal tissue from the original resection. Variant results were compared across tumour, normal tissue, and germline (blood) samples to determine concordance, false-negative, and false-positive rates. Results: Forty-one patients had confirmed tumour variants in BRCA1/2 or other HCP genes. Of these, 24 harboured a corresponding germline pathogenic variant. Archived normal tissue was available for 23 of these 24 cases, and all germline variants were detected in normal tissue, showing 100% concordance. Among the 17 patients without germline variants, all corresponding normal tissue samples were negative, also demonstrating 100% concordance. No false positives or negatives were identified. Conclusions: NGS testing of normal tissue at surgical resection reliably identifies germline pathogenic variants in patients with HGSOC. Incorporating this approach may help triage patients for clinical genetics assessment. Full article

(This article belongs to the Special Issue Advances in Genetic Counseling and Genetic Testing in Precision Medicine (2nd Edition))

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13 pages, 1885 KB

Open AccessArticle

The Role of TuACO Gene Family in Response to Biotic and Abiotic Stresses in Triticum urartu

by Min Li, Xiaoting Liu, Shuo Wang, Xinhai Wang, Pu Gao, Takele Weldu Gebrewahid, Peipei Zhang and Zaifeng Li

Genes 2025, 16(11), 1259; https://doi.org/10.3390/genes16111259 (registering DOI) - 25 Oct 2025

Abstract

Background: Ethylene is one of the most important plant hormones. ACC oxidase (ACO) plays a vital role in ethylene synthesis and responses to biotic and abiotic stresses in plants. However, its function in Triticum urartu remains unclear. This study aims to [...] Read more.

Background: Ethylene is one of the most important plant hormones. ACC oxidase (ACO) plays a vital role in ethylene synthesis and responses to biotic and abiotic stresses in plants. However, its function in Triticum urartu remains unclear. This study aims to systematically identify the members of the TuACO gene family to elucidate its response characteristics and functions under biotic and abiotic stresses. Methods: Through homologous alignment, phylogenetic evolution analysis, and investigations of gene structure and promoter cis-elements, a total of eight TuACO genes were identified in the T. urartu genome based on their homology to OsACO and AtACO protein sequences. Results: These genes were classified into five ACO subfamilies and distributed across chromosomes 1A, 4A, 5A, 6A, and 7A. TuACO gene families contained 0–3 introns and 1–4 exons. The protein sequence contains 10 different conservative motifs. QRT-PCR expression analysis revealed that the transcript levels of TuACO5a, TuACO5b, and TuACO3a were significantly upregulated at 6 and 24 h after infection with powdery mildew, a biotic stress. Under boron deficiency, an abiotic stress, the expression of TuACO6 and TuACO1b increased, whereas the expression of TuACO5b and TuACO3b was markedly induced under high-boron conditions. Conclusions: These results demonstrate that TuACO genes exhibit functional diversification in response to biotic and abiotic stresses, which lays the foundation for elucidating their gene functions. Full article

(This article belongs to the Special Issue Decoding the Plant Epigenome: Interactions Between Genomics, Transcription, and Epigenetic Regulation)

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22 pages, 690 KB

Open AccessReview

Artificial Intelligence-Assisted CRISPR/Cas Systems for Targeting Plant Viruses

by Nurgul Iksat, Almas Madirov, Kuralay Zhanassova and Zhaksylyk Masalimov

Genes 2025, 16(11), 1258; https://doi.org/10.3390/genes16111258 (registering DOI) - 24 Oct 2025

Abstract

Plant viral infections continue to pose a significant and ongoing threat to global food security, especially in the context of climatic instability and intensive agricultural practices. The CRISPR/Cas system has emerged as a powerful tool for developing virus-resistant crops by enabling precise modifications [...] Read more.

Plant viral infections continue to pose a significant and ongoing threat to global food security, especially in the context of climatic instability and intensive agricultural practices. The CRISPR/Cas system has emerged as a powerful tool for developing virus-resistant crops by enabling precise modifications to viral genomes or plant susceptibility factors. Nonetheless, the efficacy and dependability of CRISPR-based antiviral approaches are limited by challenges in guide RNA design, off-target effects, insufficiently annotated datasets, and the intricate biological dynamics of plant–virus interactions. This paper summarizes the latest advancements in the incorporation of artificial intelligence (AI) methodologies, including machine learning and deep learning algorithms, into the CRISPR design and optimization framework. It examines how convolutional and recurrent neural networks, transformer architectures, and generative models like AlphaFold2, RoseTTAFold, and ESMFold can be used to predict protein structures, score sgRNAs, and model host–virus interactions. AI-enhanced methods have been proven to improve target specificity, Cas protein performance, and in silico validation. This paper aims to establish a foundation for next-generation genome editing strategies against plant viruses and promote the adoption of AI-powered CRISPR technologies in sustainable agriculture. Full article

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

20 pages, 2592 KB

Open AccessArticle

Genome-Wide Identification and Tissue-Specific Expression Profiling of Goji CER Gene Family

by Qian Yu, Jie Li, Lijuan Jing, Feng Zhang, Bohua Liu and Liuwei Guo

Genes 2025, 16(11), 1257; https://doi.org/10.3390/genes16111257 (registering DOI) - 24 Oct 2025

Abstract

Background: Goji berry, known as a “superfood”, is widely distributed in northwest China and possesses significant medicinal and health value. The CER gene family serves as a key regulator of cuticular wax synthesis, which plays important roles in enhancing plant drought resistance and [...] Read more.

Background: Goji berry, known as a “superfood”, is widely distributed in northwest China and possesses significant medicinal and health value. The CER gene family serves as a key regulator of cuticular wax synthesis, which plays important roles in enhancing plant drought resistance and disease tolerance. However, genome-wide identification of the goji CER gene family and its expression analysis across different varieties and organs have not been reported. Methods: Based on SEM observations and wax load measurements, this study identified CER gene family members using whole genome data of the goji berry. Representative genes were selected and their expression patterns in different varieties and organs were validated by qRT‒PCR. Results: The stem wax load was significantly higher than that in other organs, while the leaf wax load of ‘Ningqi I’ goji was significantly higher than that in other varieties, consistent with SEM observations. A total of 113 CER gene family members were identified in goji berry, which were unevenly distributed on 12 chromosomes. The goji CER proteins mainly localized in the cell membrane, cytoplasm, chloroplast, and nucleus and clustered into five subfamilies. Ten conserved motifs were identified in CER proteins, with Motif5 and Motif7 being the most widely distributed. The LbaCER10-1 gene contained the highest number of exons (39). Cis-acting elements related to light-responsiveness, MeJA-responsiveness, and ABA-responsiveness showed high frequencies. Goji berry shared more homologous CER genes with tomato, potato, and tobacco than with Arabidopsis, with chr3 and chr9 being most conserved while chr7 showed greater variation. Conclusions: Integrating SEM, wax load, and qRT‒PCR results, LbaCER1-1 was identified as a candidate gene responsible for the higher wax load on goji stems, while LbaCER2-5 and LbaCER3-12 were candidate genes for greater wax load on ‘Ningqi I’ leaves. Full article

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

14 pages, 3288 KB

Open AccessArticle

The Complete Mitochondrial Genome of Stromateus stellatus (Scombriformes: Stromateidae): Organization, Gene Arrangement, and Phylogenetic Position Within the Suborder Stromateoidei

by Fernanda E. Angulo, Rodrigo Pedrero-Pacheco and José J. Nuñez

Genes 2025, 16(11), 1256; https://doi.org/10.3390/genes16111256 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: The butterfish Stromateus stellatus is undervalued and usually discarded as bycatch, leading to an inefficient and unsustainable use of marine biomass. Overall, although Stromateus is the type genus of the family Stromateidae, its species are less studied than more economically important fishes. [...] Read more.

Background/Objectives: The butterfish Stromateus stellatus is undervalued and usually discarded as bycatch, leading to an inefficient and unsustainable use of marine biomass. Overall, although Stromateus is the type genus of the family Stromateidae, its species are less studied than more economically important fishes. Methods: In this study, we determined and analyzed the complete mitochondrial genome sequence of S. stellatus. Furthermore, we performed maximum likelihood and Bayesian inference analyses to infer the phylogenetic relationships among 21 species of the order Scombriformes. Results: Using next-generation sequencing (NGS) and de novo assembly, a circular mitochondrial genome of 16,509 bp was obtained, exhibiting the typical vertebrate mitochondrial structure comprising 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. Three intergenic regions were identified, including the control region and the origin of light-strand replication, along with several gene overlaps. The heavy strand nucleotide composition was determined to be 28.79% A, 27.84% C, 16.32% G, and 27.05% T, with a GC content of 44.16%. The three Peprilus and five Pampus species formed a clade together with S. stellatus, supported by high bootstrap and posterior probability values, confirming the monophyly of Stromateidae. Conclusions: The gene order and content are consistent with those reported for other Stromateidae species and correspond to the typical arrangement observed in most bony fishes. This mitochondrial genome represents the first one reported for the genus Stromateus, providing valuable insights into the genetic makeup of S. stellatus, contributing to a better understanding of marine biodiversity. Additionally, these data will support future research on pelagic fish evolution and assist in sustainable fisheries management. Full article

(This article belongs to the Special Issue Genetic Status and Perspectives of Fisheries Resources)

19 pages, 2412 KB

Open AccessArticle

Attention-Guided Probabilistic Diffusion Model for Generating Cell-Type-Specific Gene Regulatory Networks from Gene Expression Profiles

by Shiyu Xu, Na Yu, Daoliang Zhang and Chuanyuan Wang

Genes 2025, 16(11), 1255; https://doi.org/10.3390/genes16111255 (registering DOI) - 24 Oct 2025

Abstract

Gene regulatory networks (GRN) govern cellular identity and function through precise control of gene transcription. Single-cell technologies have provided powerful means to dissect regulatory mechanisms within specific cellular states. However, existing computational approaches for modeling single-cell RNA sequencing (scRNA-seq) data often infer local [...] Read more.

Gene regulatory networks (GRN) govern cellular identity and function through precise control of gene transcription. Single-cell technologies have provided powerful means to dissect regulatory mechanisms within specific cellular states. However, existing computational approaches for modeling single-cell RNA sequencing (scRNA-seq) data often infer local regulatory interactions independently, which limits their ability to resolve regulatory mechanisms from a global perspective. Here, we propose a deep learning framework (Planet) based on diffusion models for constructing cell-specific GRN, thereby providing a systems-level view of how protein regulators orchestrate transcriptional programs. Planet jointly optimizes local network structures in conjunction with gene expression profiles, thereby enhancing the structural consistency of the resulting networks at the global level. Specifically, Planet decomposes GRN generation into a series of Markovian evolution steps and introduces a Triple Hybrid-Attention Transformer to capture long-range regulatory dependencies across diffusion time-steps. Benchmarks on multiple scRNA-seq datasets demonstrate that Planet achieves competitive performance against state-of-the-art methods and yields only a slight improvement over DigNet under comparable conditions. Compared with conventional diffusion models that rely on fixed sampling schedules, Planet employs a fast-sampling strategy that accelerates inference with only minimal accuracy trade-off. When applied to mouse-lung Cd8⁺Gzmk⁺ T cells, Planet successfully reconstructs a cell-type-specific GRN, recovers both established and previously uncharacterized regulators, and delineates the dynamic immunoregulatory changes that accompany ageing. Overall, Planet provides a practical framework for constructing cell-specific GRNs with improved global consistency, offering a complementary perspective to existing methods and new insights into regulatory dynamics in health and disease. Full article

(This article belongs to the Special Issue Single-Cell and Spatial Multi-Omics in Human Diseases)

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13 pages, 3776 KB

Open AccessArticle

Genetic Diversity and Population Structure of Farmed Longfin Batfish (Platax teira) in the South China Sea

by Yayang Gao, Baosuo Liu, Huayang Guo, Kecheng Zhu, Lin Xian, Nan Zhang, Tengfei Zhu and Dianchang Zhang

Genes 2025, 16(11), 1254; https://doi.org/10.3390/genes16111254 (registering DOI) - 24 Oct 2025

Abstract

Background: Longfin batfish (Platax teira) is an important economic species in southern China. In recent years, its wild population has significantly declined due to overfishing. Around 2015, breakthroughs in the artificial large-scale seedling technology for P. teira have promoted the growth [...] Read more.

Background: Longfin batfish (Platax teira) is an important economic species in southern China. In recent years, its wild population has significantly declined due to overfishing. Around 2015, breakthroughs in the artificial large-scale seedling technology for P. teira have promoted the growth of its aquaculture scale in regions such as Hainan and Guangdong. Methods: To study the genetic diversity, inbreeding status, and population structure of the current P. teira farming populations in China, we performed whole-genome resequencing technology and high-density SNP markers to analyze the genetics of four main farming populations. A total of 109 individuals from four populations (NA, ZP, XL, and XC) were sequenced, identifying 5,384,029 high-quality SNPs. Results: The results showed that the nucleotide diversity (π) of each population ranged from 0.00155 to 0.00165 and observed heterozygosity (Ho) ranged from 0.253 to 0.282, which indicated low levels of genetic diversity. The results of the ROH analysis show significant inbreeding in the NA population. Genetic differentiation analysis revealed that the genetic differentiation among NA, XC, and ZP populations was relatively low (F_ST = 0.021–0.029). Conclusions: NA, XC, and ZP populations likely share a common origin of their fry stocks. Based on a phylogenetic tree, principal component analysis (PCA), and population structure analysis, the four populations were divided into four genetic groups. This study is the first analysis of the genetic diversity and population structure of P. teira farming populations in China, laying the foundation for the establishment of a base breeding population and the implementation of genetic improvement programs. Full article

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

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20 pages, 5128 KB

Open AccessArticle

Bioinformatics Approach to mTOR Signaling Pathway-Associated Genes and Cancer Etiopathogenesis

by Kursat Ozdilli, Gozde Oztan, Demet Kıvanç, Ruştu Oğuz, Fatma Oguz and Hayriye Senturk Ciftci

Genes 2025, 16(11), 1253; https://doi.org/10.3390/genes16111253 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: The mTOR serine/threonine kinase coordinates protein translation, cell growth, and metabolism, and its dysregulation promotes tumorigenesis. We present a reproducible, pan-cancer, network-aware framework that integrates curated resources with genomics to move beyond pathway curation, yielding falsifiable hypotheses and prioritized candidates for [...] Read more.

Background/Objectives: The mTOR serine/threonine kinase coordinates protein translation, cell growth, and metabolism, and its dysregulation promotes tumorigenesis. We present a reproducible, pan-cancer, network-aware framework that integrates curated resources with genomics to move beyond pathway curation, yielding falsifiable hypotheses and prioritized candidates for mTOR axis biomarker validation. Materials and Methods: We assembled MTOR-related genes and interactions from GeneCards, KEGG, STRING, UniProt, and PathCards and harmonized identifiers. We formulated a concise working model linking genotype → pathway architecture (mTORC1/2) → expression-level rewiring → phenotype. Three analyses operationalized this model: (i) pan-cancer alteration mapping to separate widely shared drivers from tumor-specific nodes; (ii) expression-based activity scoring to quantify translational/nutrient-sensing modules; and (iii) topology-aware network propagation (personalized PageRank/Random Walk with Restart on a high-confidence STRING graph) to nominate functionally proximal neighbors. Reproducibility was supported by degree-normalized diffusion, predefined statistical thresholds, and sensitivity analyses. Results: Gene ontology analysis demonstrated significant enrichment for mTOR-related processes (TOR/TORC1 signaling and cellular responses to amino acids). Database synthesis corroborated disease associations involving MTOR and its partners (e.g., TSC2, RICTOR, RPTOR, MLST8, AKT1 across selected carcinomas). Across cohorts, our framework distinguishes broadly shared upstream drivers (PTEN, PIK3CA) from lineage-enriched nodes (e.g., RICTOR-linked components) and prioritizes non-mutated, network-proximal candidates that align with mTOR activity signatures. Conclusions: This study delivers a transparent, pan-cancer framework that unifies curated biology, genomics, and network topology to produce testable predictions about the mTOR axis. By distinguishing shared drivers from tumor-specific nodes and elevating non-mutated, topology-inferred candidates, the approach refines biomarker discovery and suggests architecture-aware therapeutic strategies. The analysis is reproducible and extensible, supporting prospective validation of prioritized candidates and the design of correlative studies that align pathway activity with clinical response. Full article

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

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9 pages, 765 KB

Open AccessArticle

Rare Duplication in the RYR1 Gene Causing Malignant Hyperthermia and Clinical Variability

by Brandow W. Souza, Guilherme L. Yamamoto, Isabela A. Zogbi, Pamela V. Andrade, Joilson M. Santos, Leticia N. Feitosa, Acary S. B. Oliveira, Debora R. Bertola, Soledad Levano, Thierry Girard, Helga C. A. Silva and Mariz Vainzof

Genes 2025, 16(11), 1252; https://doi.org/10.3390/genes16111252 - 24 Oct 2025

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Abstract

Background/Objectives: Variants in the RYR1 gene are associated mainly with Malignant Hyperthermia. Missense variants are largely the most common, while insertions and duplications account for less than 10%. We aimed to investigate the effect of a rare duplication in the RYR1 gene [...] Read more.

Background/Objectives: Variants in the RYR1 gene are associated mainly with Malignant Hyperthermia. Missense variants are largely the most common, while insertions and duplications account for less than 10%. We aimed to investigate the effect of a rare duplication in the RYR1 gene with the variability of the Malignant Hyperthermia susceptibility phenotype. Methods: We used exome variant screening, in vitro contracture test, anatomopathological examination of the muscle biopsy, RT-qPCR analysis for RYR1 relative expression. Results: We identified a family with two affected siblings carrying an insertion of 18 pair bases in exon 91 of the RYR1 gene, resulting in an in-frame duplication of 6 amino acids (c.12835_12852 dupGAGGGCGCGGCGGGGCTC: 162 p.G4279_T4284insAAGLEG). This variant was found at a frequency of 0.0007% in gnomAD and was absent in 1200 Brazilian controls. First classified as a Variant of Uncertain Significance (VUS), with the molecular and physiological data from our family, we were able to reclassify it, reaching 5 points, which is still a VUS but borderline likely pathogenic. Muscle relative mRNA expression of RYR1 in the two patients identified a ~50% reduction, suggesting a possible hypomorphic allele. Conclusions: The pathomechanisms of RYR1 gene variants in Malignant Hyperthermia are mainly associated with gain-of-function mechanisms, but small insertions can often lead to loss of function or improper folding protein. This study adds evidence to the possibility that duplication in this region can cause structural defects and a more severe phenotype in the patients. Full article

(This article belongs to the Special Issue Molecular Genetics of Malignant Hyperthermia Susceptibility and Related Diseases)

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15 pages, 2899 KB

Open AccessArticle

Genome-Wide Identification of the PAL Gene Family in Camellia nitidissima and Functional Characterization of CnPAL1 Gene by In Vitro Expression

by Hexia Liu and Bo Li

Genes 2025, 16(11), 1251; https://doi.org/10.3390/genes16111251 - 23 Oct 2025

Viewed by 218

Abstract

Background: PAL genes are crucial for plant growth and stress response, yet studies on the PAL gene family in Camellia nitidissima are sparse. Methods: The PAL gene family was screened from the entire genome of C. nitidissima, and their physicochemical [...] Read more.

Background: PAL genes are crucial for plant growth and stress response, yet studies on the PAL gene family in Camellia nitidissima are sparse. Methods: The PAL gene family was screened from the entire genome of C. nitidissima, and their physicochemical properties, chromosomal locations, intraspecific and interspecific collinearity, conserved motifs, phylogenetic trees, cis-acting elements, and gene structures were analyzed. The expression patterns of the CnPAL genes were compared across different tissues, and the highly expressed CnPAL1 gene was expressed in prokaryotes, and its enzyme activity was validated using UPLC-MS technology. Results: The results revealed that six CnPALs were identified in the C. nitidissima genome, distributed unevenly across six chromosomes. The CnPAL proteins shared similar physicochemical properties, with highly conserved motifs and gene structures. Promoter analysis showed multiple cis-acting elements in the CnPALs genes. Intra-species collinearity analysis revealed that all CnPALs were collinear with multiple PAL genes in C. nitidissima, while inter-species collinearity analysis indicated that CnPALs were collinear with the PAL genes in Camellia oleifera and Camellia sinensis. Furthermore, the transcriptomic data of C. nitidissima demonstrated tissue-specific expression of the CnPALs, although qRT-PCR validation showed some discrepancies with the sequencing result. The qRT-PCR revealed varied expression patterns among the six CnPALs, with the CnPAL1 gene showing relatively higher expression levels. Subsequently, cloning, prokaryotic expression, and enzyme activity analysis confirmed the effective catalytic activity of the CnPAL1 protein. Conclusions: This study lays the foundation for understanding the functions of CnPAL genes and offers insights for genetic improvement of C. nitidissima. Full article

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

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9 pages, 697 KB

Open AccessCase Report

Genetically Confirmed Familial Case of Nonsyndromic Cardiac Progeria Caused by the LMNA p.Asp300Asn Variant with Presumed Gonadal Mosaicism: Phenotypic Comparison with Previously Reported Patients

by Ekaterina Nuzhnaya, Margarita Sharova, Uliana Chubykina, Anna Orlova, Ekaterina Vorontsova and Peter Vasiliev

Genes 2025, 16(11), 1250; https://doi.org/10.3390/genes16111250 - 22 Oct 2025

Viewed by 205

Abstract

We describe the first genetically confirmed familial case of nonsyndromic cardiac progeria caused by the LMNA NM_170707.4:c.898G>A (p.Asp300Asn) variant, with evidence suggesting gonadal mosaicism as the mechanism of inheritance. The proband developed severe early-onset valvular and coronary artery disease requiring multiple surgical interventions, [...] Read more.

We describe the first genetically confirmed familial case of nonsyndromic cardiac progeria caused by the LMNA NM_170707.4:c.898G>A (p.Asp300Asn) variant, with evidence suggesting gonadal mosaicism as the mechanism of inheritance. The proband developed severe early-onset valvular and coronary artery disease requiring multiple surgical interventions, yet showed no systemic progeroid features. Genetic analysis revealed the heterozygous variant in her unaffected daughters and nieces but not in either parent. Comparison with previously reported cases highlights striking clinical heterogeneity associated with this variant, ranging from isolated cardiovascular involvement to syndromic progeroid manifestations with metabolic and skeletal abnormalities. This variability likely reflects the combined influence of genetic, epigenetic, and environmental factors. Our case expands the clinical spectrum of LMNA p.Asp300Asn and underscores the importance of considering laminopathies in patients with unexplained early-onset cardiac disease. Early genetic diagnosis is essential for the management, surveillance, and counseling of affected families. Full article

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

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15 pages, 3946 KB

Open AccessArticle

Molecular Characterization and Expression Patterns of Sox3 and Sox30 Genes and Response to Exogenous Hormones in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

by Kailin Xiao, Yue Li, Tong Ren, Ziman Wang, Junxian Zhu, Chen Chen, Liqin Ji, Xiaoli Liu, Xiaoyou Hong, Chengqing Wei, Haigang Chen, Xinping Zhu, Xiaofang Lai and Wei Li

Genes 2025, 16(11), 1249; https://doi.org/10.3390/genes16111249 - 22 Oct 2025

Viewed by 137

Abstract

Background/Objectives: The Sox transcription factor family is critical for gonadal development and sex differentiation in animals, yet its roles in chelonians, particularly in the Chinese soft-shelled turtle (Pelodiscus sinensis), have rarely been investigated. Methods: This study cloned and analyzed the cDNA [...] Read more.

Background/Objectives: The Sox transcription factor family is critical for gonadal development and sex differentiation in animals, yet its roles in chelonians, particularly in the Chinese soft-shelled turtle (Pelodiscus sinensis), have rarely been investigated. Methods: This study cloned and analyzed the cDNA sequences of Sox3 and Sox30 genes from P. sinensis, examining their amino acid sequences and structural properties. Real-time quantitative PCR (RT-qPCR) was used to assess the expression of these two genes in different adult tissues and at various stages of embryonic gonadal development. Additionally, the effects of exogenous hormones (17β-estradiol, E₂ and 17α-Methyltestosterone, MT) on the expression of Sox3 and Sox30 were also investigated. Results: The results indicated that Sox3 showed significantly elevated expression in female gonads, kidney, brain, liver, lung, spleen, and muscle relative to male counterparts, displaying a female-biased expression pattern. In contrast, Sox30 showed a male-biased pattern, with higher expression in male gonads, spleen, muscle, brain, and liver than in females, showing expression. Both genes were expressed at low levels. Exogenous hormone treatments revealed that MT significantly downregulated Sox3 expression in female embryos, whereas E₂ significantly enhanced Sox3 expression in male embryos. Furthermore, MT treatment significantly upregulated Sox30 expression in female embryos, and E₂ treatment also significantly increased Sox30 expression in male embryos. Conclusions: These findings suggest that Sox3 and Sox30 play crucial roles in the gonadal development of P. sinensis, with Sox3 potentially involved in ovarian development and Sox30 in testicular maturation. Both genes are regulated by exogenous hormones, highlighting their importance in sex differentiation and gonadal development. This study provides valuable theoretical insights for further exploration of the molecular mechanisms of sex regulation in reptiles. Full article

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

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14 pages, 3627 KB

Open AccessArticle

Comparative Analysis of Chloroplast Genome Sequences and Phylogeny in Three Macadamia integrifolia Cultivars

by Jihua Guo, Zhuanmiao Kang, Zhongchun Xiao, Chunyan Zhong, Guidong Miao, Pei Zhang, Weiwei Zhao, Rongrong Su and Kecan Xia

Genes 2025, 16(11), 1248; https://doi.org/10.3390/genes16111248 - 22 Oct 2025

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Abstract

Background/Objectives: Macadamia integrifolia is a valuable subtropical fruit tree, yet genomic studies on its cultivars are limited. This study aims to elucidate the chloroplast genome features, variations, and phylogenetic relationships of three main cultivars (‘Guilin No. 1’, ‘Nanya No. 1’, ‘Qian’ao No. [...] Read more.

Background/Objectives: Macadamia integrifolia is a valuable subtropical fruit tree, yet genomic studies on its cultivars are limited. This study aims to elucidate the chloroplast genome features, variations, and phylogenetic relationships of three main cultivars (‘Guilin No. 1’, ‘Nanya No. 1’, ‘Qian’ao No. 1’) to support germplasm identification and breeding. Methods: chloroplast genomes of three M. integrifolia cultivars from Guangxi, Guangdong, and Guizhou were sequenced using Illumina technology, followed by assembly, annotation, and comparative analyses of structure, repeats, and codon usage. Phylogenetic relationships were reconstructed using complete genome sequences. Results: The three chloroplast genomes displayed typical quadripartite structures, with lengths of 159,714 bp, 159,195 bp, and 159,508 bp, and GC contents of 38.12%, 38.16%, and 38.14%, respectively. Each encoded 135 genes. Codon usage was biased towards A/U-ending codons. We identified 81, 87, and 80 SSRs and 26, 21, and 20 long repeats, respectively. IR boundary regions were highly conserved. Phylogenetically, the cultivars showed close relationships with M. integrifolia, Macadamia tetraphylla, and Macadamiaternifolia, forming a sister clade to Platanus occidentalis. Conclusions: This study provides essential chloroplast genomic resources for three M. integrifolia cultivars, revealing conserved structures and specific variations. The findings offer crucial insights for the genus's genetic diversity, supporting future germplasm evaluation and phylogenetic research. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2025–2026)

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16 pages, 2265 KB

Open AccessArticle

Rare Genetic Variants Underlying Primary Immunodeficiency: Clinical, Pulmonary, and Genetic Insights from Two Pediatric Cases

by Nurgul Sikhayeva, Svetlana Volodchenko, Elena Kovzel, Aiganym Toleuzhanova, Aliya Romanova, Gulnar Tortayeva, Yelena Sagandykova, Marina Morenko, Aidos Bolatov, Ilyas Akhmetollayev, Anar Shakirova and Mariya Tagaeva

Genes 2025, 16(11), 1247; https://doi.org/10.3390/genes16111247 - 22 Oct 2025

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Abstract

Background/Objectives: Inborn errors of immunity (IEIs), formerly known as primary immunodeficiency disorders, are a heterogeneous group of genetic diseases characterized by recurrent infections and multisystem involvement. Although more than 500 distinct entities have been identified, reports from Central Asia remain scarce. This study [...] Read more.

Background/Objectives: Inborn errors of immunity (IEIs), formerly known as primary immunodeficiency disorders, are a heterogeneous group of genetic diseases characterized by recurrent infections and multisystem involvement. Although more than 500 distinct entities have been identified, reports from Central Asia remain scarce. This study describes two rare pediatric IEI cases from Kazakhstan, highlighting the importance of genomic diagnostics in underrepresented regions. Methods: Two unrelated male patients with early-onset recurrent infections and systemic complications were evaluated at the University Medical Center, Astana. Clinical and laboratory assessments included immunophenotyping, imaging, and histopathology. Whole-genome sequencing (WGS) was performed, followed by Sanger confirmation and segregation analysis when feasible. Variants were classified according to ACMG/AMP guidelines. Results: The first case involved a child with recurrent bronchopulmonary disease, pulmonary fibrosis, and connective tissue abnormalities, found to carry a novel homozygous FBLN5:c.53del frameshift variant consistent with autosomal recessive cutis laxa type 1A. The second case concerned an adolescent with progressive neurodegeneration, granulomatous skin lesions, and chronic pancreatitis, who was identified with a heterozygous pathogenic ATM:c.4828dup variant, confirming ataxia–telangiectasia. Both patients required lifelong subcutaneous immunoglobulin therapy. Consanguinity contributed to the genetic risk in the first case, while the second case demonstrated diagnostic delays that emphasized the value of genetic testing. Conclusions: These cases underscore the clinical heterogeneity of IEIs and illustrate the essential role of genomic diagnostics in elucidating atypical presentations. Documenting rare variants and unconventional phenotypes enhances global knowledge, elevates awareness in resource-limited regions, and emphasizes the necessity for early, multidisciplinary care and the enhancement of national registries for rare immunogenetic disorders. Full article

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

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24 pages, 3976 KB

Open AccessArticle

Multi-Omics Data Integration for Improved Cancer Subtyping via Denoising Autoencoder-Based Multi-Kernel Learning

by Xiukun Yao, Tong Wang, Qi Yang, Jiawen Wang, Yao Qi, Tong Xu, Zhiwen Wei, Yuehua Cui, Hongyan Cao and Keming Yun

Genes 2025, 16(11), 1246; https://doi.org/10.3390/genes16111246 - 22 Oct 2025

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Abstract

Objectives: Cancer, characterized by its profound complexity and heterogeneity, arises from a multitude of molecular disruptions. The pursuit of identifying distinct cancer subtypes is driven by the need to stratify patients into clinically coherent subgroups, each exhibiting unique prognostic outcomes. The integration [...] Read more.

Objectives: Cancer, characterized by its profound complexity and heterogeneity, arises from a multitude of molecular disruptions. The pursuit of identifying distinct cancer subtypes is driven by the need to stratify patients into clinically coherent subgroups, each exhibiting unique prognostic outcomes. The integration of multi-omics datasets enhances the precision of subtyping and advances precision medicine. Methods: Considering the high-dimensional nature inherent to various multi-omics data types, we introduce an innovative deep learning framework, DAE-MKL, which integrates denoising autoencoders with multi-kernel learning for identifying cancer subtypes. Leveraging the capabilities of DAE, we extract non-linearly transformed features that retain pertinent information while mitigating noise and redundancy. These refined data representations are then funneled into the MKL framework, thereby enhancing the accuracy of subtype identification. We applied the DAE-MKL framework to both simulated studies and empirical datasets derived from two distinct cancer types, low-grade glioma (LGG,

n

= 86) and kidney renal clear cell carcinoma (KIRC,

n

= 285), thereby validating its utility and feasibility. Results: In simulations, DAE-MKL achieved superior performance with NMI gains up to 0.78 compared to other state-of-the-art methods. For real datasets, DAE-MKL identified three LGG subtypes and three KIRC subtypes, showing significant survival differences (KIRC log-rank

p

= 3.33 × 10⁻⁸, LGG log-rank

p

= 3.99 × 10⁻⁸). Additionally, we explored potential cancer-related biomarkers. Conclusions: The DAE-MKL effectively identifies molecular subtypes, reduces data dimensionality, and improves prognostic stratification in multi-omics cancer datasets, providing an effective tool for precision oncology. Full article

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

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15 pages, 7840 KB

Open AccessArticle

The E3 Ligase UBR5/Hyd Ensures Meiotic Fidelity Through Catalysis-Independent Regulation of β2-Tubulin in Drosophila

by Lin Zhou, Lang Lin, Yan Zhang, Chenghao Shen, Yun Qi and Xinhua Lin

Genes 2025, 16(11), 1245; https://doi.org/10.3390/genes16111245 - 22 Oct 2025

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Abstract

Background: Spermatogenesis depends on precise cytoskeletal regulation, particularly the microtubule system; however, the mechanisms governing tubulin homeostasis during meiosis are poorly defined. While the E3 ubiquitin ligase Hyd (Hyperplastic discs), the Drosophila homolog of UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5), plays [...] Read more.

Background: Spermatogenesis depends on precise cytoskeletal regulation, particularly the microtubule system; however, the mechanisms governing tubulin homeostasis during meiosis are poorly defined. While the E3 ubiquitin ligase Hyd (Hyperplastic discs), the Drosophila homolog of UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5), plays roles in diverse cellular processes, its precise role in male meiosis is unknown. This study aims to define the function and expression dynamics of Hyd during Drosophila spermatogenesis and elucidate whether it acts independently of its canonical ligase activity. Methods: Using Drosophila genetics, immunofluorescence, CRISPR/Cas9-mediated tagging, and mosaic clonal analysis, we characterized Hyd expression and function in the testis. Hyd knockdown and rescue experiments were performed with wild-type and catalytically inactive transgenes. β2-tubulin expression and microtubule organization were assessed in hyd mutant clones. Results: Hyd exhibits a dynamic, stage-specific expression pattern, localizing to nuclear and meiotic structures. Hyd loss led to meiotic arrest, disrupted spindle formation, aberrant centrosome behavior, and failure of spermatid elongation. Genetic rescue demonstrated that both wild-type and catalytically inactive Hyd partially restored spermatid elongation, indicating a catalysis-independent role. Furthermore, Hyd deficiency resulted in β2-tubulin overexpression, disrupted microtubule organization, and abnormal spermatocyte morphology. Conclusions: Hyd ensures meiotic fidelity in Drosophila by fine-tuning β2-tubulin expression independently of its E3 ubiquitin ligase activity. These findings reveal a non-proteolytic function for UBR5/Hyd in cytoskeletal regulation during male gametogenesis, providing new insights into tubulin homeostasis in meiosis. Full article

(This article belongs to the Special Issue Genetics and Genomics of Insects)

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7 pages, 1648 KB

Open AccessCase Report

Atypical Liver Ultrasound Image in a Boy with Autosomal Recessive Polycystic Kidney Disease (ARPKD) and New PKD1 Variant—A Case Report

by Agnieszka Turczyn, Grażyna Krzemień and Dominik Nguyen

Genes 2025, 16(11), 1244; https://doi.org/10.3390/genes16111244 - 22 Oct 2025

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Abstract

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare form of PKD that leads to the development of multiple renal cysts and hepatic fibrosis. Aim: The first documented case of large hepatic cyst associated with dual PKHD1-PKD1 variants. Case report [...] Read more.

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare form of PKD that leads to the development of multiple renal cysts and hepatic fibrosis. Aim: The first documented case of large hepatic cyst associated with dual PKHD1-PKD1 variants. Case report: We present the case of a 5-year-old boy with a kidney US image typical of ARPKD and numerous large cysts in the liver not typical for this disease. Genetic analysis revealed heterozygous missense mutations in the PKHD1 gene (maternally, c.107C>T/p.Thr36Met in exon 3; paternally, c.4870C>T/p.Arg1624Rrp in exon 32) and an additional new variant in PKD1 (maternally, c.5323G>A/p.Gly1775Ser in exon 32). Genetic tests excluded mutations in genes responsible for polycystic liver disease (PCLD). However, the presence of the PKD1 mutation is clinically not clear due to the normal abdominal US image in the mother; it seems to be the most likely explanation for unusual phenotype in our patient. Conclusions: This case may contribute to the understanding of the phenotypic variability in ARPKD and the potential modifying role of mutations in other PKD-related genes. Comprehensive genetic panels are crucial for explaining atypical phenotypes and prognosis in patients with PKD. Full article

(This article belongs to the Special Issue Genetics and Genomics of Heritable Pediatric Disorders)

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22 pages, 3139 KB

Open AccessArticle

A Phylogenetic Perspective on the Evolutionary Patterns of the Animal Interleukin-10 Signaling System

by Liu Tang, Zeyu Zhou, Weibin Wang, Dawei Li, Tingting Hao and Yue Chen

Genes 2025, 16(11), 1243; https://doi.org/10.3390/genes16111243 - 22 Oct 2025

Viewed by 283

Abstract

Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to [...] Read more.

Background: The interleukin-10 (IL-10) signaling system, comprising ligands (IL-10s) and receptors (IL-10Rs), plays critical roles in immune regulation, inflammation resolution, and disease pathogenesis. “IL-10 signaling system” here refers to the immunomodulatory signaling system composed of ligands (IL-10s) and receptors (IL-10Rs), which belong to different Protein families in evolution, but achieve functional synergy through the conserved JAK-STAT pathway. Understanding their evolutionary and functional dynamics is essential for elucidating immune mechanisms and therapeutic targeting. Methods: Through phylogenetic reconstruction, homology analysis, and sequence alignment across >400 animal species, we traced the evolutionary trajectory and structural–functional diversification of IL-10s and IL-10Rs. Results and Conclusions: IL-10 signaling components emerged in early vertebrates, with IL-10Rs originating in cartilaginous fishes (~450 Mya) and IL-10s diversifying in bony fishes (~400 Mya). Functional divergence yielded immunosuppressive (IL-10), barrier-protective (IL-20 subfamily), and antiviral (type III IFN) subgroups. Structurally, conserved motifs (e.g., IL-10R1 GYXXQ, IL-22 N54-glycosylation) underpin receptor–ligand binding and JAK/STAT signaling. Evolutionarily invariant residues suggest candidate therapeutic epitopes. This study provides an evolutionary framework highlighting functional conservation and species-specific adaptation within IL-10 signaling, with implications for immunotherapy and animal breeding. Full article

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

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