Genes

16 pages, 3299 KB

Open AccessArticle

Association Mapping for Biomass and Kernel Traits in Doubled-Haploid Population Derived from Texas Wheat Cultivars

by Yahya Rauf, Zhen Wang, Kyle Parker, Shannon A. Baker, Jason A. Baker, Jackie C. Rudd, Qingwu Xue, Amir Ibrahim and Shuyu Liu

Genes 2025, 16(10), 1172; https://doi.org/10.3390/genes16101172 - 5 Oct 2025

Abstract

Background: Genetic improvement in wheat yield is the most focused research area for the breeding community to ensure sustainable production. Wheat kernel traits and biomass are considered key contributors to enhance crop yield. Methods: This study was designed to explore the genetic diversity [...] Read more.

Background: Genetic improvement in wheat yield is the most focused research area for the breeding community to ensure sustainable production. Wheat kernel traits and biomass are considered key contributors to enhance crop yield. Methods: This study was designed to explore the genetic diversity of kernel and biomass traits in popular wheat varieties from the US Southern Great Plains using 264 doubled haploid (DH) lines mainly derived from TAM 114 or TAM 204. This population was evaluated in two field environments planted in alpha lattice design during the 2020 crop season. Kernel traits were collected using the hp Scanjet G4010 photo scanner for image capturing and GrainScan v3. software for image analysis. Biomass parameters were collected and processed manually. For genotyping genomic libraries were prepared and sequenced on Illumina NovaSeq 6000 to generate paired end reads of 150 bp. Sequences were aligned to the IWGSC RefSeq genome assembly v2.1 using the Burrows Wheeler Aligner for SNP calling. Results: A total of 59,482 polymorphic SNP markers were retained for genetic analysis after the filtration at 50% missing data and 5% minor allele frequency. To investigate the marker–trait association and the genomic regions, four genome-wide association study models were implemented using the R package GAPIT version 3.5. Based on the Bonferroni correction <8.41 × 10⁻⁷ was used as a threshold to declare marker-trait associations (MTAs) significant. The BLINK model identified 12 MTAs on chromosomes 1A, 2A, 2B, 4A, 4B, and 6B. Conclusions: The identified MTAs can be used to develop diagnostic markers for efficient selection and utilization in recombination breeding and cultivar development process. Full article

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

► Show Figures

Figure 1

8 pages, 570 KB

Open AccessReview

Genetic and Molecular Insights into the Links Between Heat Stroke, Alzheimer’s Disease, and Down Syndrome: A Mini-Review

by Hisahide Nishio, Hirokuni Negishi, Hiroyuki Awano and Jumpei Oba

Genes 2025, 16(10), 1171; https://doi.org/10.3390/genes16101171 - 5 Oct 2025

Abstract

Both epidemiological and animal model studies have revealed that heat stroke is closely related to the development or exacerbation of dementia disorders. The most common form of dementia is Alzheimer’s disease, which is characterized by the accumulation of amyloid-β protein in the central [...] Read more.

Both epidemiological and animal model studies have revealed that heat stroke is closely related to the development or exacerbation of dementia disorders. The most common form of dementia is Alzheimer’s disease, which is characterized by the accumulation of amyloid-β protein in the central nervous system. Notably, a whole-genome transcriptome analysis of heat stroke patients has identified the increased expression of amyloid-β precursor protein gene and the activation of amyloid processing pathways. This finding provides a molecular basis for the theory that heat stroke is a risk factor for dementia disorders. Down syndrome—a common chromosomal abnormality—is also a dementia disorder that is characterized by the overexpression of amyloid-β precursor protein gene and the accumulation of amyloid-β protein. Thus, heat stroke may also develop or exacerbate Alzheimer’s disease-like dementia in Down syndrome. For individuals with Down syndrome, heat stroke is therefore not only a life-threatening risk factor but may also be a risk factor for accelerating intellectual decline. Full article

(This article belongs to the Special Issue Genetic and Genomic Mechanisms of Heat Stress in Disease Modulation: From Molecular Pathways to Clinical Manifestations)

► Show Figures

Figure 1

14 pages, 2539 KB

Open AccessArticle

Transcriptomic and Clinical Profiling Reveals LGALS3 as a Prognostic Oncogene in Pancreatic Cancer

by Grazia Scuderi, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Michelino Di Rosa, José Francisco Muñoz-Valle, Alexis Missael Vizcaíno-Quirarte, Gian Marco Leone, Katia Mangano, Paolo Fagone and Ferdinando Nicoletti

Genes 2025, 16(10), 1170; https://doi.org/10.3390/genes16101170 - 3 Oct 2025

Abstract

Background/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across [...] Read more.

Background/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting. Full article

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

► Show Figures

Figure 1

18 pages, 856 KB

Open AccessArticle

Blackgrass (Alopecurus myosuroides Huds.) Multiple Resistance to ACCase- and ALS-Inhibitors and Its Competition with Winter Wheat

by Aristeidis P. Papapanagiotou, Ioannis Vasilakoglou, Maria V. Alvanou, Ioannis A. Giantsis, Panagiotis Madesis and Ilias G. Eleftherohorinos

Genes 2025, 16(10), 1169; https://doi.org/10.3390/genes16101169 - 3 Oct 2025

Abstract

Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, [...] Read more.

Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, this study focused on the investigation of blackgrass resistance to herbicides at both phenotypic and molecular levels. Methods: Whole-plant rate-response pot assays were conducted to study the possible evolution of resistance (cross- or multiple-resistance) in a blackgrass population to ACCase- and ALS-inhibiting herbicides. Analysis of the ACCase gene sequence, herbicide metabolism study and competition with winter wheat studies were also conducted. Results: High levels of cross-resistance mainly to the ACCase post-emergence clodinafop-propargyl, medium to fenoxaprop-P-ethyl, cycloxydim, pinoxaden, as well as lower levels of resistance to ALS-inhibitors (mesosulfuron-methyl + iodosulfuron-methyl-sodium and pyroxsulam) were confirmed. In addition, the pre-emergence soil-applied herbicides chlorotoluron + diflufenican and prosulfocarb provided excellent control of the S and R blackgrass populations. The analysis of the ACCase gene sequence revealed a point mutation at position 1781, resulting in an amino acid substitution from isoleucine (Ile) to leucine (Leu). Furthermore, the combined application of the herbicides with piperonyl butoxide (PBO, applied 2 h before herbicide application) indicated that there was herbicide metabolism, which may be mediated by cytochrome P450. The R blackgrass population, when grown in competitive interaction with winter wheat, produced more tillers and aboveground fresh weight compared to the S population and caused greater reduction in winter wheat. Conclusions: The results suggest that a blackgrass population has developed multiple resistance to ACCase- and ALS-inhibiting herbicides, due to ACCase gene mutation and herbicide metabolism. No fitness cost and no compromised competitive ability associated with the blackgrass resistance were observed. Full article

(This article belongs to the Special Issue Forage and Grass Genetics and Genomics)

35 pages, 2877 KB

Open AccessReview

RNA-Targeting Techniques: A Comparative Analysis of Modern Approaches for RNA Manipulation in Cancer Research and Therapeutics

by Michaela A. Boti, Marios A. Diamantopoulos and Andreas Scorilas

Genes 2025, 16(10), 1168; https://doi.org/10.3390/genes16101168 - 2 Oct 2025

Abstract

RNA-targeting techniques have emerged as powerful tools in cancer research and therapeutics, offering precise and programmable control over gene expression at the post-transcriptional level. Once viewed as passive intermediates in the central dogma, RNA molecules are now recognized as dynamic regulators of cellular [...] Read more.

RNA-targeting techniques have emerged as powerful tools in cancer research and therapeutics, offering precise and programmable control over gene expression at the post-transcriptional level. Once viewed as passive intermediates in the central dogma, RNA molecules are now recognized as dynamic regulators of cellular function, capable of influencing transcription, translation, and epigenetic regulation. Advances in high-throughput sequencing technologies, transcriptomics, and structural RNA biology have uncovered a diverse landscape of coding and non-coding RNAs involved in oncogenesis, drug resistance, and tumor progression. In response, several RNA-targeting strategies have been developed to modulate these transcripts, including antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR-Cas13 systems, small molecules, and aptamers. This review provides a comparative analysis of these technologies, highlighting their molecular mechanisms, therapeutic potential, and current limitations. Emphasis is placed on the translational progress of RNA-targeting agents, including recent FDA approvals and ongoing clinical trials for cancer indications. Through a critical comparison of these strategies, this review underscores the growing significance of RNA-targeting technologies as a foundation for next-generation cancer therapeutics and precision oncology. Full article

(This article belongs to the Section RNA)

► Show Figures

Figure 1

23 pages, 1417 KB

Open AccessArticle

Beyond the Curtains: Identification of the Genetic Cause of Foetal Developmental Abnormalities Through the Application of Molecular Autopsy

by Beatrice Spedicati, Giulia Pianigiani, Aurora Santin, Vanessa Rebecca Gasparini, Ilaria Falcomer, Agnese Feresin, Maria Teresa Bonati, Daniela Mazzà, Elisa Paccagnella, Domizia Pasquetti, Elisa Rubinato, Claudio Granata, Flora Maria Murru, Maurizio Pinamonti, Rossana Bussani, Ilaria Fantasia, Tamara Stampalija, Paolo Gasparini, Stefania Zampieri and Giorgia Girotto

Genes 2025, 16(10), 1167; https://doi.org/10.3390/genes16101167 - 2 Oct 2025

Abstract

Background: Foetal structural abnormalities can be detected in approximately 3% of all pregnancies and frequently remain without a genetic diagnosis. This study aims to apply an integrated approach with the final goal of providing a molecular diagnosis in the challenging Italian setting [...] Read more.

Background: Foetal structural abnormalities can be detected in approximately 3% of all pregnancies and frequently remain without a genetic diagnosis. This study aims to apply an integrated approach with the final goal of providing a molecular diagnosis in the challenging Italian setting of early termination of pregnancy. Methods: In a cohort of 86 foetuses, post-mortem dysmorphological examination, radiological assessments, and molecular autopsy through Whole-Exome Sequencing—WES—analysis were performed. Results: Forty-two foetuses were phenotypically classified as presenting a single major malformation (i.e., central nervous system, skeletal, urogenital, or cardiac anomalies, or fluid accumulation), while 44 foetuses presented multiple malformations and/or dysmorphic features. Overall, WES provided a diagnostic yield of 26.7%; additionally, seven Variants of Uncertain Significance (VUS) potentially liked to the foetal phenotype were identified. The highest detection rate was achieved for foetuses presenting a single major urogenital (50%) or skeletal (42.9%) malformation, followed by foetuses presenting multiple malformations (27.3%). Peculiar results of particular interest were (1) the identification of two splicing variants (within the INPPL1 and RHOA genes), functionally characterised through minigene assay, which contributed to evaluate their pathogenicity, and (2) the identification of a novel de novo missense ZNF292 variant (NM_015021.3:c.6325A>C p.(Ser2109Arg)) in a foetus affected by corpus callosum hypoplasia. The ZNF292 gene is associated with the Intellectual developmental disorder, autosomal dominant 64 and this finding represents the first report of prenatally detected anomalies of the central nervous system in a foetus carrying a ZNF292 variant. Conclusions: This study underlines the diagnostic utility of an integrated approach to achieve a precise genetic diagnosis for structural foetal abnormalities, thus providing families with precise recurrence risk estimations and detailed options about future pregnancies. Additionally, a systematic implementation of this strategy could be crucial to better characterise new variants and discover new genes involved in embryonic and foetal development. Full article

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

► Show Figures

Graphical abstract

27 pages, 2302 KB

Open AccessReview

Crossroads of Iron Metabolism and Inflammation in Colorectal Carcinogenesis: Molecular Mechanisms and Therapeutic Perspectives

by Nahid Ahmadi, Gihani Vidanapathirana and Vinod Gopalan

Genes 2025, 16(10), 1166; https://doi.org/10.3390/genes16101166 - 1 Oct 2025

Abstract

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Iron metabolism and chronic inflammation are two interrelated processes that significantly influence the initiation and progression of CRC. Iron is essential for cell proliferation, but its excess promotes oxidative stress and [...] Read more.

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Iron metabolism and chronic inflammation are two interrelated processes that significantly influence the initiation and progression of CRC. Iron is essential for cell proliferation, but its excess promotes oxidative stress and DNA damage, while inflammation driven by cytokine-regulated pathways accelerates tumourigenesis. We therefore conducted this narrative review to collate the available evidence on the link between iron homeostasis and inflammatory signalling in CRC and highlight potential diagnostic and therapeutic applications. Methods: This narrative review of preclinical and clinical studies explores the molecular and cellular pathways that connect iron regulation and inflammation to CRC. Key regulatory molecules, such as the transferrin receptor (TFRC), ferroportin (SLC40A1), ferritin (FTH/FTL), hepcidin, and IL-6, were reviewed. Additionally, we summarised the findings of transcriptomic, epigenomic, and proteomic studies. Relevant therapeutic approaches, including iron chelation, ferroptosis induction, and anti-inflammatory strategies, were also discussed. Results: Evidence suggests that CRC cells exhibit altered iron metabolism, marked by the upregulation of transferrin receptor (TFRC), downregulation of ferroportin, and dysregulated expression of ferritin. Inflammatory mediators such as IL-6 activate hepcidin and STAT3 signalling, which reinforce intracellular iron retention and oxidative stress. Increased immune evasion, epithelial proliferation, and genomic instability appear to be linked to the interaction between inflammation and iron metabolism. Other promising biomarkers include ferritin, hepcidin, and composite gene expression signatures; however, their clinical application remains limited. Although several preclinical studies support the use of targeted iron therapies and combination approaches with anti-inflammatory agents or immunotherapy, there is a lack of comprehensive clinical validation confirming their efficacy and safety in humans. Conclusion: Although preclinical studies suggest that iron metabolism and inflammatory signalling form an interconnected axis closely linked to CRC, translating this pathway into reliable clinical biomarkers and effective therapeutic strategies remains a significant challenge. Future biomarker-guided clinical trials are essential to determine the clinical relevance and to establish precision medicine strategies targeting the iron–inflammation crosstalk in CRC. Full article

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

► Show Figures

Figure 1

15 pages, 374 KB

Open AccessReview

Genetic and Molecular Insights into Transforming Growth Factor-Beta Signaling in Periodontitis: A Systematic Review

by Tomasz Pawłaszek and Beniamin Oskar Grabarek

Genes 2025, 16(10), 1165; https://doi.org/10.3390/genes16101165 - 1 Oct 2025

Abstract

Background/Objectives: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in immune regulation, extracellular matrix turnover, and tissue repair. Its role in periodontitis remains controversial due to conflicting human studies. This systematic review addressed the PICO-based question: in adults with periodontitis (population), how [...] Read more.

Background/Objectives: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in immune regulation, extracellular matrix turnover, and tissue repair. Its role in periodontitis remains controversial due to conflicting human studies. This systematic review addressed the PICO-based question: in adults with periodontitis (population), how does the expression and regulation of TGF-β isoforms (intervention/exposure) compare with healthy or post-treatment states (comparator) regarding clinical outcomes (outcomes)? Methods: A systematic search of PubMed and Scopus was conducted on 1 July 2025 for human studies published in English between 2010 and 2025. Eligible studies investigated TGF-β expression, function, or genetic regulation in periodontal tissues or biological fluids. Screening and quality appraisal were performed according to PRISMA guidelines, using design-specific risk-of-bias tools. The review protocol was prospectively registered in PROSPERO (CRD420251138456). Results: Fifteen studies met inclusion criteria. TGF-β1 was the most frequently analyzed isoform and was consistently elevated in diseased gingival tissue and gingival crevicular fluid, correlating with probing depth and attachment loss. Several studies reported post-treatment reductions in TGF-β, supporting its value as a dynamic biomarker. Additional findings linked TGF-β signaling to immune modulation, fibrosis, bone turnover, and systemic comorbidities. Evidence for TGF-β2 and TGF-β3 was limited but suggested isoform-specific roles in epithelial–mesenchymal signaling and scar-free repair. Conclusions: Current evidence supports TGF-β, particularly TGF-β1, as a central mediator of periodontal inflammation and repair, with promise as both a biomarker and therapeutic target. Standardized, isoform-specific, and longitudinal studies are needed to clarify its diagnostic and translational utility. Full article

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

► Show Figures

Figure 1

51 pages, 1102 KB

Open AccessArticle

Genetic Parameters, Prediction of Genotypic Values, and Forage Stability in Paspalum nicorae Parodi Ecotypes via REML/BLUP

by Diógenes Cecchin Silveira, Annamaria Mills, Júlio Antoniolli, Victor Schneider de Ávila, Maria Eduarda Pagani Sangineto, Juliana Medianeira Machado, Roberto Luis Weiler, André Pich Brunes, Carine Simioni and Miguel Dall’Agnol

Genes 2025, 16(10), 1164; https://doi.org/10.3390/genes16101164 - 1 Oct 2025

Abstract

Background/Objectives: Paspalum nicorae Parodi is a native subtropical grass species with promising agronomic attributes, such as persistence, drought and cold tolerance, and rapid establishment. However, the species remains underutilized in breeding programs due to the absence of well-characterized germplasm and limited studies on [...] Read more.

Background/Objectives: Paspalum nicorae Parodi is a native subtropical grass species with promising agronomic attributes, such as persistence, drought and cold tolerance, and rapid establishment. However, the species remains underutilized in breeding programs due to the absence of well-characterized germplasm and limited studies on its genetic variability and agronomic potential. This study aimed to estimate genetic parameters, predict genotypic values, and identify superior ecotypes with desirable forage traits, integrating stability and adaptability analyses. Methods: A total of 84 ecotypes were evaluated over three consecutive years for twelve morphological and forage-related traits. Genetic parameters, genotypic values, and selection gains were estimated using mixed models (REML/BLUP). Stability was assessed through harmonic means of genotypic performance, and the multi-trait genotype–ideotype distance index (MGIDI) was applied to identify ecotypes with balanced performance across traits. Results: Substantial genetic variability was detected for most traits, particularly those related to biomass accumulation, such as total dry matter, the number of tillers, fresh matter, and leaf dry matter. These traits exhibited medium to high heritability and strong potential for selection. Ecotype N3.10 consistently showed superior performance across productivity traits while other ecotypes, such as N4.14 and N1.09, stood out for quality-related attributes and cold tolerance, respectively. The application of the MGIDI index enabled the identification of 17 ecotypes with balanced multi-trait performance, supporting the simultaneous selection for productivity, quality, and adaptability. Comparisons with P. notatum suggest that P. nicorae harbors competitive genetic potential, despite its lower level of domestication. Conclusions: The integration of REML/BLUP analyses, stability parameters, and ideotype-based multi-trait selection provided a robust framework for identifying elite P. nicorae ecotypes. These findings reinforce the strategic importance of this species as a valuable genetic resource for the development of adapted and productive forage cultivars in subtropical environments. Full article

(This article belongs to the Special Issue Genetics and Breeding of Forage)

14 pages, 1778 KB

Open AccessArticle

Lipid Metabolism and Circadian Regulation in Wing Polyphenism of Rhopalosiphum padi: Transcriptomic Validation of Key DEGs for Biocontrol‌

by Yan Zhang, Tao Zhang, Jianwu Mao and Shenhang Cheng

Genes 2025, 16(10), 1163; https://doi.org/10.3390/genes16101163 - 30 Sep 2025

Abstract

Background/Objectives: The bird cherry-oat aphid, Rhopalosiphum padi, is a major global pest of cereal crops and exhibits wing polyphenism, producing both winged (dispersive) and wingless (reproductive) morphs. Methods: To identify potential RNAi targets that could specifically disrupt the migratory winged morph, we [...] Read more.

Background/Objectives: The bird cherry-oat aphid, Rhopalosiphum padi, is a major global pest of cereal crops and exhibits wing polyphenism, producing both winged (dispersive) and wingless (reproductive) morphs. Methods: To identify potential RNAi targets that could specifically disrupt the migratory winged morph, we conducted a comparative transcriptomic analysis of adult aphids. Differentially expressed genes (DEGs) were identified, annotated for their functions, and analyzed for their involvement in metabolic pathways. Results: Significant differences were observed in 121 genes between morphs: 13 were upregulated in the winged morph, while 108 were downregulated. Most DEGs were enriched in lipid metabolism and circadian rhythm pathways, suggesting that wing polymorphism may be adaptively linked to energy resource allocation strategies. Conclusions: This study firstly reveals the adult-stage-specific regulatory roles of lipid metabolism and circadian rhythm pathways in wing polyphenism, identifying six candidate genes (BCORL1, AMP-L, Pfl, Lip3L, HLFL(X7), and HLFL(X4)) for RNAi-based biocontrol strategies targeting migratory morphs. Full article

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

12 pages, 2893 KB

Open AccessArticle

CRYAB Missense Mutation Reveals Shared Pathogenesis of Familial Cardiomyopathy and Arrhythmia

by Ali Nariman, Mohammad Hossein Nikoo, Nizal Sarrafzadegan, Mohammad Javad Zibanejad, Zahra Teimouri Jervekani, Karim Daliri and Mohammad Amin Tabatabaiefar

Genes 2025, 16(10), 1162; https://doi.org/10.3390/genes16101162 - 30 Sep 2025

Abstract

Background: Dilated cardiomyopathy (DCM) and long QT syndrome (LQTS) are genetically heterogeneous cardiac disorders that contribute significantly to morbidity and sudden cardiac death. Although they are typically considered distinct entities, co-occurrence within families has been increasingly recognized, complicating diagnosis and genetic counseling. [...] Read more.

Background: Dilated cardiomyopathy (DCM) and long QT syndrome (LQTS) are genetically heterogeneous cardiac disorders that contribute significantly to morbidity and sudden cardiac death. Although they are typically considered distinct entities, co-occurrence within families has been increasingly recognized, complicating diagnosis and genetic counseling. Identifying shared genetic determinants may provide insights into overlapping disease mechanisms. Methods: We investigated a multi-generational family in which several members presented with features of both DCM and LQTS. Exome sequencing was performed to identify potential disease-causing variants, and candidate findings were validated by Sanger sequencing. In silico prediction tools and evolutionary conservation analysis were used to assess the pathogenic potential of the identified variant. Results: We identified a novel heterozygous missense variant in the CRYAB gene, c.368G>A (p.Arg123Gln). This variant is located in a highly conserved region critical for protein function and was consistently predicted to be deleterious across multiple computational algorithms. Segregation analysis demonstrated co-occurrence of the variant with disease phenotypes in affected family members. Clinically, several carriers exhibited overlapping features of both DCM and prolonged QT interval, suggesting a dual cardiac phenotype associated with this mutation. Conclusions: Our findings expand the phenotypic spectrum associated with CRYAB mutations, linking them to a combined presentation of dilated cardiomyopathy and long QT syndrome. This underscores the importance of including CRYAB in comprehensive gene panels for inherited cardiac disorders and highlights the need for integrated clinical and genetic evaluation in families presenting with complex cardiac phenotypes. Full article

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

► Show Figures

Figure 1

18 pages, 716 KB

Open AccessCommunication

Significant Association Between Abundance of Gut Microbiota and Plasma Levels of microRNAs in Individuals with Metabolic Syndrome and Their Potential as Biomarkers for Metabolic Syndrome: A Pilot Study

by Sanghoo Lee, Jeonghoon Hong, Yiseul Kim, Hee-Ji Choi, Jinhee Park, Jihye Yun, Yun-Tae Kim, Kyeonghwan Choi, SaeYun Baik, Mi-Kyeong Lee and Kyoung-Ryul Lee

Genes 2025, 16(10), 1161; https://doi.org/10.3390/genes16101161 - 30 Sep 2025

Abstract

Background/Objectives: The relationship between gut microbiota (GM) and microRNAs (miRs) related to lipid metabolism in individuals with metabolic syndrome (MetS) remains unclear. This pilot study examined the relationship between Bacteroidetes and Firmicutes abundance at the phylum level and the plasma levels of miR-122 [...] Read more.

Background/Objectives: The relationship between gut microbiota (GM) and microRNAs (miRs) related to lipid metabolism in individuals with metabolic syndrome (MetS) remains unclear. This pilot study examined the relationship between Bacteroidetes and Firmicutes abundance at the phylum level and the plasma levels of miR-122 and miR-370, both of which are associated with lipid metabolism, in Korean individuals with MetS and in healthy controls. We also evaluated the potential of these miRs as biomarkers for MetS. Methods: This study enrolled 7 individuals with MetS and 8 controls. The abundance of GM was analyzed by 16S rRNA amplicon sequencing. To evaluate the relationship between the dominant phyla in the 2 groups, the log ratio of Firmicutes to Bacteroidetes (F/B) was calculated using a centered log-ratio (CLR) transformation. The abundance of the 2 plasma miRs was also quantified by real-time quantitative PCR (RT-qPCR). Pearson’s and Spearman’s correlation analyses were then performed to evaluate the relationship between Bacteroidetes and Firmicutes abundance, the clinical parameters, and plasma levels of the 2 miRs. Additionally, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was calculated to evaluate the potential of the 2 miRs as MetS biomarkers. Results: The 2 most abundant phyla were Bacteroidetes and Firmicutes. Bacteroidetes made up an average of 24.7% in the MetS group and 69.7% in the control group. Meanwhile, the average abundance of Firmicutes was 69.8% in the MetS group and 26.5% in the control group. The log F/B ratios in the MetS and control groups were 0.7 ± 0.5 and −0.4 ± 0.1 (p < 0.001), respectively. FDR analysis revealed significant correlations between Bacteroidetes abundance and BMI, DBP, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05), as well as between Firmicutes abundance and BMI, FBG, total chol, insulin and HOMA-IR (FDR-adjusted p < 0.05). Plasma levels of the 2 miRs differed significantly between the MetS and control groups: miR-122 (1.43 vs. 0.73; p = 0.0065) and miR-370 (1.39 vs. 0.83; p = 0.0089). The AUC values for miR-122 and miR-370 were 0.946 (p < 0.001) and 0.964 (p < 0.001), respectively. Pearson’s and Spearman’s correlation analyses revealed significant negative correlations between Bacteroidetes abundance and levels of miR-122 (p = 0.0048 and p = 0.0045, respectively) and miR-370 (p = 0.0003 and p < 0.0001, respectively), as well as significant positive correlations between Firmicutes abundance and levels of miR-122 (p = 0.0038 and p = 0.0027, respectively) and miR-370 (p = 0.0004 and p < 0.0001, respectively). However, as our exploratory findings were based on a small sample size, the high correlation results may partly reflect the separation between the MetS and control groups. Conclusions: Our exploratory findings suggest that the GM abundances of individuals with MetS may be significantly associated with plasma levels of miR-122 and miR-370, which are related to lipid metabolism. These miRs may therefore serve as potential MetS biomarkers. Full article

(This article belongs to the Section RNA)

31 pages, 1058 KB

Open AccessArticle

Interactions Between Monocarboxylate Transporter MCT1 Gene Variants and the Kinetics of Blood Lactate Production and Removal After High-Intensity Efforts: A Cross-Sectional Study

by Ewelina Maculewicz, Andrzej Mastalerz, Anna Mróz, Monika Johne, Katarzyna Krawczak-Wójcik, Agata Pabin, Aleksandra Garbacz, Katarzyna Komar, Myosotis Massidda, Petr Stastny and Aleksandra Bojarczuk

Genes 2025, 16(10), 1160; https://doi.org/10.3390/genes16101160 - 30 Sep 2025

Abstract

Background/Objectives: Lactate (LA) is a key metabolite in exercise metabolism, transported across cell membranes by monocarboxylate transporters (MCTs). Although genetic variation in MCT genes has been linked to LA kinetics, evidence in athletic populations remains limited. This study investigated nine MCT1 polymorphisms (rs4301628, [...] Read more.

Background/Objectives: Lactate (LA) is a key metabolite in exercise metabolism, transported across cell membranes by monocarboxylate transporters (MCTs). Although genetic variation in MCT genes has been linked to LA kinetics, evidence in athletic populations remains limited. This study investigated nine MCT1 polymorphisms (rs4301628, rs12028967, rs10857983, rs3789592, rs10776763, rs1049434, rs6537765, rs7556664, rs7169) in relation to LA metabolism. Methods: 337 Polish and Czech males (elite athletes, sub-elite competitors, physically active controls) performed two maximal Wingate tests. Buccal swabs were collected for DNA extraction and single nucleotide polymorphism (SNP) genotyping. LA was assessed before and after the tests. Results: Five variants (rs3789592, rs7556664, rs7169, rs1049434, rs6537765) remained significantly associated with LA measured 30 min after the second Wingate (LA30′) and delta clearance capacity (DCC) in elites (codominant and recessive models: p = 0.01–0.03; false discovery rate (FDR)-adjusted p = 0.02–0.04). Rs10776763 showed the broadest associations, surviving FDR for LA30′ in all models (p = 0.003–0.03; FDR-adjusted p = 0.01–0.03) and for LA accumulation capacity (ACC) in the recessive model (p = 0.01; FDR-adjusted p = 0.03). Rs12028967 also supported a clearance role, with LA30′ significant in elites (p = 0.004; FDR-adjusted p = 0.01) and DCC in the overall cohort (p = 0.02; FDR-adjusted p = 0.03). In contrast, rs4301628 and rs10857983 demonstrated isolated LA30′ effects in elites (p = 0.004–0.01; FDR-adjusted p = 0.01), and no production-phase endpoint other than rs10776763 survived FDR; ACC remained significant in the recessive model (p = 0.01; FDR-adjusted p = 0.03). Conclusions: The results suggest that MCT1 polymorphisms contribute to differences in LA metabolism and warrant replication in larger, more diverse cohorts. Full article

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

► Show Figures

Figure 1

16 pages, 871 KB

Open AccessReview

Uncovering the PML::RARA Fusion in Cytogenetically Cryptic and FISH-Negative Acute Promyelocytic Leukemia—A Case Report and Comprehensive Literature Review

by Busra N. Delikkaya, Jaime Eberle-Singh, Arianna B. Morton, Jerald Z. Gong and Jinglan Liu

Genes 2025, 16(10), 1159; https://doi.org/10.3390/genes16101159 - 29 Sep 2025

Abstract

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We [...] Read more.

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since 1995 demonstrates that RT-PCR-based methods reliably detect cryptic fusions. While advanced genomic approaches may identify these fusions at higher resolution, their accessibility, complexity, cost, and turnaround time often limit diagnostic utility in the urgent setting of APL. Given the extreme rarity of this subset, cytogenetics and FISH remain the standard frontline tests; however, these cases underscore the critical need to incorporate molecular testing into routine workflows. Early recognition and timely therapy are essential to reducing mortality in cryptic APL, and these cases also provide insight into mechanisms of atypical leukemia biology. Full article

(This article belongs to the Special Issue Cytogenetics and Cytogenomics in Clinical Diagnostics: Innovations and Applications)

► Show Figures

Figure 1

14 pages, 2135 KB

Open AccessArticle

Casparian Strip Fortification as a Defense Mechanism to Fusarium oxysporum f. sp. vasinfectum Race 4 Infection in a Highly Resistant Gossypium barbadense Cultivar

by Stephen Parris, Sonika Kumar, Zhigang Li, Jim Olvey, Mike Olvey, Don C. Jones and Christopher A. Saski

Genes 2025, 16(10), 1158; https://doi.org/10.3390/genes16101158 - 29 Sep 2025

Abstract

Background/Objectives: Fusarium wilt of cotton, caused by Fusarium oxysporum f. sp. vasinfectum (FOV), is a destructive vascular disease that severely impacts cotton production. Among its variants, race 4 (FOV4) is especially aggressive, leading to early season stand losses and yield reductions. While resistant [...] Read more.

Background/Objectives: Fusarium wilt of cotton, caused by Fusarium oxysporum f. sp. vasinfectum (FOV), is a destructive vascular disease that severely impacts cotton production. Among its variants, race 4 (FOV4) is especially aggressive, leading to early season stand losses and yield reductions. While resistant cultivars of Gossypium barbadense (pima cotton) have been developed, the molecular basis of this resistance remains unclear. This study aimed to characterize transcriptomic responses associated with FOV4 resistance in pima cotton. Methods: We conducted an in vitro infection assay using two G. barbadense cultivars with contrasting phenotypes: the highly resistant ‘DP348RF’ and the highly susceptible ‘GB1031’. Root tissues were sampled at multiple stages of infection, and RNA sequencing was performed to identify differentially expressed genes and pathways contributing to resistance. Results: Resistant plants ‘DP348RF’ showed strong induction of genes related to reactive oxygen species (ROS) metabolism, chitinase activity, and lignification compared to the susceptible cultivar. Notably, genes involved in the biosynthesis and reinforcement of the Casparian strip, a critical biochemical barrier limiting pathogen penetration into vascular tissues, were uniquely and significantly upregulated in resistant roots. These transcriptional responses suggest that fortification of cell wall barriers and enhanced antimicrobial defenses contribute to effective restriction of FOV4 colonization. Conclusions: Our findings identify a distinct molecular signature of resistance to FOV4 in pima cotton, with Casparian strip reinforcement emerging as a potential mechanism limiting vascular infection. These insights provide a foundation for breeding strategies aimed at improving Fusarium wilt resistance in cotton. Full article

(This article belongs to the Special Issue Genetic Studies on Cotton Stress Resistance, Quality Traits, and Drought Response Mechanisms)

► Show Figures

Figure 1

13 pages, 1027 KB

Open AccessArticle

Quantitative Trait Locus Mapping and Candidate Gene Identification for Fruit Acidity in Chinese Dwarf Cherry (Cerasus humilis) Using a High-Density Genetic Map

by Caizhen Guo, Fenglan Hu and Yuqi Li

Genes 2025, 16(10), 1157; https://doi.org/10.3390/genes16101157 - 29 Sep 2025

Abstract

Background/Objectives: The Chinese dwarf cherry (Cerasus humilis) is an endemic shrub fruit tree species in China. Its fruit is flavorful, nutrient-rich, and has considerable research and utilization potential. However, most currently cultivated varieties of C. humilis are highly acidic and primarily [...] Read more.

Background/Objectives: The Chinese dwarf cherry (Cerasus humilis) is an endemic shrub fruit tree species in China. Its fruit is flavorful, nutrient-rich, and has considerable research and utilization potential. However, most currently cultivated varieties of C. humilis are highly acidic and primarily used for processing. Consumer-preferred, low-acid, fresh-eating varieties are scarce, limiting industrial development. We used 208 F₁ individuals derived from a cross between high-acid “Nongda 4” and the low-acid “DS-1”. Methods: Restriction site-associated DNA sequencing (RAD-seq) was used to develop single-nucleotide polymorphism (SNP) markers and construct a high-density genetic linkage map. Using two years of fruit titratable acidity phenotypic data, quantitative trait locus (QTL) mapping and candidate gene screening were performed. Results: The genetic map contained 2491 SNP markers, assigned to eight linkage groups. The total genetic distance was 672.71 cm, with an average distance of 0.27 cm between markers, indicating high map quality. QTL mapping identified 18 loci associated with fruit titratable acidity, including 11 major-effect QTLs (logarithm of odds, LOD ≥ 3.5). These major-effect QTLs were concentrated on linkage groups LG2 and LG5, with an explained phenotypic variation of 8.6–31.13%. Two candidate genes were identified within QTL intervals: phosphoester phosphatase and MATE transmembrane transporter. The phosphatase gene’s expression showed a strong correlation with titratable acid content (p < 0.01, correlation coefficient 0.93), suggesting that it plays an important role regulating fruit acidity in C. humilis. Conclusions: This study supports marker-assisted breeding of low-acid, fresh-eating varieties, aiding commercial promotion of C. humilis. Full article

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

► Show Figures

Figure 1

14 pages, 1564 KB

Open AccessArticle

MtSIN1a Enhances Salinity Tolerance in Medicago truncatula and Alfalfa

by Huanyu Yue, Yuxue Zhang, Yafei Liu, Feng Yuan, Chuanen Zhou and Yang Zhao

Genes 2025, 16(10), 1156; https://doi.org/10.3390/genes16101156 - 29 Sep 2025

Abstract

Background/Objectives: Alfalfa is a widely cultivated high-quality forage crop, and salinity tolerance is one of the most important breeding goals. Glycine max SALT INDUCED NAC 1 (GmSIN1) was found to enhance salinity tolerance in soybean plants. The phylogenetic analysis showed [...] Read more.

Background/Objectives: Alfalfa is a widely cultivated high-quality forage crop, and salinity tolerance is one of the most important breeding goals. Glycine max SALT INDUCED NAC 1 (GmSIN1) was found to enhance salinity tolerance in soybean plants. The phylogenetic analysis showed there were two homologs of GmSIN1 in Medicago truncatula, MtSIN1a and MtSIN1b. This raised questions regarding the roles of MtSIN1s in alfalfa under salinity stress. Methods: From a Tnt1 mutant collection, we identified the mutants of MtSIN1a. We recorded the survival rate and plant height of mtsin1a-1 and mtsin1a-2 after 100 mM NaCl treatment. Subsequently, we generated 35S:MtSIN1a-GFP transgenic alfalfa lines via genetic transformation. Two lines with relatively high MtSIN1a expression, 35S:MtSIN1a-GFP#3 and 35S:MtSIN1a-GFP#4, were selected for gradient NaCl treatments. In addition, DAB and NBT staining were performed, and the H₂O₂ content and catalase (CAT) activity were determined. Then, we used RNA-seq analysis and RT-qPCR to study the mechanism of its tolerance. Results: This study found that after salt treatment, the survival rate and plant height of mtsin1a-1 and mtsin1a-2 were significantly lower than those of the WT. The mutants of MtSIN1a were sensitive to salinity stress. The transgenic alfalfa plants exhibited higher plant height, weaker DAB staining, stronger NBT staining, less H₂O₂ content, and enhanced CAT activity. The transgenic alfalfa constructed by transforming MtSIN1a showed enhanced salinity tolerance with elevated ROS scavenging. We identified MsSOD1 showing elevated expression levels in transcriptomic analysis. Conclusions: MtSIN1a is a positive regulator for enhancing salinity tolerance in alfalfa with activated ROS scavenging. Full article

(This article belongs to the Special Issue Genetics and Breeding of Forage)

► Show Figures

Figure 1

15 pages, 1827 KB

Open AccessArticle

Codon Usage Preference and Evolutionary Analysis of Pseudorabies Virus

by Aolong Xiong, Kai Li, Xiaodong Liu, Yunxin Ren, Fuchao Zhang, Xiaoqi Li, Ziqing Yuan, Junhong Bie, Jinxiang Li and Changzhan Xie

Genes 2025, 16(10), 1155; https://doi.org/10.3390/genes16101155 - 29 Sep 2025

Abstract

Background: Pseudorabies virus (PRV), a critical porcine herpesvirus, induces severe diseases in both livestock and wildlife, imposing an incalculable burden and economic losses in livestock production. In this study, we investigated the evolutionary mechanisms and host adaptation strategies of the PRV gB gene [...] Read more.

Background: Pseudorabies virus (PRV), a critical porcine herpesvirus, induces severe diseases in both livestock and wildlife, imposing an incalculable burden and economic losses in livestock production. In this study, we investigated the evolutionary mechanisms and host adaptation strategies of the PRV gB gene through genomic alignment. The gB gene is highly conserved in PRV, and its encoded gB protein exhibits functional interchangeability across different herpesvirus species. Notably, the gB protein elicits the production of both complement-dependent and complement-independent neutralizing antibodies in animals, while also being closely associated with syncytium formation. Methods: Phylogenetic analysis and codon usage pattern analysis were performed in this study. A total of 110 gB gene sequences were analyzed, which were collected from [2011 to 2024] across the following regions: [Fujian, Shanxi, Guangxi, Guangdong, Chongqing, Henan, Shaanxi, Heilongjiang, Sichuan, Jiangsu, Jilin, Huzhou, Shandong, Hubei, Jiangxi, Beijing, Shanghai, Chengdu (China)], [Budapest, Szeged (Hungary)], [Tokyo (Japan)], [London (United Kingdom)], [Athens (Greece)], [Berlin (Germany)], and [New Jersey (United States)]. Results: The gB gene of PRV employs an evolutionary “selective optimization” strategy to maintain a dynamic balance between ensuring functional expression and evading host immune pressure, with this core trend strongly supported by its codon usage bias and mutation characteristics. First, the gene exhibits significant codon usage bias [Effective Number of Codons (ENC) = 27.94 ± 0.1528], driven primarily by natural selection rather than mere mutational pressure. Second, phylogenetic analysis shows that the second codon position of gB has the highest mutation rate (1.0586)—a feature closely linked to its antigenic variation and immune escape capabilities, further reflecting adaptive evolution against host immune pressure. Additionally, ENC-GC3 plot analysis reveals the complex regulatory mechanisms underlying codon bias formation, providing molecular evidence for the “selective optimization” strategy and clarifying PRV’s core evolutionary path to balance functional needs and immune pressure over time. Conclusions: Our study findings deepen our understanding of the evolutionary mechanisms of PRV and provide theoretical support for designing vaccines and assessing the risk of cross-species transmission. Full article

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

► Show Figures

Figure 1

14 pages, 2279 KB

Open AccessArticle

Development of KASP Molecular Markers and Candidate Gene Mining for Heat Tolerance-Related Traits in Gossypium hirsutum

by Zhaolong Gong, Ni Yang, Shiwei Geng, Juyun Zheng, Zhi Liu, Fenglei Sun, Shengmei Li, Xueyuan Li, Yajun Liang and Junduo Wang

Genes 2025, 16(10), 1154; https://doi.org/10.3390/genes16101154 - 28 Sep 2025

Abstract

Background: High-temperature stress is one of the major abiotic stresses limiting cotton production. Identifying genetic loci and genes for heat tolerance is crucial for breeding heat-tolerant varieties. Methods: Given the complexity of heat tolerance phenotypes in cotton, this study, which focused [...] Read more.

Background: High-temperature stress is one of the major abiotic stresses limiting cotton production. Identifying genetic loci and genes for heat tolerance is crucial for breeding heat-tolerant varieties. Methods: Given the complexity of heat tolerance phenotypes in cotton, this study, which focused on resource materials, identified an A/C SNP mutation at position 5486185 on chromosome D06 within the heat tolerance interval through genome-wide association studies (GWAS) of natural Gossypium hirsutum populations. Results: A total of 308 resource materials were identified and evaluated for their heat tolerance phenotypes over two years of field research. Kompetitive allele-specific PCR (KASP) molecular markers were developed on the basis of the D06-5486185 SNP to characterize the heat tolerance phenotypes of these 308 resource materials. Genotyping for heat tolerance-related traits and agronomic traits was also performed. Materials with the C/C haplotype at position D06-5486185 presented increased heat tolerance (higher pollen viability (PV), leaf area (LA), chlorophyll (Chl) and number of bolls on the third fruit branch (FB3) and a lower number of dry buds (DBs) and drop rate (DR)) without negatively impacting key yield traits. This locus is located in the intergenic region of two adjacent bZIP transcription factor genes (GH_D06G0408 and GH_D06G0409). Expression analysis revealed that the expression levels of these two genes were significantly greater in heat-tolerant accessions (C/C type) than in sensitive accessions and that their expression levels were significantly correlated with multiple heat-tolerant phenotypes. Conclusions: In summary, this study developed a Kompetitive Allele Specific PCR (KASP) marker associated with heat tolerance in G. hirsutum and identified two key heat tolerance candidate genes. These results provide an efficient marker selection tool and important genetic resources for the molecular breeding of heat-tolerant G. hirsutum, laying an important foundation for further establishing a molecular marker-assisted breeding system for heat tolerance in G. hirsutum. Full article

(This article belongs to the Special Issue Genetic Research on Crop Stress Resistance and Quality Traits)

► Show Figures

Figure 1

Journal Description

Genes

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI