Genes

23 pages, 7592 KB

Open AccessArticle

The Complete Chloroplast Genome of Curcuma bakerii, an Endemic Medicinal Plant of Bangladesh: Insights into Genome Structure, Comparative Genomics, and Phylogenetic Relationships

by Mohammad Rashedul Islam, Dhafer A. Alzahrani, Enas J. Albokhari, Mohammad S. Alawfi and Arwa I. Alsubhi

Genes 2025, 16(12), 1460; https://doi.org/10.3390/genes16121460 (registering DOI) - 7 Dec 2025

Abstract

Background: Curcuma bakerii is a species of the family Zingiberaceae, endemic to Bangladesh. This genus of rhizomatous plants is widely distributed in tropical regions worldwide and is valued for its medicinal, aromatic, and culinary properties. Methods: The complete chloroplast (cp) genome [...] Read more.

Background: Curcuma bakerii is a species of the family Zingiberaceae, endemic to Bangladesh. This genus of rhizomatous plants is widely distributed in tropical regions worldwide and is valued for its medicinal, aromatic, and culinary properties. Methods: The complete chloroplast (cp) genome of C. bakerii was reconstructed using high-throughput sequencing data. Subsequently, the genome was functionally annotated, assembled, and analyzed to clarify its evolutionary dynamics and structural organization. Results: The study’s findings indicate that the genome size is 162,189 base pairs (bp) and that it has a normal quadripartite structure with a large single-copy (LSC) region also comprises a small single-copy (SSC) region and two inverted repeats (IRa and IRb). The GC content of the genome was 36.18%, consisting of 135 genes: 88 protein-coding, 39 tRNA, and 8 rRNA. The codon usage analysis revealed 22 high-frequency and five optimal codons indicative of codon bias. Analysis of repetitive sequences revealed 213 Simple Sequence Repeats (SSRs), most of which were A/T. Additionally, seven mutation hotspots were reported, with 68.08% of single-nucleotide polymorphisms (SNPs) detected in the coding region and 31.91% in the noncoding region. Nonsynonymous substitutions accounted for 63.78%, while synonymous substitutions accounted for 36.11%. Conclusions: Based on this study, cp genome sequencing is a useful tool for understanding the intrageneric relationships among Curcuma species. The research presents a complete cp genome of C. bakerii from Bangladesh and provides a useful genomic resource for the molecular evolution, phylogeny, and genetic diversity study of the genus Curcuma. Full article

(This article belongs to the Special Issue Molecular Adaptation and Evolutionary Genetics in Plants)

► Show Figures

Figure 1

22 pages, 4657 KB

Open AccessArticle

Multi-Transcriptome-Informed Network Pharmacology Reveals Novel Biomarkers and Therapeutic Candidates for Parkinson’s Disease

by Md. Al Amin Pappu, Md. Alamin, Md Al Noman, Most. Humaira Sultana, Md. Foysal Ahmed, Md. Sanoar Hossain, Md. Abdul Latif, Md. Fahim Faysal, AKM Azad, Salem A. Alyami, Naif Alotaibi and Md. Nurul Haque Mollah

Genes 2025, 16(12), 1459; https://doi.org/10.3390/genes16121459 (registering DOI) - 7 Dec 2025

Abstract

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder in aged people with multifaceted molecular underpinnings. It poses a severe threat to millions of older adults worldwide. The understanding of the molecular mechanisms of PD development and the performance of its therapeutic strategies [...] Read more.

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder in aged people with multifaceted molecular underpinnings. It poses a severe threat to millions of older adults worldwide. The understanding of the molecular mechanisms of PD development and the performance of its therapeutic strategies has not yet reached a satisfactory level. Methods: This study integrated six transcriptomic datasets to uncover key genes (KGs) and their underlying pathogenic mechanisms, providing insights into potential therapeutic strategies for PD. We designed a comprehensive computational pipeline using various bioinformatics tools and databases to investigate PD-causing KGs, focusing on their functions, pathways, regulatory mechanisms, and potential therapeutic drug molecules. Results: In order to explore PD-causing KGs, we initially identified 303 differentially expressed genes (DEGs) between PD and control samples with 204 upregulated and 99 downregulated DEGs using the LIMMA approach with threshold values at Adj. p-value < 0.05 and abs (log₂FC) ≥ 1.0. Then, protein–protein interaction (PPI) network analysis pinpointed seven top-ranked DEGs (GAPDH, PTEN, CCND1, APOE, ESR1, MAPK3/ERK1, and SNCA) as KGs or central modulators of PD pathogenesis. Regulatory network analysis of KGs identified 3 top-ranked transcription factors (FOXC1, NFKB1, and TFAP2A) and 6 microRNAs (hsa-let-7b-5p, hsa-mir-16-5p, and others) as the pivotal regulators of KGs. Gene Ontology (GO) terms and KEGG pathway enrichment analyses with KGs revealed several crucial biological processes, molecular functions, cellular components, and neurodegenerative pathways associated with the development of PD. Finally, the top five molecules guided by KGs (Nilotinib, Bromocriptine, Withaferin-A, Celastrol, and Donepezil) were identified as promising drug candidates against PD and validated computationally through ADME/T analysis and molecular dynamics simulation studies. Conclusions: The findings of this study may serve as valuable resources for developing effective treatment strategies for PD patients. Full article

(This article belongs to the Special Issue Novel Biomarkers of Neurodegenerative Diseases)

► Show Figures

Figure 1

11 pages, 207 KB

Open AccessArticle

Duchenne Muscular Dystrophy in the Republic of North Ossetia–Alania: Epidemiological Study, Diagnostic Issues, and Treatment Prospects

by Rena Zinchenko, Inna Tebieva, Aysylu Murtazina, Sofya Ionova, Alisa Zhmurova-Kriventsova, Olga Shchagina, Elena Zinina, Yulia Gabisova, Alana Khokhova, Marina Tokazova, Murat Ikaev, Oleg Remizov, Sofia Popovich, Ludmila Kuzenkova, Andrey Marakhonov and Sergey Kutsev

Genes 2025, 16(12), 1458; https://doi.org/10.3390/genes16121458 (registering DOI) - 6 Dec 2025

Abstract

Background/Objectives: The article presents data on Duchenne muscular dystrophy (DMD) in the Republic of North Ossetia-Alania (RNOA), describing the population characteristics of the disease among children in RNOA (2006–2023). Methods: The number of newborns was 172,115, with 86,057 boys from 2006 to 2023. [...] Read more.

Background/Objectives: The article presents data on Duchenne muscular dystrophy (DMD) in the Republic of North Ossetia-Alania (RNOA), describing the population characteristics of the disease among children in RNOA (2006–2023). Methods: The number of newborns was 172,115, with 86,057 boys from 2006 to 2023. During the reporting period, 19 families (23 patients, including 22 boys) were identified. The molecular and genetic characteristics of the patients were analyzed throughout the entire observation period, which began in 1998. Results: The prevalence of the disease was 1:3912 among newborn boys (95%CI: 1:2584–1:6242), which is slightly higher than in other regions of the Russian Federation (RF) and most countries around the world. The spectrum of DMD genetic variants in RNOA aligns with worldwide patterns but reveals differences in frequencies compared to RF data. The frequency of exon deletions in the DMD gene range from 65.0 to 70.0% (60% in RNOA vs. <50% in RF) worldwide, for duplications—9.0–11.0% globally (16% in RNOA), and for nonsense variants—9.7–26.5% worldwide (20% in RNOA). Twelve patients (41.0%) in RNOA qualified for therapy, and Translarna was prescribed in most cases. In the cohort of children, one girl was identified with classic DMD, confirmed by genetic studies. Different limitations of the study were hindered by the small cohort size, patients’ remote residences, and poor therapy compliance of our patients. Conclusions: The heterogeneity of mutation spectrum across different populations underscores the influence of ethnic background. Consequently, this study highlights the importance of population-specific studies for improving DMD care. Full article

(This article belongs to the Special Issue Genetic Diagnosis and Treatment of Duchenne Muscular Dystrophy)

22 pages, 2476 KB

Open AccessArticle

Integrated Transcriptomic and Metabolomic Analysis Reveals Metabolic Heterosis in Hybrid Tea Plants (Camellia sinensis)

by Yu Lei, Jihua Duan, Feiyi Huang, Ding Ding, Yankai Kang, Yi Luo, Yingyu Chen, Nianci Xie and Saijun Li

Genes 2025, 16(12), 1457; https://doi.org/10.3390/genes16121457 - 5 Dec 2025

Abstract

Background: Heterosis (hybrid vigor) is a fundamental phenomenon in plant breeding, but its molecular basis remains poorly understood in perennial crops such as tea (Camellia sinensis). This study aimed to elucidate the molecular mechanisms underlying heterosis in tea and its hybrids [...] Read more.

Background: Heterosis (hybrid vigor) is a fundamental phenomenon in plant breeding, but its molecular basis remains poorly understood in perennial crops such as tea (Camellia sinensis). This study aimed to elucidate the molecular mechanisms underlying heterosis in tea and its hybrids by performing integrated transcriptomic and metabolomic analyses of F₁ hybrids derived from two elite cultivars, Fuding Dabaicha (FD) and Baojing Huangjincha 1 (HJC). Methods: Comprehensive RNA sequencing and widely targeted metabolomic profiling were conducted on the parental lines and F₁ hybrids at the one-bud-one-leaf stage. Primary metabolites (including amino acids, nucleotides, saccharides, and fatty acids) were quantified, and gene expression profiles were obtained. Transcriptomic and metabolomic datasets were integrated using KEGG pathway enrichment and co-expression network analysis to identify coordinated molecular changes underlying heterosis. Results: Metabolomic profiling detected 977 primary metabolites, many of which displayed non-additive accumulation patterns. Notably, linoleic acid derivatives (9(S)-HODE, 13(S)-HODE) and nucleotides (guanosine, uridine) exhibited significant positive mid-parent heterosis. Transcriptomic analysis revealed extensive non-additive gene expression in F₁ hybrids, and upregulated genes were enriched in fatty acid metabolism, nucleotide biosynthesis, and stress signaling pathways. Integrated analysis demonstrated strong coordination between differential gene expression and metabolite accumulation, especially in linoleic acid metabolism, cutin/suberine biosynthesis, and pyrimidine metabolism. Positive correlations between elevated fatty acid levels and transcript abundance of lipid metabolism genes suggest that the transcriptional remodeling of lipid pathways contributes to heterosis. Conclusions: These findings provide novel insights into tea plant heterosis and identify potential molecular targets for breeding high-quality cultivars. Full article

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

7 pages, 603 KB

Open AccessCase Report

Neurodevelopmental Phenotype Associated with TRIP12: Report of a Family Carrying the p.Asp1135Val Variant

by Katia Margiotti, Marco Fabiani, Antonella Cima, Francesca Monaco, Antonella Viola, Alvaro Mesoraca and Claudio Giorlandino

Genes 2025, 16(12), 1456; https://doi.org/10.3390/genes16121456 - 5 Dec 2025

Abstract

Background: Pathogenic variants in the TRIP12 gene are associated with Clark-Baraitser syndrome, a condition characterized by neurodevelopmental disorders, including intellectual disability, autism spectrum disorder (ASD), and speech delay. Phenotypic expression is variable, and facial features are not consistently present. Familial inheritance is rare. [...] Read more.

Background: Pathogenic variants in the TRIP12 gene are associated with Clark-Baraitser syndrome, a condition characterized by neurodevelopmental disorders, including intellectual disability, autism spectrum disorder (ASD), and speech delay. Phenotypic expression is variable, and facial features are not consistently present. Familial inheritance is rare. Methods: Whole-exome sequencing (WES) was performed on a proband with speech disorder and ASD, as well as on her parents. Clinical assessment included developmental, cognitive, and physical evaluations. Results: A heterozygous missense variant c.3404A>T (p. Asp1135Val) in the TRIP12 gene was identified in both the proband and her father. Both presented with speech disorder and ASD without facial features or severe intellectual disability. Conclusions: In line with recent genotype–phenotype studies, missense TRIP12 variants tend to be associated with milder neurodevelopmental presentations, typically characterized by mild to moderate intellectual impairment, variable autistic traits, limited or absent facial features, and a low incidence of epilepsy. This familial case further presents the phenotypic spectrum of TRIP12 missense variants and highlights that ASD and speech disorder may occur as isolated neurodevelopmental findings without syndromic features. The report reinforces the relevance of TRIP12 analysis in the differential diagnosis of ASD and language disorders, even in individuals lacking physical traits, supporting more accurate genetic counseling and broader awareness of inherited TRIP12-related conditions. Full article

(This article belongs to the Section Neurogenomics)

► Show Figures

Figure 1

15 pages, 290 KB

Open AccessArticle

Antibiotic Resistance Profiles and Genetic Determinants of Listeria innocua Isolated from Food Sources in Poland

by Anna Zawiasa and Agnieszka Olejnik-Schmidt

Genes 2025, 16(12), 1455; https://doi.org/10.3390/genes16121455 - 5 Dec 2025

Abstract

Background: Antimicrobial resistance (AMR) is a growing public health concern affecting both medicine and food safety. While Listeria monocytogenes is the primary pathogen of concern, Listeria innocua—commonly found in food and food-processing environments—may serve as a reservoir for resistance genes and a [...] Read more.

Background: Antimicrobial resistance (AMR) is a growing public health concern affecting both medicine and food safety. While Listeria monocytogenes is the primary pathogen of concern, Listeria innocua—commonly found in food and food-processing environments—may serve as a reservoir for resistance genes and a useful indicator of species for surveillance. This study aimed to assess the phenotypic antibiotic susceptibility and detect resistance-associated genes in L. innocua isolates from meat products and processing environments in Poland. Methods: A total of 51 L. innocua isolates were analyzed, originating from raw and processed meat products as well as meat-processing environments. Antimicrobial susceptibility was determined using the disc diffusion method against 18 antibiotics representing multiple classes. Phenotypic resistance was interpreted following CLSI guidelines (CLSI, 2020). Isolates exhibiting resistance or intermediate resistance were further screened for resistance-associated genes using PCR. Results: All isolates were fully susceptible to ampicillin, benzylpenicillin, chloramphenicol, gentamicin, rifampin, trimethoprim-sulfamethoxazole, and vancomycin. High susceptibility was observed for ciprofloxacin, erythromycin, meropenem, trimethoprim, and nitrofurantoin, with only sporadic intermediate responses. Moderate resistance levels were noted for streptomycin (10%) and tetracycline (12%). The lowest susceptibility was recorded for clindamycin and linezolid, with most isolates exhibiting intermediate or resistant phenotypes. Universal resistance to cefotaxime and oxacillin was found. Eighteen distinct resistance patterns were identified. PCR confirmed the presence of several resistance-associated genes, including mecA, lnuA, lnuB, cfr, optrA, and poxtA, consistent with observed phenotypes. Conclusions: This study provides the first detailed characterization of AMR in L. innocua from Polish meat and processing environments. The findings highlight its heterogeneous resistance profiles and potential role as a reservoir of clinically relevant resistance genes. Incorporating L. innocua into surveillance programs may strengthen early detection of emerging resistance and enhance food safety monitoring. Full article

(This article belongs to the Special Issue Advances in Molecular Microbiology, Genetics, and Bioinformatics of Multiple-Drug-Resistant Bacteria in Public Health)

16 pages, 1616 KB

Open AccessArticle

Identification and Functional Characterization of the CrRLK1L Gene Family in Salt Tolerance in Rice (Oryza sativa L.)

by Haoqiang Du, Xingyu Wang, Jifang Hu, Kefei Tan, Chuanzeng Liu and Bo Ma

Genes 2025, 16(12), 1454; https://doi.org/10.3390/genes16121454 - 4 Dec 2025

Abstract

Background: As key members of the plant receptor-like kinase family, rice CrRLK1Ls play diverse roles in plant growth, development, and stress responses. Although rice CrRLK1Ls have been initially characterized, our understanding of their functions remains limited. Methods: We identified OsCrRLK1L genes via Hidden [...] Read more.

Background: As key members of the plant receptor-like kinase family, rice CrRLK1Ls play diverse roles in plant growth, development, and stress responses. Although rice CrRLK1Ls have been initially characterized, our understanding of their functions remains limited. Methods: We identified OsCrRLK1L genes via Hidden Markov Model (HMM) searches against the rice genome. Subsequent analyses encompassed their physicochemical properties, chromosomal distribution, gene structure, phylogenetic relationships, conserved domains, and cis-acting elements.Salt-responsive candidates were screened using a GEO dataset, and their expression profiles were validated under salt stress using quantitative real-time PCR. Result: A total of 36 OsCrRLK1L genes, all containing both Malectin and tyrosine kinase domains, were identified in the rice genome and showed an uneven chromosomal distribution. Phylogenetic analysis classified them into three subclades, with Group II and Group III being specific to rice and Arabidopsis thaliana, respectively. Promoter analysis revealed that the promoter regions of these genes contained an abundance of cis-acting elements related to hormone and stress responses. RNA-Seq and enrichment analysis indicated that OsCrRLK1L genes exhibit tissue specificity and participate in salt stress responses. Furthermore, CrRLK1L2 and CrRLK1L10 showed tissue-specific differential expression under salt stress. Conclusions: In summary, our study lays the groundwork for future research into the biological roles of OsCrRLK1L genes during salt stress. Full article

(This article belongs to the Special Issue Molecular Genetics of Stress Response in Crops)

15 pages, 5177 KB

Open AccessArticle

Genome-Wide Identification of the DFR Gene Family in Lonicera japonica Thunb. and Response to Drought and Salt Stress

by Dandan Lu, Xiaoyu Su, Yao Sun, Lei Li, Yongliang Yu, Chunming Li, Yiwen Cao, Lina Wang, Meiyu Qiao, Hongqi Yang, Mengfan Su, Zhengwei Tan and Huizhen Liang

Genes 2025, 16(12), 1453; https://doi.org/10.3390/genes16121453 - 4 Dec 2025

Abstract

Background: Dihydroflavonol 4-reductase (DFR) is pivotal for anthocyanin biosynthesis and plays a crucial role in plant development and stress adaptation. However, a systematic characterization of the DFR gene family is lacking in Lonicera japonica Thunb. Methods: In the present study, based on genome [...] Read more.

Background: Dihydroflavonol 4-reductase (DFR) is pivotal for anthocyanin biosynthesis and plays a crucial role in plant development and stress adaptation. However, a systematic characterization of the DFR gene family is lacking in Lonicera japonica Thunb. Methods: In the present study, based on genome and transcriptome data of L. japonica, the research identified six LjDFR gene family members throughout the entire genome. Results: The LjDFR genes were located on Chr.04 and Chr.09 and the full-length coding sequences of LjDFR1-LjDFR6 were cloned. Subcellular localization analysis showed that LjDFRs are primarily found at the cell membrane and in the nucleus. Phylogenetic analysis showed closer clustering of LjDFR genes with Capsicum annuum and Camellia sinensis. Promoter analysis linked LjDFR genes to light response, hormone signaling, and stress-responses. qRT-PCR analysis demonstrated tissue-specific and stage-specific expression patterns among LjDFR members. Notably, LjDFR2 expression was significantly higher in the intensely pigmented tissues of Lonicera japonica Thunb. var. chinensis (Wats.) Bak. compared to L. japonica. Coupled with its phylogenetic proximity to the anthocyanin-related CsDFRa and CaDFR5 genes, this suggests that LjDFR2 may be positively correlated with anthocyanin accumulation. Additionally, the expression of LjDFR2 and LjDFR4 was markedly induced by both drought and salt stress, indicating their roles in abiotic stress responses. Conclusions: This research provides a foundation for further functional studies of LjDFR genes in anthocyanin biosynthesis and stress resistance and offers candidate genes for molecular breeding of L. japonica. Full article

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

► Show Figures

Figure 1

15 pages, 2768 KB

Open AccessArticle

Expression and Regulation of FGF9 Gene in Chicken Ovarian Follicles and Its Genetic Effect on Laying Traits in Hens

by Yue Wang, Xinmei Shu, Yuanyuan Guo, Qingqing Wei and Yunliang Jiang

Genes 2025, 16(12), 1452; https://doi.org/10.3390/genes16121452 - 4 Dec 2025

Abstract

Objectives: Fibroblast growth factor 9 (FGF9), a crucial member of the FGF family, functions as an intercellular signaling molecule involved in angiogenesis, embryogenesis, and tissue repair. Our previous study demonstrated that FGF9 expression in chicken hierarchical granulosa cells (Post-GCs) is regulated by LSD1 [...] Read more.

Objectives: Fibroblast growth factor 9 (FGF9), a crucial member of the FGF family, functions as an intercellular signaling molecule involved in angiogenesis, embryogenesis, and tissue repair. Our previous study demonstrated that FGF9 expression in chicken hierarchical granulosa cells (Post-GCs) is regulated by LSD1 Ser54 phosphorylation and that FGF9 promotes cell proliferation. This study aims to analyze the expression and regulation of the FGF9 gene in chicken ovarian follicles and its genetic effect on laying traits in hens. Methods: Chicken FGF9 mRNA expression patterns were examined by real-time quantitative PCR (RT-qPCR). Detection of single nucleotide polymorphisms (SNPs) was performed using PCR amplification and Sanger sequencing. Transcription activity was compared using dual-luciferase reporter assay. Results: Following follicle selection, chicken FGF9 expression significantly decreased in granulosa cells (p < 0.05) while it increased in theca cells (p < 0.05). Hormonal treatments revealed differential regulation; estradiol and FSH downregulated FGF9 in both pre-hierarchical and hierarchical granulosa cells (p < 0.05), whereas progesterone exhibited opposing effects, suppressing expression in pre-hierarchical granulosa cells (Pre-GCs) but stimulating its expression in Post-GCs (p < 0.05). In theca cells, estradiol consistently inhibited FGF9 expression (p < 0.05), while FSH only affected FGF9 expression in pre-hierarchical follicles. Six SNPs in the promoter region (g.−1965G>A, g.−2177G>A, g.−2289G>A, g.−3669A>G, g.−3770A>G, g.−3906G>A) were identified, five of which (g.−1965G>A, g.−2177G>A, g.−2289G>A, g.−3669A>G, g.−3906G>A) showed significant associations with egg production traits. Notably, alleles A (g.−2289), G (g.−3669), and A (g.−3906) enhanced the transcription activity of chicken FGF9 in Pre-GCs. Conclusions: These findings provide novel insights into the expression pattern and regulatory mechanisms of chicken FGF9 during follicular development and identify some genetic markers for egg-laying traits in chickens. Full article

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

► Show Figures

Figure 1

18 pages, 5482 KB

Open AccessArticle

Genome-Wide Identification of the AMT Gene Family in Wheat: Expression Profiles Under Ammonium Nutrition and Pathogen Effects

by Yanzhen Wang, Jialu Li, Xia Liu, Rui Huang, Menglin Lei, Yaoyuan Zhang and Guoqing Cui

Genes 2025, 16(12), 1451; https://doi.org/10.3390/genes16121451 - 4 Dec 2025

Abstract

Background: Ammonium nitrogen (NH₄⁺) serves as a vital nitrogen source, playing pivotal regulatory roles in plant growth, development, and high-yield formation. Ammonium transporters (AMTs), encoded by the AMT gene family, are central to NH₄⁺ transport. However, the [...] Read more.

Background: Ammonium nitrogen (NH₄⁺) serves as a vital nitrogen source, playing pivotal regulatory roles in plant growth, development, and high-yield formation. Ammonium transporters (AMTs), encoded by the AMT gene family, are central to NH₄⁺ transport. However, the functional roles of AMT genes in wheat remain poorly understood. Methods: A comprehensive genome-wide analysis of the TaAMT gene family numbers was conducted, encompassing investigations into gene structure, protein motif composition, gene duplication events, collinearity relationships, and cis-acting regulatory elements. Furthermore, the expression patterns of distinct TaAMT members were examined under varying ammonium supply conditions and pathogen stress. Results: In this study, a total of 21 TaAMT members were identified. Additionally, all TaAMT proteins were localized to the plasma membrane. Phylogenetic analysis clustered these genes into four distinct subgroups. Comparative analyses of gene structure and conserved motifs revealed conserved domain composition and motif organization within each subgroup. Interspecific synteny analysis highlighted evolutionary conservation across species. Promoter region analysis identified multiple cis-regulatory elements associated with hormone signaling, light responsiveness, and abiotic stress adaptation. Expression profiling demonstrated that TaAMT members exhibit both tissue-specific and constitutive expression patterns across developmental stages. RT-qPCR further revealed that the expression of TaAMT members responds to varying concentrations of ammonium nitrogen supply, as well as infection stresses caused by stripe rust and powdery mildew. Conclusions: Collectively, this study uncovered the functional diversity of TaAMT members, offering novel molecular targets and theoretical foundations for breeding wheat varieties with enhanced nitrogen use efficiency and disease resistance. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

15 pages, 2411 KB

Open AccessArticle

Hepcidin from the Chinese Spiny Frog (Quasipaa spinosa) Integrates Membrane-Disruptive Antibacterial Activity with Macrophage-Mediated Protection Against Elizabethkingia miricola

by Fen Qiao, Xin-Yi Qian, Yi-Kai Feng and Jie Chen

Genes 2025, 16(12), 1450; https://doi.org/10.3390/genes16121450 - 4 Dec 2025

Abstract

Background/Objectives: Hepcidin is a cysteine-rich antimicrobial peptide that links iron homeostasis and innate immunity in vertebrates, but its functions in amphibians remain poorly understood. The Chinese spiny frog (Quasipaa spinosa) is an economically important species that suffers serious losses from [...] Read more.

Background/Objectives: Hepcidin is a cysteine-rich antimicrobial peptide that links iron homeostasis and innate immunity in vertebrates, but its functions in amphibians remain poorly understood. The Chinese spiny frog (Quasipaa spinosa) is an economically important species that suffers serious losses from bacterial diseases. This study aimed to identify and functionally characterize a hepcidin homolog (QsHep) from Q. spinosa, focusing on its antibacterial activity, immunomodulatory effects on primary macrophages, and protective efficacy against Elizabethkingia miricola infection. Methods: The QsHep gene was cloned and analyzed, its tissue distribution and inducible expression were examined by qRT-PCR, and the synthetic peptide was tested for antimicrobial, membrane-disruptive, and immunomodulatory activities in vitro, as well as for in vivo protection in an E. miricola infection model. Results: QsHep encodes a typical preprohepcidin with a signal peptide, prodomain, and a conserved mature peptide containing eight cysteine residues. QsHep was widely expressed, with the highest levels in liver, and was significantly upregulated in liver and spleen following bacterial challenge. Synthetic QsHep displayed broad-spectrum antibacterial activity, including strong inhibition of E. miricola, and induced dose-dependent membrane damage in E. miricola. QsHep showed no obvious cytotoxicity but significantly enhanced chemotaxis, phagocytic activity, and respiratory burst in primary macrophages. In vivo, QsHep treatment markedly improved the survival of E. miricola-infected frogs in a dose-dependent manner. Conclusions: QsHep is an amphibian hepcidin that combines membrane-disruptive antibacterial activity with the activation of macrophage effector functions and confers significant protection against bacterial infection in vivo. These findings expand our understanding of hepcidin-mediated innate immunity in amphibians and highlight QsHep as a promising peptide candidate for controlling bacterial diseases in frog aquaculture. Full article

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

► Show Figures

Figure 1

18 pages, 2769 KB

Open AccessArticle

Genetic Diversity of Rhodiola quadrifida (Crassulaceae) in Altai High-Mountain Populations of Kazakhstan

by Oxana Khapilina, Ainur Turzhanova, Moldir Zhumagul, Saule Magzumova, Olesya Raiser, Damelya Tagimanova, Serik Kubentayev and Vladislav Shevtsov

Genes 2025, 16(12), 1449; https://doi.org/10.3390/genes16121449 - 3 Dec 2025

Abstract

Background: Rhodiola quadrifida (Pall.) Fisch. & C.A. Mey. (Crassulaceae) is a rare medicinal species in the Kazakh Altai, yet information on its population structure and genetic diversity remains limited. This study presents findings from an investigation of natural R. quadrifida populations. Methods: [...] Read more.

Background: Rhodiola quadrifida (Pall.) Fisch. & C.A. Mey. (Crassulaceae) is a rare medicinal species in the Kazakh Altai, yet information on its population structure and genetic diversity remains limited. This study presents findings from an investigation of natural R. quadrifida populations. Methods: The morphometric characteristics, population age structure, and genetic diversity of the plants were analysed using PCR-based genome profiling. Genetic diversity within R. quadrifida populations was assessed using PCR primers for binding sites complementary to a specific region at the 3′ terminus of a particular tRNA. Results: The populations exhibited variations in morphological traits, age structures, and reproductive strategies. The IVA-1, IVA-2 and KOK populations represent the most mature stages, characterized by a dominance of vegetative reproduction and a disturbed age structure, with a predominance of senile and virgin individuals. In contrast, the LIN-1 and LIN-2 population is characterized by a balanced age structure, encompassing all ontogenetic groups, and a mixed reproductive system that includes both sexual and vegetative propagation. Genetic diversity, as measured by Shannon’s information index, ranged from 0.194 to 0.247, indicating low genetic diversity in R. quadrifida. Analysis of molecular variance (AMOVA) revealed significantly greater variation within populations (62%) than among populations (38%). Genetic diversity was higher in the LIN-1 and LIN-2 populations, which employs a mixed reproductive system (clonal and seeds), than in populations dominated by vegetative reproduction. Both LIN populations, characterized by a mixed reproductive system, exhibited higher genetic diversity than the KOK, IVA-1 and IVA-2 populations, where vegetative reproduction predominated. Conclusions: These results underscore the necessity for priority conservation measures, including monitoring population size and age structure in populations with low levels of seed reproduction and disturbed age structure. Additional measures include supporting in situ and ex situ conservation, such as clonal collection, seed banks, and tissue cultures, as well as restricting the harvesting of medicinal raw materials. Full article

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

► Show Figures

Figure 1

22 pages, 1034 KB

Open AccessReview

The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies

by Saif Dababneh, Arya Ardehali, Jasleen Badesha and Zachary Laksman

Genes 2025, 16(12), 1448; https://doi.org/10.3390/genes16121448 - 3 Dec 2025

Abstract

Inherited arrhythmias and cardiomyopathies are a group of potentially lethal genetic cardiac disorders which are often passed down through generations and pose risks to several family members. While individually rare, these conditions are collectively common and pose significant challenges for clinical management given [...] Read more.

Inherited arrhythmias and cardiomyopathies are a group of potentially lethal genetic cardiac disorders which are often passed down through generations and pose risks to several family members. While individually rare, these conditions are collectively common and pose significant challenges for clinical management given their variable severity, age of onset, and response to treatments. Earlier genetic analyses revealed crucial insights into the main genetic culprits of these disorders, such as SCN5A for Brugada syndrome, and MYH7 and MYBPC3 for hypertrophic cardiomyopathy, which have revolutionized diagnosis, risk stratification, and medical management. Nonetheless, issues such as variable expressivity and penetrance, low yield of genetic testing, and relative lack of disease-modifying therapies remain significant hurdles for clinical management. The revolution of genome-wide association studies GWASs has transformed our understanding of inherited arrhythmias and cardiomyopathies, shifting the view of these disorders from a monogenic Mendelian inheritance towards a more complex, often polygenic inheritance with nuanced interplay between genetics and environment. Moreover, GWASs have enabled the quantification of polygenic predisposition to disease using polygenic risk scores, which are often complementary to and independent of monogenic risk. In this review, we highlight how GWASs have transformed the field of inherited arrhythmias and cardiomyopathies, with a particular focus on the polygenic risk scores developed and their clinical utility for the four disorders which have been impacted by GWASs—hypertrophic cardiomyopathy, dilated cardiomyopathy, Brugada syndrome, and long QT syndrome. Full article

(This article belongs to the Special Issue Application of Genome-Wide Association Studies in Rare Diseases Research)

► Show Figures

Figure 1

40 pages, 1000 KB

Open AccessReview

Addiction Susceptibility: Genetic Factors, Personality Traits, and Epigenetic Interactions with the Gut Microbiome

by Alejandro Borrego-Ruiz and Juan J. Borrego

Genes 2025, 16(12), 1447; https://doi.org/10.3390/genes16121447 - 3 Dec 2025

Abstract

Despite valuable insights into the individual roles of genetic factors and personality traits, their combined contribution to addiction susceptibility remains insufficiently characterized. Within this framework, the potential influence of epigenetic mechanisms, particularly those mediated by the gut microbiome, also remains underexplored. This comprehensive [...] Read more.

Despite valuable insights into the individual roles of genetic factors and personality traits, their combined contribution to addiction susceptibility remains insufficiently characterized. Within this framework, the potential influence of epigenetic mechanisms, particularly those mediated by the gut microbiome, also remains underexplored. This comprehensive review aims to address these gaps in an integrative manner by examining: (i) the association of gene regulation with personality traits; (ii) the genetics of substance use disorders; (iii) the roles of genes and personality in addiction; and (iv) epigenetic influences on addiction, with a particular focus on the role of the gut microbiome. Genetic influences on personality act primarily via regulatory variants that modulate gene expression during neurodevelopment, shaping cognitive, emotional, and behavioral traits that contribute to individual differences. Substance use disorders share partially overlapping genetic foundations, with specific loci, heritability estimates, and causal pathways differing across substances, reflecting both shared vulnerability and substance-specific genetic influences on addiction susceptibility. Impulsivity, novelty-seeking, and stress responsiveness are heritable personality traits that interact to shape susceptibility to substance use disorders, with genetic factors modulating risk across different forms of addiction. Environmental factors, early-life stress, and social influences interact with the gut microbiome to shape neurobiological and behavioral pathways that modulate addiction risk. These interactions highlight the multifactorial nature of substance use disorders, in which epigenetic, microbial, and psychosocial mechanisms converge to influence susceptibility, progression, and maintenance of addictive behaviors. Full article

(This article belongs to the Section Neurogenomics)

► Show Figures

Figure 1

14 pages, 1555 KB

Open AccessArticle

Bridging East and West: Real-World Clinicogenomic Landscape of Metastatic NSCLC in Türkiye

by Kübra Canaslan, Emre Eken, Mehmet Bilici, Fahriye Merve Balcıoğlu, Banu Öztürk, Mehmet Çakmak, Öznur Bal, Görkem Turhan, Feyyaz Özdemir, Hayati Arvas, Zuhat Urakçı, Ebru Çiçek, Zeynep Hande Turna and Aziz Karaoğlu

Genes 2025, 16(12), 1446; https://doi.org/10.3390/genes16121446 - 3 Dec 2025

Abstract

Background/Objectives: Genomic profiling guides treatment in metastatic non-small-cell lung cancer (mNSCLC), yet country-level data from Türkiye remain limited. Methods: We retrospectively analyzed consecutive patients with mNSCLC diagnosed between January 2018 and March 2025 across tertiary centers in all seven regions. Variables included demographics, [...] Read more.

Background/Objectives: Genomic profiling guides treatment in metastatic non-small-cell lung cancer (mNSCLC), yet country-level data from Türkiye remain limited. Methods: We retrospectively analyzed consecutive patients with mNSCLC diagnosed between January 2018 and March 2025 across tertiary centers in all seven regions. Variables included demographics, smoking, histology, testing modality (single-gene vs. next-generation sequencing [NGS]), targetable genomic alterations (TGAs) and co-mutations, and programmed death-ligand 1 (PD-L1) tumor proportion score. Results: Among 1023 patients (mean age 64 years; 76.4% male), tobacco exposure was frequent (mean 42.1 pack-years); 16.9% were never-smokers. NGS use increased over time, exceeding 90% by 2025. TGAs were detected in 28.3% (EGFR 16.0%, ALK 5.0%, KRAS G12C 2.6%, BRAF V600E 3.2%; ROS1, MET exon 14, HER2, NTRK ≤ 2.5%; no RET). EGFR alterations occurred in 19% of non-squamous carcinomas and 6% of squamous cell carcinomas (SCCs), suggesting an intermediate East–West pattern. Among NGS-tested samples, TP53 was the most frequent co-mutation (33.1%), followed by alterations in CDKN2A, PIK3CA, FGFR, STK11, and KEAP1. Conclusions: In this large, multicenter Turkish real-world cohort, the TGA spectrum broadly mirrors global patterns while revealing local nuances; EGFR mutations were more frequent than expected in SCC, and nationwide NGS adoption is accelerating. Limitations include retrospective design, non-centralized PD-L1 testing, and missing data. Prospective, standardized studies integrating outcomes and resistance mechanisms are warranted to refine regional precision oncology. Full article

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

► Show Figures

Figure 1

20 pages, 4134 KB

Open AccessArticle

TYK2 Deficiency Presenting as Refractory Disseminated BCG/Tuberculosis Infection in a Kazakh Child: A Case Report with Genetic Confirmation

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

Genes 2025, 16(12), 1445; https://doi.org/10.3390/genes16121445 - 2 Dec 2025

Abstract

Background/Objectives: Hereditary anomalies in the TYK2 gene are the basis of a rare primary immunodeficiency, immunodeficiency-35, typified by an augmented vulnerability to mycobacterial and viral infections. Clinical overlap with chronic granulomatous disease (CGD) and other granulomatous disorders complicates diagnosis, particularly in nations where [...] Read more.

Background/Objectives: Hereditary anomalies in the TYK2 gene are the basis of a rare primary immunodeficiency, immunodeficiency-35, typified by an augmented vulnerability to mycobacterial and viral infections. Clinical overlap with chronic granulomatous disease (CGD) and other granulomatous disorders complicates diagnosis, particularly in nations where universal BCG vaccination is instituted. We present a pediatric case from Kazakhstan to broaden the clinical and molecular spectrum of TYK2-related immunodeficiency and accentuate diagnostic challenges. Methods: The proband underwent clinical assessment, immunophenotyping, and biochemical analysis during episodes of active pathology and subsequent follow-up. Whole-exome sequencing (WES) was executed, followed by confirmatory Sanger sequencing and segregation analysis in first-degree kin. Functional assays for phagocyte oxidative burst and phagocytosis were conducted to exclude CGD. Results: WES identified two rare TYK2 variants (c.209_212del, pathogenic; c.2395G>A, previously reported as pathogenic in a Chinese patient with TYK2 deficiency) and a heterozygous MEFV duplication (c.761_764dup). Paternal DNA was unavailable; therefore, allelic phase could not be formally established, but the combined genotype and phenotype are consistent with autosomal recessive TYK2 deficiency. Sanger sequencing confirmed segregation of the frameshift TYK2 variant in the mother, while the clinically healthy brother carried only the wild-type allele. The missense alteration was exclusive to the proband. Conclusions: This case exemplifies the significance of contemplating TYK2 deficiency in pediatric patients with refractory mycobacterial infections, particularly in BCG-endemic locales. Genetic validation provided a definitive diagnosis, differentiating the condition from CGD and informing patient management. To our knowledge, this constitutes one of the inaugural genetically confirmed instances of TYK2 deficiency in Central Asia, enhancing regional epidemiological comprehension and emphasizing the role of molecular diagnostics in directing treatment and vaccination policies. Full article

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

► Show Figures

Figure 1

31 pages, 2851 KB

Open AccessReview

Genetic, Clinical and Neuroradiological Spectrum of MED-Related Disorders: An Updated Review

by Alessandro Fazio, Roberta Leonardi, Lorenzo Aliotta, Manuela Lo Bianco, Gennaro Anastasio, Giuseppe Messina, Corrado Spatola, Pietro Valerio Foti, Stefano Palmucci, Antonio Basile, Martino Ruggieri and Emanuele David

Genes 2025, 16(12), 1444; https://doi.org/10.3390/genes16121444 - 2 Dec 2025

Abstract

Background/Objectives: The Mediator (MED) complex is an essential regulator of RNA polymerase II transcription. There is increasing evidence that pathogenic variants in several MED subunits are the cause of neurodegenerative and neurodevelopmental phenotypes, collectively referred to as “MEDopathies”. This review aims to summarize [...] Read more.

Background/Objectives: The Mediator (MED) complex is an essential regulator of RNA polymerase II transcription. There is increasing evidence that pathogenic variants in several MED subunits are the cause of neurodegenerative and neurodevelopmental phenotypes, collectively referred to as “MEDopathies”. This review aims to summarize current knowledge on the genetic basis, clinical manifestations, and neuroradiological features of MED-related disorders. Methods: We undertook a narrative synthesis of the literature focusing on the MED subunits most commonly associated with neurological disorders, including MED1, MED8, MED11, MED12/MED12L, MED13/MED13L, MED14, MED17, MED20, MED23, MED25, MED27, and CDK8. Sources included peer-reviewed genetic, clinical, and imaging studies, supplemented by relevant case reports and cohort analyses. In addition, representative facial phenotypes associated with selected MED variants (MED11, MED12, MED13, MED13L, MED25) were visualized for educational purposes using artificial intelligence-based image generation derived from standardized clinical descriptors. Results: All MEDopathies show converging clinical patterns: global developmental delay/intellectual disability, hypotonia, epilepsy, speech disorders, and behavioral comorbidity. Non-neurological involvement, such as craniofacial or cardiac anomalies, is subunit-specific. Neuroradiological features include callosal abnormalities (agenesis, thinning, dysmorphia), delayed or hypomyelination, progressive cerebral and cerebellar atrophy, basal ganglia signaling changes, pontine hypoplasia, and, in MED27 deficiency, a “hot cross bun” sign. Gene-specific constellations emphasize catastrophic infantile progression (MED11), X-linked syndromes with callosal defects (MED12/MED12L), language-dominant phenotypes (MED13), and syndromic intellectual disability with systemic features (MED13L). Conclusions: The growing spectrum of MEDopathies argues for their recognition as a unified nosological group with overlapping clinical and radiological signatures. Characteristic MRI constellations may serve as diagnostic clues and guide targeted molecular testing. Future directions include longitudinal imaging to describe disease progression and the integration of genomic data with curated clinical radiological datasets to refine genotype-phenotype correlations. Full article

(This article belongs to the Collection Study on Genotypes and Phenotypes of Pediatric Clinical Rare Diseases)

► Show Figures

Figure 1

20 pages, 888 KB

Open AccessReview

Role of Genetic and Epigenetic Biomarkers in Treatment-Resistant Depression: A Literature Review

by Petra Sulić, Andrea Ražić Pavičić, Biljana Đapić Ivančić, Tamara Božina, Nada Božina and Maja Živković

Genes 2025, 16(12), 1443; https://doi.org/10.3390/genes16121443 - 2 Dec 2025

Abstract

Background: Treatment-resistant depression (TRD) affects up to 30–40% of patients with major depressive disorder and remains a major therapeutic challenge. Genetic and epigenetic factors are increasingly recognized as key contributors to both vulnerability and treatment response. Methods: We conducted a narrative review of [...] Read more.

Background: Treatment-resistant depression (TRD) affects up to 30–40% of patients with major depressive disorder and remains a major therapeutic challenge. Genetic and epigenetic factors are increasingly recognized as key contributors to both vulnerability and treatment response. Methods: We conducted a narrative review of studies published between 2021 and 2025, focusing exclusively on DNA- and RNA-based biomarkers of TRD. Twelve studies met the inclusion criteria, covering candidate gene analyses, genome-wide association studies (GWAS), neuroimaging–genetic approaches, and microRNA profiling. Results: Genetic investigations consistently implicate neuroplasticity-related genes (BDNF, NTRK2, PTEN, SYN1, MAPK1, and GSK3B) in the risk of TRD and its relapse. Variants in glutamatergic receptor genes (GRIN2A, GRIN2B, GRIA2, GRIA3) were predicted to result in a rapid and sustained response to ketamine. Genomic approaches further demonstrated that composite genetic panels outperform single-variant predictors. In parallel, microRNAs such as miR-1202, miR-16, miR-135, miR-124, miR-223, and miR-146a emerged as dynamic biomarkers of treatment response, particularly in cohorts treated with ketamine or electroconvulsive therapy. Conclusions: DNA- and RNA-based biomarkers provide promising avenues for improving the understanding and management of TRD. Their integration into clinical frameworks could support patient stratification, individualized treatment selection, and real-time monitoring of therapeutic efficacy. Future research should prioritize replication, methodological harmonization, and longitudinal validation to facilitate the translation of findings into precision psychiatry. Full article

(This article belongs to the Special Issue Psychiatric Pharmacogenomics)

► Show Figures

Figure 1

28 pages, 1621 KB

Open AccessReview

From Metabolic to Epigenetic Memory: The Impact of Hyperglycemia-Induced Epigenetic Signature on Kidney Disease Progression and Complications

by Sara Cannito, Ida Giardino, Maria D’Apolito, Alessandra Ranaldi, Francesca Scaltrito, Massimo Pettoello-Mantovani and Annamaria Piscazzi

Genes 2025, 16(12), 1442; https://doi.org/10.3390/genes16121442 - 2 Dec 2025

Abstract

Chronic kidney disease is a significant global health burden and a leading cause of cardiovascular morbidity and mortality. Diabetes mellitus is the primary cause of kidney disease, driving the progression of both micro- and macrovascular complications. Sustained hyperglycemia initiates a cascade of deleterious [...] Read more.

Chronic kidney disease is a significant global health burden and a leading cause of cardiovascular morbidity and mortality. Diabetes mellitus is the primary cause of kidney disease, driving the progression of both micro- and macrovascular complications. Sustained hyperglycemia initiates a cascade of deleterious molecular and cellular events, including mitochondrial dysfunction, inflammation, oxidative stress, and dysregulated apoptosis and autophagy, which collectively contribute to the progression of renal injury. Beyond these well-established mechanisms, a compelling body of evidence highlights the pivotal role of epigenetic alterations (such as DNA methylation, histone post-translational modifications, and non-coding RNAs) in mediated long-term kidney damage. The interplay between transcriptional and epigenetic regulation underlies the phenomenon of the “metabolic memory”, wherein cellular dysfunction persists even after glycemic control is achieved. This review synthesizes the current knowledge on mechanisms sustaining metabolic and epigenetic memory, with a particular focus on the epigenetic machinery that establishes and maintains these signals, a concept increasingly termed “epigenetic memory.” Given their reversible nature, epigenetic determinants are emerging as promising biomarkers and a compelling therapeutic avenue. Targeting these “epifactors” offers a novel strategy to halt progression to end-stage renal disease, thereby paving the way for precision medicine approaches in diabetes-related renal disease. Full article

(This article belongs to the Section Epigenomics)

► 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