Genes

15 pages, 1104 KB

Open AccessArticle

Comparative Accuracy of Machine Learning and GBLUP for Predicting Genomic Estimated Breeding Values in Chickens

by Haoxiang Chai, Yuqi Yang, Dan Wang, Chao Ning, Xuguang Zhang, Wenwen Wang, Qin Zhang, Haigang Bao and Hui Tang

Genes 2026, 17(3), 315; https://doi.org/10.3390/genes17030315 - 12 Mar 2026

Abstract

Background: Machine learning (ML) holds great promise for genomic breeding value prediction in livestock and poultry, yet its application in layer breeding remains limited. Methods: In this study, we used whole-genome resequencing data from 834 Wenshui Luhua Green-Shelled (WLGS) laying hens to predict [...] Read more.

Background: Machine learning (ML) holds great promise for genomic breeding value prediction in livestock and poultry, yet its application in layer breeding remains limited. Methods: In this study, we used whole-genome resequencing data from 834 Wenshui Luhua Green-Shelled (WLGS) laying hens to predict genomic breeding values for eight egg production and egg quality traits using multilayer perceptron (MLP), random forest (RF), and genomic best linear unbiased prediction (GBLUP). Model performance was evaluated via 10-fold cross-validation, and the effects of data type and single nucleotide polymorphism (SNP) density were examined. Results: Heritability analysis indicated moderate heritability for egg number (EN) at 0.327. Egg weight-related traits (EW-30W, EW-40W, and EHD-40W) exhibited high heritability (0.570–0.631), while eggshell strength (ESS-40W) and thickness (EST-40W) showed moderate heritability at 0.228 and 0.220, respectively. Model comparisons revealed that RF performed best for egg shape index (ESI-30W, 0.395) and most egg quality traits, whereas GBLUP yielded optimal results for egg weight traits, achieving prediction accuracies of 0.392 for EW-30W and 0.432 for EW-40W. Whole-genome resequencing data consistently outperformed 50K chip data across all models, with GBLUP improving EW-40W prediction accuracy by 24.9%. SNP density analysis further showed that GBLUP remained stable under low-density conditions, while MLP and RF progressively improved with increasing density, with RF demonstrating the most pronounced advantage at high densities. Conclusions: In summary, the GBLUP model is suitable for traits with high heritability and low-density marker scenarios, while the RF model demonstrates significant predictive advantages for egg production and specific egg quality traits under high-density conditions. This study provides scientific basis for model selection in the genomic selection program for laying hens. Full article

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

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13 pages, 1530 KB

Open AccessArticle

Clinical Details of Low-Frequency Hearing Loss Observed in Autosomal Dominant MYO7A-Associated Hearing Loss Patients

by Hiromi Koizumi, Shin-ya Nishio and Shin-ichi Usami

Genes 2026, 17(3), 314; https://doi.org/10.3390/genes17030314 - 11 Mar 2026

Abstract

Background/Objectives: MYO7A is known to be the genetic cause of Usher syndrome type 1, as well as autosomal dominant and autosomal recessive non-syndromic hearing loss. In general, autosomal dominant MYO7A-associated hearing loss shows progressive high-frequency, sloping hearing loss. However, several variants are [...] Read more.

Background/Objectives: MYO7A is known to be the genetic cause of Usher syndrome type 1, as well as autosomal dominant and autosomal recessive non-syndromic hearing loss. In general, autosomal dominant MYO7A-associated hearing loss shows progressive high-frequency, sloping hearing loss. However, several variants are associated with low-frequency hearing loss. MYO7A-associated low-frequency hearing loss is relatively rare, and the clinical details remain unclear. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with variants related to MYO7A-associated low-frequency hearing loss were identified. Results: Among 18,475 hearing loss patients, we identified 60 patients from 44 unrelated families carrying five variants (p.[Asn140Lys; Glu1835Gln], p.Leu479Pro, p.Leu656Val, p.Gly660Arg, and p.Arg668His) for MYO7A-associated low-frequency hearing loss. Patients identified in this study initially showed postlingual-onset mild-to-moderate low-frequency hearing loss; however, high-frequency hearing also deteriorated after the fourth decade, eventually leading to moderate-to-severe flat-type hearing loss. In addition, we performed haplotype analysis for the recurrent variant c.1436T>C:p.Leu479Pro identified in this study and found that this variant is a founder mutation in the Japanese population. Conclusions: In this study, we were able to clarify the specific features of MYO7A-related low-frequency hearing loss in a significant number of patients. In particular, we clarified the details of hearing deterioration at each frequency. Our findings will be useful for providing more appropriate treatment and follow-up for MYO7A-associated low-frequency hearing loss. Full article

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

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11 pages, 1081 KB

Open AccessArticle

A Genome-Wide Association Study on Calcium Nephrolithiasis in Chinese Han Population Identifies Novel Susceptible Loci at 4q35.1, 5q31.2 and 18q21.2

by Lujia Wang, Zijian Zhou, Xiaoling Lin, Kangcheng Luo, Peng Gao, Deke Jiang and Zhong Wu

Genes 2026, 17(3), 313; https://doi.org/10.3390/genes17030313 - 10 Mar 2026

Abstract

Background: Nephrolithiasis is a significant global health and economic challenge, with an increasing prevalence and a high recurrence rate. However, there is limited knowledge regarding the potential associations between calcium nephrolithiasis risk and Chinese Han populations currently. Methods: To identify the [...] Read more.

Background: Nephrolithiasis is a significant global health and economic challenge, with an increasing prevalence and a high recurrence rate. However, there is limited knowledge regarding the potential associations between calcium nephrolithiasis risk and Chinese Han populations currently. Methods: To identify the genetic factors for calcium nephrolithiasis, we presented a genome-wide association study (GWAS) using a total of 1006 calcium nephrolithiasis cases and 1200 controls of Chinese Han ethnicity. Suggestive loci (p < 1.0 × 10⁻⁶) were replicated in 445 cases and 1008 controls. We also assessed the association of GWAS-level significant single-nucleotide polymorphisms (SNPs) with quantitative traits, including metabolic, kidney-related, and electrolyte traits. Results: Here we found three novel loci for calcium nephrolithiasis: SORBS2 on 4q35.1 (rs3736194; p = 2.84 × 10⁻¹³, OR = 0.6279), CXXC5 on 5q31.2 (rs356450; p = 6.09 × 10⁻¹⁶, OR = 2.0312), and MBD2 on 18q21.21 (rs55826947; p = 6.29 × 10⁻¹⁰, OR = 0.6017). Subsequent analyses revealed the association of SNP rs3736194 with higher serum carbon dioxide (p = 0.04666), rs356450 with lower serum chloride (p = 0.02992), and rs55826947 with higher BMI (p = 0.03174), respectively. Conclusions: We performed the first GWAS on calcium nephrolithiasis in a Chinese Han population cohort and identified three novel susceptibility loci on 4q35.1, 5q31.2, and 18q21.2. Further research into the molecular mechanisms underlying these variations in nephrolithiasis is warranted. Full article

(This article belongs to the Special Issue Advancing Nephrogenetics: Diagnosis, Genetic Testing, and Treatment Innovations)

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21 pages, 8574 KB

Open AccessArticle

The Complete Mitochondrial Genomes of Two Octopi of the Western Pacific Ocean, Japetella diaphana and Amphitretus pelagicus (Cephalopoda: Amphitretidae), and Their Phylogenetic Position Within Amphitretidae

by Michel Murwanashyaka, Lihua Jiang, Liyi Pei and Bilin Liu

Genes 2026, 17(3), 312; https://doi.org/10.3390/genes17030312 - 10 Mar 2026

Abstract

Background/Objectives: A comprehensive analysis of the mitochondrial genomes of Japetella diaphana and Amphitretus pelagicus was conducted to investigate their genomic composition, gene size, sequence characteristics, and phylogenetic positioning within the Amphitretidae family. Methods: A rigorous phylogenetic analysis was performed utilizing a dataset comprising [...] Read more.

Background/Objectives: A comprehensive analysis of the mitochondrial genomes of Japetella diaphana and Amphitretus pelagicus was conducted to investigate their genomic composition, gene size, sequence characteristics, and phylogenetic positioning within the Amphitretidae family. Methods: A rigorous phylogenetic analysis was performed utilizing a dataset comprising 13 protein-coding genes, two ribosomal RNAs, and 22 transfer RNAs derived from 26 cephalopod mitochondrial genomes, representing 25 species across seven families, Vampyroteuthidae, Tremoctopodidae, Octopodidae, Enteroctopodidae, Bolitaenidae, Argonautidae, and Amphitretidae, along with outgroup Nautilus macromphalus. Results: Notably, both focal species demonstrated a pronounced adenine–thymine bias in their mitochondrial genomes, with A. pelagicus exhibiting gene rearrangements and two extensive non-coding regions. The analysis, employing both the maximum likelihood and Bayesian inference methodologies, revealed a monophyletic relationship between Bolitaenidae and Vitreledonellidae, as well as a sister taxon relationship between Amphitretidae and Tremoctopodidae. The majority of species were classified into the Amphitretidae and Bolitaenidae clades, with numerous species exhibiting close phylogenetic relationships. Conclusions: This study provides novel insights into the evolutionary relationships within Octopodiformes, underscoring the significance of mitochondrial genome data in resolving phylogenetic relationships among cephalopods. The findings contribute to our understanding of the evolutionary history of octopi and pose implications for their classification and conservation. Furthermore, the results underscore the necessity for continued research into the evolutionary relationships among cephalopod taxa. Full article

(This article belongs to the Special Issue Feature Papers in the Population and Evolutionary Genetics and Genomics Field 2026)

12 pages, 27905 KB

Open AccessArticle

Knocking Down miR172f in the Hairy Roots of Grass Pea Increases β-ODAP Content and Induces Global Transcriptomic Reprogramming

by Xiaoning Liu, Xueping Zhang, Jianmeng Bai, Jiasheng Lv, Yingshan Jiang, Jiahui Zhan, Zhihong Yang, Rongze Han, Tingli You, Hao Ma, Ning Cao, Rongfang Lian, Shijun Wang, Yun Yue and Quanle Xu

Genes 2026, 17(3), 311; https://doi.org/10.3390/genes17030311 - 9 Mar 2026

Abstract

Background: There is an abundance of the neuroactive β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) in grass pea (Lathyrus sativus), pea (Pisum sativum), and several Chinese traditional herbs such as Panax notoginseng. It is well known for its dose- and context-dependent [...] Read more.

Background: There is an abundance of the neuroactive β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) in grass pea (Lathyrus sativus), pea (Pisum sativum), and several Chinese traditional herbs such as Panax notoginseng. It is well known for its dose- and context-dependent effects on its toxicological characteristics (inducing neurodegenerative neurolathyrism upon excessive consumption) or for its pharmacological effects (including neuroprotection and wound healing). Therefore, reducing β-ODAP levels improves the safety profile of β-ODAP-containing species for utilization, whereas increasing them facilitates their isolation and purification. LsBAHD3 acyltransferase, named after the first letter of BEAT benzylalcohol O-acetyltransferase (BEAT), anthocyanin O-hydroxycinnamoyltransferase (AHCT), anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT), and deacetylvindoline 4-Oacetyltransferase (DAT), was proven to be β-ODAP synthetase. Methods: In this report, the interaction of miR172f with LsBAHD3 was investigated through bioinformatic analysis and transient co-expression assays in Nicotiana benthamiana. Functions of miR172f in β-ODAP biosynthesis were also investigated through knockdown in the hairy roots of L. sativus and via transcriptomic analysis. Results: The results suggest that the knockdown of miR172f in hairy roots of L. sativus increased β-ODAP content via targets to LsBAHD3. In this process, protein ubiquitination, cysteine and methionine metabolism, enzyme regulator activity, and so on were associated with β-ODAP biosynthesis. Conclusions: These results identify miR172f as a novel regulator of β-ODAP biosynthesis through targeting of LsBAHD3, offering new insight into the gene expression of β-ODAP synthetase and the genetic network governing β-ODAP biosynthesis in L. sativus. Full article

(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Crop Resistance)

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23 pages, 7986 KB

Open AccessArticle

Leveraging Spot–Gene Heterogeneous Graphs for Unified Spatially Resolved Transcriptomics Domain Detection on Single-Slice and Multi-Slice Data

by Lina Xia, Zhenyue Ding, Xun Zhang, Kun Qian and Hongwei Li

Genes 2026, 17(3), 310; https://doi.org/10.3390/genes17030310 - 7 Mar 2026

Abstract

Background: Spatially resolved transcriptomics (SRT) enables simultaneous measurement of gene expression and spatial location, but the existing domain detection methods are limited by over-reliance on spot-to-spot proximity, rigid pre-alignment requirements for multi-slice datasets, and inadequate mitigation of batch effects. This study aims [...] Read more.

Background: Spatially resolved transcriptomics (SRT) enables simultaneous measurement of gene expression and spatial location, but the existing domain detection methods are limited by over-reliance on spot-to-spot proximity, rigid pre-alignment requirements for multi-slice datasets, and inadequate mitigation of batch effects. This study aims to develop a unified method for accurate spatial domain identification across both single-slice and multi-slice SRT datasets. Methods: We propose a novel method named spatially resolved transcriptomics heterogeneous graph contrastive learning (stHGCL), which integrates a spot–gene heterogeneous graph, a dual-stage encoder (comprising LightGCN and GCN), and a neighborhood-driven contrastive learning module. The heterogeneous graph captures high-order structural information through spot–gene connections mediated by shared genes; the dual-stage encoder refines spot embeddings by fusing gene expression and spatial location; contrastive learning enhances intra-cluster compactness and mitigates batch effects. Results: stHGCL was validated on seven benchmark datasets from platforms including 10x Visium, BaristaSeq, STARmapSeq, Slide-seq, and Stereo-seq. It outperformed nine single-slice and eight multi-slice state-of-the-art methods. It achieved the highest mean Adjusted Rand Index (ARI) and Normalized Mutual Information (NMI) scores and could accurately delineate complex spatial domains with distinct boundaries, and even achieved cross-slice spatial domain detection for unaligned multi-slice datasets. Ablation studies confirmed the effectiveness of its main modules. Conclusions: stHGCL effectively captures high-order structural and spatial information and mitigates batch effects. It provides a robust scalable solution for unified spatial domain detection in SRT, facilitating insights into the spatial domains across both single-slice and multi-slice experimental paradigms. Full article

(This article belongs to the Section Bioinformatics)

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13 pages, 1711 KB

Open AccessArticle

Short-Term Epigenetic Responses of Pinus brutia to Fire Stress: Insights from a Prescribed Burning in Greece

by Evangelia V. Avramidou, Evangelia Korakaki, Nikolaos Oikonomakis and Miltiadis Athanasiou

Genes 2026, 17(3), 309; https://doi.org/10.3390/genes17030309 - 5 Mar 2026

Abstract

Background/Objectives: Fire is a dominant ecological force in Mediterranean ecosystems, shaping the adaptive traits of forest species such as Pinus brutia. Prescribed burning (also called controlled burning) is the intentional, carefully planned use of fire under specific environmental conditions to manage [...] Read more.

Background/Objectives: Fire is a dominant ecological force in Mediterranean ecosystems, shaping the adaptive traits of forest species such as Pinus brutia. Prescribed burning (also called controlled burning) is the intentional, carefully planned use of fire under specific environmental conditions to manage vegetation and reduce wildfire risk. While morphological and physiological fire adaptations are well-documented, emerging evidence highlights the role of epigenetic mechanisms—such as DNA methylation and histone modifications—in mediating stress responses. Methods: This study investigates genome-wide epigenetic changes in P. brutia following a prescribed burning experiment on Chios Island, Greece. Using methylation-sensitive amplified polymorphism (MSAP) analysis, we compared temporal shifts on epigenetic profiles before and after fire exposure extracting DNA from the same trees. Results: A significant increase in polymorphic epiloci, epigenetic diversity indices, and private epigenetic bands after prescribed burning was revealed, suggesting a stress-induced reprogramming of the epigenome. Concurrent measurements of midday needle water potential indicated an exploratory association between water stress and epigenetic shifts. Furthermore, Fireline Intensity (FI) correlated with epigenetic diversity index signaling an immediate response of the tree. Conclusions: These findings support the hypothesis that fire stress induces epigenetic responses in P. brutia, potentially enhancing resilience to future environmental challenges. Further research is required to address the level of heritability of these epigenetic changes in next generation and connect these indexes with adaptation and sustainability of forest ecosystems. Full article

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

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18 pages, 8682 KB

Open AccessArticle

Elucidation of Response Mechanism of Potato to Nitrogen Stress by Physiological and Transcriptional Analyses

by Kaixin Ding, Ying Shan, Lichun Wang, Jiling Song, Mengping Yang, Yong Zhang, Lei Wang, Xuhong Sun, Mingxue Li, Guokui Tian, Fengyun Li and Haiyan Wang

Genes 2026, 17(3), 308; https://doi.org/10.3390/genes17030308 - 5 Mar 2026

Abstract

Background/Objectives: Nitrogen, as an indispensable macroelement for plants, is essential for tuber development. The objective of the present study was to ascertain the key factors underlying nitrogen regulation of potato tuber formation. Methods: The potato variety Kexin 37 was used as the material, [...] Read more.

Background/Objectives: Nitrogen, as an indispensable macroelement for plants, is essential for tuber development. The objective of the present study was to ascertain the key factors underlying nitrogen regulation of potato tuber formation. Methods: The potato variety Kexin 37 was used as the material, and nitrogen deficiency, normal nitrogen level and excessive nitrogen level were employed as treatments, respectively. The response of potato tuber formation to nitrogen was systematically analyzed from the perspective of physiology and transcriptomics. Results: Nitrogen deficiency led to the thickening of the cell wall and plasma membrane, an increase in intercellular space and a decrease in mitochondria in the stolon. The plant height, chlorophyll content, dry matter quality and nitrogen accumulation were significantly reduced, and the number of tubers per plant, tuber weight per plant and commodity rate were significantly reduced. Excessive nitrogen application resulted in late maturity of plants and excessive formation of small potatoes. Transcriptome analysis revealed that differentially expressed genes related to nitrogen stress were mainly enriched in pathways associated with material transport, cell division and carbohydrate metabolism. In addition, there are a series of hub genes in response to nitrogen stress, including polyubiquitin-like, auxin response factor 7-like and protein RRP6-like 2. By constructing a co-expression network, transcription factors (TFs) such as C2H2, WRKY and ARF are involved in regulating tuber formation. Conclusions: The present study constitutes an investigation into the identification of hub genes and potential pathways associated with the formation of potato tubers under varying nitrogen conditions. It provides new insights for further study on enhancing nitrogen use efficiency in potato. Full article

(This article belongs to the Special Issue Plant Responses to Abiotic Stress: Genetics, Transcription, Noncoding RNAs, and Epigenetics)

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8 pages, 1277 KB

Open AccessBrief Report

A Nanopore-Only Assembly of a Nuclear and Mitochondrial Genome of a Red Coachwhip (Masticophis flagellum piceus)

by Alan F. Scott and David W. Mohr

Genes 2026, 17(3), 307; https://doi.org/10.3390/genes17030307 - 4 Mar 2026

Abstract

We report a chromosome-level assembly of a male red coachwhip snake (Masticophis flagellum piceus) generated exclusively with nanopore sequencing. Using Hifiasm-ONT for assembly and RagTag for scaffold polishing, we produced a 1.61 Gb nuclear genome comprising 8 macrochromosomes and 10 microchromosomes [...] Read more.

We report a chromosome-level assembly of a male red coachwhip snake (Masticophis flagellum piceus) generated exclusively with nanopore sequencing. Using Hifiasm-ONT for assembly and RagTag for scaffold polishing, we produced a 1.61 Gb nuclear genome comprising 8 macrochromosomes and 10 microchromosomes with a 97.7% BUSCO completeness score. Annotation with LiftOn found 19,832 loci, including 18,025 protein-coding genes. The mitochondrial genome, assembled with MitoHiFi and annotated with MitoFinder, was 17,119 bp with 13 coding genes, 22 tRNAs and 2 rRNAs. All sequencing was performed in a simulated mobile laboratory using a portable sequencer and a laptop with analyses done both locally and remotely. These results highlight the feasibility of decentralized genomics and its potential to accelerate biodiversity research globally. Full article

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

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25 pages, 1608 KB

Open AccessArticle

Forensic Validation of the 95K SNP Panel and the Parabon Fx Forensic Analysis Platform for Identification of US Military Unknowns Using Extended Kinship Inference

by Jacqueline Tyler Thomas, Courtney L. Cavagnino, Kimberly Sturk-Andreaggi, Ellen M. Greytak, Julie A. Demarest, Suzanne M. Barritt-Ross, Timothy P. McMahon and Charla Marshall

Genes 2026, 17(3), 306; https://doi.org/10.3390/genes17030306 - 3 Mar 2026

Abstract

Background/Objectives: To identify US military unknowns, the Armed Forces Medical Examiner System’s Armed Forces DNA Identification Laboratory has historically relied upon mitochondrial DNA and Y-chromosomal short tandem repeat testing. Where no appropriate family reference sample (FRS) is available or skeletal samples are degraded, [...] Read more.

Background/Objectives: To identify US military unknowns, the Armed Forces Medical Examiner System’s Armed Forces DNA Identification Laboratory has historically relied upon mitochondrial DNA and Y-chromosomal short tandem repeat testing. Where no appropriate family reference sample (FRS) is available or skeletal samples are degraded, autosomal single nucleotide polymorphism (SNP) testing with next-generation sequencing could assist. Methods: A method utilizing hybridization capture enrichment of a 95,000 (95K) SNP panel, amenable to FRS and extremely challenging samples, was validated. The Parabon Fx Forensic Analysis Platform was used for analysis and extended kinship inference. Skeletal samples (n = 65) and associated FRS (n = 64) were selected for a performance evaluation and case-type sample study. Results: Considering FRS with ≥7 ng DNA input into library preparation, 94% yielded ≥66,320 SNPs at ≥5X coverage. SNP recovery for skeletal samples at ≥1X coverage ranged from 5 to 94,197 SNPs, averaging 40,770 SNPs. When skeletal samples resulted in ≥13,000 SNPs, the most likely relationship category was consistent with the expected relationship. A log10 likelihood ratio of ≥4 and a posterior probability of ≥99.99% were established as thresholds for strong statistical support, and 87% of inferences met these thresholds while 13% were considered inconclusive. Pairwise kinship inference between unrelated individuals yielded an unrelated result in 85% of comparisons, 66% with strong statistical support. There were 170 instances of false positive 4th degree relationship inferences with strong statistical support. All false positives involved skeletal samples from individuals of admixed ancestry. Conclusions: With this approach, autosomal SNP testing can result in reliable kinship inferences between related individuals out to 3rd, and in some cases 4th, degree relationships, increasing the scope of eligible FRS to aid in identifications. Full article

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

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19 pages, 2029 KB

Open AccessArticle

MicroRNA–Gene Networks Distinguish Hormone Receptor Status in HER2-Low Breast Cancer: An Integrative Transcriptomic Analysis

by Eduarda Carvalho, Andreia Brandão, Fernando Schmitt and Nuno Vale

Genes 2026, 17(3), 305; https://doi.org/10.3390/genes17030305 - 3 Mar 2026

Abstract

Background: HER2-low breast cancer is a biologically heterogeneous subgroup in which hormone receptor (HR) expression critically shapes prognosis and treatment, but the underlying regulatory mechanisms remain unclear. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may contribute to HR heterogeneity. This [...] Read more.

Background: HER2-low breast cancer is a biologically heterogeneous subgroup in which hormone receptor (HR) expression critically shapes prognosis and treatment, but the underlying regulatory mechanisms remain unclear. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may contribute to HR heterogeneity. This study aimed to identify deregulated miRNAs and associated gene networks distinguishing HER2-low/HR-positive from HER2-low/HR-negative tumors, elucidating the molecular mechanisms underlying this divergence. Methods: Differential expression analyses of miRNAs and genes were performed using Wilcoxon tests and DESeq2 (|log₂FC| > 1; FDR-adjusted p-value < 0.05). Survival analyses were conducted using Cox proportional hazards models to evaluate the individual miRNAs and miRNA signature. Functional enrichment analyses, including GO, KEGG and Reactome pathways, were performed. Correlation analysis and the miRNA target prediction were integrated to identify regulatory interactions. Results: Comparisons between HER2-low/HR-positive and HER2-low/HR-negative tumors identified 165 significantly deregulated miRNAs and 170 strongly deregulated genes. Intersection analysis highlighted miR-9-5p, miR-532-5p and miR-576-5p as specifically associated with HR-negative status. Survival analyses showed non-significant trends for the overall survival and progression-free interval. Functional enrichment analysis revealed hormone-related pathways in HR-positive tumors and immune, inflammatory and proliferative pathways in HR-negative tumors. Integrative correlation and target prediction analyses identified two miRNA–mRNA regulatory axes, miR-576-5p/TGFBI and miR-9-5p/POU2F2. Conclusions: Our study demonstrated that HER2-low breast cancer exhibits distinct miRNA and gene expression profiles, which highlight different transcriptomic profiles according to HR status for the first time. Specific miRNA–gene networks may drive transcriptional heterogeneity, serving as potential biomarkers for stratification and as therapeutic targets. These findings provide insight into the molecular basis of HER2-low tumor diversity and support future development of HR-directed therapeutic strategies. Full article

(This article belongs to the Section RNA)

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18 pages, 1946 KB

Open AccessReview

Non-Coding RNA: Architects of Cellular Complexity and Agents of Malignancy

by Amil Shah

Genes 2026, 17(3), 304; https://doi.org/10.3390/genes17030304 - 2 Mar 2026

Abstract

Non-coding RNAs (ncRNAs) are conserved in the genome of cells across the three domains of life. They comprise a diverse group that are particularly prominent in metazoans where they provide a crucial interface between genes and proteins, participating in key cellular processes at [...] Read more.

Non-coding RNAs (ncRNAs) are conserved in the genome of cells across the three domains of life. They comprise a diverse group that are particularly prominent in metazoans where they provide a crucial interface between genes and proteins, participating in key cellular processes at different levels: from control of DNA transcription to modulation of messenger RNA stability to modification of protein activity. The interactions of ncRNAs with one another as well as with other RNAs, DNA and proteins form the basis of a genome-wide regulatory network (GRN). Because of the mutual influence of its components on each other, the GRN is a dynamic system. Further, the GRN imposes constraints on which genes are expressed and when, leading to specific gene-expression patterns or transcriptomes. The configurations of the activities of all gene loci represent self-stabilizing cell states, referred to as “attractor” states, each of which corresponds to a distinct cell type. The cancer cell is also an attractor state that arises from a change in the topography of the epigenetic landscape caused by dysregulation of the GRN. It is proposed that the transition to a neoplastic attractor state is caused by ncRNA alterations, while subsequent somatic mutations of oncogenes and tumor suppressor genes drive cell proliferation and clonal expansion. Full article

(This article belongs to the Special Issue The Role of Non-Coding RNA in Cancer)

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31 pages, 1995 KB

Open AccessReview

Profiling Soil–Plant–Microbial Communities: DNA and Multi-Omics Techniques

by Shunlei Li, Claudia Chiodi, Carmelo Maucieri, Maria Cristina Della Lucia, Giulia Zardinoni, Samathmika Ravi, Andrea Squartini, Giuseppe Concheri, Gui Geng, Yuguang Wang and Piergiorgio Stevanato

Genes 2026, 17(3), 303; https://doi.org/10.3390/genes17030303 - 2 Mar 2026

Abstract

Interactions among plant roots, soil, and microorganisms in the rhizosphere regulate nutrient cycling, plant health, and ecosystem resilience. Recent advances in DNA sequencing and multi-omics are contributing to a shift from primarily descriptive surveys toward more mechanistic and predictive frameworks. This review synthesizes [...] Read more.

Interactions among plant roots, soil, and microorganisms in the rhizosphere regulate nutrient cycling, plant health, and ecosystem resilience. Recent advances in DNA sequencing and multi-omics are contributing to a shift from primarily descriptive surveys toward more mechanistic and predictive frameworks. This review synthesizes methodological developments and conceptual insights spanning microbial ecology, functional genomics, and agricultural applications. We first summarize DNA-based approaches—marker-gene sequencing, shotgun metagenomics, and quantitative nucleic acid assays—and then complementary omics layers, including metatranscriptomics, metaproteomics, metabolomics, epigenomics, ionomics, and phenomics. We next outline computational advances in data integration, network modeling, and visualization that help represent complex multi-layered datasets as biologically interpretable systems. Applications relevant to climate resilience and sustainable agriculture are discussed, including the design of synthetic microbial communities, the identification of biomarkers for soil health and stress tolerance, and case studies in which rhizosphere multi-omics informs crop breeding and soil management strategies. Overall, these developments underscore the potential of treating microbes as functional and, to some extent, manageable components of the plant holobiont. Looking ahead, we identify key research gaps involving standardized workflows, cross-scale causal inference, and real-time monitoring pipelines that integrate molecular diagnostics with remote sensing and edge–cloud analytics. By linking ecological mechanisms with translational practice, multi-omics frameworks may support the development of more sustainable, data-driven agriculture that better aligns productivity with environmental stewardship. Full article

(This article belongs to the Special Issue Harnessing Multi-Omics Approaches to Unravel Plant–Microbe Interactions in Cultivated Plants: Implications for Climate Resilience and Sustainable Agriculture)

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18 pages, 898 KB

Open AccessArticle

Transcriptional Modulation of Infertility-Associated Genes Following Chlamydia trachomatis Infection in Human Fallopian Tube Mesenchymal Cells: In Silico Study

by Rafaela Rodrigues, Carlos Sousa and Nuno Vale

Genes 2026, 17(3), 302; https://doi.org/10.3390/genes17030302 - 1 Mar 2026

Abstract

Background/Objectives: Chlamydia trachomatis (CT) infection is one of the most prevalent sexually transmitted infections (STIs) worldwide and has been consistently associated with adverse reproductive outcomes, including female infertility. However, the molecular mechanisms underlying this association remain incompletely understood. This study aimed to [...] Read more.

Background/Objectives: Chlamydia trachomatis (CT) infection is one of the most prevalent sexually transmitted infections (STIs) worldwide and has been consistently associated with adverse reproductive outcomes, including female infertility. However, the molecular mechanisms underlying this association remain incompletely understood. This study aimed to investigate whether genes previously associated with female infertility display altered expression patterns in response to CT infection by reanalyzing publicly available transcriptomic data derived from a human in vitro infection model. Methods: An integrative in silico approach was employed. A curated list of 106 genes associated with female infertility was compiled from publicly available databases and integrated with transcriptomic data from the Gene Expression Omnibus (GEO) dataset GSE109428, which profiles primary human fallopian tube mesenchymal cells infected in vitro with CT serovar L2. Gene expression changes were evaluated at two time points (24 and 48 h post-infection) by comparing infected cells with uninfected control samples, followed by functional and phenotype enrichment analyses. Results: One female infertility-associated gene (AKAP12) was consistently dysregulated at both 24 and 48 h post-infection. In addition, fourteen genes (ANAPC4, BMP1, BNC2, BTG4, EFHD1, FBXO43, INHBB, PATL2, SCARB1, SND1, SYNE1, TRIP13, TTC28, and TUBA1C) became significantly dysregulated exclusively at 48 h post-infection, indicating a time-dependent host transcriptional response to CT infection. Functional and phenotype enrichment analyses revealed associations with biological processes related to embryonic development and meiosis, as well as phenotypes linked to female infertility. These enriched terms were supported by a small subset of genes and were therefore interpreted cautiously. Conclusions: Overall, these findings suggest that CT infection modulates the expression of several infertility-associated genes and may influence biological pathways critical for female reproductive function. While exploratory, this study provides a molecular context that aligns with previously reported associations between CT infection and female infertility. Full article

(This article belongs to the Section Bioinformatics)

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26 pages, 5140 KB

Open AccessReview

DNA Methylation Dynamics in Plant Abiotic Stress Response: Mechanisms, Memory, and Breeding Applications

by Huanqing Huang, Chenyu Guo, Shiping Cheng and Zhe Wang

Genes 2026, 17(3), 301; https://doi.org/10.3390/genes17030301 - 28 Feb 2026

Abstract

Abiotic stresses such as drought, salinity, extreme temperatures, and heavy metal contamination severely limit global crop productivity and threaten food security. Plants have evolved epigenetic strategies, particularly DNA methylation, to perceive, adapt to, and memorize environmental challenges. This review systematically elucidates the dynamic [...] Read more.

Abiotic stresses such as drought, salinity, extreme temperatures, and heavy metal contamination severely limit global crop productivity and threaten food security. Plants have evolved epigenetic strategies, particularly DNA methylation, to perceive, adapt to, and memorize environmental challenges. This review systematically elucidates the dynamic regulatory mechanisms of DNA methylation—including establishment via RNA-directed DNA methylation (RdDM), maintenance by methyltransferases (MET1, CMT), and active removal by demethylases (ROS1)—in plant responses to diverse abiotic stresses. We highlight how stress-induced methylation reprogramming modulates gene expression, chromatin states, and physiological adaptations, contributing to both somatic and transgenerational stress memory. Furthermore, we discuss advanced detection technologies for profiling methylation patterns and evaluate their applications in epigenetic breeding, such as exploiting heritable epialleles, RdDM-based gene silencing, and methylation markers for heterosis prediction. Despite significant progress, translating epigenetic insights into predictable breeding tools remains challenging. Future efforts should focus on establishing causal links between methylation changes and stress phenotypes, improving epigenome editing precision, and integrating multi-omics approaches for the development of climate-resilient crops. This work provides a comprehensive epigenetic perspective for enhancing crop adaptability and sustainable agriculture. Full article

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

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23 pages, 4585 KB

Open AccessArticle

Genetic Diversity and Collection Structure Studies of Sesame (Sesamum indicum L.) Accessions Across Ethiopian Research Centers

by Feyisa Bejiga Gelashe, Arsénio D. Ndeve, Temesgen M. Menamo, Harish Gandhi and Rogério M. Chiulele

Genes 2026, 17(3), 300; https://doi.org/10.3390/genes17030300 - 28 Feb 2026

Abstract

Background/Objectives: Despite its economic importance, the genome-wide genetic diversity of sesame germplasm conserved in the Ethiopian national ex situ collection, a proposed center of origin, remains inadequately characterized. This study assessed genome-wide genetic diversity and population structure in 188 sesame accessions from six [...] Read more.

Background/Objectives: Despite its economic importance, the genome-wide genetic diversity of sesame germplasm conserved in the Ethiopian national ex situ collection, a proposed center of origin, remains inadequately characterized. This study assessed genome-wide genetic diversity and population structure in 188 sesame accessions from six Ethiopian Agricultural Research Centers using DArTSeq-based SNP markers. Methods: After quality filtering, 5163 high-quality markers were retained from the original set of 12,302 SNPs. Mean expected heterozygosity (He = 0.201) exceeded observed heterozygosity (Ho = 0.193), reflecting sesame’s predominantly self-pollinating nature. Results: The SNPs showed a transition/transversion ratio of 1.17:1 and an uneven distribution across 16 linkage groups. STRUCTURE, PCA, DAPC, and neighbor-joining cluster analyses revealed a clear hierarchical population structure with distinct clusters and varying admixture. Accessions from Assosa (AARC) and Bako (BARC) were genetically uniform, whereas Werer (WARC) and Gambella (GaARC) were major diversity reservoirs, exhibiting high heterozygosity and gene diversity. Pairwise FST values ranged from 0.001 to 0.356, and AMOVA indicated that 30–43% of variation occurred among collections and 57–70% within collections, highlighting substantial intra-collection diversity. Conclusions: The findings highlight that specific research centers were identified as key sources of genetic variation for breeding, conservation, and association mapping to enhance the improvement in agronomic and adaptive traits in sesame for the Ethiopian sesame gene pool. Full article

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

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10 pages, 1372 KB

Open AccessArticle

Characterization of a Familial Goldenhar Syndrome Case Using Whole-Exome Sequencing

by Yosra Bejaoui, Yasser Al-Sarraj, Jana Al-Hage, Fadi F. Bitar, Nady El Hajj, Georges Nemer and Mazen Kurban

Genes 2026, 17(3), 299; https://doi.org/10.3390/genes17030299 - 28 Feb 2026

Abstract

Background: Goldenhar syndrome (oculo–auriculo–vertebral spectrum, OAVS) is a rare congenital disorder characterized by craniofacial malformations, systemic anomalies, and significant phenotypic variability. Although it is the second most common craniofacial malformation after a cleft palate, the genetic etiology of Goldenhar syndrome remains largely unexplored. [...] Read more.

Background: Goldenhar syndrome (oculo–auriculo–vertebral spectrum, OAVS) is a rare congenital disorder characterized by craniofacial malformations, systemic anomalies, and significant phenotypic variability. Although it is the second most common craniofacial malformation after a cleft palate, the genetic etiology of Goldenhar syndrome remains largely unexplored. This study aimed to identify genetic variants contributing to Goldenhar syndrome in a Lebanese family with three affected individuals, using whole-exome sequencing and complementary genomic approaches. Methods: Whole-exome sequencing was performed on the nuclear family to identify variants associated with the syndrome. Complementary DNA methylation and gene ontology analyses were conducted to explore epigenetic modifications. Results: A missense shared variant in the MID1 between the affected individuals [NP_000372.1): p. Ile593Phe] gene was observed in the family, while current ACMG evidence was insufficient to establish causality. Additional variants were identified, including a de novo mutation in FBXW11 and a rare frameshift alteration in NDUFAF8, with limited segregation, implicating these genes in associated phenotypes such as craniofacial anomalies and cardiac defects. DNA methylation analysis revealed hypomethylation at CpG sites within the ZC3H3 gene, suggesting an epigenetic contribution to disease variability. Conclusions: Our findings underscore the genetic and epigenetic complexity of Goldenhar syndrome, providing new insights into its molecular etiology and highlighting the challenges of variant interpretation in familial cases of rare congenital disorders. Full article

(This article belongs to the Special Issue Genes and Pediatrics)

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21 pages, 1921 KB

Open AccessReview

From High-Density Genomic Mapping to Precision Molecular Breeding: A Comprehensive Review of Capsicum Genomic Resources

by Luyao Wang, Junhu Kan, Weiting Zhong, Shuo Zhang, Yanghe Zhao, Yingke Hou, Luke R. Tembrock, Xiaolin Gu and Yan Cheng

Genes 2026, 17(3), 298; https://doi.org/10.3390/genes17030298 - 28 Feb 2026

Abstract

The genus Capsicum comprises several species that are vital vegetable and spice crops cultivated worldwide, possessing significant economic, nutritional, and ornamental value due to their diverse fruit morphologies, colors, spiciness levels, and stress resistance. Historically, the large genome size (approximately 3 Gb) and [...] Read more.

The genus Capsicum comprises several species that are vital vegetable and spice crops cultivated worldwide, possessing significant economic, nutritional, and ornamental value due to their diverse fruit morphologies, colors, spiciness levels, and stress resistance. Historically, the large genome size (approximately 3 Gb) and high proportion of repetitive sequences (over 80% transposable elements) have constrained in-depth analysis of structural variations and functional genes within Capsicum species. However, recent advances in long-read sequencing, Hi-C scaffolding, and genome assembly have enabled the production of multiple high-quality and telomere-to-telomere (T2T) Capsicum genomes, which have ushered in a new era of research at the nuclear, organellar, and pan-genome levels. The publication of these omics resources has greatly expanded our understanding of the evolution of agronomically and environmentally relevant traits in peppers and their wild relatives. This review systematically summarizes recent progress in reference genomes, pan-genomes, and organellar genomes of the genus Capsicum, highlighting the enhancement of key breeding trait analyses through omics data, and outlines future integrated breeding strategies to provide theoretical and methodological references for genetic improvement and molecular breeding in pepper. Full article

(This article belongs to the Special Issue Genetic and Breeding Improvement of Horticultural Crops)

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17 pages, 3538 KB

Open AccessArticle

A Predictive Transcriptomic Approach to the Resveratrol-Mediated Reversal of Hypothalamic Alterations in a Mouse Model of Obesity

by Brenda De la Cruz-Concepción, Juan Miguel Mendoza-Bello, Fredy Omar Beltrán-Anaya, Mónica Ramírez, Yaccil Adilene Flores-Cortez, Gema Damian-Sánchez, Eugenia Flores-Alfaro, Isela Parra-Rojas, Oscar Del Moral-Hernández, Miguel Cruz and Mónica Espinoza-Rojo

Genes 2026, 17(3), 297; https://doi.org/10.3390/genes17030297 - 28 Feb 2026

Abstract

Background: Obesity is associated with hypothalamic dysfunction characterized by neuroinflammation and altered transcriptional programs. While resveratrol (RSV) has shown beneficial metabolic effects in peripheral tissues, its central effects on hypothalamic gene expression in obesity remain poorly understood. This study provides the first predictive [...] Read more.

Background: Obesity is associated with hypothalamic dysfunction characterized by neuroinflammation and altered transcriptional programs. While resveratrol (RSV) has shown beneficial metabolic effects in peripheral tissues, its central effects on hypothalamic gene expression in obesity remain poorly understood. This study provides the first predictive transcriptomic analysis of the hypothalamic response to RSV in a mouse model of diet-induced obesity. C57BL/6 male mice were fed a high-fat diet (HFD) to induce obesity and then subsequently treated with RSV. Methods: Hypothalamic RNA was extracted and analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified and functionally analyzed through KEGG pathway analysis. Results: Although RSV did not significantly alter body weight, it reversed the expression of several HFD-induced DEGs. Key genes modulated by RSV included Aqp7, Ccl27a, Lta, Rilp, M6pr-ps, C1ra, Snail1, Gbgt1, and Ppargc1b, which are involved in inflammation, lipid metabolism, mitochondrial function, and immune signaling. Pathway enrichment analysis revealed significant modulation of TNF and NF-κB signaling, cytokine–cytokine receptor interactions, glycosphingolipid biosynthesis, and phagosome-related activity. Remarkably, 45% of RSV-responsive transcripts were non-coding RNAs, suggesting epigenetic regulation. Conclusions: RSV reprograms the hypothalamic transcriptome in obesity, targeting both coding and non-coding RNAs associated with inflammation and metabolic regulation, independently of weight loss. These findings identify RSV as a potential central modulator of metabolic dysfunction and highlight the hypothalamus as a promising therapeutic target in obesity-related disease. Full article

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

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