Genes

29 pages, 1564 KB

Open AccessArticle

Genomic Selection in Rice Using Targeted Sequencing: Model Evaluation and Training Population Optimization for Breeding Applications

by Zaijie Chen, Leibo Pan, Yue Wang, Min Lin, Yan Lin, Mingji Wu, Huaqing Liu, Taijiao Hu, Shaohua Yang and Yana Song

Genes 2026, 17(10), 1240; https://doi.org/10.3390/genes17101240 - 8 Oct 2026

Abstract

Background/Objectives: Genomic selection (GS) can accelerate crop improvement, but its application in breeding programs is often constrained by the cost of high-density genotyping. This study evaluated genomic prediction using 4647 targeted sequencing-derived SNPs in 829 rice accessions and investigated the effects of prediction [...] Read more.

Background/Objectives: Genomic selection (GS) can accelerate crop improvement, but its application in breeding programs is often constrained by the cost of high-density genotyping. This study evaluated genomic prediction using 4647 targeted sequencing-derived SNPs in 829 rice accessions and investigated the effects of prediction model selection, population structure, training population optimization, and GWAS-assisted marker selection on predictive performance. Methods: Seventeen GS models were evaluated for eight agronomic traits using repeated five-fold cross-validation, cross-population prediction, STPGA-based training population optimization, and GWAS-derived marker subsets. Resaults: Predictive performance varied substantially among traits and models. For grain length (GL), EnsembleGS achieved the highest predictive performance among the 17 models (r = 0.838), while RKHS showed the highest performance for grain number per panicle (r = 0.698), RFR for heading date (r = 0.854), and EnsembleGS for length-to-width ratio (r = 0.844). Cross-population prediction generally resulted in lower predictive performance than within-population cross-validation, with substantial variation among transfer directions. STPGA retained substantial predictive performance with reduced training population sizes; for GL, the highest performance reached r = 0.800 with a 400-individual STPGA-selected training population. GWAS-guided marker prioritization also retained substantial predictive information after marker reduction. For GL, the highest performance reached r = 0.789 and 0.802 using the GWAS-Top500 and GWAS-Top1000 subsets, respectively, compared with 0.751 and 0.775 for the corresponding Random500 and Random1000 subsets. For length-to-width ratio, the corresponding values were r = 0.764 and 0.800 for GWAS-Top500 and GWAS-Top1000, compared with 0.727 and 0.783 for the random subsets. Conclusions: Integrating targeted sequencing with trait- and model-aware prediction, optimized training population design, and GWAS-guided marker prioritization can retain substantial genomic prediction performance while reducing marker and training population requirements, providing a potentially cost-effective framework for genomic selection in rice breeding. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Crop Genetic Improvement)

28 pages, 3030 KB

Open AccessArticle

Improving the Usability of Donor Data from Registries Using an Extreme Learning Machine Approach to Upgrade Low-/Mid- to High-Resolution HLA Data

by Stavros Kepentzis, Theofanis Chatzistamatiou, Jason Digalakis, Ourania Petropoulou, George K. Matsopoulos and Dimitrios Koutsouris

Genes 2026, 17(10), 1239; https://doi.org/10.3390/genes17101239 - 8 Oct 2026

Abstract

Background/Objectives: High-resolution Human Leukocyte Antigen (HLA) typing is required for unrelated donor selection, yet many registry records remain low- or intermediate-resolution. Haplotype frequency imputation is the standard remedy, but its accuracy decreases for rare haplotypes. Methods: A locus-specific Extreme Learning Machine (ELM) framework, [...] Read more.

Background/Objectives: High-resolution Human Leukocyte Antigen (HLA) typing is required for unrelated donor selection, yet many registry records remain low- or intermediate-resolution. Haplotype frequency imputation is the standard remedy, but its accuracy decreases for rare haplotypes. Methods: A locus-specific Extreme Learning Machine (ELM) framework, trained on the Greek national donor registry (n = 117,345), upgrades low-/intermediate-resolution genotypes and imputes untyped loci; output weights are solved analytically. It was validated on two independent Greek cohorts (n = 20,100; 4353) against GRIMM and two expectation maximization baselines, on the same donors. Results: Accuracy depended on the high-resolution context available (94% for HLA-A with four anchor loci; 19–22% with none) and on the posterior probability threshold (78–91% ORAM, 70–84% GRPT), while call rate fell from 98.1% to ~41%; the two cannot be maximized together. GRIMM called fewer donors (1.8–47.9%) at comparable or higher accuracy. Allele-vocabulary abridgment excluded 14–47% of external-cohort allele calls; stratified by vocabulary membership, ORAM accuracy was 94.2% for in-vocabulary donors and 73.7% for the rest. The training procedure has no convergence guarantee. Conclusions: ELM upgrading converts legacy registry data into probabilistic high-resolution calls, with registry-scale training completing in minutes. These calls can narrow donor searches but cannot substitute for confirmatory typing. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 1372 KB

Open AccessArticle

Histology-Stratified Clinical and Prognostic Associations of PDCD-Related Genes in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

by Seong-Tae Kim, Yunha Lee, Se-Young Yun, Jin-Woo Min, Eun-Chan Jeon, Se-Hyun Kim, Jin-Sub Yoo, Se-Jin Park, Ji-Hwan Jung, Jun-Chae Lee and Jae-Ho Lee

Genes 2026, 17(10), 1238; https://doi.org/10.3390/genes17101238 - 8 Oct 2026

Abstract

Background: The prognostic relevance of PDCD-related genes in non-small cell lung cancer remains uncertain. We examined PDCD2, PDCD4, PDCD5, PDCD10, and AVEN separately in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: Matched TCGA expression cohorts comprised [...] Read more.

Background: The prognostic relevance of PDCD-related genes in non-small cell lung cancer remains uncertain. We examined PDCD2, PDCD4, PDCD5, PDCD10, and AVEN separately in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: Matched TCGA expression cohorts comprised 492 LUAD and 484 LUSC tumors. Primary Cox models evaluated continuous expression per standard deviation using separate gene-specific models adjusted for age, sex, smoking history, and pathologic stage. Benjamini–Hochberg correction covered ten gene–histology tests. Proportional hazards, multicollinearity, model specification, and the incremental value of PDCD4 were assessed. GSE30219 provided 83 LUAD and 61 LUSC patients for unadjusted and clinically adjusted external analyses. Hallmark enrichment was evaluated using legacy RSEM expression and a STAR TPM sensitivity analysis. Results: The primary TCGA models included 469 LUAD patients with 167 deaths and 467 LUSC patients with 205 deaths. AVEN was associated with poorer LUAD survival after correction (HR 1.272, 95% CI 1.091–1.483; q = 0.022). PDCD4 was not significant in the primary LUAD model (HR 0.875, 95% CI 0.749–1.021; q = 0.150). Adding PDCD4 to clinical variables yielded a C-index increase of 0.014 (bootstrap 95% CI −0.004 to 0.031). No adjusted external association survived correction. PDCD4-associated enrichment differed between expression pipelines. Conclusions: AVEN showed an exploratory adverse association in TCGA LUAD, but external prognostic replication was not established. These analyses do not support a robust independent prognostic claim for PDCD4 or the clinical use of any of the five evaluated genes. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancer Diagnosis, Prognosis and Therapy)

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6 pages, 162 KB

Open AccessEditorial

15th Anniversary of Genes: Advances and Perspectives in Neurogenetics and Neurogenomics

by Claudia Ricci

Genes 2026, 17(10), 1237; https://doi.org/10.3390/genes17101237 - 8 Oct 2026

Abstract

The 15th anniversary of Genes, alongside the 10th anniversary of its initial Impact Factor, marks a significant milestone in reflecting on the remarkable advancements in the field of human molecular genetics [...] Full article

(This article belongs to the Special Issue 15th Anniversary of Genes: Feature Papers in “Neurogenetics and Neurogenomics”)

2 pages, 120 KB

Open AccessEditorial

Editorial: “Next-Generation Sequencing in Rare Genetic Diseases”

by Edoardo Errichiello and Paola Dimartino

Genes 2026, 17(10), 1236; https://doi.org/10.3390/genes17101236 - 8 Oct 2026

Abstract

Rare genetic diseases (RGDs) affect more than 300–400 million people worldwide [...] Full article

(This article belongs to the Special Issue Next-Generation Sequencing in Rare Genetic Diseases)

13 pages, 693 KB

Open AccessReview

Research Progress on the Application of Nanopore Long-Read Sequencing Combined with DNA Methylation Marking in Complex Forensic Evidence

by Qiannan Xu, Xuanman Cui, Shuyan Mei, Haojie Qin, Zhe Zheng and Xiandun Zhai

Genes 2026, 17(10), 1235; https://doi.org/10.3390/genes17101235 - 7 Oct 2026

Abstract

Background In the analysis of complex forensic material evidence, conventional detection methods for highly degraded, trace, or mixed samples present several limitations, such as low typing success rates and limited information dimensions. Methods This study systematically examines the technical principles and compatibility of [...] Read more.

Background In the analysis of complex forensic material evidence, conventional detection methods for highly degraded, trace, or mixed samples present several limitations, such as low typing success rates and limited information dimensions. Methods This study systematically examines the technical principles and compatibility of nanopore long-read sequencing combined with DNA methylation profiling, identifies optimization strategies to enhance sensitivity for trace materials, improves accuracy in methylation site interpretation, for instance, NanoFreeLunch, without raw signals and using base quality/error patterns, reaching 0.97–0.99 correlation with benchmark regional methylation levels, and streamlines library preparation workflows while evaluating its practical efficacy through domestic and international case studies. Results The research demonstrates that this technology enables simultaneous acquisition of genomic sequences and epigenetic information, facilitating multidimensional identification—including personal identification, age estimation, and body fluid identification—even in highly degraded samples, with significantly higher site detection rates compared to traditional methods. Conclusions Future efforts should focus on standardizing the technology and developing specialized databases to further refine its application frameworks for forensic investigations, thereby providing robust technical support for complex forensic evidence analysis. Full article

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

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12 pages, 1414 KB

Open AccessArticle

Genetic Background of the Hetian Rose Inferred from SNPs in Single-Copy Nuclear Loci and Plastid Genomes

by Hui Wang, Mingwei Zhou and Yuee Xiao

Genes 2026, 17(10), 1234; https://doi.org/10.3390/genes17101234 - 6 Oct 2026

Abstract

Background/Objectives: The Hetian Rose (Rosa ‘Hetian’) is a locally important oil-bearing rose cultivar grown in Hetian, Xinjiang, China, but its genetic origin remains unclear. Methods: To clarify its genetic background, we sampled R. ‘Hetian’ together with 35 related Rosa species and [...] Read more.

Background/Objectives: The Hetian Rose (Rosa ‘Hetian’) is a locally important oil-bearing rose cultivar grown in Hetian, Xinjiang, China, but its genetic origin remains unclear. Methods: To clarify its genetic background, we sampled R. ‘Hetian’ together with 35 related Rosa species and cultivars and performed phylogenetic and genetic-structure analyses using 7478 SNPs in 1851 single-copy nuclear loci. We also reconstructed a plastid genome phylogeny to assess its maternal-lineage affinity. Results: In the nuclear SNP phylogeny, R. ‘Hetian’ was associated with European rose lineages rather than Chinese Hybrid Rugosa roses. Genetic-structure analyses indicated that R. ‘Hetian’ showed its strongest nuclear genomic affinity to Gallica roses, with weaker affinities to several other Eurasian lineages. In the plastid phylogeny, R. ‘Hetian’ clustered with Gallica and Alba roses, sect. Caninae, and European sect. Synstylae accessions. Conclusions: Together, these results indicate that the genetic background of R. ‘Hetian’ is closely related to European Old Garden Roses. A Gallica-related lineage may have made a major contribution to its genomic background. Historical genetic exchange with other Eurasian Rosa lineages may also have contributed to its present genomic composition. Full article

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

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14 pages, 1897 KB

Open AccessArticle

Clinical Utility of Broad-Panel Profiling in Non-Small Cell Lung Cancer: Pairwise Co-Mutational Gene Patterns and PD-L1 Associations Define Stage-Specific Prognosis

by Carolina Sassorossi, Elisa De Paolis, Jessica Evangelista, Davide Dalfovo, Alessandra Cancellieri, Ilenia Carriero, Annalisa Campanella, Esther G. C. Troost, Steffen Löck, Róza Ádány, Núria Farré, Ece Öztürk, Rocco Trisolini, Luca Boldrini, Alessio Stefani, Andrea Urbani, Emilio Bria, Stefano Margaritora, Angelo Minucci and Filippo Lococo

Genes 2026, 17(10), 1233; https://doi.org/10.3390/genes17101233 - 5 Oct 2026

Abstract

Objectives: Precision medicine has improved outcomes in advanced lung cancer, but its implementation remains limited. The prospective LANTERN project (NCT05802771) involves comprehensive clinical and multi-omics data collection. Here, we report preliminary genomic findings, focusing on the prognostic impact of gene mutations, pairwise co-mutational [...] Read more.

Objectives: Precision medicine has improved outcomes in advanced lung cancer, but its implementation remains limited. The prospective LANTERN project (NCT05802771) involves comprehensive clinical and multi-omics data collection. Here, we report preliminary genomic findings, focusing on the prognostic impact of gene mutations, pairwise co-mutational patterns, and their stage-specific association with PD-L1 analysis on patients speciments. Methods: This prospective, multicenter observational study enrolled 271 consecutive patients between March 2023 and December 2024, including 137 with stage I–III and 134 with stage IV disease. Comprehensive genomic profiling was performed using the TruSight Oncology 500 High Throughput assay to assess single nucleotide variants, insertions/deletions, copy number alterations, tumor mutational burden and microsatellite instability. The prognostic role of mutations and co-mutations was evaluated, together with associations between genomic alterations and PD-L1 expression. Results: At least one Tier I–II alteration was identified in 84% of patients. TP53 (39%), KRAS (27%), EGFR (15%), and STK11 (11%) were the most frequently altered genes. Several co-mutations were associated with worse overall survival, including TP53/STK11, STK11/LRP1B, STK11/RB1 and RB1/LRP1B, and with reduced disease-free survival, particularly TP53/KRAS, TP53/STK11, KRAS/STK11 and STK11/LRP1B. In advanced disease, STK11 and KEAP1 mutations were associated with low PD-L1 expression, whereas PIK3CA, PTEN and ARID1A mutations correlated with higher PD-L1 expression in early-stage tumors. Conclusions: Comprehensive genomic profiling reveals substantial molecular heterogeneity across lung cancer stages and identifies co-mutational patterns with prognostic and immune-related relevance, supporting broader molecular testing at diagnosis. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancer Diagnosis, Prognosis and Therapy)

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25 pages, 3378 KB

Open AccessArticle

Long Non-Coding RNA LINC01614 Promotes Aggressive Phenotypes and Ferroptosis Resistance in Papillary Thyroid Cancer Through a Putative miR-4521/IGF2/PI3K-AKT Signaling Axis

by Danielle Quaranto, Nicole R. DeSouza, Michelle Carnazza, Sina Dadafarin, Augustine Moscatello, Codrin Iacob, Humayun K. Islam, Xiu-Min Li, Raj K. Tiwari and Jan Geliebter

Genes 2026, 17(10), 1232; https://doi.org/10.3390/genes17101232 - 5 Oct 2026

Abstract

Background/Objectives: Papillary thyroid cancer (PTC) is the most common endocrine malignancy and is generally associated with favorable clinical outcomes. However, a subset of tumors develops aggressive phenotypes characterized by increased proliferation, migration, therapeutic resistance, and disease progression. Long non-coding RNAs (lncRNAs) have emerged [...] Read more.

Background/Objectives: Papillary thyroid cancer (PTC) is the most common endocrine malignancy and is generally associated with favorable clinical outcomes. However, a subset of tumors develops aggressive phenotypes characterized by increased proliferation, migration, therapeutic resistance, and disease progression. Long non-coding RNAs (lncRNAs) have emerged as important regulators of tumor biology, yet the role of Long Intergenic Non-Protein Coding RNA 1614 (LINC01614) in PTC remains poorly understood. This study investigated the functional role of LINC01614 in PTC and its potential involvement in ferroptosis-associated molecular pathways. Methods: RNA sequencing data from a repository of 44 paired PTC and adjacent normal thyroid tissue samples were analyzed to identify differentially expressed lncRNAs. LINC01614 expression was evaluated in thyroid cell lines, and CRISPR interference (CRISPRi) was used to generate stable LINC01614 knockdown K1 cell lines. Cellular proliferation, migration, clonogenicity, intracellular iron accumulation, lipid peroxidation, cytokine secretion, and ferroptosis-associated gene expression were assessed using qRT-PCR, RNA sequencing, Western blotting, cytokine array analysis, iron quantification assays, and BODIPY C11 lipid peroxidation imaging. Results: LINC01614 was significantly overexpressed in PTC tissues and thyroid cancer cell lines. CRISPRi-mediated repression of LINC01614 reduced cellular proliferation, migration, and clonogenic capacity. Mechanistically, LINC01614 knockdown resulted in an 8.8-fold increase in miR-4521 expression and a 23-fold decrease in IGF2 expression, supporting a potential competing endogenous RNA mechanism. Reduced LINC01614 expression was associated with decreased AKT, GPX4, SLC7A11, and SLC3A2 expression, increased IL-6 secretion, a 3.4-fold increase in intracellular ferrous iron accumulation, and a marked increase in lipid peroxidation following erastin treatment, indicating enhanced sensitivity to ferroptosis. Conclusions: These findings identify LINC01614 as a novel regulator of aggressive PTC phenotypes and ferroptosis resistance. The data support a model in which LINC01614 contributes to thyroid cancer progression through modulation of a miR-4521/IGF2/PI3K/AKT signaling axis and downstream anti-ferroptotic pathways. LINC01614 may represent a promising biomarker and potential therapeutic target in papillary thyroid cancer. Full article

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

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20 pages, 1179 KB

Open AccessReview

Integration of Multi-Omics in AI-Based Models for Predictive Oncology

by Arnaud Nativel, Sarah Dandou, Florian Favier, Candice Lesage, Alain Mangé, Julien Aligon, Peter J. Coopman and Romain M. Larive

Genes 2026, 17(10), 1231; https://doi.org/10.3390/genes17101231 - 4 Oct 2026

Abstract

Cancer heterogeneity and the emergence of innovative therapeutic alternatives have made the development of tools to help in clinical decision making even more necessary. The recent advances in the field of artificial-intelligence-based predictive models make them promising allies due to their ability to [...] Read more.

Cancer heterogeneity and the emergence of innovative therapeutic alternatives have made the development of tools to help in clinical decision making even more necessary. The recent advances in the field of artificial-intelligence-based predictive models make them promising allies due to their ability to integrate vast amounts of descriptors and data, notably omic data, for grasping cancer complexity. However, it is difficult to present a complete picture of this field due to the increasing number of models and the many possible applications. The aim of this review was to offer an overview of omic-based predictive models in oncology through the prism of three important concepts: the objective, the data, and the model. We show that the consideration of these three aspects could help to assess the feasibility, validity and usability of a model and to guide its construction. Lastly, we highlight that taking into account the underlying technical, physiological and biological phenomena inherent to omic data at each step of the project may improve the model predictive capability and its explainability. Full article

(This article belongs to the Special Issue Computational Genomics and Bioinformatics of Cancer)

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14 pages, 1604 KB

Open AccessArticle

Tracking the Global Prevalence and Distribution of the AmpC-β-Lactamase-Carrying pESM Megaplasmid in Salmonella Minnesota

by Anamaria M. P. Dos Santos, Ana Beatriz Portes, Hannay Crystynah Almeida De Souza, Pedro Panzenhagen, Arlen Carvalho de Oliveira Almeida, Rafaela G. Ferrari and Carlos A. Conte-Junior

Genes 2026, 17(10), 1230; https://doi.org/10.3390/genes17101230 - 3 Oct 2026

Abstract

Background/Objectives: AmpC enzymes, encoded by the bla_CMY-2 gene, confer resistance to a broad range of β-lactam antibiotics, including first-, second-, and third-generation cephalosporins, as well as β-lactam/β-lactamase inhibitor combinations. These genes can be located either on the chromosome or plasmids, with [...] Read more.

Background/Objectives: AmpC enzymes, encoded by the bla_CMY-2 gene, confer resistance to a broad range of β-lactam antibiotics, including first-, second-, and third-generation cephalosporins, as well as β-lactam/β-lactamase inhibitor combinations. These genes can be located either on the chromosome or plasmids, with the plasmid-borne form posing a greater risk due to its potential for rapid dissemination via horizontal gene transfer. The pESM megaplasmid, identified in Salmonella Minnesota isolates, was characterized as carrying the bla_CMY-2 gene, underscoring the urgent need for surveillance and control measures to address the threat of widespread resistance. Methods: In this in silico study, we analyzed the frequency and geographic distribution of pESM among publicly available S. Minnesota genomes over the last 20 years. Results: A total of 935 sequences were identified, of which 648 (69.3%) carried pESM. The countries with the highest number of positive isolates were Saudi Arabia (n = 303) and Brazil (n = 155), with a predominance of samples derived from poultry (n = 423; 65.27%). Genes involved in yersiniabactin synthesis and transport (ybtT, ybtU, ybtS, and ybtX) exhibited high proportion within the pESM-positive genomes, as did the merA gene, which is associated with mercury tolerance. Multi-locus sequence type (MLST) analysis showed that only ST548 and ST9594 carried the pESM. Forty distinct plasmid incompatibility groups were identified, with the most frequent being IncA/C2 (79.79%), followed by Col440I (74.97%), IncR (9.95%), IncI-1 (6.74%), ColpVC (8.02%), ColRNAI (5.45%), IncQ1 (4.71%), and IncFII(S) (4.28%. All pESM-positive genomes carried bla_CMY-2, with high co-occurrence of sul2, tet(A), and the mer operon, indicating that putative pESM could mediate resistance to multiple antibiotics and heavy metals. Since 2015, the co-occurrence of these genes with pESM has increased, likely reflecting selection pressure and clonal expansion of successful lineages. Phylogenetic analysis revealed a recent clade primarily composed of poultry-derived isolates from Brazil and Saudi Arabia. Putative pESM is strongly associated with the IncA/C2 incompatibility group and the qnrB19 gene, reinforcing its role in disseminating antimicrobial resistance. Conclusions: These findings suggest putative pESM is central in spreading multidrug resistance and virulence traits in S. Minnesota, especially in poultry environments. The plasmid’s prevalence in distinct sequence types and countries underscores its potential for horizontal transfer and global dissemination. Our results emphasize the need for enhanced surveillance of megaplasmids in foodborne pathogens and strategies to mitigate their spread. Full article

(This article belongs to the Special Issue Innovative Biotechnological Strategies in Molecular Microbiology and Genomic Technologies to Overcome Multi-Drug Resistance in a One Health Perspective)

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24 pages, 6764 KB

Open AccessArticle

A Comparison of Saliva and DNA Transfer and Persistence on Skin Immediately and 6 h Following Biting, Kissing, Licking and Sucking

by Cara Woollacott, Duncan Taylor, Roland A. H. van Oorschot and Mariya Goray

Genes 2026, 17(10), 1229; https://doi.org/10.3390/genes17101229 - 3 Oct 2026

Abstract

Background: The presence or absence of saliva and saliva-derived DNA may be relevant to a range of different crime types, including sexual assault and homicide offences, where allegations of saliva transfer to the skin of a victim or offender from actions such as [...] Read more.

Background: The presence or absence of saliva and saliva-derived DNA may be relevant to a range of different crime types, including sexual assault and homicide offences, where allegations of saliva transfer to the skin of a victim or offender from actions such as biting, kissing, licking or sucking are relevant. The interpretation of skin samples following allegations of biting, kissing, licking or sucking requires an awareness of the prevalence, transfer and persistence of saliva, and its DNA composition, including self- and non-self DNA, with and without such activities occurring. The matter of persistence is especially important given that the examinations of suspects or victims do not often occur immediately after the offence. Methods: This study investigates the transfer of saliva onto human skin and its persistence following actions of biting, kissing, licking and sucking. Seven male–female couples were asked to shower and then bite, kiss, lick and suck separate defined areas of both of their partner’s arms. Following these different actions, one arm was sampled immediately, and the other arm was sampled 6 h later. Background (prior to shower) and control (post-shower but before deposition) samples were also obtained. For participants who wore long-sleeve clothing post-activity, the inner sleeves were also sampled along with the tested skin areas at 6 h sample collection. Presumptive saliva tests were carried out on all background, control, 6 h experimental and clothing samples collected, using the RSID-Saliva immunological test kits. All recovered samples (immediate, persistence, clothing, background and control) underwent DNA extraction and quantification, and all background, 6 h and clothing samples were STR-amplified, generating DNA profiles. Results: The results were considered with the questionnaire data provided by participants, to assess what factors may have influenced the presence or absence of any saliva, self (donor), partner or foreign DNA detected. Comparisons of the DNA quantities recovered from the immediate samples and 6 h samples were made. Furthermore, saliva detection rates of 6 h samples and DNA profile data were compared between all samples generated from the four different actions which resulted in saliva transfer to skin. Concussions: This research will assist forensic investigators when interpreting saliva DNA evidence recovered from the skin of victims or suspects after a prolonged period of time between the offence and collection. Full article

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

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16 pages, 540 KB

Open AccessReview

N6-Methyladenosine (m6A) RNA Modification in Periodontitis: Molecular Mechanisms and Therapeutic Potential: A Narrative Review

by Filippos Fytros, Stefanos Zisis, Vasileios Zisis, Petros Papadopoulos, Christina Charisi, Konstantinos Poulopoulos, Panagiota Dimitropoulou, Nikolaos Shinas, Joe Cordahi and Athanasios Poulopoulos

Genes 2026, 17(10), 1228; https://doi.org/10.3390/genes17101228 - 3 Oct 2026

Abstract

Background: N6-methyladenosine (m6A) is the most abundant mRNA internal modification in eukaryotes and regulates inflammatory and regenerative processes. Many studies relate the dysregulation of m6A-related pathways to periodontal inflammation, imbalance in cell homeostasis, impaired tissue regeneration, and remodeling of the alveolar bone. However, [...] Read more.

Background: N6-methyladenosine (m6A) is the most abundant mRNA internal modification in eukaryotes and regulates inflammatory and regenerative processes. Many studies relate the dysregulation of m6A-related pathways to periodontal inflammation, imbalance in cell homeostasis, impaired tissue regeneration, and remodeling of the alveolar bone. However, the mechanisms of the relationship between the m6A pathway and periodontitis have not been elucidated clearly yet. Objective: The objective of the current narrative review is to integrate the information related to the role of m6A RNA modification in the pathogenesis of periodontitis by focusing on inflammatory signaling, osteoimmune regulation, periodontal cell activity, bone remodeling, and its possible applications as a diagnosis and treatment approach. Methods: A literature search was conducted in PubMed to identify original research studies investigating the role of m6A RNA methylation and its regulators in periodontitis and periodontal tissues/cells. Out of 49 publications reviewed, 34 original research articles fulfilled the predetermined inclusion criteria. Results: The current literature suggests that N6-methyladenosine (m6A) modification is involved in various interconnected biological processes contributing to the development of periodontitis, including inflammatory responses, inflammasome activation and pyroptosis, osteoimmune reactions by macrophages, osteogenic differentiation, osteoclast formation, cellular senescence, and periodontal cells homeostasis. METTL3 has been reported to be the most widely investigated regulator, but its roles are not consistently harmful or beneficial. Depending on the RNA target, cellular environment, and state of inflammation, some of the m6A-associated pathways have been linked to periodontal inflammation and alveolar bone resorption, while others were linked to osteogenesis and regeneration. Several studies have highlighted the possibility of therapeutic interference in pathways leading to the formation of m6A, while human transcriptomic and gingival/salivary studies suggested that m6A could be used as a biomarker. Conclusions: The m6A modification of RNA is an emerging epitranscriptomic effect relating periodontal inflammation, immune responses, cellular differentiation, and bone remodeling. Even though target molecules and signaling pathways have been experimentally identified as points of potential therapeutic interference, the available evidence remains predominantly preclinical. Future work is expected to validate the diagnostic and therapeutic involvement of the m6A modification in periodontitis. Full article

(This article belongs to the Section RNA)

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27 pages, 4211 KB

Open AccessArticle

Integrated Ovarian circRNA, miRNA and mRNA Profiling Identifies Candidate ceRNA Relationships Associated with Late-Laying and Nesting Stages in Wanxi White Geese

by Kefeng Yang, Tongsheng Yang, Dexing Cui, Tao Jin, Man Ren, Qianqian Hu, Changsheng Jiang, Chunfang Zhao and Shenghe Li

Genes 2026, 17(10), 1227; https://doi.org/10.3390/genes17101227 - 2 Oct 2026

Abstract

Background: The pronounced broodiness of Wanxi white geese is associated with rapid ovarian regression and reduced egg production and reproductive efficiency. However, the extent to which circRNAs influence this physiological transition by coordinating ceRNA interactions is not yet well understood. Methods: [...] Read more.

Background: The pronounced broodiness of Wanxi white geese is associated with rapid ovarian regression and reduced egg production and reproductive efficiency. However, the extent to which circRNAs influence this physiological transition by coordinating ceRNA interactions is not yet well understood. Methods: Here, we generated ovarian microRNA (miRNA) and circRNA expression profiles by RNA sequencing in late-laying (LLG) and nesting (NG) Wanxi white geese and measured serum reproductive hormones. Results: Compared with the late-laying stage, the nesting stage was characterised by pronounced ovarian atrophy. Serum concentrations of oestradiol (E2), progesterone (P4) and luteinising hormone (LH) were lower, whereas the prolactin (PRL) concentration was higher. Transcriptome analysis identified 156 circRNAs and 64 miRNAs that met the nominal differential expressed (DE) criteria. Enrichment analysis associated genes giving rise to DE circRNAs with membrane and junctional structures, cell adhesion, small GTPase regulation, ECM–receptor interaction, adherens junction, focal adhesion and metabolic processes. Conversely, putative targets of DE miRNAs were linked to AMPK, mTOR, TGF-β and Hippo pathways, together with oocyte meiosis. The integration of the RNA datasets and Pearson correlation analysis highlighted several putative ceRNA relationships associated with ovarian functional transition. During the late-laying period, bioinformatic predictions and expression correlations supported the predicted novel_circ_001280-miR-1-y-CPEB1 and novel_circ_005385-miR-187-x-BMP6 relationships involving genes associated with oocyte development and ovarian endocrine function. By contrast, during the nesting period, bioinformatic analyses supported a putative novel_circ_002435/novel_circ_007511-miR-135-x/z-FOXO3 relationship that may be associated with cellular quiescence, stress responses and follicular atresia. The expression profiles of these network components showed stage-associated correlations with circulating reproductive hormone concentrations. Conclusions: Together, these findings suggest an exploratory ceRNA landscape associated with ovarian functional remodelling in Wanxi white geese and identify RNA relationships that warrant further functional validation. Full article

(This article belongs to the Special Issue Epigenetic Control of Animal Reproduction and Key Traits)

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34 pages, 2094 KB

Open AccessReview

Reticulocalbin-2 (RCN2) as a Context-Dependent CREC-Family Modulator: Gene Expression and Regulation, Molecular Biology, Disease Relevance, and Translational Challenges

by Abdullah A. A. Alghamdi

Genes 2026, 17(10), 1226; https://doi.org/10.3390/genes17101226 - 2 Oct 2026

Abstract

Reticulocalbin-2 (RCN2), encoded by the human RCN2 gene (HGNC:9935) and historically identified as E6-binding protein, is a CREC-family EF-hand Ca²⁺-binding protein. Although first characterized as an endoplasmic reticulum (ER)-associated protein, current evidence extends RCN2 biology to splice-variant and localization complexity, protein [...] Read more.

Reticulocalbin-2 (RCN2), encoded by the human RCN2 gene (HGNC:9935) and historically identified as E6-binding protein, is a CREC-family EF-hand Ca²⁺-binding protein. Although first characterized as an endoplasmic reticulum (ER)-associated protein, current evidence extends RCN2 biology to splice-variant and localization complexity, protein interactions, regulatory and signaling networks, extracellular activity, cancer, non-malignant disease, and the RCN2-derived hormone Raptin. This review synthesizes the fragmented and methodologically uneven RCN2 literature within an evidence-stratified framework. Mechanistic evidence, including direct biochemical assays and RCN2-directed functional studies, supports selected interaction and signaling relationships, whereas omics, database-derived and single-context observations remain hypothesis-generating. Across disease settings, RCN2 is best interpreted as a context-dependent modulator rather than a uniform oncogenic driver, validated biomarker or established therapeutic target. Translational progress will require molecular-form-specific assays, disease-specific validation and clinically grounded models. Full article

(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2026)

33 pages, 6834 KB

Open AccessSystematic Review

Recurrent Acute Liver Failure in Children: A Systematic Review of Genetic Etiologies, Diagnostic Clues, and Liver Transplantation

by Patryk Lipiński, Piotr Socha and Irena Jankowska

Genes 2026, 17(10), 1225; https://doi.org/10.3390/genes17101225 - 2 Oct 2026

Abstract

Background: Recurrent acute liver failure (RALF) is a rare phenotype with heterogeneous inherited causes. Methods: We conducted a PRISMA 2020 systematic review of PubMed/MEDLINE and Web of Science Core Collection. Reports were classified into two non-combinable evidence sets: strict RALF, requiring at least [...] Read more.

Background: Recurrent acute liver failure (RALF) is a rare phenotype with heterogeneous inherited causes. Methods: We conducted a PRISMA 2020 systematic review of PubMed/MEDLINE and Web of Science Core Collection. Reports were classified into two non-combinable evidence sets: strict RALF, requiring at least two documented pediatric acute liver failure episodes with recovery of liver synthetic function between episodes, and contextual disease-specific evidence used only to inform broader natural history, treatment, or transplantation. Results: The searches identified 128 records; 30 duplicates were removed, and 98 records were screened. Forty-eight full texts were assessed, and 44 publications representing 41 study or cohort units were retained across both evidence sets. The evidence consisted predominantly of case reports, small case series, and retrospective cohorts, with inconsistent RALF definitions and incompletely reported follow-up. The five-group framework is a pragmatic organization of reported qualifying disorders rather than an exhaustive genetic classification. Conclusions: Genomic testing during a first unexplained severe episode is proposed to avoid waiting for recurrence, but most disorder-specific treatment and transplantation conclusions remain based on limited observational evidence and expert practice. Full article

(This article belongs to the Special Issue Genomic Advances in Inherited Metabolic Diseases: From Variant Interpretation to Precision Medicine)

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22 pages, 6196 KB

Open AccessReview

Somatic Blood Mosaicism and Psychiatric Disease: Current Evidence and Causal Limits

by Andrada-Adelaida Belbe, Lorin-Manuel Pîrlog, Alissia-Nicoleta Pilatec, Mariela-Sanda Militaru, Irina-Ioana Iordănescu and Andreea Cătană

Genes 2026, 17(10), 1224; https://doi.org/10.3390/genes17101224 - 2 Oct 2026

Abstract

Somatic blood mosaicism is an established feature of ageing and a heterogeneous marker of haematologic cancer and inflammatory and vascular risk, but its psychiatric evidence base remains small. This structured critical narrative review evaluates mutation-defined clonal haematopoiesis, clonal haematopoiesis of indeterminate potential (CHIP), [...] Read more.

Somatic blood mosaicism is an established feature of ageing and a heterogeneous marker of haematologic cancer and inflammatory and vascular risk, but its psychiatric evidence base remains small. This structured critical narrative review evaluates mutation-defined clonal haematopoiesis, clonal haematopoiesis of indeterminate potential (CHIP), autosomal mosaic chromosomal alterations (mCAs), and sex-chromosome loss while separating probable developmental mosaicism from adult-acquired blood clonality. Direct human evidence comprises seven methodologically heterogeneous studies. Psychiatric CHIP findings rely mainly on one prospective UK Biobank cohort of 360,451 participants, in which CHIP was associated with any incident psychiatric disorder (hazard ratio 1.15), particularly major depressive and substance-use disorders. Separate studies report excess mosaic losses in schizophrenia and bipolar disorder and autosomal or X-chromosome mosaicism in suicide. Clone-size gradients and lesion-specific findings add biological structure, but do not provide independent replication. Most mechanistic support comes from cardiovascular, stroke and neurodegenerative research: mutant myeloid cells can alter inflammasome signalling, endothelial function, thrombosis and tissue macrophage behaviour. These pathways make indirect brain effects plausible without establishing a psychiatric mechanism. Blood detection also cannot date a mosaic event or demonstrate the same clone in neural tissue. Taken together, the available evidence supports somatic blood mosaicism as a potentially informative marker of psychiatric heterogeneity and shared inflammatory, vascular and ageing-related biology, but does not establish a causal blood-clone-to-brain pathway. Routine psychiatric screening for CHIP or mCAs is therefore not currently justified. The immediate research priority is independent replication in longitudinal cohorts with repeated sequencing, detailed exposure and treatment histories, and direct testing of inflammatory, vascular and neuroimaging intermediates capable of distinguishing cause, consequence and shared risk. Full article

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

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13 pages, 706 KB

Open AccessArticle

Functional Consequence of IRF6 Variants in Van der Woude Syndrome

by Mojisola Olujitan, Rose Gogal, Tamara Busch, Chloe Ovel, Anjolaoluwa Awe, Jorge Ceballos, Kikanwa Okiosor, Natalie Ibarra, Emmanuel Aladenika, Waheed Awotoye, Veronica Sule, Babatunde Faparusi, Benjamin Bass, Rishitha Gadde, Thirona Naicker, Lord J. J. Gowans, Mekonen Eshete, Wasiu Lanre Adeyemo, Aline Petrin, Martine Dunnwald, Carmen J. Buxo, Peter Mossey, Michael Schnieders and Azeez Butali Show full author list Hide full author list

Genes 2026, 17(10), 1223; https://doi.org/10.3390/genes17101223 - 2 Oct 2026

Abstract

Van der Woude syndrome (VWS) is the most common syndromic form of orofacial clefts (OFCs). The heritability of VWS is largely (~70%) explained by variants in the IRF6 gene. Experimental studies to confirm genetic variant effects are essential but are time intensive and [...] Read more.

Van der Woude syndrome (VWS) is the most common syndromic form of orofacial clefts (OFCs). The heritability of VWS is largely (~70%) explained by variants in the IRF6 gene. Experimental studies to confirm genetic variant effects are essential but are time intensive and expensive. Advancing next-generation sequencing techniques has made it possible to identify genetic variation quicker than their causal effects in disease processes can be ascertained. Therefore, employing computational tools to reliably predict their causal effects is crucial for advancing translational research. We conducted Sanger sequencing of the IRF6 gene in 46 VWS cases across 34 families to identify likely causal missense variants. We then assessed structure-informed stability changes to the IRF6 protein when these variants were incorporated into the protein, using DDGun3D. We compared DDGun3D predictions to results from previous experimental studies. Among four variants previously shown to prevent functional rescue in zebrafish, only the variant IRF6(NM_006147.4):c.881T>C, shown to cause rupture of zebrafish embryo, exhibited a high free energy change (∆∆G_fold = 3.5 kcal/mol), indicating that substantial predicted thermodynamic destabilization does not capture all disruptive function of IRF6. Our study demonstrates the utility of a protein structure-based computational approach for functional variant interpretation, providing a complementary method for studying genetic variation. Integrating computational predictions with experimental data can enhance our understanding of genetic conditions. However, success depends on fully elucidating protein structures, which is an active area of research. Full article

(This article belongs to the Special Issue Perspectives on Craniofacial Genomics, Genetics, and Development)

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25 pages, 4279 KB

Open AccessArticle

Complementary Genomic and Functional Potential of Bacillus subtilis RKM-1 and Bacillus licheniformis RKM-2 for Organic Waste Bioconversion and Composting

by Tekebayeva Zhanar, Abilkhadirov Arman, Begakhmet Akbota, Kulzhanova Kamshat, Temirbekova Aliya, Nurbekova Zhadyrassyn, Aslan Temirkhanov, Bekshin Zhandarbek and Abzhalelov Akhan

Genes 2026, 17(10), 1222; https://doi.org/10.3390/genes17101222 - 1 Oct 2026

Abstract

Background: Efficient bioconversion of organic waste requires microorganisms with the potential to degrade complex organic compounds and transform biogenic elements. Methods: In this study, two thermophilic bacterial strains, RKM-1 and RKM-2, isolated from sewage sludge, were characterized using whole-genome sequencing and comparative genomics [...] Read more.

Background: Efficient bioconversion of organic waste requires microorganisms with the potential to degrade complex organic compounds and transform biogenic elements. Methods: In this study, two thermophilic bacterial strains, RKM-1 and RKM-2, isolated from sewage sludge, were characterized using whole-genome sequencing and comparative genomics to establish their taxonomic positions and assess their functional potential. Results: RKM-1 and RKM-2 were identified as Bacillus subtilis and Bacillus licheniformis, respectively, with maximum ANI values of 98.76% and 99.76%. Comparative genomic analysis revealed differences in the functional potential of the two strains. RKM-1 exhibited genomic features associated with the transformation of biogenic elements and secondary metabolite biosynthesis, whereas RKM-2 showed greater genetic potential for the utilization and transformation of complex carbohydrates, supported by the presence of genes such as amyA, bglC, celA, glcT, galE, galU, and glgABCD. These differences indicate potentially complementary functional profiles of the two strains in the bioconversion of organic substrates. During sewage sludge composting, inoculation with both strains accelerated the onset of the thermophilic phase. Bacillus subtilis RKM-1 reached the highest compost temperature (60 °C), whereas Bacillus licheniformis RKM-2 most effectively promoted compost maturation, reducing the C:N ratio to 9:1 within 60 days. Conclusions: These findings demonstrate a strong relationship between the genomic characteristics and functional traits of the investigated strains and highlight the value of comparative genomics as a powerful tool for identifying promising thermophilic microorganisms for efficient bioconversion of organic wastes. Full article

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

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