Genes

18 pages, 3339 KiB

Open AccessArticle

Analysis of Multi-Target Synergistic Mechanism of Coix Seed Therapy for Herpes Zoster Based on Machine Learning and Network Pharmacology

by Zhiqin Song, Lin Yang, Jing He, Yuchao Li, Ningxian Yang, Min Yang and Mingkai Wu

Genes 2025, 16(5), 580; https://doi.org/10.3390/genes16050580 - 14 May 2025

Abstract

Objective: To explore the efficacy and mechanism of Coix seeds in treating herpes zoster (HZ) using an integrated computational approach. Methods: Network pharmacology, molecular docking, and machine learning were employed. Disease-related targets were collected from multiple databases, and intersection targets with Coix seed [...] Read more.

Objective: To explore the efficacy and mechanism of Coix seeds in treating herpes zoster (HZ) using an integrated computational approach. Methods: Network pharmacology, molecular docking, and machine learning were employed. Disease-related targets were collected from multiple databases, and intersection targets with Coix seed were analyzed via PPI, GO, and KEGG enrichment. A “TCM-Ingredient-Target” network was constructed using Cytoscape. Molecular docking and dynamics simulations were performed for validation. Results: Fifty-five overlapping targets were identified, with core targets including TNF, EGF, and GAPDH. Enrichment analysis revealed key pathways such as inflammation and immune regulation. Molecular docking confirmed strong binding affinity between active compounds and targets. Conclusion: This study demonstrates that Coix seed exerts anti-HZ effects through multi-target mechanisms, providing a theoretical basis for developing novel multi-pathway treatment strategies. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)

20 pages, 2786 KiB

Open AccessArticle

Genome-Wide Identification of the Polygalacturonase Gene Family and Its Potential Association with Abscission Zone in Capsicum annuum L.

by Lei He, Chen Lu, Xi Yan, Sha Yang, Peng Zhou, Wei Lai and Jianwen He

Genes 2025, 16(5), 579; https://doi.org/10.3390/genes16050579 - 14 May 2025

Abstract

Background: Polygalacturonase (PG) genes regulate plant organ abscission by degrading pectin in the cell wall. However, their association with pedicel abscission susceptibility in pepper remains poorly understood. Methods: 47 CaPG genes were identified were identified in the ‘Zunla1’ genome and characterized [...] Read more.

Background: Polygalacturonase (PG) genes regulate plant organ abscission by degrading pectin in the cell wall. However, their association with pedicel abscission susceptibility in pepper remains poorly understood. Methods: 47 CaPG genes were identified were identified in the ‘Zunla1’ genome and characterized by structural, evolutionary, and comparative genomic analyses. Their expression profiles across various tissues and fruit development stages were examined using transcriptome data. Ethephon treatment and qRT-PCR were employed to assess gene responses during ethylene-induced pedicel abscission. Results: The 47 CaPG genes were distributed across 12 chromosomes, with CaPG1 to CaPG5 unanchored. Most proteins were hydrophilic, nuclear-localized, and had promoters enriched in light-responsive elements. Collinearity analysis revealed limited segmental duplication, and Ka/Ks values indicated strong purifying selection. Phylogenetic and collinearity analyses showed that CaPG genes are more closely related to those in tomato than in Arabidopsis or maize. Expression profiling revealed tissue- and stage-specific patterns, with 21 CaPG genes associated with pedicel abscission susceptibility. Ethephon treatment enhanced abscission and upregulated several CaPG genes. Conclusions: This study offers insights into the CaPG gene family’s structure, evolution, and function. Specific CaPG genes likely contribute to ethylene-mediated pedicel abscission, providing potential targets for improving fruit-retention traits in pepper. Full article

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

17 pages, 615 KiB

Open AccessReview

Gene–Diet Interactions in Diabetes Mellitus: Current Insights and the Potential of Personalized Nutrition

by Angeliki Kapellou, Effie Salata, Dimitrios Miltiadis Vrachnos, Sevastiani Papailia and Spiros Vittas

Genes 2025, 16(5), 578; https://doi.org/10.3390/genes16050578 - 14 May 2025

Abstract

Type 2 diabetes mellitus (T2DM) remaina significant global health challenge, with its increasing prevalence and associated complications contributing to high morbidity and economic burden. Genetic factors play a crucial role in T2DM susceptibility, yet individual responses to dietary interventions vary widely, emphasizing the [...] Read more.

Type 2 diabetes mellitus (T2DM) remaina significant global health challenge, with its increasing prevalence and associated complications contributing to high morbidity and economic burden. Genetic factors play a crucial role in T2DM susceptibility, yet individual responses to dietary interventions vary widely, emphasizing the importance of gene–diet (G × D) interactions. This review synthesizes the current literature on the genetic basis of T2DM and the role of G × D interactions in shaping individual responses to diet. We examine the genetics implication in T2DM risk and modulation by dietary factors, with a focus on the potential of Nutrigenetics in guiding personalized nutrition (PN) strategies. Moreover, the clinical implications of these interactions for the personalized prevention and management of T2DM are explored, highlighting the promise of tailoring dietary recommendations based on genetic profiles. Critical research gaps, including the need for diverse and longitudinal studies, the integration of multi-omic data, and the inclusion of digital health technologies in PN are discussed. Finally, future directions for the field are outlined, advocating for more inclusive, large-scale studies to optimize PN approaches for diverse populations and improve the efficacy of T2DM prevention and management. This review underscores the potential of an individualized, genetically informed dietary approach in modulating the global burden of T2DM. Full article

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

17 pages, 5019 KiB

Open AccessArticle

PAX3 Regulatory Signatures and Gene Targets in Melanoma Cells

by Stephen P. G. Moore, Shripushkar Ganesh Krishnan, Rutu Jaswanth Kothari, Noah B. Prince, Colin Kenny, Chao Zhang and Deborah Lang

Genes 2025, 16(5), 577; https://doi.org/10.3390/genes16050577 - 14 May 2025

Abstract

Background/Objectives: PAX3 is a transcription factor that drives melanoma progression by promoting cell growth, migration, and survival, while inhibiting cellular terminal differentiation. However, known PAX3 target genes are limited and cannot fully explain the wide impact of PAX3 function. The PAX3 protein can [...] Read more.

Background/Objectives: PAX3 is a transcription factor that drives melanoma progression by promoting cell growth, migration, and survival, while inhibiting cellular terminal differentiation. However, known PAX3 target genes are limited and cannot fully explain the wide impact of PAX3 function. The PAX3 protein can regulate DNA through two separate binding domains, the Paired Domain (PD) and Homeodomain (HD), which bind different DNA motifs. It is not clear if these two domains bind and work together to regulate genes and if they promote all or only a subset of downstream cellular events. Methods: PAX3 direct downstream targets were identified using Cleavage Under Targets & Release Using Nuclease (CUT&RUN) assays in SK-MEL-5 melanoma cells. PAX3-binding genomic regions were identified through MACS2 peak calling, and peaks were categorized based on the presence of PD and/or HD binding sites (or neither) through HOMER motif analysis. The peaks were further characterized as Active, Primed, Poised, Repressed, or Closed based on ATAC-seq data and CUT&RUN for histone Post-Translational Modifications H3K4me1, H3K4me3, H3K27me3, and H3K27Ac. Results: This analysis revealed that most of the PAX3 binding sites in the SK-MEL-5 cell line were primarily through the PD and connected to Active genes. Surprisingly, PAX3 does not commonly act as a repressor in SK-MEL-5 cells. Pathway analysis identified genes involved with transcription, RNA modification, and cell growth. Peaks located in distal enhancer elements were connected to genes involved in neuronal growth, function, and signaling. Conclusions: Our results reveal novel PAX3 regulatory regions and putative genes in a melanoma cell line, with a predominance of PAX3 PD binding on active sites. Full article

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

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13 pages, 3873 KiB

Open AccessArticle

Establishment of Reference Measurement Procedure for TP53 R175H/R248W Detection and a Novel Preparation Method for ctDNA Reference Material

by Yanru Tang, Chunyan Niu, Jiejie Zhang, Lianhua Dong and Jingya Yang

Genes 2025, 16(5), 576; https://doi.org/10.3390/genes16050576 - 14 May 2025

Abstract

Background/Aims: Circulating tumor DNA (ctDNA) is becoming a valuable cancer biomarker for clinical decision-making. Nevertheless, the lack of quality control materials to assess the reliability of test results remains a challenge. This study aimed to establish digital PCR (dPCR) assays for detecting TP53 [...] Read more.

Background/Aims: Circulating tumor DNA (ctDNA) is becoming a valuable cancer biomarker for clinical decision-making. Nevertheless, the lack of quality control materials to assess the reliability of test results remains a challenge. This study aimed to establish digital PCR (dPCR) assays for detecting TP53 variants (R175H and R248W) and develop a preparation method for ctDNA reference materials to improve detection reliability. Methods: Two dPCR assays targeting TP53-R175H and TP53-R248W variants were developed and validated for repeatability, sensitivity, and linearity. Additionally, a ctDNA reference material preparation protocol was developed by digesting nucleosomes from cultured cancer cell lines with micrococcal nuclease, followed by magnetic beads purification. The size distribution and quality of the generated ctDNA fragments was analyzed, and the developed dPCR assays were applied to detect the variants in the ctDNA samples. Results: The dPCR assays demonstrated high repeatability (RSD of 0.16% to 7.65%) and excellent linearity (R² values of 1.0000 and 0.9981) across variant allele frequencies of 50%–0.1%. The limits of detection (LOD) and quantification (LOQ) were 0.143% (R175H) and 0.092% (R248W). The ctDNA reference materials exhibited single dominant peaks at 128 bp (R175H) and 143 bp (R248W). The dPCR assays successfully detected variants in these reference materials, confirming their applicability for ctDNA samples. onclusion: Firstly, accurate measurement procedures for TP53-R175H and TP53-R248W variants based on dPCR were established in this study. Furthermore, a protocol for preparing ctDNA reference material was established here. By digesting nucleosomal DNA derived from cancer cell lines with micrococcal nuclease, this method can closely mimic the properties of clinical ctDNA. The dPCR method and ctDNA reference material preparation approach established here could be used in ctDNA detection and for improving its reliability. Full article

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

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17 pages, 2313 KiB

Open AccessArticle

Mapping Inherited Genetic Variation with Opposite Effects on Autoimmune Disease and Four Cancer Types Identifies Candidate Drug Targets Associated with the Anti-Tumor Immune Response

by Junyu Chen, Michael P. Epstein, Joellen M. Schildkraut and Siddhartha P. Kar

Genes 2025, 16(5), 575; https://doi.org/10.3390/genes16050575 - 14 May 2025

Abstract

Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying [...] Read more.

Background: Germline alleles near genes encoding certain immune checkpoints (CTLA4, CD200) are associated with autoimmune/autoinflammatory disease and cancer, but in opposite ways. This motivates a systematic search for additional germline alleles with this pattern with the aim of identifying potential cancer immunotherapeutic targets using human genetics. Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with in silico follow-up. Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with p < 5 × 10⁻⁸ associated with at least one of the cancer types at p < 10⁻³ and one of the autoimmune/autoinflammatory diseases at p < 10⁻³. At each lead variant, the allele that conferred autoimmune/autoinflammatory disease risk was protective for cancer. Mapping led variants to nearest genes as putative functional targets and focusing on immune-related genes implicated 32 genes. Tumor bulk RNA-Seq data highlighted that the tumor expression of 5/32 genes (IRF1, IKZF1, SPI1, SH2B3, LAT) was each strongly correlated (Spearman’s ρ > 0.5) with at least one intra-tumor T/myeloid cell infiltration marker (CD4, CD8A, CD11B, CD45) in every one of the cancer types. Tumor single-cell RNA-Seq data from all cancer types showed that the five genes were more likely to be expressed in intra-tumor immune versus malignant cells. The five lead SNPs corresponding to these genes were linked to them via the expression of quantitative trait locus mechanisms and at least one additional line of functional evidence. Proteins encoded by the genes were predicted to be druggable. Conclusions: We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded by IRF1, IKZF1, SPI1, SH2B3 and LAT as possible targets for cancer immunotherapy. Full article

(This article belongs to the Special Issue Genetics of Cancer Immunology)

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17 pages, 2090 KiB

Open AccessArticle

The Analysis of Autosomal STRs Draws the Current Genetic Map and Evolutionary History of Northernmost South America

by Julie Moncada Madero, Fernanda Mogollón Olivares, Dayana Suárez Medellín, Alejandra Coronel Guzmán, Andrea Casas-Vargas and William Usaquén Martínez

Genes 2025, 16(5), 574; https://doi.org/10.3390/genes16050574 - 14 May 2025

Abstract

Objectives: To analyze Colombia’s current human population, we employed a population genetics approach enriched by genealogical, demographic, cultural, and historical data to learn about its evolutionary history and to elucidate ethnic belonging and relationship patterns between its various population groups. Materials and Methods: [...] Read more.

Objectives: To analyze Colombia’s current human population, we employed a population genetics approach enriched by genealogical, demographic, cultural, and historical data to learn about its evolutionary history and to elucidate ethnic belonging and relationship patterns between its various population groups. Materials and Methods: This study relied on ten autosomal microsatellite markers (STRs) from 1364 individuals surveyed throughout the country. Aside from employing descriptive population genetics, substructure, and distance analysis, this investigation evaluated genealogical, demographic, cultural, and historical data gathered from fieldwork surveys. Results: We present a genetic diversity and ethnic belonging map of Colombia that suggests a nine-population classification (under Afro-descendant, Native American, and Admixed ethnicity labels) that reveals traces of evolutionary processes discussed in the light of the recent literature based on modern molecular markers. Colombia’s genetic trace from Africa varies among territories, as shown here by two differentiated Afro ancestral components, Chocó and San Andrés, in addition to the Afro admixture category. Some Native American peoples like the Wayúu, Zenú, Ticuna, Huitoto, and Cocama have a genetic configuration that remains relatively preserved. Nevertheless, other self-determined indigenous peoples who remain in their ancestral territories exhibit genetic introgression that is also reflected by their acculturation levels such as the Pijaos, Kankuamos, and Mokaná. The population classified as European admixture also shows an ancestral component that seems to be more fixed throughout neighboring territories but whose fluctuation depends on its specific demographic histories. Conclusions: This study combines STRs, a targeted sampling strategy, and advanced analytical tools to explore Colombia’s genetic diversity and evolutionary history. Locally, these findings enhance the understanding of genetics in a post-conflict society, crucial for human identification. Globally, they contribute to human population genetics, helping address evolutionary questions using data from diverse human ancestries and geographies. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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18 pages, 17046 KiB

Open AccessArticle

Olig1/2 Drive Astrocytic Glioblastoma Proliferation Through Transcriptional Co-Regulation of Various Cyclins

by Yu Tian, Ziwu Wang, Mengge Sun, Jialin Li, Wenhui Zheng, Feihong Yang and Zhuangzhi Zhang

Genes 2025, 16(5), 573; https://doi.org/10.3390/genes16050573 - 13 May 2025

Abstract

As the most aggressive primary brain tumor, glioblastoma (GBM) is considered incurable due to its molecular heterogeneity and therapy resistance. Identifying key regulatory factors in GBM is critical for developing effective therapeutic strategies. Based on the analysis of TCGA data, we confirmed a [...] Read more.

As the most aggressive primary brain tumor, glioblastoma (GBM) is considered incurable due to its molecular heterogeneity and therapy resistance. Identifying key regulatory factors in GBM is critical for developing effective therapeutic strategies. Based on the analysis of TCGA data, we confirmed a robust co-expression and correlation of OLIG1 and OLIG2 in human GBM. However, their roles in the astrocytic GBM subtype remain unclear. In this study, we first establish an astrocytic-featured GBM mouse model by introducing PiggyBac-driven hEGFRvIII plasmids and demonstrate that both OLIG1 and OLIG2 are highly expressed within this context. Next, using CRISPR/Cas9 technology to knockout Olig1/2, we found that astrocyte differentiation markers such as GFAP, SOX9, and HOPX were preserved, but tumor cell proliferation was significantly diminished. Mechanistically, CUT&Tag-seq revealed that OLIG1/2 directly binds to the promoter region of various cyclins (Cdk4, Ccne2, Ccnd3, and Ccnd1), where an enrichment of the active histone marker H3K4me3 was observed, indicating transcriptional activation of the genes. Notably, Olig1/2 knockout did not suppress tumor initiation or migration, suggesting that their primary role is to amplify proliferation rather than to drive tumorigenesis. This study defines Olig1 and Olig2 as master regulators of GBM proliferation through various cyclins, thereby offering a novel therapeutic target. Full article

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

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15 pages, 2359 KiB

Open AccessArticle

The Effects of Ferulic Acid on the Growth Performance, Immune Function, Antioxidant Capacity, and Intestinal Microbiota of Broiler Chickens

by Xianguo Yi, Quanchao Ma, Zhili Li, Yuli Hu, Haigang Wu, Rui Wang, Xuyang Sun, Enen Wang, Chaofeng Ma and Qingmin Qin

Genes 2025, 16(5), 572; https://doi.org/10.3390/genes16050572 - 13 May 2025

Abstract

Objectives: Ferulic acid is a natural and safe herbal feed additive. This study aims to evaluate the effects of ferulic acid on the growth performance, anti-inflammatory and antioxidant capacities, immune function, and intestinal microbiota of broiler chickens. Methods: A total of 320 broiler [...] Read more.

Objectives: Ferulic acid is a natural and safe herbal feed additive. This study aims to evaluate the effects of ferulic acid on the growth performance, anti-inflammatory and antioxidant capacities, immune function, and intestinal microbiota of broiler chickens. Methods: A total of 320 broiler chickens, aged 14 days, were randomly divided into four groups: a blank control group (MA group), a low-concentration ferulic acid group (BM group, 10 mg/kg), a medium-concentration ferulic acid group (CM group, 30 mg/kg), and a high-concentration ferulic acid group (DM group, 90 mg/kg) after a 14-day acclimatization period. The experiment lasted for 28 days, and the chickens were dissected on day 29. Results: The results showed that compared to the MA group, the feed-to-meat ratio in the CM and DM groups was significantly reduced. The activity of duodenal trypsin in the CM and DM groups was significantly enhanced, and the activity of pancreatic protease in the DM group was significantly increased. The serum levels of urea nitrogen, creatinine, and triglycerides were significantly elevated in the CM and DM groups. The serum malondialdehyde (MDA) levels in the BM, CM, and DM groups were significantly reduced, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased in the CM and DM groups. The serum interleukin-2 (IL-2) levels in the BM group were significantly decreased, while interferon-gamma (IFN-γ) levels in the CM group and complement component 3 (C-3) levels in the DM group were significantly increased. The mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, NLRP3, IL-1β, and IL-18 in the jejunum of the DM group were significantly reduced. The diversity of cecal microbiota in the ferulic acid groups changed, with a certain degree of increase in the relative abundance of Spirulina and Ruminococcus. The relative abundance of Escherichia coli in the DM group significantly increased, altering the metabolic function of the cecal microbiota in broiler chickens. Conclusions: The above results indicate that ferulic acid, as a novel feed additive for broiler chickens, has an impact on the growth performance, anti-inflammatory and antioxidant capacity, immune function, and intestinal microbiota of broiler chickens. Full article

(This article belongs to the Special Issue Genetic Breeding of Poultry)

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9 pages, 529 KiB

Open AccessCase Report

A Patient with a Small Deletion Affecting Only Exon 1-Intron 1 of the NXF5 Gene: Potential Evidence Supporting Its Role in Neurodevelopmental Disorders

by Yessica Yesenia Tapia, Claudia Ciaccio, Merve Begüm Bacınoğlu, Stefano D’Arrigo and Francesca Luisa Sciacca

Genes 2025, 16(5), 571; https://doi.org/10.3390/genes16050571 - 13 May 2025

Abstract

Genetic studies have identified numerous candidate genes for neurodevelopmental disorders associated with intellectual disability (ID) and autism spectrum disorders (ASD). Some genetic anomalies are very rare or challenging to detect, making it essential to validate the presence of gene mutations or copy number [...] Read more.

Genetic studies have identified numerous candidate genes for neurodevelopmental disorders associated with intellectual disability (ID) and autism spectrum disorders (ASD). Some genetic anomalies are very rare or challenging to detect, making it essential to validate the presence of gene mutations or copy number variations in additional patients with similar clinical phenotypes. Background/Objectives: Case reports play a crucial role in this process by validating rare variants in phenotypically matched patients, shedding light on novel candidate genes linked to these disorders. Methods: Patients with ID and ASD underwent neurological examinations, brain magnetic resonance imaging (MRI), sleep and wake electroencephalogram (EEG), neuropsychological evaluations, and laboratory tests including molecular analysis for fragile-X syndrome and array comparative genomic hybridization (aCGH). Results: We observed a patient with ID and ASD who carried a microdeletion in Xq22.1 that affects only exon 1 and intron 1 of the Nuclear RNA Export Factor 5 (NXF5) gene. The patient’s phenotypic features overlap with those of the only four previously reported cases of variations involving the same gene. Conclusions: Our findings suggest that NXF5 may play a role in neurodevelopmental disorders and should be considered in the spectrum of X-linked ID associated with ASD. Full article

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

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11 pages, 1953 KiB

Open AccessArticle

Genetic Background and Gene Essentiality

by Paulina Gąsienica, Katarzyna Toch, Kamila Stefania Zając-Garlacz and Marta Labocha-Derkowska

Genes 2025, 16(5), 570; https://doi.org/10.3390/genes16050570 - 13 May 2025

Abstract

Background/Objectives: Essential genes are those required for an organism’s survival and reproduction. However, gene essentiality is not absolute; it can be highly context-dependent, varying across genetic and environmental conditions. Most previous studies have assessed gene essentiality in a single genetic background, limiting our [...] Read more.

Background/Objectives: Essential genes are those required for an organism’s survival and reproduction. However, gene essentiality is not absolute; it can be highly context-dependent, varying across genetic and environmental conditions. Most previous studies have assessed gene essentiality in a single genetic background, limiting our understanding of its variability. The objective of this study was to investigate how genetic background influences gene essentiality in the multicellular model organism Caenorhabditis elegans. Methods: We examined gene essentiality in three genetically distinct C. elegans strains: N2, LKC34, and MY16. A total of 294 genes were selected for RNA interference (RNAi) knockdown: 101 previously classified as essential, 175 as nonessential and 18 as conditional (condition-dependent essentiality). Each gene–strain combination was tested in multiple biological and technical replicates, and rigorous quality control and statistical analyses were used to identify strain-specific effects. Results: Our results demonstrate substantial variation in gene essentiality across genetic backgrounds. Among the 101 genes previously identified as essential in the N2 strain, only 56% were consistently essential in all three strains. We identified 23 genes that were newly essential across all strains, 13 genes essential in two strains, and 9 genes essential in only one strain. These results reveal that a significant proportion of essential genes exhibit strain-dependent essentiality. Conclusions: This study underscores the importance of genetic context in determining gene essentiality. Our findings suggest that relying on a single genetic background, such as N2, may lead to an incomplete or misleading view of gene essentiality. Understanding context-dependent gene essentiality has important implications for functional genomics, evolutionary biology, and potentially for translational research where genetic background can modulate phenotypic outcomes. Full article

(This article belongs to the Section Genes & Environments)

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20 pages, 587 KiB

Open AccessReview

Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects

by Iwona Ziółkowska-Suchanek and Natalia Rozwadowska

Genes 2025, 16(5), 569; https://doi.org/10.3390/genes16050569 - 12 May 2025

Viewed by 46

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, characterized by late diagnosis and resistance to conventional therapies. Gene therapy has emerged as a promising alternative for NSCLC therapy, especially for patients with advanced disease who have exhausted conventional [...] Read more.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, characterized by late diagnosis and resistance to conventional therapies. Gene therapy has emerged as a promising alternative for NSCLC therapy, especially for patients with advanced disease who have exhausted conventional treatments. This article delved into the current developments in gene therapy for NSCLC, including gene replacement and tumor suppressor gene therapy, gene silencing, CRISPR/Cas9 gene editing, and immune modulation with CAR-T cell therapy. In addition, the challenges and future prospects of gene-based therapies for NSCLC were discussed. Full article

(This article belongs to the Special Issue Recent Advances in the Molecular Genetics of Lung Cancer)

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12 pages, 2533 KiB

Open AccessArticle

Genome-Wide Analysis of Copy Number Variations in Three Populations of Nanyang Cattle Using Whole-Genome Resequencing

by Dong Dang, Lilian Zhang, Lutao Gao, Lin Peng, Yao Rao and Linnan Yang

Genes 2025, 16(5), 568; https://doi.org/10.3390/genes16050568 - 12 May 2025

Viewed by 65

Abstract

Copy number variation (CNV) serves as a crucial contributor to genetic diversity, exerting a profound influence on phenotypic diversity, traits of economic significance, and the evolutionary trajectory of livestock species. This study aimed to dissect the genome-wide CNV landscape of the Nanyang cattle [...] Read more.

Copy number variation (CNV) serves as a crucial contributor to genetic diversity, exerting a profound influence on phenotypic diversity, traits of economic significance, and the evolutionary trajectory of livestock species. This study aimed to dissect the genome-wide CNV landscape of the Nanyang cattle line (Nanyang, Pinnan, and Xianan cattle) to identify functionally relevant CNVs associated with key economic traits and breed differentiation. In this study, 27 resequencing datasets were utilized to analyze the genome-wide distribution of CNVs in three breeds of Nanyang cattle (Nanyang cattle, Pinnan cattle, and Xianan cattle) based on the latest reference genome ARS-UCD2.0. This study identified a total of 97,564 CNVs, and after merging CNVs with overlapping genomic positions, we obtained 10,349 CNV regions (CNVRs), accounting for 1.48% of the reference genome. Functional enrichment analysis showed that CNVR genes were mainly involved in organ development, neural regulation, immune regulation, and metabolism. In addition, 131 CNVRs overlapped with 81 quantitative trait loci (QTLs), such as growth and carcass QTL, multiple birth QTL, tenderness score QTL, and antal follicle number QTL. Additionally, AOX1, KRT72, and ZBTB7C were found to overlap with body weight QTLs. Furthermore, a selective sweep analysis of CNVR revealed that numerous genes (KIF26A, SPINT4, OR5W1, etc.) exhibited divergent copy numbers between breeds. Conclusively, this study facilitates comprehension of the genetic characteristics of the Nanyang cattle line at the CNV level and furnishes valuable information for the advancement of the Nanyang cattle line breeding system. Full article

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

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14 pages, 3412 KiB

Open AccessArticle

The Complete Mitochondrial Genome of Petalocephala arcuata Cai Et Kuoh, 1992 (Hemiptera: Cicadellidae: Ledrinae: Petalocephalini) and Its Phylogenetic Implications

by Yujian Li, Yihong Guo, Ran Li, Yongcheng Liu, Chao Xue, Lina Jiang, Sai Jiang, Wei Wang and Xianfeng Yi

Genes 2025, 16(5), 567; https://doi.org/10.3390/genes16050567 - 10 May 2025

Viewed by 144

Abstract

Background/Aims: Ledrinae comprises about 460 described species across five tribes and represents an early-branching, morphologically distinctive lineage of leafhoppers, yet its intra-subfamilial relationships remain ambiguous owing to limited mitogenomic sampling. Here, we sequence and annotate the complete mitochondrial genome of Petalocephala arcuata—only [...] Read more.

Background/Aims: Ledrinae comprises about 460 described species across five tribes and represents an early-branching, morphologically distinctive lineage of leafhoppers, yet its intra-subfamilial relationships remain ambiguous owing to limited mitogenomic sampling. Here, we sequence and annotate the complete mitochondrial genome of Petalocephala arcuata—only the 18th Ledrinae mitogenome—to broaden taxon coverage within the genus and furnish critical molecular data for rigorously testing Ledrinae monophyly and refining tribal and genus level phylogenetic hypotheses. Methods: In this study, we sequenced and annotated the complete mitochondrial genome of P. arcuata via Illumina sequencing and de novo assembly, and reconstructed the phylogeny of 62 Cicadellidae species using maximum likelihood and Bayesian inference methods. Results: The 14,491 bp circular mitogenome of P. arcuata contains 37 genes with 77.4% A+T. All PCGs use ATN start codons except ND5 (TTG), and codon usage is A or U biased. Of 22 tRNAs, only trnS1 lacks a DHU arm, while the others adopt the canonical cloverleaf structure. Bayesian inference and maximum likelihood analyses produced broadly congruent topologies with mostly high nodal support, recovering Ledrinae as monophyletic and clustering all Petalocephala species into a well-supported clade. Conclusions: In this study, we enriched the molecular resources for the genus Petalocephala by sequencing, annotating, and analyzing the complete mitochondrial genome of P. arcuata. Phylogenetic reconstructions based on these genomic data align closely with previous morphological diagnoses, further confirming the monophyly of the genus Petalocephala. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals: 2024–2025)

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34 pages, 1707 KiB

Open AccessReview

Natural Bioproducts with Epigenetic Properties for Treating Cardiovascular Disorders

by Olaia Martínez-Iglesias, Vinogran Naidoo, Iván Carrera, Lola Corzo and Ramón Cacabelos

Genes 2025, 16(5), 566; https://doi.org/10.3390/genes16050566 - 10 May 2025

Viewed by 97

Abstract

Cardiovascular disorders (CVDs) are the leading cause of mortality worldwide, highlighting an urgent need for innovative therapeutic strategies. Recent advancements highlight the potential of naturally derived bioproducts with epigenetic properties to offer protection against CVDs. These compounds act on key epigenetic mechanisms, DNA [...] Read more.

Cardiovascular disorders (CVDs) are the leading cause of mortality worldwide, highlighting an urgent need for innovative therapeutic strategies. Recent advancements highlight the potential of naturally derived bioproducts with epigenetic properties to offer protection against CVDs. These compounds act on key epigenetic mechanisms, DNA methylation, histone modifications, and non-coding RNA regulation to modulate gene expression essential for cardiovascular health. This review explores the effects of various bioproducts, such as polyphenols, flavonoids, and other natural extracts, on these epigenetic modifications and their potential benefits in preventing and managing CVDs. We discuss recent discoveries and clinical applications, providing insights into the epigenetic regulatory mechanisms of these compounds as potential epidrugs, naturally derived agents with promising therapeutic prospects in epigenetic therapy for CVDs. Full article

(This article belongs to the Section Epigenomics)

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13 pages, 17357 KiB

Open AccessArticle

Comparative Mitochondrial Genomic and Phylogenetic Study of Eight Species of the Family Lonchodidae (Phasmatodea: Euphasmatodea)

by Ting Luo, Qianwen Zhang, Siyu Pang, Yanting Qin, Bin Zhang and Xun Bian

Genes 2025, 16(5), 565; https://doi.org/10.3390/genes16050565 - 10 May 2025

Viewed by 185

Abstract

Background: Lonchodidae is the largest family within the order Phasmatodea, and although many studies have been conducted on this family, the monophyly of the family has not been established. Methods: Eight mitogenomes from Lonchodidae, including the first complete mitogenomes of four genera, were [...] Read more.

Background: Lonchodidae is the largest family within the order Phasmatodea, and although many studies have been conducted on this family, the monophyly of the family has not been established. Methods: Eight mitogenomes from Lonchodidae, including the first complete mitogenomes of four genera, were sequenced and annotated to explore their features and phylogenetic relationships. Results: The total length ranged from 15,942–18,021 bp, and the mitogenome consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a control region (CR). atp8 had the highest A + T content in Lonchodidae, except for Neohirasea stephanus and Asceles clavatus, in which the highest A + T contents were detected in nad6. The phylogenetic trees were reconstructed via Bayesian inference (BI) and maximum likelihood (ML) based on the PCG123 and PCG12 datasets. As the phylogenetic trees show, Necrosciinae is recognized as monophyletic, but the monophyly of Lonchodinae has not been supported. Gene deletion and rearrangement have occurred mainly in Lonchodidae and Aschiphasmatidae. The most common reason for gene rearrangements was tandem duplication random loss (TDRL), but trnI of Stheneboea repudiosa inverted into the CR. In addition, genes within the same family or genus share related sequences and conserved gene blocks. Conclusions: we expanded the mitochondrial genomic data for this family, thereby establishing a foundational dataset for future studies. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals: 2024–2025)

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14 pages, 2034 KiB

Open AccessArticle

Body Mass Index as an Example of a Negative Confounder: Evidence and Solutions

by Zhu Liduzi Jiesisibieke and C. Mary Schooling

Genes 2025, 16(5), 564; https://doi.org/10.3390/genes16050564 - 10 May 2025

Viewed by 181

Abstract

Background: Adequate control for confounding is key to many observational study designs. Confounders are often identified based on subject matter knowledge from empirical investigations. Negative confounders, which typically generate type 2 error, i.e., false nulls, can be elusive. Such confounders can be identified [...] Read more.

Background: Adequate control for confounding is key to many observational study designs. Confounders are often identified based on subject matter knowledge from empirical investigations. Negative confounders, which typically generate type 2 error, i.e., false nulls, can be elusive. Such confounders can be identified comprehensively by using Mendelian randomization (MR) to search the wealth of publicly available data systematically. Here, to demonstrate the concept, we examined whether a common positive confounder, body mass index (BMI), is also a negative confounder of any common physiological exposures on health outcomes, overall and specifically by sex. Methods: We used an MR study, based on the largest overall and sex-specific genome-wide association studies of BMI (i.e., from the Genetic Investigation of ANthropometric Traits and the UK Biobank) and of relevant exposures likely affected by BMI, to assess, overall and sex-specifically, whether BMI is a negative confounder potentially obscuring effects of harmful physiological exposures. Inverse variance weighting was the main method. We assessed sex differences using a z-test. Results: BMI was a potential negative confounder for apolipoprotein B and total testosterone in men, and for both sexes regarding low-density lipoprotein cholesterol, choline, linoleic acid, polyunsaturated fatty acids, and cholesterol. Conclusions: Using BMI as an illustrative example, we demonstrate that negative confounding is an easily overlooked bias. Given negative confounding is not always obvious or known, using MR systematically to identify potential negative confounders in relevant studies may be helpful. Full article

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

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17 pages, 1755 KiB

Open AccessArticle

F_ST-Based Marker Prioritization Within Quantitative Trait Loci Regions and Its Impact on Genomic Selection Accuracy: Insights from a Simulation Study with High-Density Marker Panels for Bovines

by Sajjad Toghiani, Samuel E. Aggrey and Romdhane Rekaya

Genes 2025, 16(5), 563; https://doi.org/10.3390/genes16050563 - 10 May 2025

Viewed by 182

Abstract

Background/Objectives: Genomic selection (GS) has improved accuracy compared to traditional methods. However, accuracy tends to plateau beyond a certain marker density. Prioritizing influential SNPs could further enhance the accuracy of GS. The fixation index (F_ST) allows for the identification of SNPs [...] Read more.

Background/Objectives: Genomic selection (GS) has improved accuracy compared to traditional methods. However, accuracy tends to plateau beyond a certain marker density. Prioritizing influential SNPs could further enhance the accuracy of GS. The fixation index (F_ST) allows for the identification of SNPs under selection pressure. Although the F_ST method was shown to be able to prioritize SNPs across the whole genome and to increase accuracy, its performance could be further improved by focusing on the prioritization process within QTL regions. Methods: A trait with heritability of 0.1 and 0.4 was generated under different simulation scenarios (number of QTL, size of SNP windows around QTL, and number of selected SNPs within a QTL region). In total, six simulation scenarios were analyzed. Each scenario was replicated five times. The population comprised 30K animals from the last 2 generations (G9–G10) of a 10-generation (G1–G10) selection process. All animals in G9–10 were genotyped with a 600K SNP panel. F_ST scores were calculated for all 600K SNPs. Two prioritization scenarios were used: (1) selecting the top 1% SNPs with the highest F_ST scores, and (2) selecting a predetermined number of SNPs within each QTL window. GS accuracy was evaluated using the correlation between true and estimated breeding values for 5000 randomly selected animals from G10. Results: Prioritizing SNPs using F_ST scores within QTL window regions increased accuracy by 5 to 18%, with the 50-SNP windows showing the best performance. Conclusions: The increase in GS accuracy warrants the testing of the algorithm when the number and position of QTL are unknown. Full article

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

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13 pages, 296 KiB

Open AccessArticle

Enhanced Reliability of the Evaluation of Fertility Traits in Pura Raza Española Horses Using Single-Step Genomic Best Linear Unbiased Prediction

by Chiraz Ziadi, Mercedes Valera, Nora Laseca, Davinia Perdomo-González, Sebastián Demyda-Peyrás, Arancha Rodríguez-Sainz de los Terreros and Antonio Molina

Genes 2025, 16(5), 562; https://doi.org/10.3390/genes16050562 - 9 May 2025

Viewed by 130

Abstract

Background/Objectives: By simultaneously integrating both genotyped and non-genotyped animals into genetic evaluation, the single-step genomic BLUP method enhanced the accuracy of genetic assessments. This study aimed to compare the increase in prediction reliability (R²) between restricted maximum likelihood (REML) and single-step [...] Read more.

Background/Objectives: By simultaneously integrating both genotyped and non-genotyped animals into genetic evaluation, the single-step genomic BLUP method enhanced the accuracy of genetic assessments. This study aimed to compare the increase in prediction reliability (R²) between restricted maximum likelihood (REML) and single-step genomic REML (ssGREML) in the Pura Raza Española (PRE) horse breed. Methods: The dataset comprised reproductive records for seven fertility traits from 47,502 females, with a total of 57,316 animals represented in the pedigree. A total of 4009 animals were genotyped using the EQUIGENE 90K SNP array, and 71,322 SNPs were retained for analysis after quality control. Genetic parameters were estimated using a multivariate model with the BLUPF90+ v2.60 software. Results: Heritability estimates were similar between REML and ssGREML, ranging from 0.07 for IF12 to 0.349 for ALF. An increase in R² was observed with ssGREML compared to REML across all traits, with overall gains ranging from 2.20% to 3.71%. Among genotyped animals, R² values ranged from 17.81% to 24.04%, while significantly lower values (0.80% to 2.34%) were observed in non-genotyped animals. Notably, individuals with low initial R² values under the REML approach exhibited the most significant gains using ssGREML. This improvement was particularly pronounced among stallions with fewer than 40 controlled foals. Conclusions: Our results demonstrated that incorporating genomic data improves the reliability of genetic evaluations for mare fertility in PRE horses. Full article

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

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13 pages, 2545 KiB

Open AccessArticle

Mitochondrial Genomes of the Robberflies Clephydroneura jiangxiensis and Maira xizangensis (Diptera: Asilidae) and Phylogeny of Three Superfamilies

by Keyao Zhang, Junhui Lu and Sheng-Quan Xu

Genes 2025, 16(5), 561; https://doi.org/10.3390/genes16050561 - 8 May 2025

Viewed by 222

Abstract

Background: Asilomorpha, an infraorder of predatory Diptera (Brachycera), is of significant evolutionary interest due to their remarkable ecological diversity, broad size range, and specialized feeding behaviors. However, phylogenetic studies of this group have been limited by sampling challenges. Methods: In this study, we [...] Read more.

Background: Asilomorpha, an infraorder of predatory Diptera (Brachycera), is of significant evolutionary interest due to their remarkable ecological diversity, broad size range, and specialized feeding behaviors. However, phylogenetic studies of this group have been limited by sampling challenges. Methods: In this study, we sequenced the complete mitochondrial genomes of two Chinese endemic species, Clephydroneura jiangxiensis (C. jiangxiensis) and Maira xizangensis (M. xizangensis), using whole-genome random sequencing. By integrating these novel data with published sequences from NCBI, we reconstructed the phylogeny of three superfamilies (Asiloidea, Empidoidea, and Nemestrinoidea). Results: Both mitochondrial genomes exhibit the typical 37 genes (13 protein-coding genes, 22 tRNAs, and 2 rRNAs) and display pronounced AT bias. Congruent results from maximum likelihood analysis and Bayesian inference strongly supported the ideas that both new species are placed in Asilidae and that the Asilidae family is monophyletic. However, relationships among the three superfamilies remain unclear. Our results suggest that (1) although Asiloidea and Nemestrinidea are closely related, the potential positioning of Nemestrinoidea as an independent superfamily is worth investigating; and (2) Empidoidea may form a sister group to Asiloidea + Nemestrinidae, though this hypothesis requires further corroboration given the basal position of Hemipenthes hebeiensis (Bombyliidae). Conclusions: These findings highlight the need for expanded taxon sampling, particularly of underrepresented families, to resolve deep-level relationships within Asilomorpha. Clarifying the phylogenetic relationships within Asilomorpha will facilitate future investigations into their evolutionary origins and the evolution of characteristic traits. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals: 2024–2025)

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28 pages, 708 KiB

Open AccessReview

The Role of Artificial Intelligence in Identifying NF1 Gene Variants and Improving Diagnosis

by Vasiliki Sofia Grech, Kleomenis Lotsaris, Theano Eirini Touma, Vassiliki Kefala and Efstathios Rallis

Genes 2025, 16(5), 560; https://doi.org/10.3390/genes16050560 - 7 May 2025

Viewed by 617

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene, typically diagnosed during early childhood and characterized by significant phenotypic heterogeneity. Despite advancements in next-generation sequencing (NGS), the diagnostic process remains challenging due to the gene’s complexity, [...] Read more.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene, typically diagnosed during early childhood and characterized by significant phenotypic heterogeneity. Despite advancements in next-generation sequencing (NGS), the diagnostic process remains challenging due to the gene’s complexity, high mutational burden, and frequent identification of variants of uncertain significance (VUS). This review explores the emerging role of artificial intelligence (AI) in enhancing NF1 variant detection, classification, and interpretation. A systematic literature search was conducted across PubMed, IEEE Xplore, Google Scholar, and ResearchGate to identify recent studies applying AI technologies to NF1 genetic analysis, focusing on variant interpretation, structural modeling, tumor classification, and therapeutic prediction. The review highlights the application of AI-based tools such as VEST3, REVEL, ClinPred, and NF1-specific models like DITTO and RENOVO-NF1, which have demonstrated improved accuracy in classifying missense variants and reclassifying VUS. Structural modeling platforms like AlphaFold contribute further insights into the impact of NF1 mutations on neurofibromin structure and function. In addition, deep learning models, such as LTC neural networks, support tumor classification and therapeutic outcome prediction, particularly in NF1-associated complications like congenital pseudarthrosis of the tibia (CPT). The integration of AI methodologies offers substantial potential to improve diagnostic precision, enable early intervention, and support personalized medicine approaches. However, key challenges remain, including algorithmic bias, limited data diversity, and the need for functional validation. Ongoing refinement and clinical validation of these tools are essential to ensure their effective implementation and equitable use in NF1 diagnostics. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 4586 KiB

Open AccessArticle

Identification of Mustard Aldehyde Dehydrogenase (ALDH) Gene Family and Expression Analysis Under Salt and Drought Stress

by Yuling Zheng, Shanshan Wang, Ling He, Rui Chen, Wei Zhang, Huachuan He, Hanbing Hu, Xiaoyun Liu, Heping Wan and Chunhong Wu

Genes 2025, 16(5), 559; https://doi.org/10.3390/genes16050559 - 7 May 2025

Viewed by 138

Abstract

Background/Objectives: Abiotic stresses severely constrain the yield of Brassica juncea, and aldehyde dehydrogenases (ALDHs) play a pivotal role in plant stress resistance. This study aims to systematically identify the ALDH gene family members in B. juncea and elucidate their expression patterns under salt [...] Read more.

Background/Objectives: Abiotic stresses severely constrain the yield of Brassica juncea, and aldehyde dehydrogenases (ALDHs) play a pivotal role in plant stress resistance. This study aims to systematically identify the ALDH gene family members in B. juncea and elucidate their expression patterns under salt and drought stress. Methods: Using the Arabidopsis thaliana AtALDH proteins as seed sequences, BLASTp alignment was performed against the B. juncea whole-protein sequence database, combined with the conserved domain PF00171 of the ALDH proteins. A total of 39 BjALDH gene family members were identified, and their physicochemical properties, structures, phylogenetic relationships, interspecies collinearity, and intraspecies collinearity were analyzed. The qRT-PCR method was employed to quantify the relative expression levels of the BjALDH genes potentially associated with stress resistance under various treatments, and their effects on drought and salt stress tolerance were evaluated. Results: The results demonstrated that BjALDH were universally significantly upregulated under salt stress, while exhibiting predominantly upregulated trends under drought stress. These findings suggest that BjALDH may enhance plant resistance to both salt and drought stress by modulating the aldehyde metabolic pathways. Conclusions: This study provides a theoretical basis for elucidating the functional roles and molecular genetic mechanisms of the BjALDH gene family in B. juncea under salt and drought stress. Full article

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

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13 pages, 5236 KiB

Open AccessArticle

De Novo Transcriptome Sequencing Analysis Revealed the Expression Patterns of Genes in Different Organs and the Molecular Basis of Polysaccharide Synthesis in Bletilla striata

by Wenkui Liu, Jinxing Jiang, Zhonghai Tang, Zemao Yang and Jingping Qin

Genes 2025, 16(5), 558; https://doi.org/10.3390/genes16050558 - 6 May 2025

Viewed by 197

Abstract

Background: Bletilla striata (Thunb.) Rchb.f., a perennial medicinal plant in the genus Bletilla of the Orchidaceae family, is renowned for its hemostatic, anti-inflammatory, and tissue-regenerative properties. Despite the established importance of polysaccharides as key bioactive components in B. striata, the genes and [...] Read more.

Background: Bletilla striata (Thunb.) Rchb.f., a perennial medicinal plant in the genus Bletilla of the Orchidaceae family, is renowned for its hemostatic, anti-inflammatory, and tissue-regenerative properties. Despite the established importance of polysaccharides as key bioactive components in B. striata, the genes and molecular mechanisms underlying their synthesis remain largely unexplored. Methods: This study conducted transcriptomic analysis on the roots, tubers, and leaves of B. striata, and identified gene expression profiles and candidate genes for polysaccharide synthesis in different organs. Results: The results indicated that there were 7699 differentially expressed genes (DEGs) in Tuber vs. Leaf, 7695 DEGs in Luber vs. Root, and 6151 DEGs in Tuber vs. Root. There were significant differences in polysaccharide metabolism pathways (photosynthesis, starch, and sucrose metabolism) in different organs of B. striata. The overall enrichment levels were ranked as tubers > leaves > roots. It is worth noting that enzyme genes involved in polysaccharide synthesis exhibit significant organ specificity, with HK genes expression significantly higher in roots than in tubers and leaves, PMM, GMPP, pgm, and UGP2 genes highly expressed in tubers, while scrK, manA, and GPI genes have similar expression levels in the three organs. Conclusions: These findings identify key enzyme genes involved in the synthesis of polysaccharides in B. striata, providing a theoretical framework for enhancing its medicinal value through genetic improvement. Full article

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

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11 pages, 933 KiB

Open AccessReview

Leveraging Spatial Transcriptomics to Decode Craniofacial Development

by Jeremie Oliver Piña, Resmi Raju, Aye Chan Myo, Evan Stipano, Malachi Wright and Rena N. D’Souza

Genes 2025, 16(5), 557; https://doi.org/10.3390/genes16050557 - 3 May 2025

Viewed by 375

Abstract

Understanding how intricate cellular networks and signaling pathways communicate during the formation of craniofacial tissues like the palate and tooth has been the subject of intense investigation for several decades. Both organ systems undergo patterning morphogenesis and the subsequent terminal differentiation of matrix-producing [...] Read more.

Understanding how intricate cellular networks and signaling pathways communicate during the formation of craniofacial tissues like the palate and tooth has been the subject of intense investigation for several decades. Both organ systems undergo patterning morphogenesis and the subsequent terminal differentiation of matrix-producing cells that form biomineralized matrices like bone, enamel, dentin, and cementum. Until recently, gene expression profiles could only be assessed for a select number of cells without the context of the entire milieu of genes expressed by neighboring cells and tissues. Today, the cutting-edge field of spatial transcriptomics offers a remarkable suite of innovative technologies of multiplex gene analyses and imaging that can assess the expression of a vast library of genes that are present in situ during normal and abnormal conditions. In this review, we summarize some key technologies which have in recent years enabled an unprecedented breadth and depth of transcriptomic analyses in craniofacial development. We focus in detail on select methods that our research group has applied to better understand the cellular and molecular events that drive palate and tooth development. Our overall goal is to unravel the complexities of these unique biological systems to provide meaningful biological insights into the cellular and molecular events that drive normal development. As a work-in-progress, we strive for a deeper understanding of the temporal and spatial gene expression profiles within cells and tissues during normal and abnormal palate and tooth development. Such knowledge provides the framework for further studies that can characterize the function of new or novel genes that have the potential of serving as therapeutic targets for correcting disorders like cleft palate and tooth agenesis. Full article

(This article belongs to the Special Issue Genetic, Epigenetic and Environmental Factors in Dental Development and Pathologies: Genes, Interactions and Dental Development)

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10 pages, 458 KiB

Open AccessArticle

Clinicopathological Characteristics of Ovarian and Breast Cancer in PALB2, RAD51C, and RAD51D Germline Pathogenic Variant Carriers

by Jella-Rike J. A. H. Spijkervet, L. Lanjouw, L. P. V. Berger, M. D. Dorrius, B. van der Vegt and G. H. de Bock

Genes 2025, 16(5), 556; https://doi.org/10.3390/genes16050556 - 2 May 2025

Viewed by 308

Abstract

Background/Objectives: Germline pathogenic variants (GPVs) in PALB2, RAD51C, and RAD51D increase breast cancer (BC) and ovarian cancer (OC) risk. Limited data on clinicopathological characteristics of BC and OC in women with these GPVs hamper guideline development. Therefore, this study aims to [...] Read more.

Background/Objectives: Germline pathogenic variants (GPVs) in PALB2, RAD51C, and RAD51D increase breast cancer (BC) and ovarian cancer (OC) risk. Limited data on clinicopathological characteristics of BC and OC in women with these GPVs hamper guideline development. Therefore, this study aims to describe these characteristics in a consecutive series of female PALB2, RAD51C, and RAD51D GPV carriers. Methods: Women with a PALB2, RAD51C, or RAD51D GPV determined before July 2023 at the University Medical Center Groningen were included. Cancer diagnoses were obtained through linkage with the Dutch Nationwide Pathology Databank (Palga). Median onset age and histopathological subtypes were compared to the data of The Netherlands Cancer Registry (NCR). Results: Among 164 GPV carriers (125 PALB2, 30 RAD51C, and 9 RAD51D), 54 BC and 6 OC cases were identified. The median BC onset age was 52 (n = 50), 71 (n = 3), and 43 years (n = 1) for PALB2, RAD51C, and RAD51D, respectively, compared with 62 years in the NCR. No BC histological subtype differences were observed in PALB2 carriers. The populations of RAD51C and RAD51D carriers were too small to compare to NCR data. No OC cases occurred in PALB2 carriers. The median OC onset age was 66 (n = 4) and 56 years (n = 2) for RAD51C and RAD51D carriers, respectively, versus 67 years in the NCR. All RAD51D carriers had high-grade serous carcinoma, compared to 51.5% in the NCR. Conclusions: Differences in onset age and histological subtypes were observed between GPV carriers and national data. Further research on cancer characteristics is needed to optimize counseling and cancer prevention in these women. Full article

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

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19 pages, 33327 KiB

Open AccessArticle

Genome-Wide Characterization and Analysis of the FH Gene Family in Medicago truncatula Under Abiotic Stresses

by Jiatong Wang and Chunyang Zhou

Genes 2025, 16(5), 555; https://doi.org/10.3390/genes16050555 - 1 May 2025

Viewed by 245

Abstract

Background: The formin family proteins play an important role in guiding the assembly and nucleation of linear actin and can promote the formation of actin filaments independently of the Arp2/3 complex. As a key protein that regulates the cytoskeleton and cell morphological structure, [...] Read more.

Background: The formin family proteins play an important role in guiding the assembly and nucleation of linear actin and can promote the formation of actin filaments independently of the Arp2/3 complex. As a key protein that regulates the cytoskeleton and cell morphological structure, the formin gene family has been widely studied in plants such as Arabidopsis thaliana and rice. Methods: In this study, we conducted comprehensive analyses, including phylogenetic tree construction, conserved motif identification, co-expression network analysis, and transcriptome data mining. Results: A total of 18 MtFH gene family members were identified, and the distribution of these genes on chromosomes was not uniform. The phylogenetic tree divided the FH proteins of the four species into two major subgroups (Clade I and Clade II). Notably, Medicago truncatula and soybean exhibited closer phylogenetic relationships. The analysis of cis-acting elements revealed the potential regulatory role of the MtFH gene in light response, hormone response, and stress response. GO enrichment analysis again demonstrated the importance of FH for reactions such as actin nucleation. Expression profiling revealed that MtFH genes displayed significant transcriptional responsiveness to cold, drought, and salt stress conditions. And there was a temporal complementary relationship between the expression of some genes under stress. The protein interaction network indicated an interaction relationship between MtFH protein and profilin, etc. In addition, 22 miRNAs were screened as potential regulators of the MtFH gene at the post-transcriptional level. Conclusions: In general, this study provides a basis for deepening the understanding of the physiological function of the MtFH gene and provides a reference gene for stress resistance breeding in agricultural production. Full article

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

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18 pages, 4864 KiB

Open AccessArticle

The Complete Mitochondrial Genome of Red Costate Tiger Moth (Aloa lactinea [Cramer, 1777]), and Phylogenetic Analyses of the Subfamily Arctiinae

by Chengrong Pan, Sheng Xu, Yu Shu and Jie Fang

Genes 2025, 16(5), 554; https://doi.org/10.3390/genes16050554 - 30 Apr 2025

Viewed by 170

Abstract

Background/Objectives: Aloa lactinea, class Insecta, order Lepidoptera, superfamily Noctuoidea, family Erebidae, and subfamily Arctiinae, is a polytrophic agricultural pest. However, there are still many sequences missing for Arctiinae from mitochondrial whole-genome sequences. Methods: In this study, we determined and analyzed the complete [...] Read more.

Background/Objectives: Aloa lactinea, class Insecta, order Lepidoptera, superfamily Noctuoidea, family Erebidae, and subfamily Arctiinae, is a polytrophic agricultural pest. However, there are still many sequences missing for Arctiinae from mitochondrial whole-genome sequences. Methods: In this study, we determined and analyzed the complete mitochondrial genome sequence of A. lactinea. Furthermore, based on the sequencing results, we used the Bayesian inference, maximum likelihood, and maximum reduction methods to analyze the phylogenies of 18 species of the Hypophora subfamily. Results: The mitochondrial genome was found to be a circular double-stranded DNA with a length of 15,380 bp and included 13 protein-coding genes (PCG_S), 22 tRNA genes, 2 rRNA genes, and one control region. With the exception of tRNA^Ser(AGC), all the tRNA genes could form conventional clover structures. There were 23 intergenic spacer regions with lengths of 1–52 bp and six gene overlaps with lengths of 1–8 bp. The control region was located between rrnS and tRNA^Met genes and comprised 303 bp and an AT content of 74.25%. Conclusions: The results showed that A. lactinea is closely related to Hyphantria cunea. Our results suggest that Syntomini is phylogenetically distinct from Arctiini and may warrant separate tribal status within Arctiinae. This study is dedicated to researching the mitochondrial genome and phylogenetic relationships of A. lactinea, providing a molecular basis for its classification. Full article

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

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21 pages, 7303 KiB

Open AccessReview

Updates on the Regulatory Framework of Edited Organisms in Brazil: A Molecular Revolution in Brazilian Agribusiness

by Nicolau B. da Cunha, Jaim J. da Silva Junior, Amanda M. M. Araújo, Ludmila R. de Souza, Michel L. Leite, Gabriel da S. Medina, Gustavo R. Rodriguez, Renan M. dos Anjos, Júlio C. M. Rodrigues, Fabrício F. Costa, Simoni C. Dias, Elíbio L. Rech and Giovanni R. Vianna

Genes 2025, 16(5), 553; https://doi.org/10.3390/genes16050553 - 30 Apr 2025

Viewed by 495

Abstract

Genome editing technologies have revolutionized the production of microorganisms, plants, and animals with phenotypes of interest to agriculture. Editing previously sequenced genomes allows for the punctual, discreet, precise, and accurate alteration of DNA for genetic analysis, genotyping, and phenotyping, as well as the [...] Read more.

Genome editing technologies have revolutionized the production of microorganisms, plants, and animals with phenotypes of interest to agriculture. Editing previously sequenced genomes allows for the punctual, discreet, precise, and accurate alteration of DNA for genetic analysis, genotyping, and phenotyping, as well as the production of edited organisms for academic and industrial purposes, among many other objectives. In this context, genome editing technologies have been causing a revolution in Brazilian agriculture. Thanks to the publication of Normative Resolution No. 16 (in Portuguese Resolução Normativa No. 16-RN16) in 2018, Brazilian regulatory authorities have adapted to the new genetic manipulation technologies available to the scientific community. This review aims to describe the effects of updates to the regulatory framework for edited organisms in Brazil and to point out their impacts on research and development of emerging technologies in the Brazilian agricultural sector. The implementation of RN16 rationalized the regulatory aspects regarding the production, manipulation, exploration and commercial release of edited organisms and led to the faster, cheaper and safer obtaining of edited technologies, which are more productive and better adapted to different environmental conditions in Brazil. Full article

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

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21 pages, 1417 KiB

Open AccessReview

Non-Invasive Preimplantation Genetic Testing

by Daniela N. Bakalova, Luis Navarro-Sánchez and Carmen Rubio

Genes 2025, 16(5), 552; https://doi.org/10.3390/genes16050552 - 30 Apr 2025

Viewed by 177

Abstract

To minimise the influence of chromosomal abnormalities during IVF treatment, embryos can be screened before transfer using preimplantation genetic testing. This typically involves an invasive trophectoderm biopsy at the blastocyst stage, where 4–8 cells are collected and analysed. However, emerging evidence indicates that, [...] Read more.

To minimise the influence of chromosomal abnormalities during IVF treatment, embryos can be screened before transfer using preimplantation genetic testing. This typically involves an invasive trophectoderm biopsy at the blastocyst stage, where 4–8 cells are collected and analysed. However, emerging evidence indicates that, as embryos develop in vitro in culture media, they release cell-free DNA into the media, providing an alternative source of genetic material that can be accessed non-invasively. Spent blastocyst media samples that contain embryo cell-free DNA demonstrate high informativity rates and ploidy concordance when compared with the corresponding trophectoderm, inner cell mass, or whole blastocyst results. However, optimising this non-invasive approach requires several changes to embryo culture protocols, including additional embryo washes to tackle contamination and extending embryo culture time to maximise the amount of cell-free DNA released into the culture media. In this review, we discuss this novel non-invasive approach for aneuploidy detection and embryo prioritisation, as well as the current data and future prospects for utilising cell-free DNA analysis to identify structural rearrangements and single gene disorders. Full article

(This article belongs to the Special Issue Current Advances and Future Perspectives on Preimplantation Genetic Testing)

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20 pages, 1663 KiB

Open AccessArticle

Isolation, Enrichment and Analysis of Aerobic, Anaerobic, Pathogen-Free and Non-Resistant Cellulose-Degrading Microbial Populations from Methanogenic Bioreactor

by Lyudmila Dimitrova, Yana Ilieva, Dilnora Gouliamova, Vesselin Kussovski, Venelin Hubenov, Yordan Georgiev, Tsveta Bratanova, Mila Kaleva, Maya M. Zaharieva and Hristo Najdenski

Genes 2025, 16(5), 551; https://doi.org/10.3390/genes16050551 - 30 Apr 2025

Viewed by 156

Abstract

Background: Nowadays, the microbial degradation of cellulose represents a new perspective for reducing cellulose waste from industry and households and at the same time obtaining energy sources. Methods: We isolated and enriched two aerobic (at 37 °C and 50 °C) and one anaerobic [...] Read more.

Background: Nowadays, the microbial degradation of cellulose represents a new perspective for reducing cellulose waste from industry and households and at the same time obtaining energy sources. Methods: We isolated and enriched two aerobic (at 37 °C and 50 °C) and one anaerobic microbial consortium from an anaerobic bioreactor for biogas production by continuous subculturing on peptone cellulose solution (PCS) medium supplemented with 0.3% treated or untreated Whatman filter paper under static conditions. Samples were taken every 7 days until day 21 to determine the percentage of cellulose biodegradation. We determined the antimicrobial resistance of aerobic and anaerobic consortia and some single colonies by disc diffusion method, against 42 clinically applied antibiotics. PCR analyses were performed to search for the presence of eight genes for cellulolytic activity and nine genes for antibiotic resistance. By metagenomics analysis, the bacterial and fungal genus distributions in the studied populations were determined. Results: Aerobes cultured at 50 °C degraded cellulose to the greatest extent (47%), followed by anaerobes (24–38%) and aerobes (8%) cultured at 37 °C. The bacterial sequence analysis showed that the dominant phyla are Bacillota and Bacteroidetes and genera—Paraclostridium, Defluvitalea, Anaerobacillus, Acetivibrio, Lysinibacillus, Paenibacillus, Romboutsia, Terrisporobacter, Clostridium, Sporanaerobacter, Lentimicrobium, etc. in a different ratio depending on the cultivation conditions and the stage of the process. Some of these representatives are cellulolytic and hemicellulolytic microorganisms. We performed lyophilization and proved that it is suitable for long-term storage of the most active consortium, which degrades even after the 10th re-inoculation for a period of one year. We proved the presence of ssrA, ssrA BS and blaTEM genes. Conclusions: Our findings demonstrated the potential utility of the microbial consortium of anaerobes in the degradation of waste lignocellulose biomass. Full article

(This article belongs to the Section Genes & Environments)

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Genes, Volume 16, Issue 5 (May 2025) – 110 articles

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