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Volume 16
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Genes, Volume 16, Issue 3 (March 2025) – 119 articles

Cover Story (view full-size image): Fragile X syndrome (FXS) arises from CGG-repeat expansion-induced epigenetic silencing of FMR1, guided by its own nascent RNA. 5-aza-deoxycytidine (5-aza-dC) reactivates FMR1 by inhibiting DNA methylation, but withdrawal causes resilencing. We show that 2HE-5NMe, an RNA-binding small molecule, prevents resilencing by blocking CGG-repeat RNA from forming RNA-DNA hybrids, which trigger silencing. This sustains the FMR1 expression, restores FMRP, and reverses dendritic spine defects. Unlike broad epigenetic drugs, 2HE-5NMe enables gene-specific control. This study demonstrates the potential of developing RNA-targeted small molecules for epigenetic therapy in FXS and similar disorders. View this paper
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12 pages, 1551 KiB  
Article
Cross-Kingdom Communication via Plant-Derived Extracellular Vesicle Nucleic Acids in Genetically Engineered Nicotiana tabacum
by Lorena Urbanelli, Federica Delo, Giada Cerrotti, Emidio Albertini, Jacopo Lucci, Sandra Buratta, Eleonora Calzoni, Stefano Giovagnoli, Luana Lugini, Cristina Federici, Federica Fratini, Valentino Mercati and Carla Emiliani
Genes 2025, 16(3), 356; https://doi.org/10.3390/genes16030356 - 20 Mar 2025
Viewed by 744
Abstract
Background/Objectives: Plants release extracellularly lipid bilayer-enclosed vesicles of nanometric size that can be retrieved in their fluids. Plant-derived extracellular vesicles (PDEVs) have mostly been involved in modulating host–pathogen interaction, making them a tool for cross-kingdom communication with a key role in plant immunity. [...] Read more.
Background/Objectives: Plants release extracellularly lipid bilayer-enclosed vesicles of nanometric size that can be retrieved in their fluids. Plant-derived extracellular vesicles (PDEVs) have mostly been involved in modulating host–pathogen interaction, making them a tool for cross-kingdom communication with a key role in plant immunity. In addition, PDEVs have demonstrated promising therapeutic features, not only in terms of intrinsic nutraceutical properties but also of active molecules’ delivery. Transgenic plants have been developed for a variety of purposes, i.e., to improve their functional properties like crops, but also to produce therapeutic molecules. However, it is unclear whether transgenes can end up in PDEVs, thus making them a vehicle for their cross-kingdom diffusion into the environment. Methods: Here, we investigated the association of transgenic DNA and RNA with PDEVs secreted by tobacco (Nicotiana tabacum) engineered to express the neomycine phosphotransferase II (Npt-II) gene. PDEVs were isolated from leaf apoplastic fluid by ultracentrifugation and characterized for their morphology and size. The association of DNA and RNA was assessed by qRT-PCR and their immunomodulatory properties by assaying PDEVs-induced IL1β and IL10 on THP1 monocytes. Results: Npt-II RNA, but not DNA, could be amplified from PDEVs, whereas no differences were observed between wt and transgenic tobacco PDEVs in terms of immunomodulatory properties. Conclusions: Although a different behaviour by other types of RNAs or DNAs could still be possible, our findings indicate that in this model, PDEVs are not associated with transgenic DNA, but they can protect RNA, including transgenic RNA, from degradation, contributing to their cross-kingdom spreading. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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14 pages, 4165 KiB  
Article
The First Complete Mitochondrial Genomes for the Genus Dianema (Siluriformes: Callichthyidae): Dianema longibarbis and D. urostriatum
by Seong Duk Do and Jae-Sung Rhee
Genes 2025, 16(3), 355; https://doi.org/10.3390/genes16030355 - 20 Mar 2025
Viewed by 307
Abstract
Background/Objectives: To date, no information is available on the complete mitochondrial genome of the genus Dianema (Siluriformes: Callichthyidae), a callichthyid catfish. In this study, we report on two complete mitochondrial genome sequences of Dianema longibarbis Cope, 1872, and Dianema urostriatum Miranda Ribeiro, 1912, the [...] Read more.
Background/Objectives: To date, no information is available on the complete mitochondrial genome of the genus Dianema (Siluriformes: Callichthyidae), a callichthyid catfish. In this study, we report on two complete mitochondrial genome sequences of Dianema longibarbis Cope, 1872, and Dianema urostriatum Miranda Ribeiro, 1912, the only two recognized species within the genus Dianema. Methods: DNA sequencing was performed using the HiSeq platform to obtain their complete mitogenomes. To confirm phylogenetic distance, two phylogenetic trees were established using maximum-likelihood and Bayesian inference methods with all concatenated protein-coding sequences (PCGs) and two ribosomal RNA (rRNA) genes from the D. longibarbis and D. urostriatum mitogenomes, along with 32 mitogenomes retrieved from Siluriformes. Results: The complete mitogenomes of D. longibarbis and D. urostriatum are 16,493 and 16,495 base pairs in length, respectively. Their nucleotide compositions are 31.79% A, 27.53% T, 25.86% C, and 14.82% G for D. longibarbis, and 31.69% A, 27.04% T, 26.36% C, and 14.91% G for D. urostriatum. Both mitogenomes contain 13 PCGs, 22 transfer RNA (tRNA) genes, and two rRNA genes. Phylogenetic results based on all PCGs and two rRNAs genes confirm D. longibarbis as a sister species to D. urostriatum in the subfamily Callichthyinae. Conclusions: In contrast to the extensive mitochondrial studies on species in the Corydoradinae, species in the Callichthyinae have been largely understudied. This study provides valuable insights into genetic diversity and evolutionary complexity by presenting the first mitochondrial genome analysis of two Dianema species, a genus within the Callichthyinae. Full article
(This article belongs to the Special Issue Mitochondrial DNA Replication and Transcription)
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10 pages, 1154 KiB  
Case Report
Unique Case Report: A Rare Association of 21-Hydroxylase Deficiency with Triple X Karyotype
by Rossana Santiago de Sousa Azulay, Alexandre Nogueira Facundo, Sarah Sousa e Sousa, Gilvan Cortes Nascimento, Marcelo Magalhães, Clariano Pires de Oliveira Neto, Joana D’arc Matos França de Abreu, Débora Cristina Ferreira Lago, Sabrina da Silva Pereira Damianse, Viviane Chaves de Carvalho, Caio Andrade Nascimento, Vandilson Pinheiro Rodrigues, Fernanda Borchers Coeli-Lacchini, Margaret de Castro and Manuel dos Santos Faria
Genes 2025, 16(3), 354; https://doi.org/10.3390/genes16030354 - 20 Mar 2025
Viewed by 391
Abstract
Background: Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders characterized by impaired cortisol synthesis in the adrenal glands. Over 90% of CAH cases result from a deficiency of the enzyme 21-hydroxylase (21OHD). The clinical spectrum of 21OHD ranges from [...] Read more.
Background: Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders characterized by impaired cortisol synthesis in the adrenal glands. Over 90% of CAH cases result from a deficiency of the enzyme 21-hydroxylase (21OHD). The clinical spectrum of 21OHD ranges from the severe, life-threatening salt-wasting classic form, often presenting with prenatal virilization in females, to the non-classic (milder) form, which lacks glucocorticoid deficiency. Females with the non-classic form may experience symptoms of hyperandrogenism or infertility later in life, while males with non-classic CAH are often undiagnosed due to the subtler presentation. The coexistence of genetic anomalies and CAH is rarely reported in the literature, particularly in cases involving Triple X syndrome—a condition typically associated with a mild and frequently underdiagnosed clinical course. Case presentation: Here, we present a unique case of a 38-year-old woman with a history of premature ovarian failure and subsequent clinical features of hyperandrogenism. Further investigation revealed a novel association between partial 21OHD and a Triple X karyotype—an association not previously documented in the literature. Conclusions: This case highlights the potential for coexisting rare genetic conditions and underscores the critical importance of thorough and meticulous clinical evaluation. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 2116 KiB  
Article
Identification of Antimicrobial Peptides from Nibribacter radioresistens, a UV and Gamma Radiation Tolerant Bacterium
by Sam Woong Kim and Woo Young Bang
Genes 2025, 16(3), 353; https://doi.org/10.3390/genes16030353 - 19 Mar 2025
Viewed by 356
Abstract
Background: Nibribacter radioresistens, a UV and gamma radiation-tolerant bacterium, was reported to have superior antibacterial activities against a variety of pathogenic bacteria through the production of antimicrobial peptides (AMPs), but nothing is known about its AMPs. Methods/Results: In this study, our genomic [...] Read more.
Background: Nibribacter radioresistens, a UV and gamma radiation-tolerant bacterium, was reported to have superior antibacterial activities against a variety of pathogenic bacteria through the production of antimicrobial peptides (AMPs), but nothing is known about its AMPs. Methods/Results: In this study, our genomic and transcriptomic data showed that the N. radioresistens genome contains 11 AMP gene candidates, designated as NB_AMP1 to NB_AMP11, which are expressed differently in logarithmic growth and stationary phase. Moreover, the cell-free supernatant of all Escherichia coli DH5α strains containing cloned AMPs except for NB_AMP5 and NB_AMP7 exhibited antibacterial activities against both Gram-negative and Gram-positive bacteria such as E. coli and Staphylococcus aureus. Synthetic AMPs supported the antibacterial activities of cloned AMPs, and, in particular, the synthetic NB_AMP2 showed superior antibacterial activities against both E. coli and S. aureus. Conclusions: Altogether, these results suggest that the AMP candidates from N. radioresistens may function as antimicrobial peptides, effectively causing cellular lysis through pore formation in the bacterial membrane. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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10 pages, 728 KiB  
Article
Genetic Diversity and Forensic Parameters of 27 Y-STRs in Two Mestizo Populations from Western Mexico
by Astrid Desireé Sánchez-Méndez, Silvia Elena Narvaez-Rivera, Héctor Rangel-Villalobos, Jorge Hernández-Bello, Andrés López-Quintero, José Miguel Moreno-Ortíz, Benito Ramos-González and José Alonso Aguilar-Velázquez
Genes 2025, 16(3), 352; https://doi.org/10.3390/genes16030352 - 19 Mar 2025
Viewed by 588
Abstract
Background: Analyzing Y-chromosome short tandem repeats (Y-STRs) is essential in forensic genetics and population studies. The Yfiler™ Plus kit, which includes 27 Y-STR markers, enhances the discrimination power for forensic and kinship applications. However, this genetic system has not been analyzed in Mexican [...] Read more.
Background: Analyzing Y-chromosome short tandem repeats (Y-STRs) is essential in forensic genetics and population studies. The Yfiler™ Plus kit, which includes 27 Y-STR markers, enhances the discrimination power for forensic and kinship applications. However, this genetic system has not been analyzed in Mexican populations, which limits its application and representativeness in international databases. Objectives: We wished to examine the genetic diversity and forensic parameters of the 27 Y-STRs included in the YFiler™ Plus kit in two populations from Western Mexico (Jalisco and Michoacán). Methods: Male DNA samples were amplified using the Yfiler™ Plus kit, followed by a fragment analysis via capillary electrophoresis (CE). The haplotype frequencies and forensic parameters were calculated. The haplogroups of all samples were predicted, and the distribution and percentages of ancestries were determined. The Rst genetic distances, including reference populations, were calculated and graphically represented in a multidimensional scaling (MDS) plot. Results: A total of 224 haplotypes were identified in all of the samples, of which 98.66% corresponded to unique haplotypes. Bi- and tri-allelic patterns were observed in both populations. The observed discriminatory capacity was 98.4% for Jalisco and 98.9% for Michoacán, while the haplotype diversity values were 0.9998 and 0.9997, respectively. The most frequent haplogroup was R1b, followed by Q, representing the European and Native American ancestries, in both populations. Conclusions: This study is the first to report the haplotype diversity and forensic parameters of the 27 Y-STRs included in the Yfiler™ Plus kit in Mexican populations. These findings confirm the forensic utility of these markers for human identification, biological relationship testing, and criminal investigations, reinforcing their applicability in forensic casework. Full article
(This article belongs to the Special Issue The Genetic Diversification of Human Populations)
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18 pages, 2344 KiB  
Article
SARS-CoV-2 Genetic Variants Identified in Selected Regions of Ethiopia Through Whole Genome Sequencing: Insights from the Fifth Wave of COVID-19
by Getnet Hailu, Mengistu Legesse, Andargachew Mulu, Girmay Medhin, Mesfin Mengesha Tsegaye, Dawit Hailu Alemayehu, Abaysew Ayele, Atsbeha Gebreegziabxier, Adamu Tayachew, Adimkewu Aguine, Haileyesus Dejene, Sofonias K. Tessema, Harris Onywera, Assohoun Egomli Stanislas, Ebba Abate, Alessandro Marcello and Molalegne Bitew
Genes 2025, 16(3), 351; https://doi.org/10.3390/genes16030351 - 18 Mar 2025
Viewed by 765
Abstract
Background: The COVID-19 pandemic highlighted SARS-CoV-2 variants with increased transmissibility and immune evasion. In Ethiopia, where cases surged, the understanding of the virus’s dynamics was limited. This study analyzed SARS-CoV-2 variants during the fifth wave, crucial for guiding vaccines, therapeutics, diagnostics, and understanding [...] Read more.
Background: The COVID-19 pandemic highlighted SARS-CoV-2 variants with increased transmissibility and immune evasion. In Ethiopia, where cases surged, the understanding of the virus’s dynamics was limited. This study analyzed SARS-CoV-2 variants during the fifth wave, crucial for guiding vaccines, therapeutics, diagnostics, and understanding disease severity. Method: From June to August 2022, 150 SARS-CoV-2-positive samples were randomly selected from the Ethiopian Public Health Institute repository. Sixty-three high-quality genome sequences were analyzed. Results: Of the 63 sequences, 70% were from males and 30% from females, with a median age of 34. Omicron dominated (97%, 61/63), primarily clade 22A (64%, 40/63), followed by 22B (18%, 11/63) and 21K (14%, 9/63). Delta accounted for 3.2% (2/63). Omicron was identified in all (25) vaccinated study participants. Ethiopian sequences showed limited evolutionary divergence and lower genetic diversity compared to global sequences. Conclusion: Omicron was the predominant variant during Ethiopia’s fifth wave, indicating recent community transmission. Despite minor genetic diversity differences, ongoing surveillance remains critical for tracking variants and informing public health interventions. Full article
(This article belongs to the Section Viral Genomics)
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14 pages, 3676 KiB  
Article
Alternative Splicing Events and ABA Hormone Regulation in Drought Response of Hippophae gyantsensis L.
by Fanfan Lin, Yifan Cai, Shihai Yang and Yunqiang Yang
Genes 2025, 16(3), 350; https://doi.org/10.3390/genes16030350 - 18 Mar 2025
Viewed by 366
Abstract
(1) Background: Hippophae gyantsensis, a drought-tolerant plant native to the Tibetan Plateau, plays a crucial ecological and economic role. While its drought tolerance mechanisms have been extensively studied, the role of alternative splicing (AS) in drought resistance remains insufficiently explored. This [...] Read more.
(1) Background: Hippophae gyantsensis, a drought-tolerant plant native to the Tibetan Plateau, plays a crucial ecological and economic role. While its drought tolerance mechanisms have been extensively studied, the role of alternative splicing (AS) in drought resistance remains insufficiently explored. This study aims to elucidate how AS events regulate gene expression to enhance drought tolerance in H. gyantsensis under water-deficit conditions. (2) Methods: H. gyantsensis plants were subjected to progressive drought stress followed by rehydration. Physiological responses, transcriptomic data, and hormonal profiles were analyzed to investigate the plant’s adaptive mechanisms to drought stress, with a particular focus on abscisic acid (ABA) signaling-related genes. (3) Results: The results showed that H. gyantsensis maintained high leaf water content even under severe drought stress, emphasizing its strong drought resistance. A transcriptomic analysis revealed 11,962 differentially expressed genes, primarily enriched in hormone signaling and metabolic pathways. Notably, the accumulation of ABA was closely associated with AS events in ABA-related genes, such as ZEPs, ABCG, and PP2C. These genes produced multiple splice variants, indicating their role in modulating the ABA signaling pathway and enhancing drought tolerance. (4) Conclusions: This study highlights the pivotal role of AS in ABA signaling and drought tolerance in H. gyantsensis. It provides new insights into how AS contributes to plant adaptation to drought stress, bridging the knowledge gap in drought resistance mechanisms and emphasizing the importance of AS in plant stress responses. Full article
(This article belongs to the Section Genes & Environments)
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31 pages, 1512 KiB  
Review
Circulating microRNAs as Potential Biomarkers of Overweight and Obesity in Adults: A Narrative Review
by Francisca Villagrán-Silva, Pía Loren, Cristian Sandoval, Fernando Lanas and Luis A. Salazar
Genes 2025, 16(3), 349; https://doi.org/10.3390/genes16030349 - 17 Mar 2025
Viewed by 539
Abstract
In an obesogenic environment, such as the one we have been experiencing in recent decades, epigenetics provides answers to the relationship between hereditary and environmentally acquired patterns that have significantly contributed to the global rise in obesity prevalence. MicroRNA (miRNA) constitutes a diminutive [...] Read more.
In an obesogenic environment, such as the one we have been experiencing in recent decades, epigenetics provides answers to the relationship between hereditary and environmentally acquired patterns that have significantly contributed to the global rise in obesity prevalence. MicroRNA (miRNA) constitutes a diminutive non-coding small RNA molecule, 20 to 24 nucleotides in length, that functions as a regulator of gene regulation at the post-translational level. Circulating miRNAs (c-miRNAs) have been detected in multiple body fluids, including blood, plasma, serum, saliva, milk from breastfeeding mothers, and urine. These molecules hold significant therapeutic value and serve as extracellular biomarkers in metabolic diseases. They aid in the diagnosis and tracking of therapy responses, as well as dietary and physical habit modifications. Researchers have studied c-miRNAs as potential biomarkers for diagnosing and characterizing systemic diseases in people of all ages and backgrounds since then. These conditions encompass dyslipidemia, type 2 diabetes mellitus (T2DM), cardiovascular risk, metabolic syndrome, cardiovascular diseases, and obesity. This review therefore analyzes the usefulness of c-miRNAs as therapeutic markers over the past decades. It also provides an update on c-miRNAs associated with general obesity and overweight, as well as with the most prevalent pathologies in the adult population. It also examines the effect of different nutritional approaches and physical activity regarding the activity of miRNAs in circulation in adults with overweight or general obesity. All of this is done with the aim of evaluating their potential use as biomarkers in various research contexts related to overweight and obesity in adults. Full article
(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers, 2nd Edition)
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18 pages, 14851 KiB  
Article
Dissecting Metabolic Functions and Sugar Transporters Using Genome and Transportome of Probiotic Limosilactobacillus fermentum KUB-D18
by Yuke He, Kevin Mok, Pramote Chumnanpuen, Massalin Nakphaichit and Wanwipa Vongsangnak
Genes 2025, 16(3), 348; https://doi.org/10.3390/genes16030348 - 17 Mar 2025
Viewed by 1034
Abstract
Background/Objectives: Limosilactobacillus fermentum KUB-D18, a heterofermentative lactic acid bacterium with promising probiotic properties, is known for promoting gut health and nutrient absorption. Originally isolated from chicken intestines, this strain demonstrates versatile metabolic capabilities in diverse gastrointestinal environments. However, the metabolic functions and [...] Read more.
Background/Objectives: Limosilactobacillus fermentum KUB-D18, a heterofermentative lactic acid bacterium with promising probiotic properties, is known for promoting gut health and nutrient absorption. Originally isolated from chicken intestines, this strain demonstrates versatile metabolic capabilities in diverse gastrointestinal environments. However, the metabolic functions and sugar transport-related genes remain largely unexplored. This study thus aimed to dissect metabolic functions and sugar transports of L. fermentum KUB-D18. Methods: Next-generation and third-generation sequencing techniques using integrative genomic platform towards transportome analysis were performed. Results: The complete genome, sized at 2.12 Mbps with a GC content of 51.36%, revealed 2079 protein-encoding genes, of which 1876 protein functions were annotated and identified in top categories involved in amino acids, nucleotide, energy, and carbohydrate transports and metabolisms. Comparative genes analysis identified 50 core and 12 strain-specific genes linked to probiotic properties, e.g., acid resistances and bile tolerances, antioxidant functions, or anti-inflammatory properties. Further, sugar transportome analysis uncovered 57 transporter genes, demonstrating diverse carbon utilization and phosphotransferase (PTS) systems, corroborated by API 50 CHL test results for carbohydrate metabolism profile. Conclusions: These findings enhance the comprehensive metabolic understanding of L. fermentum KUB-D18, supporting its industrial potential and applications in engineered probiotics. Full article
(This article belongs to the Section Bioinformatics)
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18 pages, 288 KiB  
Review
Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review
by Khaled K. Abu-Amero, Bashaer Almadani, Shereen Abualkhair, Syed Hameed, Altaf A Kondkar, Andrea Sollazzo, Angeli Christy Yu, Massimo Busin and Giorgio Zauli
Genes 2025, 16(3), 347; https://doi.org/10.3390/genes16030347 - 17 Mar 2025
Viewed by 578
Abstract
Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. [...] Read more.
Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber’s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA’s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
27 pages, 7777 KiB  
Article
The Prognostic Value and Immunomodulatory Role of Spsb2, a Novel Immune Checkpoint Molecule, in Hepatocellular Carcinoma
by Lv Tian, Yiming Wang, Jiexin Guan, Lu Zhang and Jun Fan
Genes 2025, 16(3), 346; https://doi.org/10.3390/genes16030346 - 17 Mar 2025
Viewed by 529
Abstract
Background: Liver cancer, specifically hepatocellular carcinoma (LIHC), ranks as the second most common cause of cancer-related fatalities globally. Moreover, the occurrence rate of LIHC is steadily increasing. A recently identified gene, SPSB2, has been implicated in cell signaling, impacting the development and [...] Read more.
Background: Liver cancer, specifically hepatocellular carcinoma (LIHC), ranks as the second most common cause of cancer-related fatalities globally. Moreover, the occurrence rate of LIHC is steadily increasing. A recently identified gene, SPSB2, has been implicated in cell signaling, impacting the development and progression of non-small cell lung cancer. Nevertheless, studies on the role of SPSB2 in the pathogenesis of LIHC are lacking. Methods: Using the TCGA, GTEx, and GEO databases, we obtained differentially expressed genes that affect the prognosis of patients with LIHC. We utilized the Kruskal–Wallis test, along with univariate and multivariate COX regression analyses, to determine the correlation between SPSB2 and patient clinical indicators. Potential biological functions of SPSB2 in LIHC were explored by enrichment analysis, ssGSEA, and Spearman correlation analysis. Finally, LIHC cell lines Huh7 and SMMC-7721 were used to validate the biological function of SPSB2. Results: The results showed LIHC patients with higher SPSB2 expression had a poorer prognosis, and SPSB2 expression was significantly correlated with LIHC patients’ Histologic grade, Pathologic T stage, Prothrombin time, Pathologic stage, BMI, weight, adjacent hepatic tissue inflammation, AFP level, and OS event (p < 0.05). SPSB2 shows notable enrichment in pathways linked to tumorigenesis and the immune system. Moreover, its expression is strongly connected to immune cells and immune checkpoints. Knockdown of SPSB2 expression in Huh7 cells and SMMC-7721 cells inhibits SPSB2’s biological functions, including proliferation, invasion, metastasis, and other phenotypes. Conclusions: SPSB2 plays a crucial role in the development of LIHC. It is related to the immune response and unfavorable outcomes. SPSB2 may function as a clinical biomarker for prognosis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 1925 KiB  
Review
Clinical Significance of Early-Onset Alzheimer’s Mutations in Asian and Western Populations: A Scoping Review
by Prevathe Poniah, Aswir Abdul Rashed, Julaina Abdul Jalil and Ernie Zuraida Ali
Genes 2025, 16(3), 345; https://doi.org/10.3390/genes16030345 - 17 Mar 2025
Viewed by 502
Abstract
Background/Objectives: Background: Early-onset Alzheimer’s disease (EOAD) is primarily inherited in an autosomal dominant pattern, with mutations in the APP, PSEN1, and PSEN2 genes being central contributors. Diagnosing Alzheimer’s poses challenges due to the coexistence of various co-pathologies, and treatment options remain [...] Read more.
Background/Objectives: Background: Early-onset Alzheimer’s disease (EOAD) is primarily inherited in an autosomal dominant pattern, with mutations in the APP, PSEN1, and PSEN2 genes being central contributors. Diagnosing Alzheimer’s poses challenges due to the coexistence of various co-pathologies, and treatment options remain limited for most patients, apart from familial cases linked to specific genetic mutations. While significant research on Alzheimer’s genetics has been conducted in both Asian and Caucasian populations, the specific mutations and their clinical impacts in EOAD are still inadequately explored. This review aims to provide a detailed analysis of commonly reported genetic mutations and associated clinical features in EOAD patients from Asian and Western populations. Methods: Following the PRISMA-ScR guidelines, a systematic database search was conducted for studies published between 2016 and 2023. After screening 491 records, 36 studies from Asian cohorts and 40 from Western cohorts met the inclusion criteria. Results: The analysis revealed 127 unique mutations in the Asian population and 190 in the Western population. About 16.7% of Asian and 21.9% of Western studies covered both familial and sporadic AD, with consistent patterns across groups. Some mutations were shared between the populations and displayed similar clinical features, while others were population-specific. Conclusions: These findings underscore the considerable variability in EOAD mutations and phenotypes, emphasizing the importance of genetic testing in younger patients to enhance diagnostic accuracy and guide treatment strategies effectively. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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12 pages, 8548 KiB  
Article
Analysis of WRKY Gene Family in Acer fabri and Their Expression Patterns Under Cold Stress
by Gongwei Chen, Yixiao Zhou, Dandan Zhang, Fengyuan Chen, Xuyang Qin, Hongyu Cai, Heng Gu, Yuanzheng Yue, Lianggui Wang and Guohua Liu
Genes 2025, 16(3), 344; https://doi.org/10.3390/genes16030344 - 17 Mar 2025
Viewed by 362
Abstract
Background/Objectives: The WRKY gene family plays a critical role in plant stress responses; however, its function in Acer fabri (A. fabri) under cold stress conditions remains poorly understood. This study aims to identify WRKY genes in A. fabri, analyze their [...] Read more.
Background/Objectives: The WRKY gene family plays a critical role in plant stress responses; however, its function in Acer fabri (A. fabri) under cold stress conditions remains poorly understood. This study aims to identify WRKY genes in A. fabri, analyze their structural characteristics, and investigate their expression patterns under cold stress, thereby establishing a foundation for further exploration of their roles in cold stress responses. Methods: Using transcriptional data from A. fabri subjected to cold stress, we identified 46 WRKY family genes. We employed bioinformatics tools to conduct a comprehensive analysis of the physical and chemical properties of these genes, predict their subcellular localization, and construct a phylogenetic tree. A heatmap was generated to visualize the expression levels of WRKY genes across different treatment conditions. To validate our findings, qRT-PCR was performed on 10 highly expressed WRKY genes to analyze their temporal expression patterns during cold stress exposure. Results: The analysis revealed that WRKY genes in A. fabri are predominantly localized to the nucleus, with protein lengths ranging from 55 to 1027 amino acids. Notably, all WRKY genes possessed the conserved WRKYGQK domain. Under cold stress conditions, the WRKY gene expression exhibited a general trend of increasing followed by decreasing, with peak expression observed at 24 h post-treatment. qRT-PCR analysis corroborated this pattern for the selected genes. Conclusions: This study represents the first comprehensive structural and expression analysis of the A. fabri WRKY gene family under cold stress conditions. Our findings provide valuable insights into their potential roles in plant cold stress responses, and lay the groundwork for future investigations into the molecular mechanisms underlying WRKY-mediated cold stress tolerance in A. fabri. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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18 pages, 1683 KiB  
Review
Detection of mRNA Transcript Variants
by Kevin Vo, Sharmin Shila, Yashica Sharma, Grace J. Pei, Cinthia Y. Rosales, Vinesh Dahiya, Patrick E. Fields and M. A. Karim Rumi
Genes 2025, 16(3), 343; https://doi.org/10.3390/genes16030343 - 16 Mar 2025
Viewed by 651
Abstract
Most eukaryotic genes express more than one mature mRNA, defined as transcript variants. This complex phenomenon arises from various mechanisms, such as using alternative transcription start sites and alternative post-transcriptional processing events. The resulting transcript variants can lead to synthesizing proteins that possess [...] Read more.
Most eukaryotic genes express more than one mature mRNA, defined as transcript variants. This complex phenomenon arises from various mechanisms, such as using alternative transcription start sites and alternative post-transcriptional processing events. The resulting transcript variants can lead to synthesizing proteins that possess distinct functional domains or may even generate noncoding RNAs, each with unique roles in cellular processes. The generation of these transcript variants is not merely a random occurrence; it is cell-type specific and varies with developmental stages, aging processes, or pathogenesis of diseases. This highlights the biological significance of transcript variants in regulating gene expression and their potential impact on cellular functionality. Despite the biological importance, investigating transcript variants has been hampered by challenges associated with detecting their expression. This review article addresses the advancements in molecular techniques in detecting transcript variants. Traditional methods such as RT-PCR and RT-qPCR can easily detect known transcript variants using primers that target unique exons associated with the variants. Other techniques like RACE-PCR and hybridization-based methods, including Northern blotting, RNase protection assays, and microarrays, have also been utilized to detect transcript variants. Nevertheless, RNA sequencing (RNA-Seq) has emerged as a powerful technique for identifying transcript variants, especially those with previously unknown sequences. The effectiveness of RNA sequencing in transcript variant detection depends on the specific sequencing approach and the precision of data analysis. By understanding the strengths and weaknesses of each laboratory technique, researchers can develop more effective strategies for detecting mRNA transcript variants. This ability will be crucial for our comprehensive understanding of gene regulation and the implications of transcript diversity in various biological contexts. Full article
(This article belongs to the Special Issue Feature Papers: RNA)
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12 pages, 903 KiB  
Review
Genetic Diversity and Ethnic Tapestry of Kazakhstan as Inferred from HLA Polymorphism and Population Dynamics: A Comprehensive Review
by Aida Turganbekova, Saniya Abdrakhmanova, Zhaksylyk Masalimov and Wassim Y. Almawi
Genes 2025, 16(3), 342; https://doi.org/10.3390/genes16030342 - 15 Mar 2025
Viewed by 503
Abstract
Background: The human leukocyte antigen (HLA) system represents the most polymorphic segment within human DNA sequences and constitutes a core component of immune defense responses and in understanding population genetics. This research investigates the distribution of HLA class I and II polymorphisms across [...] Read more.
Background: The human leukocyte antigen (HLA) system represents the most polymorphic segment within human DNA sequences and constitutes a core component of immune defense responses and in understanding population genetics. This research investigates the distribution of HLA class I and II polymorphisms across different ethnic groups in Kazakhstan, offering valuable insights into the genetic diversity and demographic evolution within this region. Methods: We performed an in-depth examination of HLA class I and II polymorphisms across diverse ethnic communities living in Kazakhstan, including Kazakhs, Russians, Uzbeks, Ukrainians, Germans, Tatars, and Koreans. Utilizing data from high-resolution HLA typing studies allowed us to assess allele frequencies alongside haplotype distributions while analyzing genetic interrelations between these populations. Additionally, we performed comparative assessments with global HLA databases to determine the genetic affiliations between these groups and their relationships with neighboring and more distant populations. Results: Our study revealed over 200 HLA alleles within the analyzed populations, and significant variations were observed in their allele and haplotype frequencies. Notably, the Kazakh group exhibited strong genetic ties to Asian and Siberian demographics; conversely, other ethnicities showed associations reflective of their historical roots. Notable alleles included HLA-A*02:01, B*07:02, C*07:02, DRB1*07:01, and DQB1*03:01, commonly observed across various groups. Linkage disequilibrium analysis revealed the presence of population-specific haplotypes, highlighting distinct genetic structures within these communities. Conclusions: The findings highlight the significant genetic diversity in Kazakhstan, influenced by its geographical location at the crossroads of Europe and Asia. These results are pertinent to immunogenetics, transplantation medicine, and personalized healthcare within Kazakhstan and adjacent regions. Future research should expand the sample size and explore disease associations to enhance our comprehension of HLA genetics across Central Asia. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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19 pages, 2996 KiB  
Review
MYOSLID: A Critical Modulator of Cancer Hallmarks
by Kanupriya Medhi, Sagarika Mukherjee, Aastha Dagar, Ashutosh Kumar Tiwari, Sia Daffara, Sanjana Bana, Vivek Uttam, Md Rizwan Ansari, Vikas Yadav, Hardeep Singh Tuli and Aklank Jain
Genes 2025, 16(3), 341; https://doi.org/10.3390/genes16030341 - 14 Mar 2025
Viewed by 736
Abstract
Despite being the leading cause of death worldwide, cancer still lacks precise biomarkers for effective targeting, limiting efforts to reduce mortality rates. This review explores the role and clinical significance of a newly identified long non-coding RNA, MYOSLID, in cancer progression. MYOSLID [...] Read more.
Despite being the leading cause of death worldwide, cancer still lacks precise biomarkers for effective targeting, limiting efforts to reduce mortality rates. This review explores the role and clinical significance of a newly identified long non-coding RNA, MYOSLID, in cancer progression. MYOSLID has emerged as a critical modulator in cancer progression by influencing key hallmarks such as proliferation, immune evasion, metastasis, and metabolic reprogramming. It promotes tumor cell growth by stabilizing hypoxia-inducible factor 1 and acting as a competing endogenous RNA (ceRNA) to sequester tumor-suppressive microRNAs like miR-29c-3p, thereby enhancing oncogene expression. It facilitates immune evasion by upregulating PD-L1, suppressing T cell activation, and modulating necroptosis pathways involving RIPK1 and RIPK3. Additionally, MYOSLID drives metastasis by regulating epithelial–mesenchymal transition markers such as LAMB3 and Slug while promoting RAB13-mediated cytoskeletal remodeling and enhancing cancer cell invasion. We have obtained the expression of MYOSLID from TCGA and the ENCORI database. The expression of colorectal adenocarcinoma (COAD) and head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and lower survival rate. Given its significant potential as a diagnostic biomarker and therapeutic target, further research is required to elucidate its precise molecular mechanisms and therapeutic applications in cancer treatment. Full article
(This article belongs to the Special Issue Multifaceted Implications of Non-Coding RNAs in Cancer: From Biomarker Discovery to Therapeutic Target)
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15 pages, 732 KiB  
Article
Expression Profile of Twelve Transcripts as a Supporting Tool for the Molecular Characterization of Canine Cutaneous Mast Cell Tumors at Diagnosis: Association with Histological Grading and Clinical Staging
by Mery Giantin, Ludovica Montanucci, Rosa Maria Lopparelli, Roberta Tolosi, Alfredo Dentini, Valeria Grieco, Damiano Stefanello, Silvia Sabattini, Laura Marconato, Marianna Pauletto and Mauro Dacasto
Genes 2025, 16(3), 340; https://doi.org/10.3390/genes16030340 - 14 Mar 2025
Viewed by 617
Abstract
Background/Objectives: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior [...] Read more.
Background/Objectives: Mast cell tumors (MCTs) are the second most common malignant neoplasms in dogs. Histopathological grading and clinical staging are the main tools for estimating biological behavior and disease extent; thus, both are essential for therapeutic decision-making and prognostication. However, the biological behavior of MCTs in dogs is variable, and it sometimes deviates from expectations. In a previous study, we identified 12 transcripts whose expression profile allowed a clear distinction between Kiupel low-grade and high-grade cutaneous MCTs (cMCTs) and was associated with prognosis. Building on these findings, this study evaluated the predictive potential of these transcripts’ expression profiles in classifying cMCTs into low-grade and high-grade. Methods: A logistic regression classifier based on the expression profiles of the identified transcripts and able to classify cMCTs as low- or high-grade was developed and subsequently tested on a novel dataset of 50 cMCTs whose expression profiles have been determined in this study through qPCR. Results: The developed logistic regression classifier reaches an accuracy of 67% and an area under the receiver operating characteristic curve (AUC) of 0.76. Interestingly, the molecular classification clearly identifies stage-IV disease (90% true positive rate). Conclusions: qPCR analysis of these biomarkers combined with the machine learning-based classifier might serve as a tool to support cMCT clinical management at diagnosis. Full article
(This article belongs to the Special Issue Animal Models, Genetic and Genomic Studies in Cancer and Its Therapy)
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23 pages, 4971 KiB  
Article
Common Regulatory Mechanisms Mediated by Cuproptosis Genes in Inflammatory Bowel Disease and Major Depressive Disorder
by Jiyuan Shi, Qianyi Wu, Mengmeng Sang and Liming Mao
Genes 2025, 16(3), 339; https://doi.org/10.3390/genes16030339 - 14 Mar 2025
Viewed by 482
Abstract
Background: The prevalence of major depressive disorder (MDD) among patients with inflammatory bowel disease (IBD) is significantly higher compared to the general population, suggesting a potential link between their pathogeneses. Cuproptosis, defined as cell death caused by intracellular copper accumulation, has not been [...] Read more.
Background: The prevalence of major depressive disorder (MDD) among patients with inflammatory bowel disease (IBD) is significantly higher compared to the general population, suggesting a potential link between their pathogeneses. Cuproptosis, defined as cell death caused by intracellular copper accumulation, has not been thoroughly investigated in the context of IBD and MDD. This study aims to uncover the molecular mechanisms of cuproptosis-related genes (CRGs) in both conditions and to explore novel therapeutic strategies by the modulation of CRGs. Methods: In this study, we identified differentially expressed CRGs between normal and disease samples. We calculated the correlation among CRGs and between CRGs and immune cell infiltrations across various tissues. Four machine learning algorithms were employed to identify key CRGs associated with IBD and MDD. Additionally, drug sensitivity, molecular docking, and molecular dynamics simulations were conducted to predict therapeutic drugs for IBD and MDD. Results: We identified DLD, DLAT, DLST, PDHB, and DBT as common DE-CRGs, and DLD, LIAS, SLC31A1, SCO2, and CDKN2A as key CRGs associated with both IBD and MDD. Consequently, DLD was recognized as a shared biomarker in both diseases. A total of 37 potential therapeutic drugs were identified for IBD and MDD. Based on the molecular docking and molecular dynamics simulation analyses, barasertib and NTP-TAE684, which target DLAT, were predicted to be the most effective compounds. Conclusions: These findings have substantially enhanced our understanding of the similarities and differences in the regulatory mechanisms of CRGs within brain–gut axis diseases. Key biomarkers have been identified, and potential therapeutic drugs have been predicted to effectively target IBD and MDD. Full article
(This article belongs to the Special Issue Machine Learning in Cancer and Disease Genomics)
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17 pages, 294 KiB  
Review
Genomics May Be the Key to Understanding Endurance Training Pillars
by Ricardo Muller Bottura and Daniel Blasioli Dentillo
Genes 2025, 16(3), 338; https://doi.org/10.3390/genes16030338 - 13 Mar 2025
Viewed by 1032
Abstract
Endurance performance is primarily determined by three key physiological pillars: maximal oxygen uptake (VO2max), anaerobic threshold, and economy of movement. Recent research has suggested physiological resilience as a potential fourth dimension, referring to an athlete’s ability to sustain performance despite accumulating [...] Read more.
Endurance performance is primarily determined by three key physiological pillars: maximal oxygen uptake (VO2max), anaerobic threshold, and economy of movement. Recent research has suggested physiological resilience as a potential fourth dimension, referring to an athlete’s ability to sustain performance despite accumulating fatigue. While the role of genetic factors in endurance has been widely studied, their influence on these pillars, particularly on fatigue resistance and long-term adaptation, remains an area of growing interest. This narrative review explores the genomic basis of endurance performance, analyzing genetic contributions to oxygen transport, metabolic efficiency, muscle composition, and recovery. Additionally, it discusses how genetic variability may modulate an athlete’s response to training, including aspects of physiological adaptation, injury susceptibility, sleep, and nutrition. The review highlights physiological resilience in the context of endurance sports, discussing its connection to neuromuscular and metabolic regulation. By integrating genetic insights with established physiological principles, this review provides a comprehensive perspective on endurance adaptation. Future research directions are outlined to enhance our understanding of the genetic underpinnings of endurance, with implications for personalized training and performance optimization. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
16 pages, 1019 KiB  
Article
Relationship Between Vitamin D Receptor Gene BsmI Polymorphism and 25-Hydroxyvitamin D Total Levels in Slovak Postmenopausal Women with Reduced Bone Mineral Density
by Marta Mydlárová Blaščáková, Zuzana Lőrinczová, Lenka Anderková, Olga Czerwińska-Ledwig, Ľudmila Mikulová, Hedviga Hrušovská, Bernadeta Jędrzejkiewicz and Anna Piotrowska
Genes 2025, 16(3), 337; https://doi.org/10.3390/genes16030337 - 13 Mar 2025
Viewed by 523
Abstract
Objectives: The BsmI polymorphism of the VDR gene (vitamin D receptor) is one of the important genetic variants influencing the development of osteoporosis. Measurement and evaluation of the 25-hydroxyvitamin D (25(OH)D) concentration in individuals with reduced bone mineral density are essential because deficiency [...] Read more.
Objectives: The BsmI polymorphism of the VDR gene (vitamin D receptor) is one of the important genetic variants influencing the development of osteoporosis. Measurement and evaluation of the 25-hydroxyvitamin D (25(OH)D) concentration in individuals with reduced bone mineral density are essential because deficiency of this hormone causes impaired bone mineralization, leads to low BMD (bone mineral density), and influences fracture formation. The aim of the study was to investigate the relationship between the VDR gene BsmI polymorphism and 25(OH)D levels in Slovak postmenopausal women. Materials and Methods: The study population consisted of 287 untreated postmenopausal women, who were divided into three groups based on T-scores: normal (CG = 65), osteopenia (OPE = 126), and osteoporosis (OPO = 96). DNA isolation was performed using a standard protocol. Genetic analyses of the BsmI (rs1544410) polymorphism of the VDR gene were performed using the TaqMan SNP genotyping assays. Biochemical analysis of total 25(OH)D was performed in blood serum using the electrochemiluminescence method. Results: The chi-square test confirmed that the mutant T allele was not associated with the development of osteoporosis (p = 0.419). Through Kruskal–Wallis analysis, we found significant differences (p < 0.05, p < 0.01) in total 25(OH)D concentrations in individual genotypes of the BsmI variant of the VDR gene between the groups of women studied. Conclusions: It can be concluded that the VDR gene and its variant BsmI as well as 25(OH)D total may be relevant markers in the etiology of the search for individuals at risk of osteoporosis. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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23 pages, 10700 KiB  
Article
Centenary Progress on Orchidaceae Research: A Bibliometric Analysis
by Yonglu Wei, Jie Li, Jianpeng Jin, Jie Gao, Qi Xie, Chuqiao Lu, Genfa Zhu and Fengxi Yang
Genes 2025, 16(3), 336; https://doi.org/10.3390/genes16030336 - 13 Mar 2025
Viewed by 646
Abstract
Background: Research on orchids has experienced substantial growth since the early 20th century, reflecting their ecological and evolutionary significance. Methods: This paper provides a comprehensive bibliometric analysis of orchid-related literature published between 1902 and 2024, based on data retrieved from the Web of [...] Read more.
Background: Research on orchids has experienced substantial growth since the early 20th century, reflecting their ecological and evolutionary significance. Methods: This paper provides a comprehensive bibliometric analysis of orchid-related literature published between 1902 and 2024, based on data retrieved from the Web of Science Core Collection™ (WoS). Results: The primary goal is to assess the global research landscape of orchids by identifying key authors, institutions, and journals, as well as major research themes in the field. A thorough analysis of publication trends, citation frequencies, and keyword co-occurrence networks was conducted to uncover significant research hotspots. The findings indicate that orchid research has evolved from foundational topics such as taxonomy and classification to more intricate subjects, including conservation strategies, orchid-pollinator dynamics, and the role of orchids in ecosystem functions. Additionally, biotechnology-related research is emerging as a dominant trend. This study also highlights that China has the highest publication output, while collaboration between the United States and Europe continues to grow. The co-word analysis of keywords suggests that future research is likely to continue to focus on orchid conservation, the impacts of climate change, pollination biology, and symbiotic relationships with mycorrhizal fungi. Conclusions: This review offers valuable insights for researchers and conservationists, helping to identify future research priorities and strategies for the preservation and sustainable use of orchids. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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8 pages, 2149 KiB  
Case Report
Effects of Levetiracetam on Episodic Ataxia Type 2 and Spinocerebellar Ataxia Type 6 with Episodic Ataxic Symptoms: A Case Series
by Haruo Shimazaki
Genes 2025, 16(3), 335; https://doi.org/10.3390/genes16030335 - 13 Mar 2025
Viewed by 474
Abstract
Background: Episodic ataxia type 2 (EA2) is a rare disorder characterized by paroxysmal gait instability, dysarthria, and dizziness. It is caused by CACNA1A mutations. Spinocerebellar ataxia type 6 (SCA6) rarely causes episodic ataxia-like symptoms. Acetazolamide has limited effectiveness for treating episodic ataxia. Methods: [...] Read more.
Background: Episodic ataxia type 2 (EA2) is a rare disorder characterized by paroxysmal gait instability, dysarthria, and dizziness. It is caused by CACNA1A mutations. Spinocerebellar ataxia type 6 (SCA6) rarely causes episodic ataxia-like symptoms. Acetazolamide has limited effectiveness for treating episodic ataxia. Methods: We investigated the effect of drug therapy in two patients with EA2 and one patient with SCA6 who presented with episodic ataxia. All three cases were CACNA1A-associated diseases. Results: In these three cases, acetazolamide administration was partially and transiently effective for episodic ataxia attacks. After levetiracetam addition, the number of ataxic attacks was significantly reduced, although the durations of attacks were not changed. The effect of levetiracetam was stable and continued for seven years. Levetiracetam and acetazolamide reduced chronic cerebellar ataxia in an SCA6 patient. Conclusions: In this small number of cases, levetiracetam was considered effective in two patients with EA2 and mildly effective in one patient with SCA6. Full article
(This article belongs to the Special Issue Rare Neurogenetic Disorders in the Third Millennium: Diagnostic and Therapeutic Challenges)
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22 pages, 584 KiB  
Review
Advancing the Metabolic Dysfunction-Associated Steatotic Liver Disease Proteome: A Post-Translational Outlook
by Kushan Chowdhury, Debajyoti Das and Menghao Huang
Genes 2025, 16(3), 334; https://doi.org/10.3390/genes16030334 - 12 Mar 2025
Viewed by 880
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder with limited treatment options. This review explores the role of post-translational modifications (PTMs) in MASLD pathogenesis, highlighting their potential as therapeutic targets. We discuss the impact of PTMs, including their phosphorylation, ubiquitylation, [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder with limited treatment options. This review explores the role of post-translational modifications (PTMs) in MASLD pathogenesis, highlighting their potential as therapeutic targets. We discuss the impact of PTMs, including their phosphorylation, ubiquitylation, acetylation, and glycosylation, on key proteins involved in MASLD, drawing on studies that use both human subjects and animal models. These modifications influence various cellular processes, such as lipid metabolism, inflammation, and fibrosis, contributing to disease progression. Understanding the intricate PTM network in MASLD offers the potential for developing novel therapeutic strategies that target specific PTMs to modulate protein function and alleviate disease pathology. Further research is needed to fully elucidate the complexity of PTMs in MASLD and translate these findings into effective clinical applications. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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12 pages, 2086 KiB  
Article
Development of Publicly Available Forensic DNA Sequence Mixture Data
by Erica L. Romsos, Kevin M. Kiesler, Carolyn R. Steffen, Lisa A. Borsuk, Sarah Riman, Lauren E. Mullen, Jodi A. Irwin, Peter M. Vallone and Katherine B. Gettings
Genes 2025, 16(3), 333; https://doi.org/10.3390/genes16030333 - 12 Mar 2025
Viewed by 526
Abstract
Background: In 2018, the Next-Generation Sequencing Committee of SWGDAM queried bioinformatic and statistical interpretation method developers regarding data needs for the development of sequence-based probabilistic genotyping software. Methods: Based on this engagement, a set of 74 mixture samples was conceived and [...] Read more.
Background: In 2018, the Next-Generation Sequencing Committee of SWGDAM queried bioinformatic and statistical interpretation method developers regarding data needs for the development of sequence-based probabilistic genotyping software. Methods: Based on this engagement, a set of 74 mixture samples was conceived and created using 11 single-source samples. The allelic overlap among these samples was evaluated and sample combinations of varying complexity were selected, aiming to represent the variability observed in forensic casework. Results: The samples were distributed into a 96-well plate design containing several features: (1) three-person mixtures of 1% to 5% minor components in triplicate with varying levels of input DNA to provide information on sensitivity and reproducibility, (2) three-person mixtures containing degraded DNA of either only the major contributor or all three contributors, (3) four- and five-person mixtures with varying ratios and donors, (4) a single-source dilution series. Conclusions: Mixture samples were prepared and have been sequenced thus far with three commercially available kits targeting forensic short tandem repeat (STR) and single nucleotide polymorphism (SNP) markers, with FASTQ data files and metadata publicly available at doi.org/10.18434/M32157. Full article
(This article belongs to the Special Issue Strategies and Techniques in DNA Forensic Investigations)
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16 pages, 291 KiB  
Review
Usher Syndrome: New Insights into Classification, Genotype–Phenotype Correlation, and Management
by Fabiana D’Esposito, Giuseppe Gagliano, Caterina Gagliano, Antonino Maniaci, Alessandro Avitabile, Rosa Giglio, Michele Reibaldi, Maria Francesca Cordeiro and Marco Zeppieri
Genes 2025, 16(3), 332; https://doi.org/10.3390/genes16030332 - 12 Mar 2025
Viewed by 707
Abstract
Background: Usher syndrome (USH), the most common cause of combined deaf-blindness, is a genetically and phenotypically heterogeneous disorder characterized by congenital hearing impairment and progressive vision loss due to rod-cone dystrophy. Although the original classification in three subtypes (USH I, USH II, and [...] Read more.
Background: Usher syndrome (USH), the most common cause of combined deaf-blindness, is a genetically and phenotypically heterogeneous disorder characterized by congenital hearing impairment and progressive vision loss due to rod-cone dystrophy. Although the original classification in three subtypes (USH I, USH II, and USH III) is still valid, recent findings have changed and widened perspectives in its classification, genotype–phenotype correlations, and management strategies: Objective: This study aims to provide new insights into the classification of Usher syndrome, explore the genotype-phenotype correlations, and review current and emerging management strategies. Methods: A comprehensive literature review has been conducted, incorporating data from clinical studies, genetic databases, and patient registries. Results: Recent studies have led to the identification of several novel pathogenic variants in the USH genes, leading to refined subclassifications of Usher syndrome. Interactions between different genes being part of the network of this ciliopathy have been investigated and new mechanisms unveiled. Significant correlations were found between certain genotypes and the presentation of both auditory and visual phenotypes. For instance, pathogenic variants in the MYO7A gene (USH1B) were generally associated with more severe hearing impairment and earlier onset of retinal dystrophy, if compared to other USH genes-related forms. Other genes, such as USH1G, traditionally considered as causing a specific subtype, can display phenotypic heterogeneity in some patients. Conclusions: This review provides insights into a better understanding of Usher syndrome that considers recent findings regarding its genetic causes and clinical features. Precise genotype–phenotype correlations can lead to better genetic counselling, more precise characterization of the natural history of the condition, and a personalized and effective management approach. Recent progress has been made in research into gene-specific therapies that appear promising for improving the quality of life for individuals affected by Usher syndrome. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
23 pages, 10624 KiB  
Review
Curious Dichotomies of Apolipoprotein E Function in Alzheimer’s Disease and Cancer—One Explanatory Mechanism of Inverse Disease Associations?
by Claire M. Perks, Rachel M. Barker, Mai Alhadrami, Omar Alkahtani, Emily Gill, Mary Grishaw, Abigail J. Harland, Peter Henley, Haonan Li, Ellie O’Sullivan, Gideon Stone, Xiaoyu Su and Patrick G. Kehoe
Genes 2025, 16(3), 331; https://doi.org/10.3390/genes16030331 - 12 Mar 2025
Viewed by 630
Abstract
An apparent “inverse” relationship exists between two seemingly unconnected conditions, Alzheimer’s disease (AD) and cancer, despite sharing similar risk factors, like increased age and obesity. AD is associated with amyloid beta (Aβ) plaques and neurofibrillary tau tangles that cause neural degeneration; [...] Read more.
An apparent “inverse” relationship exists between two seemingly unconnected conditions, Alzheimer’s disease (AD) and cancer, despite sharing similar risk factors, like increased age and obesity. AD is associated with amyloid beta (Aβ) plaques and neurofibrillary tau tangles that cause neural degeneration; cancer, in contrast, is characterized by enhanced cell survival and proliferation. Apolipoprotein E (ApoE) is the main lipoprotein found in the central nervous system and via its high affinity with lipoprotein receptors plays a critical role in cholesterol transport and uptake. ApoE has 3 protein isoforms, ApoE E2, ApoE E3, and ApoE E4, respectively encoded for by 3 allelic variants of APOE (ε2, ε3, and ε4). This review examines the characteristics and function of ApoE described in both AD and cancer to assimilate evidence for its potential contribution to mechanisms that may underly the reported inverse association between the two conditions. Of the genetic risk factors relevant to most cases of AD, the most well-known with the strongest contribution to risk is APOE, specifically the ε4 variant, whereas for cancer risk, APOE has not featured as a significant genetic contributor to risk. However, at the protein level in both conditions, ApoE contributes to disease pathology via affecting lipid physiology and transport. In AD, Aβ-dependent and -independent interactions have been suggested, whereas in cancer, ApoE plays a role in immunoregulation. Understanding the mechanism of action of ApoE in these diametrically opposed diseases may enable differential targeting of therapeutics to provide a beneficial outcome for both. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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42 pages, 3151 KiB  
Review
Methods for Extracellular Vesicle Isolation: Relevance for Encapsulated miRNAs in Disease Diagnosis and Treatment
by Maria Ljungström and Elisa Oltra
Genes 2025, 16(3), 330; https://doi.org/10.3390/genes16030330 - 12 Mar 2025
Viewed by 582
Abstract
Extracellular vesicles (EVs) are nanovesicles that facilitate intercellular communication by carrying essential biomolecules under physiological and pathological conditions including microRNAs (miRNAs). They are found in various body fluids, such as blood, urine, and saliva, and their levels fluctuate with disease progression, making them [...] Read more.
Extracellular vesicles (EVs) are nanovesicles that facilitate intercellular communication by carrying essential biomolecules under physiological and pathological conditions including microRNAs (miRNAs). They are found in various body fluids, such as blood, urine, and saliva, and their levels fluctuate with disease progression, making them valuable diagnostic tools. However, isolating EVs is challenging due to their small size and biological complexity. Here, we summarize the principles behind the most common EV isolation methods including ultracentrifugation, precipitation, immunoaffinity, sorting, ultrafiltration, size exclusion chromatography, and microfluidics while highlighting protocol strengths and weaknesses. We also review the main strategies to identify and quantify circulating miRNAs with a particular focus on EV-encapsulated miRNAs. Since these miRNAs hold special clinical interest derived from their superior stability and therapeutic potential, the information provided here should provide valuable guidance for future research initiatives in the promising field of disease diagnostic and treatment based on EV-encapsulated miRNAs. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 6186 KiB  
Article
Cloning, Characterization, and Expression Analysis of the DEAD-Box Family Genes, Vasa and PL10, in Pacific Abalone (Haliotis discus hannai)
by Fei Chen, Wenwei Wu, Min Li, Ying Su, Miaoqing Huang, Xuan Luo, Weiwei You and Caihuan Ke
Genes 2025, 16(3), 329; https://doi.org/10.3390/genes16030329 - 11 Mar 2025
Viewed by 505
Abstract
Background/Objectives: Vasa and PL10 belong to the DEAD-box protein family, which plays crucial roles in various cellular functions, such as DNA replication, DNA repair, and RNA processing. Additionally, DEAD-box family genes have also been identified as being related to gonadal development in many [...] Read more.
Background/Objectives: Vasa and PL10 belong to the DEAD-box protein family, which plays crucial roles in various cellular functions, such as DNA replication, DNA repair, and RNA processing. Additionally, DEAD-box family genes have also been identified as being related to gonadal development in many species. However, the function of vasa and PL10 in abalone is poorly understood on a molecular level. Methods: In the present study, we individually isolated and characterized the vasa and PL10 orthologs in Haliotis discus hannai (Hdh-vasa and Hdh-PL10). We also characterized the mRNA distributions of vasa and PL10 in various tissues from adult organisms and different embryonic developmental stages using real-time PCR (RT-qPCR) techniques. Furthermore, spatial and temporal expression of Hdh-vasa and Hdh-PL10 throughout embryonic and larval development was examined by whole-mount in situ hybridization (WMISH). Results: The two predicted amino acid sequences contained all of the conserved motifs characterized by the DEAD-box family. Homology and phylogenetic analyses indicate that they belong to the vasa and PL10 subfamilies. We found that vasa and PL10 mRNA were not solely restricted to gonads but were widely expressed in various tissues. WMISH showed that Hdh-vasa and Hdh-PL10 largely overlapped, with both being maternally expressed and specifically localized to the micromere lineage cells during early cleavage stages. By the gastrulation stage, Hdh-vasa were expressed strongly in two bilaterally symmetrical paraxial clusters, but Hdh-PL10 was dispersed in entire endodermal region. Our results suggest that Hdh-vasa-expressing cells are located as a subpopulation of undifferentiated multipotent cells that express Hdh-PL10. As such, we infer that primordial germ cells are specified from these vasa-expressing cells at some point during development, and inductive signals (epigenesis) play an important role in specifying primordial germ cells (PGCs) in H. discus hannai. Conclusions: This study provides valuable insights into the molecular characteristics and expression patterns of Hdh-vasa and Hdh-PL10, contributing to a better understanding of their roles in germ cell specification and early embryonic development in H. discus hannai. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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21 pages, 5835 KiB  
Article
Transcriptome and Metabolome Analysis of Low-Pressure Regulation in Saussurea involucrata Leaves
by Xinyu Quan, Fenggui Fan, Hanbo Cao, Na Tang, Changgen Xu and Changhe Wang
Genes 2025, 16(3), 328; https://doi.org/10.3390/genes16030328 - 11 Mar 2025
Viewed by 433
Abstract
Saussurea involucrata, an endangered medicinal plant, thrives in high mountain regions at altitudes ranging from 3500 to 5000 m. Being a plant that grows at high altitudes means it possesses unique physiological mechanisms and stress-responsive genes that regulate and adapt to the [...] Read more.
Saussurea involucrata, an endangered medicinal plant, thrives in high mountain regions at altitudes ranging from 3500 to 5000 m. Being a plant that grows at high altitudes means it possesses unique physiological mechanisms and stress-responsive genes that regulate and adapt to the high-altitude environment. While many cold-resistant genes have been cloned and their mechanisms studied, the genes and molecular mechanisms involved in adaptation to hypobaric hypoxia remain largely unexplored. This study conducted transcriptomic and metabolomic analyses on the leaves of S. involucrata under normal atmosphere (101 kPa) and low pressure (60 kPa). A total of 2383 differentially expressed genes (DEGs) and 336 differentially accumulated metabolites (DAMs) were identified utilizing RNA-seq and UPLS-MS techniques. The results indicated that S. involucrata exhibits responses to hypobaric hypoxia environments by engaging in DNA repair, membrane transport, hypoxic response, reproductive processes, and various metabolic activities associated with nutrient uptake and the effective utilization of chemical components. It is worth noting that under low-pressure treatment, flavonoids are predominantly negatively regulated, whereas terpenoids are primarily positively regulated. These findings identify key genes and metabolites in S. involucrata that respond to hypobaric hypoxia treatment, providing a theoretical basis for the development of its medicinal value and for low-altitude cultivation. Full article
(This article belongs to the Topic Vegetable Breeding, Genetics and Genomics, 2nd Volume)
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Article
Genomic Patterns of Homozygosity and Genetic Diversity in the Rhenish German Draught Horse
by Johanna Sievers and Ottmar Distl
Genes 2025, 16(3), 327; https://doi.org/10.3390/genes16030327 - 11 Mar 2025
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Abstract
Background/Objectives: The Rhenish German draught horse is an endangered German horse breed, originally used as working horse in agriculture. Therefore, the objective of this study was to evaluate the breed’s genetic diversity using pedigree and genomic data in order to analyze classical and [...] Read more.
Background/Objectives: The Rhenish German draught horse is an endangered German horse breed, originally used as working horse in agriculture. Therefore, the objective of this study was to evaluate the breed’s genetic diversity using pedigree and genomic data in order to analyze classical and ancestral pedigree-based inbreeding, runs of homozygosity, ROH islands, and consensus ROH. Methods: We studied the genome-wide genotype data of 675 Rhenish German draught horses and collated pedigree-based inbreeding coefficients for these horses. The final dataset contained 64,737 autosomal SNPs. Results: The average number of ROH per individual was 43.17 ± 9.459 with an average ROH length of 5.087 Mb ± 1.03 Mb. The average genomic inbreeding coefficient FROH was 0.099 ± 0.03, the pedigree-based classical inbreeding coefficient FPED 0.016 ± 0.021, and ancestral inbreeding coefficients ranged from 0.03 (Fa_Kal) to 0.51 (Ahc). Most ROH (55.85%) were classified into the length category of 2–4 Mb, and the minority (0.43%) into the length category of >32 Mb. The effective population size (Ne) decreased in the last seven generations (~65 years) from 189.43 to 58.55. Consensus ROH shared by 45% of the horses were located on equine chromosomes 3 and 7, while ROH islands exceeding the 99th percentile threshold were identified on chromosomes 2, 3, 5, 7, 9, 10, and 11. These ROH islands contained genes associated with morphological development (HOXB cluster), fertility (AURKC, NLRP5, and DLX3), muscle growth, and skin physiology (ZNF gene cluster). Conclusions: This study highlights how important it is to monitor genetic diversity in endangered populations with genomic data. The results of this study will help to develop breeding strategies to ensure the conservation of the German Rhenish draught horse population and show whether favorable alleles from the overrepresented candidate genes within ROH were transmitted to the next generation. Full article
(This article belongs to the Special Issue The Whole-Genome Analysis and Breed Evolution of Horses)
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