Genes

20 pages, 5763 KiB

Open AccessArticle

Genome-Wide Identification and Characterization of the CDPK Family of Genes and Their Response to High-Calcium Stress in Yinshania henryi

by Liangfeng An, Huihui Fang, Ximin Zhang, Jing Tang, Jiyi Gong, Yin Yi and Ming Tang

Genes 2025, 16(1), 109; https://doi.org/10.3390/genes16010109 - 20 Jan 2025

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Abstract

Background/Objectives: Calcium-dependent protein kinases (CDPKs) are a crucial class of calcium-signal-sensing and -response proteins that significantly regulate abiotic stress. Yinshania henryi is a member of the Brassicaceae family that primarily grows in the karst regions of southwestern China, with a notable tolerance to [...] Read more.

Background/Objectives: Calcium-dependent protein kinases (CDPKs) are a crucial class of calcium-signal-sensing and -response proteins that significantly regulate abiotic stress. Yinshania henryi is a member of the Brassicaceae family that primarily grows in the karst regions of southwestern China, with a notable tolerance to high-calcium soils. Currently, the function of the CDPK family of genes in Y. henryi has yet to be explored. Methods: This study employed a comprehensive approach starting with bioinformatic methods to analyze the whole-genome sequencing data of Y. henryi and identified YhCDPK genes by combining phylogenetic characteristics and protein domain analysis. Results: It then delved into the physicochemical properties, gene structure, chromosomal localization, phylogenetic tree, and promoter cis-acting elements of these YhCDPK genes. Subsequently, RNA-seq data and qRT-PCR analysis were utilized to understand the expression patterns of YhCDPK genes. Twenty-eight YhCDPK genes were found to be unevenly distributed across six chromosomes; these can be classified into four subfamilies, with many cis-acting elements in their promoter regions involved in plant growth and stress responses. Furthermore, the differential expression patterns of YhCDPK genes under different concentrations of calcium treatments were investigated using RNA-seq data and qRT-PCR analysis. Conclusions: These results are a critical first step in understanding the functions of YhCDPK genes, and they lay a foundation for further elucidating the adaptability and response mechanism of YhCDPK genes in Y. henryi to the karst environment. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Genetics and Genomics)

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17 pages, 3769 KiB

Open AccessArticle

Atypical Leber Hereditary Optic Neuropathy (LHON) Associated with a Novel MT-CYB:m.15309T>C(Ile188Thr) Variant

by Sanja Petrovic Pajic, Ana Fakin, Martina Jarc-Vidmar, Maja Sustar Habjan, Lucija Malinar, Kasja Pavlovic, Nina Krako Jakovljevic, Andjelka Isakovic, Sonja Misirlic-Dencic, Marija Volk, Ales Maver, Gregor Jezernik, Damjan Glavac, Borut Peterlin, Ivanka Markovic, Nebojsa Lalic and Marko Hawlina

Genes 2025, 16(1), 108; https://doi.org/10.3390/genes16010108 - 20 Jan 2025

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Abstract

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the [...] Read more.

Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Diseases)

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20 pages, 757 KiB

Open AccessReview

Gene Therapy and Diabetes: A Narrative Review of Recent Advances and the Role of Multidisciplinary Healthcare Teams

by Nadia Khartabil and Ani Avoundjian

Genes 2025, 16(1), 107; https://doi.org/10.3390/genes16010107 - 20 Jan 2025

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Abstract

Introduction: Gene therapy has emerged as a promising frontier in the management of diabetes, offering innovative approaches to address both type 1 and type 2 diabetes. This narrative review examines the advancements in gene therapy applications, focusing on both animal and human studies, [...] Read more.

Introduction: Gene therapy has emerged as a promising frontier in the management of diabetes, offering innovative approaches to address both type 1 and type 2 diabetes. This narrative review examines the advancements in gene therapy applications, focusing on both animal and human studies, and includes a total of 11 studies in adherence to PRISMA guidelines. These studies utilize various viral vectors, such as adeno-associated virus (AAV) and lentivirus, to deliver genes that regulate insulin production and enhance angiogenesis. This review aims to synthesize recent advancements in gene therapy for both type 1 and type 2 diabetes and its complications, and to explore the evolving role of pharmacists in this emerging field. Methods: A comprehensive search was conducted to identify relevant studies on gene therapy for diabetes. Databases such as PubMed, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Google Scholar were queried using keywords such as “Diabetes”, “gene therapy”, “Type 1 diabetes”, and “Type 2 diabetes”. Both animal and human studies were included to provide a broad perspective on the advancements in this field. Results: Animal model studies have shown promising results, including sustained insulin production, improved glucose homeostasis, and enhanced wound healing. Human studies, though fewer in number, have reported significant advancements. Patients with diabetic neuropathy treated with plasmid VEGF and recombinant adeno-associated virus (rAAV) showed improvements in neuropathic symptoms and glycemic control. Other studies involving intramuscular injections of VM202 and bicistronic VEGF165/HGF plasmid have reported pain reduction, improved healing of ischemic lesions, and increased angiogenesis. Conclusions: Despite these encouraging results, limitations such as small sample sizes, short follow-up periods, and the necessity for more extensive clinical trials persist. Diabetes is a metabolic syndrome that requires the collaboration of a multidisciplinary team to assist in several aspects of implementing successful gene therapy. Several healthcare providers and policy makers may play a crucial role in patient education, counseling, and the management of gene therapy treatments. Full article

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

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22 pages, 14926 KiB

Open AccessArticle

Origin and Genealogy of Rare mtDNA Haplotypes Detected in the Serbian Population

by Slobodan Davidović, Jelena M. Aleksić, Marija Tanasković, Pavle Erić, Milena Stevanović and Nataša Kovačević-Grujičić

Genes 2025, 16(1), 106; https://doi.org/10.3390/genes16010106 - 20 Jan 2025

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Abstract

Background: The Balkan Peninsula has served as an important migration corridor between Asia Minor and Europe throughout humankind’s history and a refugium during the Last Glacial Maximum. Past migrations such as the Neolithic expansion, Bronze Age migrations, and the settlement of Slavic [...] Read more.

Background: The Balkan Peninsula has served as an important migration corridor between Asia Minor and Europe throughout humankind’s history and a refugium during the Last Glacial Maximum. Past migrations such as the Neolithic expansion, Bronze Age migrations, and the settlement of Slavic tribes in the Early Middle Ages, are well known for their impact on shaping the genetic pool of contemporary Balkan populations. They have contributed to the high genetic diversity of the region, especially in mitochondrial DNA (mtDNA) lineages. Serbia, located in the heart of the Balkans, reflects this complex history in a broad spectrum of mtDNA subhaplogroups. Methods: To explore genetic diversity in Serbia and the wider Balkan region, we analyzed rare mtDNA subclades—R0a, N1a, N1b, I5, W, and X2—using publicly available data. Our dataset included already published sequences from 3499 HVS-I/HVS-II and 1426 complete mitogenomes belonging to West Eurasian and African populations, containing both contemporary and archaeological samples. We assessed the parameters of genetic diversity found in different subclades across the studied regions and constructed detailed phylogeographic trees and haplotype networks to determine phylogenetic relationships. Results: Our analyses revealed the observable geographic structure and identified novel mtDNA subclades, some of which may have originated in the Balkan Peninsula (e.g., R0a1a5, I5a1, W1c2, W3b2, and X2n). Conclusions: The geographic distribution of rare subclades often reveals patterns of past population movements, routes, and gene flows. By tracing the origin and diversity of these subclades, our study provided new insights into the impact of historical migrations on the maternal gene pool of Serbia and the wider Balkan region, contributing to our understanding of the complex genetic history of this important European crossroads. Full article

(This article belongs to the Special Issue The Genetic Diversification of Human Populations)

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17 pages, 4703 KiB

Open AccessArticle

Transcriptome Reveals the Differential Regulation of Sugar Metabolism to Saline–Alkali Stress in Different Resistant Oats

by Naiyu Chen, Shuya Xing, Jiaxin Song, Shutong Lu, Lei Ling and Lina Qu

Genes 2025, 16(1), 105; https://doi.org/10.3390/genes16010105 - 20 Jan 2025

Viewed by 346

Abstract

Background: Saline–alkali stress is a major factor limiting the growth of oats. Sugar is the primary carbon and energy source in plants which regulates plant development and growth by regulating enzyme activity and gene expression. Sucrose, glucose, and fructose are ubiquitous plant-soluble sugars [...] Read more.

Background: Saline–alkali stress is a major factor limiting the growth of oats. Sugar is the primary carbon and energy source in plants which regulates plant development and growth by regulating enzyme activity and gene expression. Sucrose, glucose, and fructose are ubiquitous plant-soluble sugars that act as signalling molecules in the transcriptional regulation of various metabolic and defence-related genes. Methods: In this study, soluble sugars, fructose, sucrose, and starch contents were measured, and transcriptomics was used to determine the differentially expressed genes (DEGs) in saline-sensitive and saline-tolerant oats after 6, 12, 24, and 48 h. DEGs annotated to carbohydrates were selected using the Kyoto Encyclopedia of Genes and Genomes. Results: DEGs involved in carbohydrate metabolism were mainly enriched in the glycolysis/gluconeogenesis and pentose phosphate pathways, fructose and mannose metabolism, and starch and sucrose metabolism. GAPDH, SUPI, SUS2, ATP-PEK, HXK6, FBA4, TBA4, TKT, ISA3, PPDK1, and BAM2 were significantly expressed, and a quantitative reverse transcription polymerase chain reaction verified the transcriptome sequencing results. Conclusions: In this study, oats with different salinity tolerances were used to determine sugar contents under four salinity stress durations, and transcriptome sequencing was used to explore the regulatory mechanism of sugars and provide a reference for elucidating the sugar signalling regulatory mechanism under abiotic stress. Full article

(This article belongs to the Special Issue Molecular Biology of Crop Abiotic Stress Resistance)

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9 pages, 595 KiB

Open AccessArticle

The Epigenetic Machinery and Energy Expenditure: A Network to Be Revealed

by Elisabetta Prada, Giulia Bruna Marchetti, Denise Pires Marafon, Alessandra Mazzocchi, Giulietta Scuvera, Lidia Pezzani, Carlo Agostoni and Donatella Milani

Genes 2025, 16(1), 104; https://doi.org/10.3390/genes16010104 - 19 Jan 2025

Viewed by 417

Abstract

Mendelian disorders of the epigenetic machinery (MDEMs) include a large number of conditions caused by defective activity of a member of the epigenetic machinery. MDEMs are characterized by multiple congenital abnormalities, intellectual disability and abnormal growth. that can be variably up- or down-regulated. [...] Read more.

Mendelian disorders of the epigenetic machinery (MDEMs) include a large number of conditions caused by defective activity of a member of the epigenetic machinery. MDEMs are characterized by multiple congenital abnormalities, intellectual disability and abnormal growth. that can be variably up- or down-regulated. Background/Objectives: In several MDEMs, a predisposition to metabolic syndrome and obesity since childhood has been reported. Methods: To investigate the metabolic bases of this abnormal growth, we collected physical data from a heterogeneous pool of 38 patients affected by MDEMs. Thirty-five patients performed indirect calorimetry (as a measure of resting energy expenditure, REE) and blood tests to monitor plasmatic nutritional parameters. Conclusions: Although limited by a small-sized and heterogeneous sample, our study demonstrates a linear correlation between REE and physical parameters, OFC, height and weight, and observed a slight imbalance on several plasmatic spies of metabolic syndrome predisposition. Furthermore, we demonstrated a significantly higher REE in Sotos Syndrome type 1 patients compared to the controls, which resulted independent from height, suggesting that impaired metabolism in these patients may go beyond overgrowth. Full article

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

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14 pages, 2490 KiB

Open AccessFeature PaperArticle

Arabidopsis thaliana DNA Damage Response Mutants Challenged with Genotoxic Agents—A Different Experimental Approach to Investigate the TDP1α and TDP1β Genes

by Anna Bertoncini, Paola Pagano and Anca Macovei

Genes 2025, 16(1), 103; https://doi.org/10.3390/genes16010103 - 19 Jan 2025

Viewed by 366

Abstract

Background/Objectives: DNA damage response (DDR) is a highly conserved and complex signal transduction network required for preserving genome integrity. DNA repair pathways downstream of DDR include the tyrosyl-DNA phosphodiesterase1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine residue of topoisomerase I [...] Read more.

Background/Objectives: DNA damage response (DDR) is a highly conserved and complex signal transduction network required for preserving genome integrity. DNA repair pathways downstream of DDR include the tyrosyl-DNA phosphodiesterase1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine residue of topoisomerase I (TopI) and 3′-phosphate end of DNA. A small TDP1 subfamily, composed of TDP1α and TDP1β, is present in plants. The aim of this work was to investigate the role of the two TDP1 genes in the DDR context. Methods: A series of Arabidopsis thaliana DDR single and double mutants defective in the sog1, e2fb, pol2A, atm, and atr genes, treated with the genotoxic agents camptothecin (CPT, inhibitor of TopI) and NSC120686 (NSC, inhibitor of TDP1), were used. These compounds were specifically used due to their known impact on the TDP1 function. The effect of the treatments was assessed via phenotypic analyses that included germination percentage, speed, and seedling growth. Subsequently, the expression of the TDP1α and TDP1β genes was monitored through qRT-PCR. Results: Overall, the gathered data indicate that the atm mutant was highly sensitive to NSC120686, both phenotypically and concerning the TDP1α gene expression profiles. Alternatively, the upregulation of TDP1β in e2fb, pol2a, and atr supports its implication in the replication stress response. Conclusions: The current study demonstrates that genotoxic stress induced by CPT and NSC has a genotype-dependent effect reflected by a differential expression of TDP1 genes and early phenotypic development. Full article

(This article belongs to the Special Issue DNA Damage Repair and Plant Stress Response)

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14 pages, 1609 KiB

Open AccessFeature PaperArticle

Genomic Rewilding of Domestic Animals: The Role of Hybridization and Selection in Wolfdog Breeds

by Alžběta Báčová, José Ignacio Lucas Lledó, Kristýna Eliášová, Silvie Neradilová, Astrid Vik Stronen, Romolo Caniglia, Marco Galaverni, Elena Fabbri, Frederica Mattucci, Adam Boyko, Pavel Hulva and Barbora Černá Bolfíková

Genes 2025, 16(1), 102; https://doi.org/10.3390/genes16010102 - 19 Jan 2025

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Abstract

Background/Objectives: The domestication of the grey wolf (Canis lupus) and subsequent creation of modern dog breeds have significantly shaped the genetic landscape of domestic canines. This study investigates the genomic effects of hybridization and breeding management practices in two hybrid [...] Read more.

Background/Objectives: The domestication of the grey wolf (Canis lupus) and subsequent creation of modern dog breeds have significantly shaped the genetic landscape of domestic canines. This study investigates the genomic effects of hybridization and breeding management practices in two hybrid wolfdog breeds: the Czechoslovakian Wolfdog (CSW) and the Saarloos Wolfdog (SAW). Methods: We analyzed the genomes of 46 CSWs and 20 SAWs, comparing them to 12 German Shepherds (GSHs) and 20 wolves (WLFs), which served as their ancestral populations approximately 70–90 years ago. Results: Our findings highlight that hybridization can increase genetic variability and mitigate the effects of inbreeding, as evidenced by the observed heterozygosity levels in both wolfdog breeds. However, the SAW genome revealed a higher coefficient of inbreeding and longer runs of homozygosity compared to the CSW, reflecting significant inbreeding during its development. Discriminant Analysis of Principal Components and fixation index analyses demonstrate that the CSW exhibits closer genetic proximity to the GSH than the SAW, likely due to differences in the numbers of GSHs used during their creation. Maximum likelihood clustering further confirmed clear genetic differentiation between these hybrid breeds and their respective ancestors, while shared ancestral polymorphism was detectable in all populations. Conclusions: These results highlight the role of controlled hybridization with captive-bred wolves and peculiar breeding strategies in shaping the genetic structure of wolfdog breeds. To ensure the long-term genetic health of these breeds, it is recommended to promote adequate and sustainable breeding practices to maintain genetic diversity, minimize inbreeding, and incorporate the careful selection of unrelated individuals from diverse lineages, while avoiding additional, uncontrolled crossings with wild wolves. Full article

(This article belongs to the Special Issue Genetics in Canines: From Evolution to Conservation)

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20 pages, 1552 KiB

Open AccessArticle

Further Development of SAMPDI-3D: A Machine Learning Method for Predicting Binding Free Energy Changes Caused by Mutations in Either Protein or DNA

by Prawin Rimal, Shamrat Kumar Paul, Shailesh Kumar Panday and Emil Alexov

Genes 2025, 16(1), 101; https://doi.org/10.3390/genes16010101 - 19 Jan 2025

Viewed by 487

Abstract

Background/Objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein–DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein–DNA binding, accurately predicting changes in binding free energy (ΔΔG) [...] Read more.

Background/Objectives: Predicting the effects of protein and DNA mutations on the binding free energy of protein–DNA complexes is crucial for understanding how DNA variants impact wild-type cellular function. As many cellular interactions involve protein–DNA binding, accurately predicting changes in binding free energy (ΔΔG) is valuable for distinguishing pathogenic mutations from benign ones. Methods: This study describes the development and optimization of the SAMPDI-3Dv2 machine learning method, which is trained on an expanded database of experimentally measured ΔΔGs. This enhanced model incorporates new features, including the 3D structure of the mutant protein, features of the mutant structure, and a position-specific scoring matrix (PSSM). Benchmarking was conducted using 5-fold cross-validation. Results: The updated SAMPDI-3D model (SAMPDI-3Dv2) achieved Pearson correlation coefficients (PCCs) of 0.68 for protein and 0.80 for DNA mutations. These results represent significant improvements over existing tools. Additionally, the method’s rapid execution time enables genome-scale predictions. Conclusions: The improved SAMPDI-3Dv2 shows enhanced predictive performance for analyzing mutations in protein–DNA complexes. By leveraging structural information and an expanded training dataset, SAMPDI-3Dv2 provides researchers with a more accurate and efficient tool for mutation analysis, contributing to identifying pathogenic variants and improving our understanding of cellular function. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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16 pages, 5633 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis Under Abiotic Stress of the Lipoxygenase Gene Family in Maize (Zea mays)

by Sinan Li, Shuai Hou, Yuanqing Sun, Minghao Sun, Yan Sun, Xin Li, Yunlong Li, Luyao Wang, Quan Cai, Baitao Guo and Jianguo Zhang

Genes 2025, 16(1), 99; https://doi.org/10.3390/genes16010099 - 18 Jan 2025

Viewed by 354

Abstract

Background/Objectives: Abiotic stresses impose significant constraints on crop growth, development, and yield. However, the comprehensive characterization of the maize (Zea mays) lipoxygenase (LOX) gene family under stress conditions remains limited. LOXs play vital roles in plant stress responses by [...] Read more.

Background/Objectives: Abiotic stresses impose significant constraints on crop growth, development, and yield. However, the comprehensive characterization of the maize (Zea mays) lipoxygenase (LOX) gene family under stress conditions remains limited. LOXs play vital roles in plant stress responses by mediating lipid oxidation and signaling pathways. Methods: In this study, 13 ZmLOX genes were identified in maize and characterized to explore their functions under abiotic stresses. Results: Phylogenetics revealed that ZmLOX genes share evolutionary origins with LOX genes in Arabidopsis and rice. Promoter analysis identified cis-acting elements associated with growth, light response, hormone signaling, and stress response, indicating their diverse biological roles. Gene Ontology (GO) and KEGG enrichment analyses showed that ZmLOX genes are involved in jasmonic acid metabolism, lipid signaling, and photosynthetic processes, while protein–protein interaction (PPI) analysis positioned ZmLOX proteins as central hubs in stress-related regulatory networks. Differential expression and qRT-PCR analyses revealed stress-specific (including heat, drought, salt, and cold) expression patterns, with ZmLOX2 and ZmLOX13 showing key roles in drought and cold tolerance, respectively. Conclusions: These findings provide new insights into the regulatory functions of ZmLOX genes, offering potential targets for enhancing maize resilience to abiotic stresses and improving agricultural productivity. Full article

(This article belongs to the Special Issue Genetics of Abiotic Stress Tolerance in Plants Volume II)

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25 pages, 1769 KiB

Open AccessReview

Research Progress and Clinical Translation Potential of Coronary Atherosclerosis Diagnostic Markers from a Genomic Perspective

by Hanxiang Liu, Yuchen Zhang, Yueyan Zhao, Yuzhen Li, Xiaofeng Zhang, Lingyu Bao, Rongkai Yan, Yixin Yang, Huixian Zhou, Jinming Zhang and Siyuan Song

Genes 2025, 16(1), 98; https://doi.org/10.3390/genes16010098 - 18 Jan 2025

Viewed by 435

Abstract

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent [...] Read more.

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD’s polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine. Methods: We conducted a systematic review of CAD genomic studies from PubMed and Web of Science databases, analyzing findings from genome-wide association studies (GWASs), gene sequencing, transcriptomics, and epigenomics research. Results: GWASs and sequencing studies have identified key genetic variations associated with CAD, including JCAD/KIAA1462, GUCY1A3, PCSK9, and SORT1, which regulate inflammation, lipid metabolism, and vascular function. Transcriptomic and epigenomic analyses have revealed disease-specific gene expression patterns, DNA methylation signatures, and regulatory non-coding RNAs (miRNAs and lncRNAs), providing new approaches for early detection. Conclusions: While genetic marker research in CAD has advanced significantly, clinical implementation faces challenges including marker dynamics, a lack of standardization, and integration with conventional diagnostics. Future research should prioritize developing standardized guidelines, conducting large-scale prospective studies, and enhancing multi-omics data integration to advance genomic diagnostics in CAD, ultimately improving patient outcomes through precision medicine. Full article

(This article belongs to the Special Issue Genomic Approaches for Disease Diagnosis and Prognosis)

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13 pages, 223 KiB

Open AccessReview

History of Biological Databases, Their Importance, and Existence in Modern Scientific and Policy Context

by Mikołaj Danielewski, Marlena Szalata, Jan Krzysztof Nowak, Jarosław Walkowiak, Ryszard Słomski and Karolina Wielgus

Genes 2025, 16(1), 100; https://doi.org/10.3390/genes16010100 - 18 Jan 2025

Viewed by 442

Abstract

With the development of genome sequencing technologies, the amount of data produced has greatly increased in the last two decades. The abundance of digital sequence information (DSI) has provided research opportunities, improved our understanding of the genome, and led to the discovery of [...] Read more.

With the development of genome sequencing technologies, the amount of data produced has greatly increased in the last two decades. The abundance of digital sequence information (DSI) has provided research opportunities, improved our understanding of the genome, and led to the discovery of new solutions in industry and medicine. It has also posed certain challenges, i.e., how to store and handle such amounts of data. This, coupled with the need for convenience, international cooperation, and the possibility of independent validation, has led to the establishment of numerous databases. Spearheaded with the idea that data obtained with public funds should be available to the public, open access has become the predominant mode of accession. However, the increasing popularity of commercial genetic tests brings back the topic of data misuse, and patient’s privacy. At the previous United Nations Biodiversity Conference (COP15, 2022), an issue of the least-developed countries exploiting their natural resources while providing DSI and the most-developed countries benefitting from this was raised. It has been proposed that financial renumeration for the data could help protect biodiversity. With the goal of introducing the topic to those interested in utilizing biological databases, in this publication, we present the history behind the biological databases, their necessity in today’s scientific world, and the issues that concern them and their content, while providing scientific and policy context in relation to United Nations Biodiversity Conference (COP16, 21.10—1.11.24). Full article

(This article belongs to the Section Bioinformatics)

16 pages, 9517 KiB

Open AccessArticle

Identification and Functional Analysis of Candidate Genes Influencing Citrus Leaf Size Through Transcriptome and Coexpression Network Approaches

by Xiaoxiao Wu, Yuanhui Xiao, Ping Liu, Qiuling Pang, Chongling Deng, Cuina Fu, Haimeng Fang and Chuanwu Chen

Genes 2025, 16(1), 97; https://doi.org/10.3390/genes16010097 - 17 Jan 2025

Viewed by 595

Abstract

Background: Leaves are the main organs involved in photosynthesis. They capture light energy and promote gas exchange, and their size and shape affect yield. Identifying the regulatory networks and key genes that control citrus leaf size is essential for increasing citrus crop yield. [...] Read more.

Background: Leaves are the main organs involved in photosynthesis. They capture light energy and promote gas exchange, and their size and shape affect yield. Identifying the regulatory networks and key genes that control citrus leaf size is essential for increasing citrus crop yield. Methods: In this study, transcriptome sequencing was performed on three leaf materials: the ‘Cuimi’ kumquat (Nor) variety and its leaf variants, larger-leaf (VarB) and smaller-leaf (VarS) varieties. Results: Correlation and principal component analyses revealed a relatively close correlation between Nor and VarS. A total of 7264 differentially expressed genes (DEGs), including 2374 transcription factors (TFs), were identified, and 254 DEGs were common among the three materials. GO and KEGG enrichment analyses revealed significant enrichment in glucose metabolism, cell wall composition, starch biosynthesis, and photosynthesis pathways. WGCNA identified three specific modules related to the different leaf sizes of these three citrus materials. Fifteen candidate genes related to leaf size, including three transcription factors, Fh5g30470 (MYB), Fh7g07360 (AP2/ERF), and Fh5g02470 (SAP), were identified on the basis of connectivity and functional annotations. Conclusions: These findings provide a theoretical foundation for a deeper understanding of the molecular mechanisms underlying citrus leaf size and offer new genetic resources for the study of citrus leaf size. Full article

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

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16 pages, 5296 KiB

Open AccessArticle

Construction of a High-Density Genetic Linkage Map and QTL Mapping for Stem Rot Resistance in Passion Fruit (Passiflora edulis Sims)

by Yanyan Wu, Weihua Huang, Jieyun Liu, Junniu Zhou, Qinglan Tian, Xiuzhong Xia, Haifei Mou and Xinghai Yang

Genes 2025, 16(1), 96; https://doi.org/10.3390/genes16010096 - 17 Jan 2025

Viewed by 346

Abstract

Background: The passion fruit (Passiflora edulis Sims) is a diploid plant (2n = 2x = 18) and is a perennial scrambling vine in Southern China. However, the occurrence and spread of stem rot in passion fruit severely impact its yield and quality. [...] Read more.

Background: The passion fruit (Passiflora edulis Sims) is a diploid plant (2n = 2x = 18) and is a perennial scrambling vine in Southern China. However, the occurrence and spread of stem rot in passion fruit severely impact its yield and quality. Methods: In this study, we re-sequenced a BC₁F₁ population consisting of 158 individuals using whole-genome resequencing. We constructed a high-density genetic linkage map and identified the quantitative trait locus (QTL), and analyzed candidate genes associated with stem rot resistance in passion fruit. Results: Based on the passion fruit reference genome (MER), a high-density genetic linkage map was constructed with 1,180,406 single nucleotide polymorphisms (SNPs). The map contains nine linkage groups, covering a total genetic distance of 1559.03 cM, with an average genetic distance of 311.81 cM. The average genetic distance between 4206 bins was 0.404 cM, and the average gap length was 10.565 cM. The collinearity correlation coefficient between the genetic map and the passion fruit genome was 0.9994. Fusarium solani was used to infect the BC₁F₁ population, and the resistance to stem rot showed a continuous distribution. A QTL, qPSR5, was mapped to the 113,377,860 bp–114,811,870 bp genomic region on chromosome 5. We performed RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction (RT-qPCR) to analyze the expression levels of predicted genes in the candidate region and identified ZX.05G0020740 and ZX.05G0020810 as ideal candidate genes for stem rot resistance in passion fruit. Conclusions: The findings in this study not only lay the foundation for cloning the qPSR5 responsible for stem rot resistance but also provide genetic resources for the genetic improvement of passion fruit. Full article

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

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22 pages, 955 KiB

Open AccessReview

Hallmarks of DNA Damage Response in Germination Across Model and Crop Species

by Federico Sincinelli, Shraddha Shridhar Gaonkar, Sri Amarnadh Gupta Tondepu, Conrado Jr Dueñas and Andrea Pagano

Genes 2025, 16(1), 95; https://doi.org/10.3390/genes16010095 - 17 Jan 2025

Viewed by 445

Abstract

DNA damage response (DDR) contributes to seed quality by guarding genome integrity in the delicate phases of pre- and post-germination. As a key determinant of stress tolerance and resilience, DDR has notable implications on the wider scale of the agroecosystems challenged by harsh [...] Read more.

DNA damage response (DDR) contributes to seed quality by guarding genome integrity in the delicate phases of pre- and post-germination. As a key determinant of stress tolerance and resilience, DDR has notable implications on the wider scale of the agroecosystems challenged by harsh climatic events. The present review focuses on the existing and documented links that interconnect DDR efficiency with an array of molecular hallmarks with biochemical, molecular, and physiological valence within the seed metabolic networks. The expression of genes encoding DDR sensors, transducers, mediators, and effectors is interpreted as a source of conserved hallmarks, along with markers of oxidative damage reflecting the seed’s ability to germinate. Similarly, the accumulation patterns of proteins and metabolites that contribute to DNA stability are predictive of seed quality traits. While a list of candidates is presented from multiple models and crop species, their interaction with chromatin dynamics, cell cycle progression, and hormonal regulation provides further levels of analysis to investigate the seed stress response holistically. The identification of novel hallmarks of DDR in seeds constitutes a framework to prompt validation with different experimental systems, to refine the current models of pre-germinative metabolism, and to promote targeted approaches for seed quality evaluation. Full article

(This article belongs to the Special Issue DNA Damage Repair and Plant Stress Response)

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19 pages, 3458 KiB

Open AccessArticle

Casein Kinase I Protein Hrr25 Is Required for Pin4 Phosphorylation and Mediates Cell Wall Integrity Signaling in Saccharomyces cerevisiae

by Amita Bhattarai, Manika Bhondeley and Zhengchang Liu

Genes 2025, 16(1), 94; https://doi.org/10.3390/genes16010094 - 17 Jan 2025

Viewed by 401

Abstract

Background: Casein kinase I protein Hrr25 plays important roles in many cellular processes, including autophagy, vesicular trafficking, ribosome biogenesis, mitochondrial biogenesis, and the DNA damage response in Saccharomyces cerevisiae. Pin4 is a multi-phosphorylated protein that has been reported to be involved in [...] Read more.

Background: Casein kinase I protein Hrr25 plays important roles in many cellular processes, including autophagy, vesicular trafficking, ribosome biogenesis, mitochondrial biogenesis, and the DNA damage response in Saccharomyces cerevisiae. Pin4 is a multi-phosphorylated protein that has been reported to be involved in the cell wall integrity (CWI) pathway and DNA damage response. Pin4 was reported to interact with Hrr25 in yeast two-hybrid and large-scale pulldown assays. Methods/Objectives: Co-immunoprecipitation and yeast two-hybrid assays were utilized to confirm whether Pin4 and Hrr25 interact and to determine how they interact. Genetic interaction analysis was conducted to examine whether hrr25 mutations form synthetic growth defects with mutations in genes involved in CWI signaling. Immunoblotting was used to determine whether Hrr25 phosphorylates Pin4. Results: We show that Hrr25 interacts with Pin4 and is required for Pin4 phosphorylation. pin4 mutations result in synthetic slow-growth phenotypes with mutations in genes encoding Bck1 and Slt2, two of the protein kinases in the MAP kinase cascade that regulates CWI in the budding yeast. We show that hrr25 mutations result in similar phenotypes to pin4 mutations. Hrr25 consists of an N-terminal kinase domain, a middle region, and a C-terminal proline/glutamine-rich domain. The function of the C-terminal P/Q-rich domain of Hrr25 has been elusive. We found that the C-terminal region of Hrr25 is required both for Pin4 interaction and CWI. Conclusions: Our data suggest that Hrr25 is implicated in cell wall integrity signaling via its association with Pin4. Full article

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

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24 pages, 1857 KiB

Open AccessReview

Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health

by Aris Kaltsas, Eleftheria Markou, Maria-Anna Kyrgiafini, Athanasios Zikopoulos, Evangelos N. Symeonidis, Fotios Dimitriadis, Athanasios Zachariou, Nikolaos Sofikitis and Michael Chrisofos

Genes 2025, 16(1), 93; https://doi.org/10.3390/genes16010093 - 17 Jan 2025

Viewed by 607

Abstract

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, and non-coding RNA activity—are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these [...] Read more.

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, and non-coding RNA activity—are crucial both for spermatogenesis and sperm maturation. However, oxidative stress, driven by excessive reactive oxygen species, disrupts these processes, leading to impaired sperm function and male infertility. This disruption extends to epigenetic modifications, resulting in abnormal gene expression and chromatin remodeling that compromise genomic integrity and fertilization potential. Importantly, oxidative-stress-induced epigenetic alterations can be inherited, affecting the health and fertility of offspring and future generations. This review investigates how oxidative stress influences epigenetic regulation in male reproduction by modifying DNA methylation, histone modifications, and non-coding RNAs, ultimately compromising spermatogenesis. Additionally, it discusses the transgenerational implications of these epigenetic disruptions and their potential role in hereditary infertility and disease predisposition. Understanding these mechanisms is vital for developing therapeutic strategies that mitigate oxidative damage and restore epigenetic homeostasis in the male germline. By integrating insights from molecular, clinical, and transgenerational research, this work emphasizes the need for targeted interventions to enhance male reproductive health and prevent adverse outcomes in progeny. Furthermore, elucidating the dose–response relationships between oxidative stress and epigenetic changes remains a critical research priority, informing personalized diagnostics and therapeutic interventions. In this context, future studies should adopt standardized markers of oxidative damage, robust clinical trials, and multi-omic approaches to capture the complexity of epigenetic regulation in spermatogenesis. Such rigorous investigations will ultimately reduce the risk of transgenerational disorders and optimize reproductive health outcomes. Full article

(This article belongs to the Section Epigenomics)

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12 pages, 1643 KiB

Open AccessArticle

The Prevalence and Clinical Characteristics of MYO3A-Associated Hearing Loss in 15,684 Hearing Loss Patients

by Karuna Maekawa, Shin-ya Nishio, Hiromitsu Miyazaki, Yoko Ohta, Naoki Oishi, Misato Kasai, Ai Yamamoto, Mayuri Okami, Koichiro Wasano, Akihiro Sakai and Shin-ichi Usami

Genes 2025, 16(1), 92; https://doi.org/10.3390/genes16010092 - 16 Jan 2025

Viewed by 406

Abstract

Background/Objectives: MYO3A belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in MYO3A have been reported to cause the deformation of hair cells into abnormally long [...] Read more.

Background/Objectives: MYO3A belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in MYO3A have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. MYO3A is a rare causative gene of autosomal recessive sensorineural hearing loss (DFNB30), with only 13 cases reported to date. In this study, we aimed to elucidate the phenotypes caused by MYO3A variations. Methods: Massively parallel DNA sequencing was performed on 15,684 Japanese hearing loss patients (mean age 27.5 ± 23.1 years old, 6574 male, 8612 female and 498 patients for whom information was unavailable), identifying nine candidate patients with MYO3A variants. Results: We identified eight causative MYO3A variants by massively parallel DNA sequencing, including six novel variants, and reported nine individuals possessing MYO3A gene variants, which is the largest group of non-related patients yet to be detected. Our findings confirmed that MYO3A variants cause progressive hearing loss, with its onset varying from birth to the second decade, eventually leading to severe-to-profound hearing loss. Conclusions: We clarified that patients with MYO3A gene variants present with late-onset, progressive hearing loss. Our findings have enabled us to predict the outcomes of hearing loss in patients with candidate MYO3A gene variants and to provide intervention in a timely manner. Full article

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

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11 pages, 1616 KiB

Open AccessCase Report

Genotype–Phenotype Correlations of Nance–Horan Syndrome in Male and Female Carriers of a Novel Variant

by Olivia A. Zin, Luiza M. Neves, Fabiana L. Motta, Daltro C. Junior, Daniela P. Cunha, Bruna N. S. Agonigi, Jocieli Malacarne, Ana Paula S. Rodrigues, Gabriela D. Rodrigues, Maria Luisa C. Tinoco, Dafne D. G. Horovitz, Adriana B. Carvalho, Andrea A. Zin, Zilton F. M. Vasconcelos and Juliana M. Ferraz Sallum

Genes 2025, 16(1), 91; https://doi.org/10.3390/genes16010091 - 16 Jan 2025

Viewed by 382

Abstract

Background: Nance–Horan syndrome (NHS) is a rare, frequently underdiagnosed, X-linked disease caused by mutations in the NHS gene. In males, it causes bilateral dense pediatric cataracts, dental anomalies, and facial dysmorphisms. Females traditionally have a more subtle phenotype with discrete lens opacities as [...] Read more.

Background: Nance–Horan syndrome (NHS) is a rare, frequently underdiagnosed, X-linked disease caused by mutations in the NHS gene. In males, it causes bilateral dense pediatric cataracts, dental anomalies, and facial dysmorphisms. Females traditionally have a more subtle phenotype with discrete lens opacities as an isolated feature. The objective of this case report is to describe a novel variant in NHS, as well as to discuss genotype–phenotype correlations. Methods: Whole-exome sequencing was performed in 3 affected individuals (2 males and 1 female) with pediatric cataracts from the same family, as well as in 2 unaffected members from the same family. Ophthalmological and clinical genetic evaluations were conducted. Results: The likely pathogenic variant c.3333del (p.Phe1111Leufs*9) was found in all affected individuals, as well as in one unaffected female family member. Our family was initially diagnosed with isolated hereditary cataracts, but only after the sequencing results was the phenotype revealed, with the systemic features being identified. Conclusions: This reinforces the importance of genetic testing of bilateral familial pediatric cataracts, especially since systemic features such as dental anomalies and intellectual disability may take years before they develop. Not only did genetic testing help to identify extraocular features, but it also made possible accurate family counseling essential in all pediatric cataract cases. Full article

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

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11 pages, 234 KiB

Open AccessArticle

Comparison and Classification of LMW-GS Genes at Glu-3 Loci of Common Wheat

by Yongying Zhao, Xianlin Zhao, Zhiguo Xiang, Dan Zhang and Hongshan Yang

Genes 2025, 16(1), 90; https://doi.org/10.3390/genes16010090 - 16 Jan 2025

Viewed by 393

Abstract

Background: The low molecular weight glutenin subunits (LMW-GS) of wheat have great effects on food processing quality, but the resolution of LMW-GS and the scoring of their alleles by direct analysis of proteins are difficult due to the larger number of expressed subunits [...] Read more.

Background: The low molecular weight glutenin subunits (LMW-GS) of wheat have great effects on food processing quality, but the resolution of LMW-GS and the scoring of their alleles by direct analysis of proteins are difficult due to the larger number of expressed subunits and high similarity of DNA sequences. It is important to identify and classify the LMW-GS genes in order to recognize the LMW-GS alleles clearly and develop the functional markers. Methods: The LMW-GS genes registered in GenBank were searched at NCBI, and 593 Glu-3 genes with complete coding sequences were obtained, including 146 Glu-A3, 136 Glu-B3, and 311 Glu-D3. Sequence analysis and characterization of DNA and deduced amino acids were performed using the software DNAman. Results: The alignment and classification showed that there were at least 9 genes with 69 allelic variants at the Glu-A3 locus, 11 genes with 64 allelic variants at the Glu-B3 locus, and 10 genes with 96 variants at the Glu-D3 locus, respectively. Furthermore, the specificity of some Glu-3 genes and their variations was analyzed. Conclusions: The results were beneficial to understanding the LMW-GS genes fully and to developing the functional markers and will provide a theoretical reference for the quality improvement of wheat variety. Full article

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

20 pages, 7469 KiB

Open AccessArticle

Genome Sequencing Reveals the Potential of Enterobacter sp. Strain UNJFSC003 for Hydrocarbon Bioremediation

by Gianmarco Castillo, Sergio Eduardo Contreras-Liza, Carlos I. Arbizu and Pedro Manuel Rodriguez-Grados

Genes 2025, 16(1), 89; https://doi.org/10.3390/genes16010089 - 16 Jan 2025

Viewed by 869

Abstract

Bioremediation induced by bacteria offers a promising alternative for the contamination of aromatic hydrocarbons due to their metabolic processes suitable for the removal of these pollutants, as many of them are carcinogenic molecules and dangerous to human health. Our research focused on isolating [...] Read more.

Bioremediation induced by bacteria offers a promising alternative for the contamination of aromatic hydrocarbons due to their metabolic processes suitable for the removal of these pollutants, as many of them are carcinogenic molecules and dangerous to human health. Our research focused on isolating a bacterium from the rhizosphere of the tara tree with the ability to degrade polycyclic aromatic hydrocarbons, using draft genomic sequencing and computational analysis. Enterobacter sp. strain UNJFSC 003 possesses 4460 protein-coding genes, two rRNA genes, 77 tRNA genes, and a GC content of 54.38%. A taxonomic analysis of our strain revealed that it has an average nucleotide identity (ANI) of 87.8%, indicating that it is a new native Enterobacteria. Additionally, a pangenomic analysis with 15 strains demonstrated that our strain has a phylogenetic relationship with strain FDAARGOS 1428 (Enterobacter cancerogenus), with a total of 381 core genes and 4778 accessory genes. Orthologous methods predicted that strain UNJFSC 003 possesses genes with potential for use in hydrocarbon bioremediation. Genes were predicted in the sub-pathways for the degradation of homoprotocatechuate and phenylacetate, primarily located in the cytoplasm. Studies conducted through molecular modeling and docking revealed the affinity of the predicted proteins in the degradation of benzo[a]pyrene in the homoprotocatechuate sub-pathway, specifically hpcB, which has enzymatic activity as a dioxygenase, and hpcC, which functions as an aldehyde dehydrogenase. This study provides information on native strains from Lomas de Lachay with capabilities for the bioremediation of aromatic hydrocarbons and other compounds. Full article

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

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14 pages, 1958 KiB

Open AccessArticle

Complete Mitochondrial Genome of King Threadfin, Polydactylus macrochir (Günther, 1867): Genome Characterization and Phylogenetic Analysis

by Jiufu Wen

Genes 2025, 16(1), 88; https://doi.org/10.3390/genes16010088 - 15 Jan 2025

Viewed by 356

Abstract

Background: Polydactylus macrochir (Günther; 1867) is a member of the family Polynemidae. The placement of Polynemidae among teleosts has varied over the years. Methods: Therefore, in this study, we sequenced the complete mitochondrial genome of P. macrochir, analyzed the characterization of the [...] Read more.

Background: Polydactylus macrochir (Günther; 1867) is a member of the family Polynemidae. The placement of Polynemidae among teleosts has varied over the years. Methods: Therefore, in this study, we sequenced the complete mitochondrial genome of P. macrochir, analyzed the characterization of the mitochondrial genome, and investigated the phylogenetic relationships of Polynemidae. Results: The length of the P. macrochir mitogenome was 16,738 bp, with a typical order. Nucleotide composition analysis showed that the P. macrochir mitogenome was AT-biased (54.15%), and the PCGs tended to use A and C rather than T and G at the third codon. All the PCGs started with the regular codon ATG, except for cox1, which started with GTG. The termination codon varied across the PCGs. It was shown that the ka/ks ratios of all the PCGs were less than one. Phylogenetic analysis, based on the maximum likelihood (ML) and Bayesian inference (BI) methods, indicated that eight threadfins formed a well-supported monophyletic cluster. Polynemidae and Sphyraenidae clustered together as a monophyletic group. According to TimeTree analyses, the most recent common ancestor (MRCA) of Polynemidae was traced back to about 52.81 million years ago (MYA), while six species within Polynemidae diverged from 11.70 MYA to 20.05 MYA. Conclusions: The present study provides valuable mitochondrial information for the classification of P. macrochir and new insights into the phylogenetic relationships of Polynemidae. Full article

(This article belongs to the Special Issue Studies on the Origin, Evolution, Genetic Diversity and Adaptive Evolution of Fish)

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13 pages, 1078 KiB

Open AccessCommentary

Novel Reassortants of Oropouche Virus (OROV) Are Causing Maternal–Fetal Infection During Pregnancy, Stillbirth, Congenital Microcephaly and Malformation Syndromes

by David A. Schwartz

Genes 2025, 16(1), 87; https://doi.org/10.3390/genes16010087 - 15 Jan 2025

Viewed by 549

Abstract

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and [...] Read more.

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever. Full article

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

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13 pages, 2525 KiB

Open AccessArticle

Cytogenomics of Frieseomelitta varia (Hymenoptera: Apidae) and the Sharing of a Satellite DNA Family in Several Neotropical Meliponini Genera

by Zulemara B. M. Vignati, Gisele A. Teixeira, Marina S. Cunha, Jaqueline A. Pereira and Denilce M. Lopes

Genes 2025, 16(1), 86; https://doi.org/10.3390/genes16010086 - 15 Jan 2025

Viewed by 412

Abstract

Background/Objectives: A striking feature of the karyotypes of stingless bees is the large amount of heterochromatin present in most species. Cytogenomic studies performed in some Meliponini species have suggested that evolutionary events related to the diversification and amplification of satellite DNA families in [...] Read more.

Background/Objectives: A striking feature of the karyotypes of stingless bees is the large amount of heterochromatin present in most species. Cytogenomic studies performed in some Meliponini species have suggested that evolutionary events related to the diversification and amplification of satellite DNA families in the heterochromatin may reflect the structuring of phylogenetic clades in this tribe. In this study, we performed a genomic analysis in Frieseomelitta varia to characterize different satDNA families in its genome. We also investigated the presence of the most abundant satDNA family of F. varia in its own chromosomes, in two other Frieseomelitta species, and in other Meliponini genera encompassing the three main clades of Neotropical Meliponini, according to the available molecular phylogeny. Methods: Genomic analyses were performed using RepeatExplorer2 on the Galaxy platform, and chromosomal investigations were conducted using fluorescent in situ hybridization. Results: Seven satDNA families were recovered, which together totaled an abundance of 11.223% of the analyzed F. varia genomic fraction. The most abundant satDNA family, FvarSat01-306, predominates in the analyzed repetitive fraction (representing around 89%) and was recently amplified and homogenized in almost all the heterochromatin of F. varia. In addition, the data revealed an unprecedented sharing of this satDNA family in the centromeric/pericentromeric heterochromatin among different Meliponini genera, with independent amplifications and loss of this sequence in some taxa. Conclusions: One family of satellite DNA makes up most of the heterochromatin in this species and is shared with other Meliponini. Full article

(This article belongs to the Special Issue Genomics and Cytogenetics of Insects)

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13 pages, 2538 KiB

Open AccessArticle

Integrative Analysis of Radiation-Induced Senescence-Associated Secretory Phenotype Factors in Kidney Cancer Progression

by Shubhankar Suman

Genes 2025, 16(1), 85; https://doi.org/10.3390/genes16010085 - 15 Jan 2025

Viewed by 379

Abstract

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) [...] Read more.

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) cells and their role in promoting renal cell carcinoma (RCC) progression. Methods: Proteomic data from the SASP Atlas were analyzed to identify IR-induced factors unique to RCE cells, with subsequent evaluations performed at both the gene and protein levels. Thirty-seven proteins were identified as exclusively upregulated and secreted by senescent RCE cells. Gene expression analysis of these RCE-specific SASP factors was conducted using the Gene Expression database of Normal and Tumor tissues (GENT2) and The Cancer Genome Atlas (TCGA). To assess their prognostic relevance in RCC, the corresponding proteins were further analyzed using the Human Protein Atlas (HPA), emphasizing the relationship between SASP factor expression and RCC progression. Results: ALDH18A1 and ASPH emerged as key RCE-specific SASP factors with significant upregulation at both the gene and protein levels (Log2 ratio > 1.15, p < 0.05). These proteins are implicated in pro-cancer activities and are strongly associated with poor prognostic outcomes in RCC. Their critical roles in RCC progression underscore their potential as promising therapeutic targets for the prevention and treatment of the disease. Conclusions: This study provides novel insights into the role of IR-induced SASP in renal carcinogenesis, marking the first identification of ALDH18A1 and ASPH as specific secreted proteins associated with tumor progression in RCC. This study suggests that ALDH18A1 and ASPH hold promise as early biomarkers for RCC and as therapeutic targets for disease prevention and treatment. Full article

(This article belongs to the Special Issue Molecular Mechanisms Responsible for Radiation-Induced Toxicity of Normal Tissue)

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15 pages, 2667 KiB

Open AccessArticle

Missing Regulation Between Genetic Association and Transcriptional Abundance for Hypercholesterolemia Genes

by Aaron Hakim, Noah J. Connally, Gavin R. Schnitzler, Michael H. Cho, Z. Gordon Jiang, Shamil R. Sunyaev and Rajat M. Gupta

Genes 2025, 16(1), 84; https://doi.org/10.3390/genes16010084 - 15 Jan 2025

Viewed by 419

Abstract

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci [...] Read more.

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels. One hypothesis is that genetically mediated variation in transcript abundance, detected via the analysis of expressed quantitative trait loci (eQTLs), is key to the biologic function of causal variants. Here, we investigate the hypothesis that non-coding GWAS risk variants affect the homeostatic expression of a nearby putatively causal gene for serum LDL-C levels. Methods: We establish a set of twenty-one expert-curated and validated genes implicated in hypercholesterolemia via dose-dependent pharmacologic modulation in human adults, for which the relevant tissue type has been established. We show that the expression of these LDL-C genes is impacted by eQTLs in relevant tissues and that there are significant genomic-risk loci in LDL-GWAS near these causal genes. We evaluate, using statistical colocalization, whether a single variant or set of variants in each genetic locus is responsible for the GWAS and eQTL signals. Results: Genome-wide association study results for serum LDL-C levels demonstrate that the 402 identified genomic-risk loci for LDL-C are highly enriched for known causal genes for LDL-C (OR 527, 95% CI 126–5376, p < 2.2 × 10⁻¹⁶). However, we find limited evidence for colocalization between GWAS signals near validated hypercholesterolemia genes and eQTLs in relevant tissues (colocalization rate of 26% at a locus-level colocalization probability > 50%). Conclusions: Our results highlight the complexity of genetic regulatory effects for causal hypercholesterolemia genes; we suggest that context-responsive eQTLs may explain the effects of non-coding GWAS hits that do not overlap with standard eQTLs. Full article

(This article belongs to the Special Issue Cardiovascular Disease: From Genetics to Therapeutics)

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14 pages, 2311 KiB

Open AccessArticle

Identifying Genetic Predisposition to Dozer Lamb Syndrome: A Semi-Lethal Muscle Weakness Disease in Sheep

by Morgan R. Stegemiller, Margaret A. Highland, Kathleen M. Ewert, Holly Neaton, David S. Biller and Brenda M. Murdoch

Genes 2025, 16(1), 83; https://doi.org/10.3390/genes16010083 - 14 Jan 2025

Viewed by 394

Abstract

Background: Lamb health is crucial for producers; however, the percentage of lambs that die before weaning is still 15–20%. One factor that can contribute to lamb deaths is congenital diseases. A novel semi-lethal disease has been identified in newborn Polypay lambs and termed [...] Read more.

Background: Lamb health is crucial for producers; however, the percentage of lambs that die before weaning is still 15–20%. One factor that can contribute to lamb deaths is congenital diseases. A novel semi-lethal disease has been identified in newborn Polypay lambs and termed dozer lamb syndrome. This study aims to determine if there is a genetic predisposition to dozer lamb syndrome. These lambs are weak and unable to lift their heads, suckle, and swallow, resulting in nasal reflux. Methods: Genetic analyses, including a genome-wide association, runs of homozygosity, and fine mapping to determine haploblock within regions of interest, were utilized in determining genetic predispositions to dozer lamb syndrome. Results: The genome-wide association study identified a region of chromosome 15 with three significant SNPs (p-values of 6.81 × 10⁻⁶, 5.71 × 10⁻⁶, and 8.52 × 10⁻⁶). Genetic analysis identified a run of homozygosity on the same region of chromosome 15 with an odds ratio of 236.7. Fine mapping of this region identified three haploblocks associated with the dozer lamb syndrome (p-value = 2.41 × 10⁻⁵). Conclusions: The most significant and promising gene in this region is CELF1, which is known to play an important role in muscle development. Abnormal CELF1 abundance and cellular location are reported to result in abnormal muscle development. Identification of genetic aberrations associated with dozer lamb syndrome provides a tool for decreasing or eliminating the genotype and, thus, the associated phenotype(s) from Polypay sheep. Full article

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

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29 pages, 575 KiB

Open AccessReview

Hereditary Breast Cancer: Comprehensive Risk Assessment and Prevention Strategies

by Eliza Del Fiol Manna, Davide Serrano, Laura Cazzaniga, Sara Mannucci, Cristina Zanzottera, Francesca Fava, Gaetano Aurilio, Aliana Guerrieri-Gonzaga, Matilde Risti, Mariarosaria Calvello, Irene Feroce, Monica Marabelli, Cecilia Altemura, Lucio Bertario, Bernardo Bonanni and Matteo Lazzeroni

Genes 2025, 16(1), 82; https://doi.org/10.3390/genes16010082 - 13 Jan 2025

Viewed by 800

Abstract

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors [...] Read more.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease. However, there are gaps in translating how individual genomic variation affects phenotypic presentation. The expansion of criteria for genetic testing and the increasing utilization of comprehensive genetic panels may enhance the identification of individuals carrying P/LP variants linked to hereditary breast cancer. Individualized risk assessment could facilitate the implementation of personalized risk-reduction strategies for these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through breast imaging, and risk-reducing surgeries. This review addresses the current literature’s inconsistencies and limitations, particularly regarding risk factors and the intensity of preventive strategies for women with P/LP variants in moderate- and high-penetrance genes. In addition, it synthesizes the latest evidence on risk assessment and primary and secondary prevention in women at high risk of breast cancer. Full article

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

14 pages, 3490 KiB

Open AccessArticle

Evaluation of Genetic Diversity and Identification of Cultivars in Spray-Type Chrysanthemum Based on SSR Markers

by Manjulatha Mekapogu, So-Hyeon Lim, Youn-Jung Choi, Su-Young Lee and Jae-A Jung

Genes 2025, 16(1), 81; https://doi.org/10.3390/genes16010081 - 13 Jan 2025

Viewed by 489

Abstract

Background/Objectives: Chrysanthemum (Chrysanthemum morifolium), a key ornamental and medicinal plant, presents challenges in cultivar identification due to high phenotypic similarity and environmental influences. This study assessed the genetic diversity and discrimination of 126 spray-type chrysanthemum cultivars. Methods: About twenty-three simple sequence [...] Read more.

Background/Objectives: Chrysanthemum (Chrysanthemum morifolium), a key ornamental and medicinal plant, presents challenges in cultivar identification due to high phenotypic similarity and environmental influences. This study assessed the genetic diversity and discrimination of 126 spray-type chrysanthemum cultivars. Methods: About twenty-three simple sequence repeat (SSR) markers were screened for the discrimination of 126 cultivars, among which six SSR markers showed polymorphic fragments. Results: Results showed high polymorphism across six markers, with an average of 3.8 alleles per locus and a mean polymorphism information content (PIC) of 0.52, indicating strong discriminatory efficiency. The average observed heterozygosity (Ho) was 0.72, reflecting significant genetic diversity within the cultivars. Cluster analysis using the unweighted pair group method with arithmetic mean (UPGMA) grouped the cultivars into seven clusters, correlating well with the PCA. Bayesian population structure analysis suggested two primary genetic subpopulations. Conclusions: These findings confirm SSR markers as an effective tool for the genetic characterization and precise discrimination of spray type chrysanthemum cultivars, offering significant applications in breeding, cultivar registration, and germplasm conservation. The SSR marker-based approach thus provides a reliable and efficient strategy to enhance the management and commercialization of diverse chrysanthemum germplasm collections. Full article

(This article belongs to the Special Issue Genetics and Breeding of Ornamental Plants)

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Open AccessArticle

Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons

by Mayra Martinez-Sanchez, William Skarnes, Ashish Jain, Sampath Vemula, Liang Sun, Shira Rockowitz and Mary C. Whitman

Genes 2025, 16(1), 80; https://doi.org/10.3390/genes16010080 - 12 Jan 2025

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Abstract

Background/Objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the [...] Read more.

Background/Objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843). Methods: Using CRISPR and bridging oligos, we introduced the duplication into the Kolf2.1J iPSC line. We differentiated the parent line and the line with the duplication into cortical neurons using a three-dimensional differentiation protocol, and performed bulk RNASeq on neural progenitors (day 14) and differentiated neurons (day 63). Results: We successfully introduced the duplication into Kolf2.1J iPSCs by nucleofecting a bridging oligo for the newly formed junction along with cas9 ribonucleoparticles. We confirmed that the cells had a tandem duplication without inversion or deletion. The parent line and the line with the duplication both differentiated into neurons reliably. There were a total of 37 differentially expressed genes (DEGs) at day 63, 25 downregulated and 12 upregulated. There were 55 DEGs at day 14, 18 of which were also DEGs at day 63. The DEGs included a number of protocadherins, several genes involved in neuronal development, including SLITRK2, CSMD1, and VGF, and several genes of unknown function. Conclusions: A copy number variant (CNV) that confers risk for strabismus affects gene expression of several genes involved in neural development, highlighting that strabismus most likely results from abnormal neural development, and identifying several new genes and pathways for further research into the pathophysiology of strabismus. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Diseases)

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Genes, Volume 16, Issue 1 (January 2025) – 109 articles

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