Genes

10 pages, 9871 KB

Open AccessArticle

Mutation of the Thyroid Hormone Receptor Beta Gene (THRB) Causes Vitelliform Macular Dystrophy with High Intrafamilial Variability

by Elisa A. Mahler, Lars C. Moeller, Katharina Wall, Marlene Saßmannshausen, Bettina Kron, Hanno J. Bolz, Frank G. Holz and Philipp Herrmann

Genes 2025, 16(10), 1240; https://doi.org/10.3390/genes16101240 - 20 Oct 2025

Abstract

Background/Objectives: Herein, we report the clinical cases of two affected first-degree relatives from a family with highly variable macular dystrophy, expanding the known phenotype spectrum with mutations in the thyroid hormone receptor beta gene (THRB). Methods: Multimodal retinal imaging included wide-field [...] Read more.

Background/Objectives: Herein, we report the clinical cases of two affected first-degree relatives from a family with highly variable macular dystrophy, expanding the known phenotype spectrum with mutations in the thyroid hormone receptor beta gene (THRB). Methods: Multimodal retinal imaging included wide-field fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) imaging, performed alongside functional testing (visual fields, electroretinogram (ERG)), metabolic blood analyses, and genetic testing of both cases. Results: A 67-year-old female patient presenting with reading difficulties and visual impairment since childhood was referred for evaluation and counseling for potential treatment options. Extensive ophthalmologic examination, including multimodal retinal imaging and functional testing, revealed an occult macular dystrophy. Her 39-year-old son reported similar visual symptoms in combination with mild photophobia. In multimodal retinal imaging, he also showed a macular dystrophy but with a vitelliform phenotype. Genetic testing identified the heterozygous pathogenic variant c.283+1G>A in the thyroid hormone receptor beta gene (THRB) in both patients. Conclusions: This report shows a high intrafamilial variability of macular dystrophy caused by a heterozygous THRB mutation, which has only recently been recognized as a cause of macular dystrophy. Here, we describe a novel clinical presentation characterized by a vitelliform lesion, expanding the phenotypic spectrum of THRB-associated macular dystrophy. Full article

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

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16 pages, 2954 KB

Open AccessArticle

SARS-CoV-2 Infection of Lung Epithelia Leads to an Increase in the Cleavage and Translocation of RNase-III Drosha; Loss of Drosha Is Associated with a Decrease in Viral Replication

by Michael T. Winters, Emily S. Westemeier-Rice, Travis W. Rawson, Kiran J. Patel, Gabriel M. Sankey, Maya Dixon-Gross, Olivia R. McHugh, Nasrin Hashemipour, McKenna L. Carroll, Isabella R. Wilkerson and Ivan Martinez

Genes 2025, 16(10), 1239; https://doi.org/10.3390/genes16101239 - 20 Oct 2025

Abstract

Background/Objectives: Since its emergence, COVID-19—caused by the novel coronavirus SARS-CoV-2—has affected millions globally and led to over 1.2 million deaths in the United States alone. This global impact, coupled with the emergence of five new human coronaviruses over the past two decades, underscores [...] Read more.

Background/Objectives: Since its emergence, COVID-19—caused by the novel coronavirus SARS-CoV-2—has affected millions globally and led to over 1.2 million deaths in the United States alone. This global impact, coupled with the emergence of five new human coronaviruses over the past two decades, underscores the urgency of understanding its pathogenic mechanisms at the molecular level—not only for managing the current pandemic but also preparing for future outbreaks. Small non-coding RNAs (sncRNAs) critically regulate host and viral gene expression, including antiviral responses. Among the molecular regulators implicated in antiviral defense, the microRNA-processing enzyme Drosha has emerged as a particularly intriguing factor. In addition to its canonical role, Drosha also exerts a non-canonical, interferon-independent antiviral function against several RNA viruses. Methods: To investigate this, we employed q/RT-PCR, Western blot, and immunocytochemistry/immunofluorescence in an immortalized normal human lung/bronchial epithelial cell line (NuLi-1), as well as a human colorectal carcinoma Drosha CRISPR knockout cell line. Results: In this study, we observed a striking shift in Drosha isoform expression following infection with multiple SARS-CoV-2 variants. This shift was absent following treatment with the viral mimetic poly (I:C) or infection with other RNA viruses, including the non-severe coronaviruses HCoV-OC43 and HCoV-229E. We also identified a distinct alteration in Drosha’s cellular localization post SARS-CoV-2 infection. Moreover, Drosha ablation led to reduced expression of SARS-CoV-2 genomic and sub-genomic targets. Conclusions: Together, these observations not only elucidate a novel aspect of Drosha’s antiviral role but also advance our understanding of SARS-CoV-2 host–pathogen interactions, highlighting potential therapeutic avenues for future human coronavirus infections. Full article

(This article belongs to the Section RNA)

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14 pages, 3455 KB

Open AccessArticle

Computational Identification of Genetic Background of Infertility and Calculating Inbreeding Coefficient in Dromedary Camel Herds

by Fahad A. Alshanbari and Abdulrahman Aloraini

Genes 2025, 16(10), 1238; https://doi.org/10.3390/genes16101238 - 19 Oct 2025

Abstract

Background: Inbreeding is a major genetic problem that reduces fertility and causes genetic disorders. Some breeders of dromedary camels use the same bull for many years due to its excellent characteristics, leading to mating with offspring and subsequent generations, resulting in increased [...] Read more.

Background: Inbreeding is a major genetic problem that reduces fertility and causes genetic disorders. Some breeders of dromedary camels use the same bull for many years due to its excellent characteristics, leading to mating with offspring and subsequent generations, resulting in increased homozygosity and genetic disorders. We hypothesize that inbreeding is associated with infertility in dromedary camels with normal and uninfected reproductive tracts. Methods: We genotyped 96 samples from seven camel breeds using the Illumina 55K SNP BeadChip, including five confirmed infertile individuals. Inbreeding coefficients (F) were calculated using PLINK based on heterozygosity and runs of homozygosity. Genome-wide association analysis using logistic regression was performed to identify potential genomic regions associated with infertility. Results: All five infertile camels showed significantly higher F values (>0.15) compared to 91 fertile individuals (<0.10, p < 0.001). The genome-wide association analysis failed to identify specific genomic regions linked to infertility, likely due to limited statistical power (n = 5 cases) and the polygenic nature of fertility traits. Population structure analysis revealed genetic differentiation related to coat color, with two significant SNPs on chromosome 3 near SLC30A5 (p <

10^{- 7}

). Conclusions: Our results demonstrate that elevated inbreeding is strongly associated with infertility in dromedary camels. Future studies should employ larger sample sizes (≥50 infertile individuals) or whole-genome sequencing (35× coverage) to identify specific genomic regions. Implementation of breeding strategies avoiding related matings (F < 0.10) is recommended to maintain reproductive performance in camel herds. Full article

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

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20 pages, 4652 KB

Open AccessArticle

Genome-Wide Identification of GATA Family Genes and Functional Analysis of IbGATA17 Under Drought Stress in Sweetpotato

by Yinghui Yang, Ruitao Liu, Qingchang Liu, Shaozhen He, Shaopei Gao, Huan Zhang, Ning Zhao and Hong Zhai

Genes 2025, 16(10), 1237; https://doi.org/10.3390/genes16101237 - 19 Oct 2025

Abstract

Background/Objectives: GATA transcription factors play pivotal roles in regulating plant growth and development, physiological metabolism, and responses to environmental stress. However, research on GATA genes in sweetpotato remains limited. Methods: In this study, we identified 25 IbGATA genes in sweetpotato (Ipomoea batatas [...] Read more.

Background/Objectives: GATA transcription factors play pivotal roles in regulating plant growth and development, physiological metabolism, and responses to environmental stress. However, research on GATA genes in sweetpotato remains limited. Methods: In this study, we identified 25 IbGATA genes in sweetpotato (Ipomoea batatas [Lam.] L.) through a genome-wide analysis. These genes were analyzed for their physicochemical properties, chromosomal localization, synteny, phylogenetic relationships, gene structure, promoter cis-elements, protein interaction networks, and expression profiles across various tissues and under drought stress. To elucidate the function of drought-resistant candidate genes, an in situ one-step transformation method was employed. Results: Sweetpotato GATA genes have a complex evolutionary history, including replication events, different selection pressures, and functional diversification. They may be involved in multiple plant stress signaling pathways. Furthermore, functional analysis revealed that IbGATA17 enhances drought tolerance in sweetpotato by promoting proline biosynthesis and reinforcing ROS scavenging capacity. Our findings provide novel insights into the roles of IbGATAs, particularly IbGATA17, in mediating drought-stress responses in sweetpotato. Conclusions: This study provides foundational insights into the GATA gene family in sweetpotato and reveals the pivotal role of IbGATA17 in simulated drought-stress response, providing a potential candidate gene for the development of drought-resistant varieties. Full article

(This article belongs to the Special Issue Genetic and Functional Genomics Insights into the Genetic Improvement of Stress Resistance in Economic Crops)

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15 pages, 2568 KB

Open AccessArticle

Complete Mitochondrial Genomes of Two Water Mite Species in the Family Sperchontidae (Acari: Hydrachnidiae): Characterization and Phylogenetic Implications

by Xu Zhang, Xingru Nie, Xuhang Xia, Jiahui Song, Qingyu Wen and Ke Sun

Genes 2025, 16(10), 1236; https://doi.org/10.3390/genes16101236 - 19 Oct 2025

Abstract

Background: The family Sperchontidae Thor, 1900 is proposed as a transitional group between the “lower” and “higher” water mites (Subcohort Hydrachnidiae), and is important for understanding the evolutionary history of Hydrachnidiae. However, mitogenomic data are lacking. Methods: The first complete mitogenomes of Sperchontidae [...] Read more.

Background: The family Sperchontidae Thor, 1900 is proposed as a transitional group between the “lower” and “higher” water mites (Subcohort Hydrachnidiae), and is important for understanding the evolutionary history of Hydrachnidiae. However, mitogenomic data are lacking. Methods: The first complete mitogenomes of Sperchontidae were sequenced from two species, Sperchon plumifer and Sperchon sp. Structural features were analyzed, gene rearrangements were compared with five published water mite mitogenomes, and phylogenetic relationships among 31 species within the order Trombidiformes were reconstructed. Results: Both mitogenomes contained the typical 37 genes and exhibited a strong A+T bias (73.1–73.6%), positive AT-skew, and negative GC-skew. Protein-coding genes (PCGs) were generally initiated with ATN/TTG codons and terminated with TAA/TAG or incomplete T–, with codon usage biased toward T/U-ending codons; all PCGs were under purifying selection (Ka/Ks < 1). Most tRNAs lacked canonical cloverleaf structures due to D- or T-arm loss. Gene rearrangements occurred in all examined water mite mitogenomes, with intrageneric rearrangements restricted to tRNAs in Hygrobatidae and Unionicolidae but involving both tRNAs and PCGs in Sperchontidae. Phylogenetic analyses using ML and BI (13 PCGs + 2 rRNAs) strongly supported a close relationship between Hydrachnidiae and Trombidiae (BS = 100%, PP = 1.00) and confirmed the three supercohorts in Trombidiformes (Eleutherengonides, Anystides, Eupodides), though relationships among them remained unresolved. Conclusions: This study reports the first two complete mitogenomes of Sperchontidae, providing preliminary insights into gene rearrangement patterns in water mites. The phylogenetic analyses based on mitochondrial genomes provide additional support for the consistency with traditional morphology at lower taxonomic levels, such as within genera and families, whereas relationships among supercohort-level taxa remain unstable and require additional data for further clarification. Full article

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

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19 pages, 10901 KB

Open AccessArticle

Cadmium Stress Response of ABC Transporters in Ligusticum chuanxiong: Genome-Wide Identification and Bioinformatic Characterization

by Yun Zhen, Xiang Chen, Ruoshi Li, Shunlu Chen, Can Wang, Chi Song, Guihua Jiang and Xianmei Yin

Genes 2025, 16(10), 1235; https://doi.org/10.3390/genes16101235 - 18 Oct 2025

Abstract

Background: Ligusticum chuanxiong Hort. is a well-known traditional Chinese medicinal herb whose clinical application and international trade had been constrained by cadmium (Cd) contamination. However, the molecular mechanisms underlying its response to cadmium stress remained poorly understood. The ATP-binding cassette (ABC) transporter [...] Read more.

Background: Ligusticum chuanxiong Hort. is a well-known traditional Chinese medicinal herb whose clinical application and international trade had been constrained by cadmium (Cd) contamination. However, the molecular mechanisms underlying its response to cadmium stress remained poorly understood. The ATP-binding cassette (ABC) transporter family plays crucial roles in various plant processes, including growth and development, hormone transduction, and stress responses. This study aimed to analyze the ABC transporter genes in L. chuanxiong to better understand their roles during cadmium stress responses. Methods: Genome-wide identification of ABC genes in L. chuanxiong was performed, and transcriptome sequencing of rhizomes under cadmium stress was conducted. Differentially expressed LcABC genes were screened using bioinformatic analysis. Results: A total of 368 LcABC genes were identified. Transcriptome analysis revealed 37 upregulated LcABC genes, which were classified into six subfamilies. Cis-element analysis indicated that their promoters contain hormone-, growth-, and stress-responsive elements. Notably, LcABCG8, LcABCG48, and LcABCG108 contain stress-responsive elements and show close evolutionary relationships with heavy metal-responsive genes such as AtABCC1/2/3 and AtABCG36/40, suggesting that they could be key candidates. qRT-PCR validation of nine LcABC genes confirmed their differential sensitivity to cadmium stress. Conclusions: This study conducted a comprehensive identification of the ABC gene family in L. chuanxiong. By integrating transcriptomic data with systematic bioinformatic analyses, we identified several LcABC transporters that may play important roles in cadmium stress responses. The results provide insights into the molecular mechanisms of ABC transporters in cadmium stress responses in L. chuanxiong and offer strategies for reducing cadmium accumulation. Full article

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

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16 pages, 2353 KB

Open AccessArticle

Genome-Wide Identification of the CRY Gene Family in Solanum tuberosum and Response to Abiotic Stresses

by Yan Gao, Xueying Yang, Xin Lv, Yuxuan Li, Kuihua Li and Yuliang Gao

Genes 2025, 16(10), 1234; https://doi.org/10.3390/genes16101234 - 18 Oct 2025

Viewed by 49

Abstract

Background: Cryptochromes (CRYs) are not only blue-light receptors in plants but also participate in abiotic stress responses, making them essential for plant growth and development. Methods: In this study, the CRY gene family in potato (StCRY) was identified and analyzed using [...] Read more.

Background: Cryptochromes (CRYs) are not only blue-light receptors in plants but also participate in abiotic stress responses, making them essential for plant growth and development. Methods: In this study, the CRY gene family in potato (StCRY) was identified and analyzed using bioinformatics approaches, and the expression patterns of StCRY genes under different abiotic stresses were validated through transcriptome datasets and RT-qPCR analysis. Results: A total of 7 StCRY genes were identified, unevenly distributed across 4 chromosomes. The StCRY genes exhibit conserved structures, with predicted subcellular localization primarily in the nucleus, cytoplasm, and plastids. Promoter region analysis revealed the significant presence of cis-acting elements related to light, plant growth and development, hormones, and stress responses. Phylogenetic analysis classified the CRY gene family into three subgroups and identified one pair of collinear genes. StCRY genes show a closer evolutionary relationship with tomato, followed by Arabidopsis thaliana, and are least related to rice. Transcriptome and RT-qPCR analyses under cold, drought, and salt stresses revealed differential expression among StCRY genes: StCRY3 and StCRY7 respond positively to cold stress, StCRY1 and StCRY5 are upregulated under drought and salt stresses, and StCRY7 expression is positively correlated with salt stress. Conclusions: Collectively, this study provides a preliminary characterization of the CRY gene family in potato and establishes a theoretical foundation for further investigations into the molecular mechanisms of blue-light receptors in abiotic stress responses. Full article

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

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7 pages, 513 KB

Open AccessBrief Report

CRISPR/Cas Tools for the Detection of Borrelia sensu lato in Human Samples

by Ermanno Nardon, Eros Azzalini, Dino Paladin, Diego Boscarino and Serena Bonin

Genes 2025, 16(10), 1233; https://doi.org/10.3390/genes16101233 - 18 Oct 2025

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Abstract

Background/Objectives: Lyme disease diagnosis remains challenging due to the limitations of current methods. While PCR-based assays are widely used, their sensitivity can be affected by sample type and the inhibition of host DNA. This study aimed to evaluate the feasibility and sensitivity of [...] Read more.

Background/Objectives: Lyme disease diagnosis remains challenging due to the limitations of current methods. While PCR-based assays are widely used, their sensitivity can be affected by sample type and the inhibition of host DNA. This study aimed to evaluate the feasibility and sensitivity of a CRISPR/Cas12-based detection system for Borrelia burgdorferi sensu lato, comparing its performance with real-time PCR. Methods: DNA from three Borrelia genospecies (B. burgdorferi, B. garinii, and B. afzelii) was amplified targeting the OspA gene. Detection was performed using a Cas12/crRNA system with a fluorescent ssDNA reporter. Sensitivity assays were conducted on serial dilutions of Borrelia DNA, with and without human genomic DNA, and results were compared with qPCR. Results: Direct detection of Borrelia DNA without amplification was not feasible. However, when combined with PCR, the Cas12/crRNA system reliably detected as few as 5 genome copies per reaction. End-point PCR extended to 60 cycles improved detection robustness for B. garinii and B. afzelii, although sensitivity decreased in the presence of human genomic DNA. Conclusions: The Cas12/crRNA-based system offers a sensitive and accessible alternative to qPCR, especially in settings lacking real-time PCR instrumentation. Future developments may include integration with isothermal amplification and microfluidic platforms to enhance direct detection capabilities. Full article

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

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14 pages, 2273 KB

Open AccessCase Report

Population Structure and Genetic Diversity of Tibetan Sheep Revealed by Whole-Genome Resequencing: Implications for Conservation and Breeding

by Junxia Zhang, Litan Zhang, Yuxiang Zhang, Yuting Deng and Xiaocheng Wen

Genes 2025, 16(10), 1232; https://doi.org/10.3390/genes16101232 - 18 Oct 2025

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Abstract

Background: Tibetan sheep (Ovis aries) have evolved remarkable adaptations to the extreme high-altitude environment of the Qinghai–Tibet Plateau. While previous studies have identified some genetic features underlying these adaptations, a comprehensive understanding of their population genetics and selection signatures remains incomplete. [...] Read more.

Background: Tibetan sheep (Ovis aries) have evolved remarkable adaptations to the extreme high-altitude environment of the Qinghai–Tibet Plateau. While previous studies have identified some genetic features underlying these adaptations, a comprehensive understanding of their population genetics and selection signatures remains incomplete. We hypothesized that Tibetan sheep harbor unique genetic diversity and population structure distinct from low-altitude sheep (Hu sheep and Small Tail Han sheep), and that whole-genome resequencing could identify key positively selected genes driving their high-altitude adaptation and economic trait variation. Thus, this study aimed to characterize the population structure and genetic diversity of Tibetan sheep via whole-genome resequencing and identify genomic regions and candidate genes under positive selection related to high-altitude adaptation and important economic traits (growth, meat quality, wool, reproduction). Results: Using whole-genome resequencing of 90 Tibetan sheep (ZY) compared to 90 Hu sheep (HY) and 90 Small Tail Han sheep (XWHY), we identified significantly higher genetic diversity in Tibetan sheep (Pn = 0.6399, PIC = 0.1731). Population structure analyses revealed distinct clustering of Tibetan sheep, with principal components explaining 20.69% (PCA1), 12.26% (PCA2), and 14.18% (PCA3) of genetic variation. Selective sweep analysis identified 713 genomic regions (containing 207 genes) under positive selection, including key hypoxia adaptation genes (HDAC5, BMP2/BMPR1B, DUOX2) and economic trait genes (FGF9 for growth; SLC27A2 for meat quality; KRTAP for wool; IZUMO1R for reproduction). Functional enrichment highlighted pathways in oxygen transport (EPO regulation), energy metabolism (fatty acid β-oxidation), and vascular remodeling (TGF-β signaling). Conclusions: Our study provides the most comprehensive genomic characterization of Tibetan sheep to date, revealing both their unique genetic diversity and molecular mechanisms of high-altitude adaptation. The identified candidate genes offer valuable targets for marker-assisted breeding to improve productivity while maintaining adaptive traits, supporting sustainable development of plateau animal husbandry. Full article

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

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20 pages, 4116 KB

Open AccessArticle

Stability Matters: Revealing Causal Roles of G-Quadruplexes (G4s) in Regulation of Chromatin and Transcription

by Ke Xiao, Rongxin Zhang, Tiantong Tao, Huiling Shu, Hao Huang, Xiao Sun and Jing Tu

Genes 2025, 16(10), 1231; https://doi.org/10.3390/genes16101231 - 17 Oct 2025

Viewed by 208

Abstract

Background: G-quadruplexes (G4s) are non-canonical higher-order nucleic acid structures that form at guanine-rich motifs, with features spanning both secondary and tertiary structural levels. These dynamic structures play pivotal roles in diverse cellular processes. Endogenous G4s (eG4s) function through their dynamically formed structures, prompting [...] Read more.

Background: G-quadruplexes (G4s) are non-canonical higher-order nucleic acid structures that form at guanine-rich motifs, with features spanning both secondary and tertiary structural levels. These dynamic structures play pivotal roles in diverse cellular processes. Endogenous G4s (eG4s) function through their dynamically formed structures, prompting the hypothesis that their thermostability, as a key structural property, may critically influence their functionality. This study investigates the relationship between G4 stability and other functional genomic signals within eG4 regions and examines its broader impact on chromatin organization and transcriptional regulation. Methods: We developed a mapping strategy to associate in vitro-derived thermostability metrics and multi-omics functional signals with eG4 regions. A stability-centric analytical framework combining correlation analysis and causal inference using the Bayesian networks was applied to decipher causal relationships between G4 stability and the other related signals. We further analyzed the association between the stability of transcription start site (TSS)-proximal eG4s and the biological functions of their downstream genes. Results: Our analyses demonstrate that G4 thermostability exerts causal effects on epigenetic states and transcription factor binding, thereby influencing chromatin and transcription regulation. We further show distinct network architectures for G4-binding versus non-binding transcription factors. Additionally, we find that TSS-proximal eG4s are enriched in genes involved in core proliferation and stress-response pathways, suggesting that eG4s may serve as regulatory elements facilitating rapid stress responses through genome-wide coordination. Conclusions: These findings establish thermostability—though measured in vitro—as an intrinsic property that shapes eG4 functionality. Our study not only provides novel insights into the functional relevance of G4 thermostability but also introduces a generalizable framework for high-throughput G4 data interpretation, significantly advancing the functional decoding of eG4s across biological contexts. Full article

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

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20 pages, 1471 KB

Open AccessReview

HOXA10 and HOXA11 Methylation: Epigenetic Barriers to Endometrial Receptivity in ART

by Dmitry Kudlay, Vsevolod Kiselev and Gennady Sukhikh

Genes 2025, 16(10), 1230; https://doi.org/10.3390/genes16101230 - 17 Oct 2025

Viewed by 231

Abstract

The global prevalence of infertility has reached critical levels, making it one of the most pressing issues in modern society. Assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF), are the primary treatment methods for infertility. However, even under optimal conditions, the pregnancy [...] Read more.

The global prevalence of infertility has reached critical levels, making it one of the most pressing issues in modern society. Assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF), are the primary treatment methods for infertility. However, even under optimal conditions, the pregnancy rate per IVF cycle does not exceed 40%, while the live birth rate remains around 30%. A key unresolved challenge in ART is impaired endometrial receptivity (ER), which significantly contributes to repeated implantation failure (RIF). Advances in molecular and genetic diagnostics have revealed that gynecological conditions associated with infertility, such as chronic endometritis, uterine fibroids, polycystic ovary syndrome (PCOS), and tuboperitoneal factor infertility, are often linked to epigenetic alterations. Specifically, abnormal hypermethylation of the promoter regions of the HOXA10 and HOXA11 genes has been observed in women of reproductive age with these conditions. Such epigenetic dysregulation negatively impacts ER and is associated with infertility. The methylation status of HOXA10 and HOXA11 may serve as a potential diagnostic marker for evaluating and treating infertility. These markers can be assessed using available molecular genetic techniques, including real-time PCR. A promising therapeutic approach to improve ER involves the use of epigallocatechin-3-gallate and indole-3-carbinol, which have been shown to demethylate and restore the expression of HOXA10 and HOXA11. Epigenetic regulation holds significant potential for enhancing the effectiveness of ART programs, offering new avenues for addressing infertility and improving reproductive outcomes. This review consolidates the current body of knowledge regarding the epigenetic regulation of endometrial receptivity. It outlines fundamental scientific data on epigenetic mechanisms and discusses contemporary diagnostic and pharmacological intervention strategies. Full article

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

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13 pages, 1956 KB

Open AccessArticle

Expanding Clinical and Genetic Landscape of SATB2-Associated Syndrome

by Verdiana Pullano, Federico Rondot, Ilaria Carelli, Slavica Trajkova, Silvia Carestiato, Simona Cardaropoli, Diana Carli, Elisa Biamino, Fabio Sirchia, Giuseppe Reynolds, Roberto Keller, Elena Shukarova-Angelovska, Giovanni Battista Ferrero, Alfredo Brusco and Alessandro Mussa

Genes 2025, 16(10), 1229; https://doi.org/10.3390/genes16101229 - 17 Oct 2025

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Abstract

Background: SATB2-associated syndrome (SAS), also known as Glass syndrome, is a neurodevelopmental disorder (NDD) characterized by intellectual disability, developmental delay, absent or limited speech, and distinctive craniofacial and dental anomalies. It is caused by autosomal dominant pathogenic variants in the SATB2 gene, [...] Read more.

Background: SATB2-associated syndrome (SAS), also known as Glass syndrome, is a neurodevelopmental disorder (NDD) characterized by intellectual disability, developmental delay, absent or limited speech, and distinctive craniofacial and dental anomalies. It is caused by autosomal dominant pathogenic variants in the SATB2 gene, which plays a crucial role in brain, dental, and jaw development. Due to its variable phenotype, clinical diagnosis can be challenging, necessitating genetic confirmation. Methods: We present six new cases of SAS with SATB2 germline variants identified through next generation sequencing (NGS) technologies, expanding the known genetic and clinical spectrum of the syndrome. Detailed clinical phenotyping was performed for all patients. Results: Our cohort exhibits a broad range of clinical manifestations consistent with SAS, encompassing severe intellectual disability, profound speech delay, various palatal and dental abnormalities. We report the oldest adult patient (56 years old) carrying an in-frame duplication, and a pediatric patient with a missense variant who presented a significant reduction in visual acuity, likely of neurological or cortical origin, in the absence of ophthalmological abnormalities. SATB2 variants include three missenses, two in-frame deletion/duplication and one frameshift variant, several of which are novel and classified as likely pathogenic or pathogenic according to ACMG guidelines. Conclusions: This report provides new clinical and genetic insights into the landscape of SAS. Our findings confirm the phenotypic heterogeneity of SAS and highlight the critical role of comprehensive genetic testing for accurate diagnosis in NDD patients. Full article

(This article belongs to the Section Genetic Diagnosis)

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16 pages, 1912 KB

Open AccessArticle

Prevalence of Pathogenic and Likely Pathogenic Variants Associated with Cardiovascular Diseases in Russian Adults and Long-Living Individuals

by Irina Dzhumaniiazova, Elena Zelenova, Veronika Daniel, Mariia Gusakova, Dariia Kashtanova, Mikhail Ivanov, Olga Blinova, Vladimir Yudin, Lorena Matkava, Sergey Mitrofanov, Alexandra Nekrasova, Ekaterina Petriaikina, Marina Erokhina, Aleksey Ivashechkin, Ekaterina Maralova, Olesya Marchenko, Valentina Maksyutina, Valentin Makarov, Anton Keskinov, Sergey Kraevoy and Sergey Yudin Show full author list Hide full author list

Genes 2025, 16(10), 1228; https://doi.org/10.3390/genes16101228 - 17 Oct 2025

Viewed by 192

Abstract

Background: Cardiovascular diseases remain a leading cause of death worldwide, yet the prevalence of pathogenic and likely pathogenic genetic variants associated with them is still underassessed in some populations. This study aimed to assess the frequency and geographic distribution of such variants within [...] Read more.

Background: Cardiovascular diseases remain a leading cause of death worldwide, yet the prevalence of pathogenic and likely pathogenic genetic variants associated with them is still underassessed in some populations. This study aimed to assess the frequency and geographic distribution of such variants within a representative sample of the Russian population. Additionally, it explored potential links between genotype and phenotype in a cohort of long-lived adults. Methods: We analyzed whole-genome sequencing data from 75,144 adults and 2,872 individuals aged 90 and older. Variants within 37 ACMG v3.1 genes were examined using InterVar, focusing on nonsynonymous variants and indels across exons and splicing sites. Variants were grouped based on ClinVar (as of 24 April 2023) annotations, with most subjected to manual review to confirm their significance. Results: Among the adult participants, 3,817 (5.1%) carried at least one of the variants under consideration. Of these, 141 (0.19%) carried pathogenic, 580 (0.77%) likely pathogenic, and 3,127 (4.16%) variants of uncertain significance. Variants not registered in ClinVar were found in 1,782 individuals (2.37%). Notably, one participant with cardiomyopathy carried a heterozygous TTN variant. In the long-lived cohort, 15 variants were classified as pathogenic or likely pathogenic, alongside 72 uncertain variants; overall, 19 individuals (0.66%) carried pathogenic or likely pathogenic variants. No significant difference was observed in variant frequency between the adult and long-lived groups. Conclusions: This study provided essential insights into the prevalence and geographic distribution of cardiovascular disease-related variants in Russia, laying the foundation for targeted genetic screening disease prevention strategies within this population. Full article

(This article belongs to the Special Issue Insights into the Genomic and Genetic Basis of Cardiovascular Disease)

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14 pages, 866 KB

Open AccessReview

Genetic Prediction of Eye, Hair, and Skin Color: Forensic Applications and Challenges in Latin American Populations

by Beatriz Armida Flores-López, Anna Guadalupe López-Ceballos, Cristal Azucena López-Aguilar, Manuel Alejandro Rico-Méndez, Kesia Lyvier Acosta-Ramírez, Alan Cano-Ravell, Gildardo Gembe-Olivarez, Andres López-Quintero, José Alonso Aguilar-Velázquez, Jorge Adrian Ramírez-de-Arellano Sánchez and José Miguel Moreno-Ortiz

Genes 2025, 16(10), 1227; https://doi.org/10.3390/genes16101227 - 16 Oct 2025

Viewed by 237

Abstract

Forensic DNA phenotyping (FDP) is an important innovation approach in forensics sciences, especially when traditional DNA profiling results are limited, mostly due to the absence of reference samples. FDP is based on the detection of genetic variants in specific genes whose function is [...] Read more.

Forensic DNA phenotyping (FDP) is an important innovation approach in forensics sciences, especially when traditional DNA profiling results are limited, mostly due to the absence of reference samples. FDP is based on the detection of genetic variants in specific genes whose function is related to pigmentation mechanisms and uses the genotypes found in the sample to determine the externally visible traits (EVT) such as the iris, hair, and skin tone or color of the individual; this prediction would help and expedite human identification processes and solve criminal cases. Several technologies have been developed to facilitate EVT prediction; however, most of them have been validated only in European populations. Implementing techniques for FDP in Latin American countries is essential given the problems of disappearance and human identification that have persisted for years. Nonetheless, scientists have a great challenge due to the admixed genetic structure of the population. This review explores the current application of FDP, emphasizing its significance, practical uses, and limitations within Latin American populations. Full article

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

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35 pages, 8150 KB

Open AccessArticle

Analysis of Semen Proteomic Differences Among Three Genotypes of FecB Rams in Duolang Sheep

by Yanlong Zhang, Zhigang Niu, Jiabao Yan, Yang Chen, Zhengfen Xue, Jie Xu, Yifan Ma and Hongcai Shi

Genes 2025, 16(10), 1226; https://doi.org/10.3390/genes16101226 - 16 Oct 2025

Viewed by 157

Abstract

Backgrouds: To explore the differences in semen proteins among rams of three FecB genotypes (++, B+, and BB) in Duolang sheep. Methods: This study employed DIA quantitative proteomics technology to identify semen proteins from four wild-type (Group A), two heterozygous (Group B), and [...] Read more.

Backgrouds: To explore the differences in semen proteins among rams of three FecB genotypes (++, B+, and BB) in Duolang sheep. Methods: This study employed DIA quantitative proteomics technology to identify semen proteins from four wild-type (Group A), two heterozygous (Group B), and three homozygous (Group C) rams. Results: Compared with the ++ genotype, the differentially expressed proteins (DEPs) in the semen of B+ genotype rams are significantly involved in the biological process of innate immune response and are significantly enriched in the oxidative phosphorylation pathway in KEGG analysis. From a biological perspective, the innate immune response may affect the immune health of Duolang sheep, while oxidative phosphorylation influences energy metabolism, which in turn impacts reproductive performance. Compared with the BB genotype, the DEPs in the semen of B+ genotype rams participate in biological processes such as protein phosphorylation and protein hydrolysis during cellular protein catabolism. These DEPs are also significantly enriched in pathways related to Parkinson’s disease and non-alcoholic fatty liver disease in KEGG analysis. These differences may affect the cellular metabolism and physiological functions of Duolang sheep, thereby being associated with their reproductive performance. Compared with the ++ genotype, the DEPs in the semen of BB genotype rams exhibit differences in molecular function, cellular component, KEGG pathway, domain function, and subcellular localization. For instance, they are involved in threonine-type endopeptidase activity and associated with pathways like Alzheimer’s disease and retrograde endocannabinoid signaling. Conclusions: These differences may have potential impacts on the physiology and reproductive performance of Duolang sheep. Full article

(This article belongs to the Topic Advances in Molecular Genetics and Breeding of Cattle, Sheep, and Goats)

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13 pages, 1911 KB

Open AccessArticle

Integrated GWAS and Transcriptome Analysis to Identify Genes Underlying Plant Height and Ear Height Plasticity in Maize Germplasm

by Liang Tu, Pengfei Liu, Angui Wang, Dong Wang, Yunfang Zhu, Gang Li, Yulin Jiang, Xun Wu, Zhiming Zhang, Zehui Chen and Xiangyang Guo

Genes 2025, 16(10), 1225; https://doi.org/10.3390/genes16101225 - 16 Oct 2025

Viewed by 221

Abstract

Background: Integrating tropical and temperate maize germplasm represents a pivotal strategy for driving genetic innovation, with phenotypic plasticity serving as a critical indicator of successful integration. Methods: We analyzed 155 inbred lines across 5 contrasting environments to investigate variation and plasticity in plant [...] Read more.

Background: Integrating tropical and temperate maize germplasm represents a pivotal strategy for driving genetic innovation, with phenotypic plasticity serving as a critical indicator of successful integration. Methods: We analyzed 155 inbred lines across 5 contrasting environments to investigate variation and plasticity in plant height (PH) and ear height (EH). Results: Genome-wide association studies (GWAS) identified 77 loci associated with phenotypic plasticity, while the transcriptome profiling of Mo17 and T32 in Zhangye and Sanya revealed 9 candidate genes potentially regulating these traits, including Zm00001d043110, Zm00001d053972, and Zm00001d010154. Conclusions: These results provide valuable genetic resources and theoretical foundations for germplasm improvement. The identified genes hold promise for molecular marker development, facilitating the breeding of elite lines with stable PH and EH across environments, thereby contributing to maize improvement and enhancing global food security. Full article

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

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13 pages, 1418 KB

Open AccessArticle

Investigating the “Dark” Genome: First Report of Partington Syndrome in Cyprus

by Constantia Aristidou, Athina Theodosiou, Pavlos Antoniou, Angelos Alexandrou, Ioannis Papaevripidou, Ludmila Kousoulidou, Pantelitsa Koutsou, Anthi Georghiou, Türem Delikurt, Elena Spanou, Nicole Salameh, Paola Evangelidou, Kyproula Christodoulou, Alain Verloes, Violetta Christophidou-Anastasiadou, George A. Tanteles and Carolina Sismani

Genes 2025, 16(10), 1224; https://doi.org/10.3390/genes16101224 - 15 Oct 2025

Viewed by 260

Abstract

Background/Objectives: X-linked intellectual disability (XLID) is a highly heterogeneous disorder accounting for ~10% of all males with ID. Next-generation sequencing (NGS) has revolutionized the discovery of causal XLID genes and variants; however, many cases remain unresolved. We present a four-generation syndromic XLID [...] Read more.

Background/Objectives: X-linked intellectual disability (XLID) is a highly heterogeneous disorder accounting for ~10% of all males with ID. Next-generation sequencing (NGS) has revolutionized the discovery of causal XLID genes and variants; however, many cases remain unresolved. We present a four-generation syndromic XLID family with multiple males exhibiting variable degree of ID, focal dystonia and epilepsy. Methods: Extensive cytogenetic and targeted genetic testing was initially performed, followed by whole-exome sequencing (WES) and short-read whole-genome sequencing (WGS). Apart from the routine NGS analysis pipelines, sequencing data was revisited by focusing on poorly covered/mapped regions on chromosome X (chrX), to potentially reveal unidentified clinically relevant variants. Candidate variant validation and family segregation analysis were performed with Sanger sequencing. Results: All initial diagnostic testing was negative. Subsequently, 300 previously reported “dark” chrX coding DNA sequences, overlapping 97 genes, were cross-checked against 29 chrX genes highly associated (p < 0.05) with ID and focal dystonia, according to Phenomizer. Manual inspection of the existing NGS data in two low-coverage regions, chrX:25013469-25013696 and chrX:111744737-111744820 (hg38), revealed a recurrent pathogenic ARX variant NM_139058.3:c.441_464dup p.(Ala148_Ala155dup) (ARXdup24) associated with non-syndromic or syndromic XLID, including Partington syndrome. Sanger sequencing confirmed ARXdup24 in all affected males, with carrier status in their unaffected mothers, and absence in other unaffected relatives. Conclusions: After several years of diagnostic odyssey, the pathogenic ARXdup24 variant was unmasked, supporting a genotype–phenotype correlation in the first Partington syndrome family in Cyprus. This study highlights that re-examining underrepresented genomic regions and using phenotype-driven tools can provide critical diagnostic insights in unresolved XLID cases. Full article

(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)

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23 pages, 3051 KB

Open AccessArticle

Comparative Analysis of Deep Learning Models for Predicting Causative Regulatory Variants

by Gaetano Manzo, Kathryn Borkowski and Ivan Ovcharenko

Genes 2025, 16(10), 1223; https://doi.org/10.3390/genes16101223 - 15 Oct 2025

Viewed by 254

Abstract

Background/Objective: Genome-wide association studies (GWAS) have linked many noncoding variants to complex traits and diseases, but distinguishing as-sociation from causation remains difficult. Deep learning models—particularly CNN- and Transformer-based architectures—are widely used for this task, yet comparisons are hindered by inconsistent benchmarks and evaluation [...] Read more.

Background/Objective: Genome-wide association studies (GWAS) have linked many noncoding variants to complex traits and diseases, but distinguishing as-sociation from causation remains difficult. Deep learning models—particularly CNN- and Transformer-based architectures—are widely used for this task, yet comparisons are hindered by inconsistent benchmarks and evaluation practices. We aimed to establish a standardized assessment of leading models for predicting variant effects in enhancers and for prioritizing putative causal SNPs. Methods: We evaluated state-of-the-art deep learning models under consistent training and evaluation conditions on nine datasets derived from MPRA, raQTL, and eQTL ex-periments. These datasets profile the regulatory impact of 54,859 single-nucleotide polymorphisms (SNPs) across four human cell lines. Performance was compared for two related tasks: predicting the direction and magnitude of regulatory impact in enhancers and identifying likely causal SNPs within linkage disequilibrium (LD) blocks. We addi-tionally assessed the effect of fine-tuning on Transformer-based models and the impact of certainty in experimental results. Results: CNN models such as TREDNet and SEI performed best for predicting the reg-ulatory impact of SNPs in enhancers. Hybrid CNN–Transformer models (e.g., Borzoi) performed best for causal variant prioritization within LD blocks. Fine-tuning benefits Transformers but remains insufficient to close the performance gap. Conclusions: Under a unified benchmark, CNN architectures are most reliable for esti-mating enhancer regulatory effects of SNPs, while hybrid CNN–Transformer models are superior for causal SNP identification within LD. These comparisons help guide model selection for variant-effect prediction in noncoding regions. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 751 KB

Open AccessReview

Genetic Therapy of Fuchs Endothelial Corneal Dystrophy: Where Are We? A Review

by Spela Stunf Pukl

Genes 2025, 16(10), 1222; https://doi.org/10.3390/genes16101222 - 15 Oct 2025

Viewed by 212

Abstract

Objectives: The incidence of Fuchs endothelial corneal dystrophy (FECD) is growing, and with it, the unmet need for a corneal transplant. Among alternative treatment modalities, only genetic therapy represents a causal therapy. Methods: Following the SNARA protocol, the PubMed and ClinicalTrials databases were [...] Read more.

Objectives: The incidence of Fuchs endothelial corneal dystrophy (FECD) is growing, and with it, the unmet need for a corneal transplant. Among alternative treatment modalities, only genetic therapy represents a causal therapy. Methods: Following the SNARA protocol, the PubMed and ClinicalTrials databases were searched using the keywords Fuchs endothelial corneal dystrophy, FECD, genetic therapy, and CRISPR-Cas9. Results: FECD is polyfactorial disease and mutations or polymorphisms in at least 15 different genes were connected to the disease. For the early-onset form of the disease, exclusive connection to mutations in COL8A2 was confirmed, while for the late-onset form, the most characteristic mutation is the expansion of the CTG18.1 triplet in the TCF4 gene, making these two possible targets. While the CRISPR-Cas9 approach represents the mainstay of genetic therapy development recently, the application of this method to FECD contains several obstacles, studied in preclinical settings. DT-168 and the Ad-Cas9-Col8a2gRNA molecules were developed for FECD treatment and preclinically tested, and phase I and II clinical studies for DT-168 are also already being performed. Conclusions: The review of the literature proved that genetic therapy for FECD is at the level of preclinical research and that there are several specific challenges connected to the target genetic mutation as well as the delivery of possible treatment and duration of the effect. Further studies in the field might bring solutions in the future for alternative treatments for this common corneal disease. Full article

(This article belongs to the Special Issue Genetic Diagnosis and Therapeutics of Eye Diseases)

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66 pages, 1748 KB

Open AccessReview

Transcriptional Activation Mechanisms and Target Genes of the Oncogene Product Tax of Human T-Cell Leukemia Virus Type 1

by Mashiro Shirasawa, Rinka Nakajima, Yaxuan Zhou, Mariana Fikriyanti, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki and Kiyoshi Ohtani

Genes 2025, 16(10), 1221; https://doi.org/10.3390/genes16101221 - 15 Oct 2025

Viewed by 362

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). The trans-activator protein Tax of HTLV-1 is thought to play a crucial role in the early-stage transformation of the virus-infected cells. Tax is a multi-functional protein and [...] Read more.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). The trans-activator protein Tax of HTLV-1 is thought to play a crucial role in the early-stage transformation of the virus-infected cells. Tax is a multi-functional protein and modulates cellular signaling pathways that promote proliferation and survival of HTLV-1-infected cells, primarily through the trans-activation of cellular target genes. Tax interacts with a variety of host cell factors including signal transducers and transcription factors, leading to the activation of transcription factors such as CREB, NF-κB, and SRF and activates both its own promoter and those of a variety of host cellular genes. Tax activates its own promoter mainly through CREB and host cellular genes through NF-κB, SRF, and CREB. Accumulating evidence indicates that the Tax-mediated trans-activation of target genes through NF-κB plays an essential role in the transformation of HTLV-1 infected cells. However, the repertoire of Tax target genes, especially those crucial for leukemogenesis, are not known in detail. In this review, we summarize transcriptional activation mechanisms and target genes of Tax, especially focusing on transformation, to facilitate understanding of the underlying mechanisms of leukemogenesis induced by HTLV-1 infection. Full article

(This article belongs to the Special Issue Progress in Hematology: Non-Malignant, Pre-Malignant, and Malignant Disorders, and Genetically Based Therapies)

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15 pages, 2914 KB

Open AccessArticle

Whole-Exome Sequencing of Discordant Monozygotic Twins for Congenital Scoliosis: A Family Case Study

by Diana Samarkhanova, Madina Seidualy, Ulykbek Kairov, Nurbek Nadirov and Maxat Zhabagin

Genes 2025, 16(10), 1220; https://doi.org/10.3390/genes16101220 - 15 Oct 2025

Viewed by 255

Abstract

Background/Objectives: Congenital scoliosis (CS) is a developmental disorder characterized by abnormal vertebral development during embryogenesis. Despite the identification of genes involved in vertebral development, the underlying genetic causes of CS remain largely unknown. Monozygotic (MZ) twins discordant for CS offer a unique [...] Read more.

Background/Objectives: Congenital scoliosis (CS) is a developmental disorder characterized by abnormal vertebral development during embryogenesis. Despite the identification of genes involved in vertebral development, the underlying genetic causes of CS remain largely unknown. Monozygotic (MZ) twins discordant for CS offer a unique opportunity to explore de novo or postzygotic causes. This exploratory case study aimed to investigate potential causative variants underlying CS using whole-exome sequencing (WES). Methods: We performed WES on a Kazakhstani family with MZ twins discordant for congenital scoliosis. Variant prioritization included homozygous mutation analysis in the affected twin, family-based comparisons via de novo, autosomal recessive, and autosomal dominant models, and cross-referencing with variants previously implicated in spinal deformities. Results: Key findings include potential associations of the STOX1 (storkhead box 1), HOXD8 (homeobox D8), and C1QTNF9 (C1q- and TNF-related 9) genes with congenital scoliosis. However, subsequent validation revealed low read depth and strand bias. Notably, no unique variants were detected in genes previously known to cause CS. Conclusions: The first WES analysis of CS-discordant twins from a single family highlights the feasibility of a combined family-based and twin-comparative analytical pipeline. Our results provide new insights into the genetic architecture of CS and establish a foundation for future twin studies to elucidate the genetic basis of rare developmental disorders. Full article

(This article belongs to the Section Bioinformatics)

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14 pages, 2239 KB

Open AccessArticle

DNA Barcoding and Analysis of Nutritional Properties as a Tool for Enhancing Traceability of Anchovies (Engraulis encrasicolus L.) Fished in the Italian Southern Adriatic Sea

by Maddalena de Virgilio, Domenico De Paola, Maria Selvaggi, Claudia Carbonara, Marco Ragni, Anna Caputi Jambrenghi, Francesco Giannico, Maria Antonietta Colonna and Simona Tarricone

Genes 2025, 16(10), 1219; https://doi.org/10.3390/genes16101219 - 15 Oct 2025

Viewed by 215

Abstract

Background: Anchovies (Engraulis encrasicolus L.) are a component of the Mediterranean diet and among the most fished species. Despite Italian consumers showing a strong preference and willingness to pay more for locally caught anchovies, cases of mislabeling with non-local or different species [...] Read more.

Background: Anchovies (Engraulis encrasicolus L.) are a component of the Mediterranean diet and among the most fished species. Despite Italian consumers showing a strong preference and willingness to pay more for locally caught anchovies, cases of mislabeling with non-local or different species have been documented. Molecular techniques like DNA barcoding offer reliable species identification, even in processed products, where morphological traits are no longer detectable. This pilot study applied a DNA barcoding technique targeting the mitochondrial cytochrome b gene to authenticate anchovies caught in the Italian Southern Adriatic Sea. Objectives: The study evaluated seasonal variations in the chemical and nutritional composition of anchovies, particularly the fatty acid profiles, highlighting their health benefits. Methods: During 2021, two fish samplings of anchovies were conducted per season from two fishing areas in Southern Adriatic Sea, one sample was used for mitochondrial DNA analyses, the other was used for morphometric measurements, physical, bromatological and chemical analyses. Results: Fish collected in summer showed higher total weight and edible yield relative to those fished in winter (p < 0.05). Anchovies fished in summer contained the highest concentration of proteins (p < 0.05) as compared to those caught during winter and autumn, while, in turn, they showed the highest amount of fat (p < 0.01). Fillets from anchovies fished during spring and summer contained a greater (p < 0.05) concentration of polyunsaturated fatty acids, and n-3 fatty acids than samples collected in autumn and winter. Conclusions: This study paves the way for further investigation to refine and validate the genetic identification and nutritional features of anchovies caught in the Italian Southern Adriatic Sea and marketed to consumers. Full article

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

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9 pages, 3819 KB

Open AccessArticle

Genomic Relationship Between Brochothrix campestris and Its Phages: A Cross-Replicon and Interspecies Perspective

by Sabrina A. Attéré, Laurie C. Piché and Antony T. Vincent

Genes 2025, 16(10), 1218; https://doi.org/10.3390/genes16101218 - 15 Oct 2025

Viewed by 224

Abstract

Background/Objectives: The bacterium Brochothrix campestris is closely related to Brochothrix thermosphacta, a known food spoilage agent, and Listeria monocytogenes, the causative agent of listeriosis. B. campestris garnered attention several years ago because it produces brochocin-C, a bacteriocin capable of inhibiting [...] Read more.

Background/Objectives: The bacterium Brochothrix campestris is closely related to Brochothrix thermosphacta, a known food spoilage agent, and Listeria monocytogenes, the causative agent of listeriosis. B. campestris garnered attention several years ago because it produces brochocin-C, a bacteriocin capable of inhibiting the growth of certain pathogens. It has been recently suggested that phages play a significant role in the evolution of B. thermosphacta, similar to the role they play for L. monocytogenes. However, understanding the role of phages in the evolution of B. campestris has been challenging because only a draft of genome sequences of a single B. campestris strain was previously available. Methods: In this study, DNA from the B. campestris type strain DSM 4712 was sequenced using Oxford Nanopore and Illumina technologies to obtain complete, high-quality genome sequences. Results: The assembly revealed the presence of a plasmid and a phage-plasmid. Additionally, chromosomal analysis identified several genomic islands, including one harboring the brochocin genes, suggesting that these genes may have undergone horizontal transfer. Conclusions: This study underscores the potential importance of phages in the evolution of B. campestris, and also highlights the need for further research into the interactions between Brochothrix species and their associated phages to better understand these complex biological relationships. Full article

(This article belongs to the Special Issue Feature Papers in Microbial Genetics and Genomics)

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10 pages, 1892 KB

Open AccessArticle

The Complete Chloroplast Genome of Camellia tianeensis (Camellia L.) and Phylogenetic Relationships with Other Plants of the Genus Camellia

by Juyan Chen, He Li and Lunxiu Deng

Genes 2025, 16(10), 1217; https://doi.org/10.3390/genes16101217 - 15 Oct 2025

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Abstract

Background/Objectives: Species within section Chrysantha represent the only camellias known to produce golden-yellow petals. The primary objectives of this study were to characterize the chloroplast genome structure of Camellia tianeensis and to elucidate its phylogenetic position with sect. Chrysantha. Methods: The complete [...] Read more.

Background/Objectives: Species within section Chrysantha represent the only camellias known to produce golden-yellow petals. The primary objectives of this study were to characterize the chloroplast genome structure of Camellia tianeensis and to elucidate its phylogenetic position with sect. Chrysantha. Methods: The complete chloroplast genome of C. tianeensis was sequenced, assembled, and annotated. Phylogenetic inference was conducted using maximum likelihood and Bayesian methods based on complete chloroplast genomic sequences. Results: The chloroplast genome of C. tianeensis is 156,865 bp in length and exhibits a typical quadripartite structure consisting of a large single-copy (LSC) region (86,579 bp), a small single-copy (SSC) region (18,236 bp), and two inverted repeat (IR) regions (26,025 bp each). The genome encodes 164 genes, including 111 protein-coding genes, 45 tRNAs, and 8 rRNA genes. The overall GC content was 37.32%, with regional values of 35.33% (LSC), 30.59% (SSC), and 42.99% (IRs). Sixty-nine simple sequence repeats (SSRs) were identified, predominantly mononucleotide repeats, Thirty-eight dispersed repeats were categorized into three types (forward, reverse, and palindromic), with no complement repeats detected. Phylogenetic analysis strongly supported that C. tianeensis is a member within sect. Chrysantha. Conclusions: C. tianeensis is phylogenetically closely related to C. huana, forming a well-supported clade. This study enhances the molecular research available for sect. Chrysantha and provides a genomic foundation for future phylogenetic and taxonomic studies in this group. Full article

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

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18 pages, 6623 KB

Open AccessArticle

Mitochondrial and Nuclear DNA Analyses of Rhipicephalus microplus from Mizoram, Northeast India: Insights into Genetic Diversity and Endosymbiont

by Khawlhring Lalawmpuii, Siju Susan Jacob, Thingujam Chaa Tolenkhomba, Parthasarathi Behera, Joy Lalmuanpuia, Hmar Tlawmte Lalremsanga, Khawlhring Lalrintluanga, Chhakchhuak Lalchhandama, Lal Biakzuala and Hmar Lalrinkima

Genes 2025, 16(10), 1216; https://doi.org/10.3390/genes16101216 - 15 Oct 2025

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Abstract

Background/Objectives: In this study, we conducted molecular identification of R.microplus and explored the genetic diversity of R. microplus for the first time in Mizoram, a Northeastern Hill (NEH) state of India bordering Myanmar. Methods: To assess genetic variation and evolutionary relationships, [...] Read more.

Background/Objectives: In this study, we conducted molecular identification of R.microplus and explored the genetic diversity of R. microplus for the first time in Mizoram, a Northeastern Hill (NEH) state of India bordering Myanmar. Methods: To assess genetic variation and evolutionary relationships, we employed phylogenetic analyses, genetic divergence metrics, and haplotype network construction based on mitochondrial (COX1 and 16S rDNA) and nuclear (ITS-2 and 18S rDNA) markers. Additionally, multivariate Principal Coordinate Analysis (PCoA) was used to visualize genetic differentiation among R. microplus populations. Results: Our analyses indicated that populations of R. microplus sensu lato from India, Bangladesh, and Pakistan form a closely related matrilineal lineage distinct from R. microplus sensu stricto, clustering within clade C of the COX1-based phylogeny. Globally, 24 COX1 haplotypes were recovered, with 1 haplotype identified in India. The Mizoram population exhibited a single 16S rDNA haplotype; however, intraspecific divergence was evident across India, with seven matrilineal haplotypes detected and nineteen globally. Further, five haplotypes were identified within R. microplus using the ITS-2 marker, while five haplotypes were observed within the Rhipicephalus genus using the 18S rDNA marker. Moreover, this study revealed the presence of Coxiella-like endosymbionts in 95% of the tick specimens analyzed. Conclusions: This study fills a critical knowledge gap by providing the first molecular documentation of tick diversity in Mizoram, a strategic region along the Indo–Myanmar border, and offers novel insights into the phylogeography and symbiotic associations of R. microplus and related tick taxa. Full article

(This article belongs to the Special Issue Genetics and Epidemiology of Parasites)

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17 pages, 15704 KB

Open AccessArticle

The Genome Survey Analysis of Female and Male Sepiella japonica

by Yuting Ren, Yinquan Qu, Fenglin Wang, Tianxiang Gao and Xiumei Zhang

Genes 2025, 16(10), 1215; https://doi.org/10.3390/genes16101215 - 15 Oct 2025

Viewed by 236

Abstract

Background/Objectives: Sepiella japonica is a highly adaptable cephalopod with an advanced nervous system and complex reproductive behavior, capable of reproducing two to three generations annually depending on water temperature. However, the absence of a complete genome assembly has limited molecular investigations of its [...] Read more.

Background/Objectives: Sepiella japonica is a highly adaptable cephalopod with an advanced nervous system and complex reproductive behavior, capable of reproducing two to three generations annually depending on water temperature. However, the absence of a complete genome assembly has limited molecular investigations of its unique biological characteristics. This study aimed to perform a genome survey of female and male S. japonica, systematically characterize and compare key genomic characteristics. Methods: Quality-filtered short reads enabled K-mer-based estimation of genome size, heterozygosity, repeat content, and GC content; generation of draft genome assemblies, SSR identification from the draft assemblies, complete mitogenome assemblies and annotations with ML phylogeny based on 13 concatenated PCGs, and PSMC-based demographic inference. Results: The estimated genome sizes were 4317 Mb (female) and 4222 Mb (male), with revised estimates of 4310 Mb and 4215 Mb, respectively. K-mer analysis revealed heterozygosity rates of 0.85% (female) and 0.77% (male) and repeat content of 76.05% (female) and 75.91% (male). The assembled genome sizes were 4197 Mb for females (N50: 508 bp) and 4206 Mb for males (N50: 511 bp); the GC content was 34.15% for both genomes. Deduplicated data showed GC content of 35.16% (female) and 35.27% (male). Microsatellite analysis revealed that mononucleotide repeats were the most abundant simple sequence repeat motif. The mitochondrial genome sequences measured 16,729 bp for the female genome and 16,725 bp for the male genome. Conclusions: This study provides fundamental data for subsequent high-quality whole-genome assembly and comparative analysis of female and male genomes. Full article

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

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23 pages, 2734 KB

Open AccessArticle

Epigenetic Modulation and Neuroprotective Effects of Neurofabine-C in a Transgenic Model of Alzheimer’s Disease

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

Genes 2025, 16(10), 1214; https://doi.org/10.3390/genes16101214 - 15 Oct 2025

Viewed by 283

Abstract

Background: Currently, there are limited therapeutic or preventative strategies for neurodegenerative disorders due to the challenges in alleviating the progressive neuronal loss and neuroinflammation which are the primary characteristics of these diseases, ultimately leading to cell death and functional impairment. Cocoa-derived flavanols [...] Read more.

Background: Currently, there are limited therapeutic or preventative strategies for neurodegenerative disorders due to the challenges in alleviating the progressive neuronal loss and neuroinflammation which are the primary characteristics of these diseases, ultimately leading to cell death and functional impairment. Cocoa-derived flavanols (Theobroma cacao) have been studied as potential bioactive compounds to modify and reverse various inflammation-associated diseases because of their remarkable antioxidant properties and capacity to modulate metabolic imbalance and reactive inflammatory responses. The faba bean (Vicia faba) extract obtained through nondenaturing biotechnological processes is a potent dopamine (DA) enhancer that has shown promising results as a neuroprotective agent against degeneration. Objective: This study will examine the synergistic effects of Neurofabine-C, a hybrid compound derived from cocoa and faba bean extracts, on various brain biomarkers in mice related to inflammatory, metabolic, and neurodegenerative processes. Methods: A triple-transgenic mouse model of neurodegeneration was treated with Neurofabine-C, and biomolecular data were obtained by performing biochemical and immunohistochemical analysis. Results: Neurofabine-C prevented neuronal degeneration (NeuN), mitigated the neuro-inflammatory processes triggered (decreased expression of reactive astrocytes (GFAP)), and induced an increase in neurogenesis in the treated cortical mice brain (PAX6). Epigenetic analysis revealed significant chromatin remodeling in the hippocampus. Neuroprotective genes, including FOXO3, ATM, and TRP73, were upregulated, whereas the expression of HIF1α and APOE decreased. In parallel, DNMT3A expression increased 20-fold, HDAC3 decreased by 60%, and global 5-methylcytosine levels increased four-fold. These coordinated changes suggest that Neurofabine-C promotes neuroprotective programs through enhanced DNA methylation and reduced histone deacetylation. Conclusions: The findings indicate that Neurofabine-C exhibits multiple neuroprotective mechanisms, making it a potent bioproduct for mitigating neuroinflammatory processes associated with neurodegenerative disorders. Full article

(This article belongs to the Section Neurogenomics)

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20 pages, 5947 KB

Open AccessArticle

Integrative Single-Cell and Bulk Transcriptomic Analysis Identifies Macrophage-Related Gene Signatures Predictive of Hepatocellular Carcinoma in Cirrhosis

by Zhongyuan Zhang, Chuisheng Zeng, Xuetong Yong, Wenping Zhou, Yongfang Xie and Jianzhong Shu

Genes 2025, 16(10), 1213; https://doi.org/10.3390/genes16101213 - 15 Oct 2025

Viewed by 376

Abstract

Background/Objectives: Liver cirrhosis is a major global health challenge and a key risk factor for hepatocellular carcinoma (HCC), a malignancy with high mortality due to late diagnosis. This study aimed to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) [...] Read more.

Background/Objectives: Liver cirrhosis is a major global health challenge and a key risk factor for hepatocellular carcinoma (HCC), a malignancy with high mortality due to late diagnosis. This study aimed to integrate single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data, using single-cell data to identify macrophage-associated transcriptomic changes during the progression from cirrhosis to HCC, and using bulk data to validate these findings in independent cohorts, while developing predictive models for early risk assessment. Methods: We integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets derived from liver tissues of cirrhosis and HCC patients. Single-cell data were used to identify macrophage subtypes and their dynamic transcriptional changes, while bulk data provided validation in independent cohorts. Gene expression and network analyses were performed, and candidate genes were used to construct diagnostic models with Lasso regression, Random Forest, and Extreme Gradient Boosting (XGBoost). Model performance was evaluated using receiver operating characteristic curves. Results: We identified eleven macrophage-associated genes, among which KLK11, MARCO, CFP, KRT19, GAS1, SOD3, and CYP2C8 were downregulated in HCC, indicating loss of tumor-suppressive and pro-apoptotic functions, while TOP2A, CENPF, MKI67, and NUPR1 were upregulated, reflecting enhanced cell cycle progression, proliferation, and M2 polarization. These are all associated with the progression from liver cirrhosis to HCC. Based on these findings, we established predictive models using Lasso, Random Forest, and XGBoost, which stratified cirrhotic patients into high- and low-risk groups according to cutoff values using liver tissue transcriptomic data. All three models demonstrated high diagnostic performance. Conclusions: This study highlights the critical role of macrophage-associated transcriptomic remodeling in liver disease progression. The machine learning–based predictive models offer a promising approach for early diagnosis and clinical decision-making in patients with cirrhosis. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 1868 KB

Open AccessArticle

Cystoid Macular Lesions in Inherited Retinal Diseases: Prevalence, Characteristics, and Genetic Associations in a Hungarian Cohort

by Barbara Asboth, Alessandra Sanrocco, Barbara Besztercei, Balazs Lesch, Agnes Takacs, Rita Vamos, Balazs Varsanyi, Andras Vegh, Krisztina Knezy, Viktoria Szabo, Zoltan Zsolt Nagy and Ditta Zobor

Genes 2025, 16(10), 1212; https://doi.org/10.3390/genes16101212 - 14 Oct 2025

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Abstract

Background/Objectives: Cystoid macular lesion (CML) is a treatable cause of central vision loss in inherited retinal diseases (IRDs). We aimed to determine the frequency of CML in a large Hungarian IRD cohort and examine associations with causative genes. Methods: This longitudinal, [...] Read more.

Background/Objectives: Cystoid macular lesion (CML) is a treatable cause of central vision loss in inherited retinal diseases (IRDs). We aimed to determine the frequency of CML in a large Hungarian IRD cohort and examine associations with causative genes. Methods: This longitudinal, retrospective, monocentric study included patients with genetically confirmed IRD identified from our database. Targeted next-generation sequencing (351-gene panel) and comprehensive ophthalmic evaluation were performed, including best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT). CML was defined as intraretinal hyporeflective spaces with well-defined borders visible on at least two B-scans within the SD-OCT macular volume and was categorized as cystoid macular edema (CME) or non-CME. Results: We enrolled 430 patients with genetically confirmed IRDs. CML was detected in 93 eyes of 57 patients. Mean age at OCT was 36.6 ± 18.7 years (range, 3–76); 32 were male (56.1%). Inheritance patterns were autosomal recessive in 24 (42.1%), X-linked in 19 (33.3%), and autosomal dominant in 14 (24.6%). Frequently implicated genes were RS1 (12/57), USH2A (7/57), NR2E3 (7/57), PRPF31 (4/57), RPGR (4/57), and RHO (4/57). CME predominated in retinitis pigmentosa (32/57, 56%), with mean BCVA 0.44 ± 0.29 (decimal) and central retinal thickness (CRT) 401 ± 181 µm. Non-CME CML occurred in 25/57 (44%)—notably in X-linked retinoschisis and enhanced S-cone syndrome—with BCVA 0.40 ± 0.23 and CRT 465 ± 258 µm. BCVA did not correlate with CRT (r_S = 0.18). Conclusions: CML occurred in 13.2% of patients within a large Hungarian cohort of genetically confirmed IRDs. Patients with IRD—mainly RP—are at higher risk for CML. Gene therapy is promising for retinal diseases, but CMLs can compromise effectiveness. Reducing and managing CME before gene therapy corroborates retinal stability and the functional state essential for the proper delivery and penetration of corrective genes to the target cells. Full article

(This article belongs to the Special Issue Inherited Retinal Diseases: Genetic Research and Novel Therapeutic Prospects)

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Open AccessArticle

Pedigree-Based Estimation of Y-STR Mutation and Male Differentiation Rates: Application to Historical Remains Identification

by Jasmine R. Connell, Toni White, Thais Zielke, Luke Armstrong, Natasha Mitchell and Lyn R. Griffiths

Genes 2025, 16(10), 1211; https://doi.org/10.3390/genes16101211 - 14 Oct 2025

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Abstract

Background/Objectives: High differentiation rates provided by Y-chromosomal short tandem repeats (Y-STRs) are highly advantageous in most forensic and genealogical casework, as they enhance the ability to exclude close or moderately related individuals, refine an individual’s position within a pedigree, and uncover the population [...] Read more.

Background/Objectives: High differentiation rates provided by Y-chromosomal short tandem repeats (Y-STRs) are highly advantageous in most forensic and genealogical casework, as they enhance the ability to exclude close or moderately related individuals, refine an individual’s position within a pedigree, and uncover the population substructure in otherwise homogeneous groups. However, the impact for historical remains identification casework is underexplored. Methods: We present a pedigree analysis of 366 males from 183 pedigrees, separated by 4 to 16 meioses at 27 Y-STR loci, from the Yfiler Plus kit. The differentiation rate for a given degree of separation was defined as the proportion of pairs at that specific number of meioses showing at least one allelic difference, relative to the total number of such pairs. Results: Our pedigree-based locus-specific mutation rates were consistent with published father–son values for 22 of 25 loci, with 3 loci (DYS389II, DYS449, and DYS570) being significantly different (p < 0.05). These results were consistent with previous pedigree-based estimates, and the strong agreement between father–son and pedigree-based mutation rates supports the use of pedigrees as a reliable method for estimating mutation rates. The probability of differentiating male relatives reached 60.1%, which is similar to previous studies using the Yfiler Plus kit. Conclusions: This high male differentiation rate is advantageous for distinguishing unrelated individuals within the same population, reducing false inclusions. However, when comparing distantly related individuals, excessive mutations accumulated over many generations may obscure genuine patrilineal relationships, increasing the risk of false exclusions. Our findings are likely to be highly valuable for future interpretation of Y-STR haplotypes from patrilineal relatives across a wide range of applications, with significant relevance to historical remains identification casework. Full article

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

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Genes, Volume 16, Issue 10 (October 2025) – 121 articles

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