Genes

13 pages, 281 KiB

Open AccessReview

Genetics and Clinical Findings Associated with Early-Onset Myopia and Retinal Detachment in Saudi Arabia

by Mariam M. AlEissa, Abrar A. Alhawsawi, Doaa Milibari, Patrik Schatz, Hani B. AlBalawi, Naif M. Alali, Khaled K. Abu-Amero, Syed Hameed and Moustafa S. Magliyah

Genes 2025, 16(7), 848; https://doi.org/10.3390/genes16070848 - 21 Jul 2025

Viewed by 429

Abstract

Autosomal recessive types of both syndromic and non-syndromic inherited myopia are common in Saudi Arabia (SA) because many people marry their relatives. The prevalence of syndromic myopathies in SA, like Stickler syndrome (SS), Knobloch syndrome (KS), and Marfan syndrome (MFS), further complicates the [...] Read more.

Autosomal recessive types of both syndromic and non-syndromic inherited myopia are common in Saudi Arabia (SA) because many people marry their relatives. The prevalence of syndromic myopathies in SA, like Stickler syndrome (SS), Knobloch syndrome (KS), and Marfan syndrome (MFS), further complicates the disease spectrum. The causative genes linked to the Knobloch, Marfan, and Pierson syndromes are COL18A1, FBN1, and LAMB2, respectively. Additionally, we found recessive types of non-syndromic high myopia that have a high chance of causing retinal detachment, like those linked to LRPAP1 and LEPREL1. In these cases, regular evaluation and early intervention, including prophylactic laser photocoagulation and pars plana vitrectomy, may improve the outcome. Advancements in genetic testing for diagnosis and prevention accelerate detection, facilitate early interventions, and provide genetic counseling. The utilization of artificial intelligence (AI), machine learning (ML), and the advancement of gene therapy offer promising avenues for personalized care. We place a high value on using genetic knowledge to create a national screening program and patient registry aimed at understanding the national burden of myopia, knowing that we have a high rate of consanguinity, which reflects pathogenic homozygous alleles and founder mutations. This initiative will incorporate genetic counseling and leverage innovative technologies, which are crucial for disease management, early identification, and prevention in Saudi Arabia’s healthcare system. Full article

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

20 pages, 481 KiB

Open AccessReview

Advances in Precision Therapeutics and Gene Therapy Applications for Retinal Diseases: Impact and Future Directions

by Mariam M. AlEissa, Abrar A. Alhawsawi, Raghad Alonazi, Enas Magharbil, Abeer Aljahdali, Hani B. AlBalawi, Naif M. Alali, Syed Hameed, Khaled K. Abu-Amero and Moustafa S. Magliyah

Genes 2025, 16(7), 847; https://doi.org/10.3390/genes16070847 - 21 Jul 2025

Viewed by 779

Abstract

Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, [...] Read more.

Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, thanks to advances in gene therapy, many disorders can now be effectively targeted and genetically changed, providing a safer, more direct, maybe even curative approach. By introducing, altering, or repairing specific genes inside the eye, gene therapy seeks to fix the defective genes causing these disorders, thereby improving general eye health and visual ability. Voretigene neparvovec is one FDA- and EMA-approved treatment for RPE65 mutations. Retinitis pigmentosa, age-related macular degeneration, X-linked retinoschisis, choroideremia, and Stargardt disease are among the several eye disorders still under clinical trials, and experimental treatment is in progress. As research on gene therapy develops, it opens the path for groundbreaking treatments that could fundamentally change the ophthalmic care scene. Full article

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

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19 pages, 12441 KiB

Open AccessArticle

Mitogenome Characteristics and Intracellular Gene Transfer Analysis of Four Adansonia Species

by Tingting Hu, Fengjuan Zhou, Lisha Wang, Xinwei Hu, Zhongxiang Li, Xinzeng Li, Daoyuan Zhou and Hui Wang

Genes 2025, 16(7), 846; https://doi.org/10.3390/genes16070846 - 21 Jul 2025

Viewed by 236

Abstract

Adansonia L. (1753) belongs to the family Malvaceae and is commonly known as the baobab tree. This species holds significant cultural and ecological value and is often referred to as the ‘tree of life.’ Although its nuclear genome has been reported, the mitogenome [...] Read more.

Adansonia L. (1753) belongs to the family Malvaceae and is commonly known as the baobab tree. This species holds significant cultural and ecological value and is often referred to as the ‘tree of life.’ Although its nuclear genome has been reported, the mitogenome has not yet been studied. Mitogenome research is crucial for understanding the evolution of the entire genome. In this study, we assembled and analyzed the mitogenomes of four Adansonia species by integrating short-read and long-read data. The results showed that the mitogenomes of all four Adansonia species were resolved as single circular sequences. Their total genome lengths ranged from 507,138 to 607,344 bp and contained a large number of repetitive sequences. Despite extensive and complex rearrangements between the mitogenomes of Adansonia and other Malvaceae species, a phylogenetic tree constructed based on protein-coding genes clearly indicated that Adansonia is more closely related to the Bombax. Selection pressure analysis suggests that the rps4 gene in Adansonia may have undergone positive selection compared to other Malvaceae species, indicating that this gene may play a significant role in the evolution of Adansonia. Additionally, by analyzing intracellular gene transfer between the chloroplast, mitochondria, and nuclear genomes, we found that genes from the chloroplast and mitochondria can successfully transfer to each chromosome of the nuclear genome, and the psbJ gene from the chloroplast remains intact in both the mitochondrial and nuclear genomes. This study enriches the genetic information of Adansonia and provides important evidence for evolutionary research in the family Malvaceae. Full article

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

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26 pages, 3710 KiB

Open AccessArticle

Global Transcriptome and Weighted Gene Co-Expression Network Analyses of Cold Stress Responses in Chinese Cabbage

by Jizong Zhang, Songtao Liu, Huibin Li, Mengmeng Sun, Baoyue Yan, Peng Zhang and Lifeng Zhang

Genes 2025, 16(7), 845; https://doi.org/10.3390/genes16070845 - 20 Jul 2025

Viewed by 379

Abstract

Background/Objectives: Chinese cabbage (Brassica rapa ssp. Pekinensis, AA) growth and development is highly sensitive to cold temperatures. Prolonged low-temperature exposure during early growth stages can induce premature bolting, which reduces market quality and yield. Methods: Here, using comparative leaf RNA-seq transcriptome [...] Read more.

Background/Objectives: Chinese cabbage (Brassica rapa ssp. Pekinensis, AA) growth and development is highly sensitive to cold temperatures. Prolonged low-temperature exposure during early growth stages can induce premature bolting, which reduces market quality and yield. Methods: Here, using comparative leaf RNA-seq transcriptome analysis of plants grown at 6, 9, 12, and 15 °C, we explored key genes and metabolic pathways regulating Chinese cabbage cold response. Results: RNA-seq transcriptome analysis identified a total of 1832 differentially expressed genes (DEGs) in the three comparison groups, with 5452, 1861, and 752 DEGs specifically expressed in the A6_vs_A15, A9_vs_A15, and A12_vs_A15 groups, respectively. KEGG enrichment analysis of DEGs showed that sulfur metabolism, secondary metabolites biosynthesis and photosynthesis pathways were mostly affected by cold stress. K-means clustering revealed distinct expression profiles among the DEGs enriched in cold stress response-associated clusters. Subsequently, DEGs were divided into 18 modules by WGCNA, whereupon co-expression genes that clustered into similar modules exhibited diverse expression and were annotated to various GO terms at different temperatures. Module-trait association analysis revealed M1, M2, M3, and M6 modules as key clusters potentially linked to vernalization-related processes. These modules harbored candidate hub genes encoding transcription factors (including MYB, bZIP, and WRKY), protein kinases, and cold-stress-responsive genes. Additionally, phenotypic analysis showed that 12 °C to 15 °C supported optimal growth, whereas <9 °C temperature inhibited growth. Physiological measurements showed increased antioxidant enzyme activity and proline accumulation at 6 °C. Conclusions: Overall, our study provides a set of candidate cold-stress-responsive genes and co-expression modules that may support cold stress tolerance breeding in Chinese cabbage. Full article

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

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11 pages, 857 KiB

Open AccessArticle

Placental Expression of Sirtuins in Women with Gestational Diabetes

by Michał Czerewaty, Łukasz Ustianowski, Kajetan Kiełbowski, Estera Bakinowska, Krzysztof Safranow, Maciej Tarnowski, Tomasz Sroczyński and Andrzej Pawlik

Genes 2025, 16(7), 844; https://doi.org/10.3390/genes16070844 - 20 Jul 2025

Viewed by 317

Abstract

Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnant women. It can lead to several complications, such as preterm delivery, macrosomia, or metabolic disorders in newborns. Studies have revealed morphological and transcriptional differences between the placentas of patients with GDM [...] Read more.

Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnant women. It can lead to several complications, such as preterm delivery, macrosomia, or metabolic disorders in newborns. Studies have revealed morphological and transcriptional differences between the placentas of patients with GDM and women with normal glucose tolerance. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent deacetylases that interact with and regulate the activity of numerous proteins. However, little is known about their role in the pathogenesis of GDM. This study was performed to analyze the placental expression of SIRTs and investigate their correlations with clinical parameters. Methods: GDM was diagnosed based on the 75 g oral glucose tolerance test in accordance with the criteria developed by the International Association of Diabetes and Pregnancy Study Groups. Placental tissues were collected, and the expression of SIRT1,-3,-4 and a reference gene (β-2 microglobulin) was analyzed. Results: The placental expression of SIRT1 and SIRT3 was elevated in women with GDM. However, there was no significant difference in SIRT4 expression between women with GDM and those with normal glucose tolerance. Furthermore, we found no significant correlations between SIRT1, SIRT3, and SIRT4 expression and clinical parameters. Conclusions: The findings of this study demonstrate elevated expression of SIRT1 and SIRT3 in the placentas of women with GDM. Further studies are required to confirm our observations and demonstrate the precise role of these enzymes in GDM. Full article

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

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14 pages, 777 KiB

Open AccessArticle

Increased Prevalence of Psychiatric Disorders in Children with RASopathies: Comparing NF1, Noonan Syndrome Spectrum Disorder, and the General Population

by Yaffa Serur, Odeya Russo, Chloe Alexa McGhee and Tamar Green

Genes 2025, 16(7), 843; https://doi.org/10.3390/genes16070843 - 19 Jul 2025

Viewed by 595

Abstract

Background/Objectives: Neurofibromatosis type 1 (NF1) and Noonan syndrome spectrum disorders (NSSD) are the most common RASopathies, resulting from germline mutations that affect the RAS-MAPK signaling pathway. Both are associated with increased risk for neurodevelopmental and psychiatric conditions, yet few studies have used [...] Read more.

Background/Objectives: Neurofibromatosis type 1 (NF1) and Noonan syndrome spectrum disorders (NSSD) are the most common RASopathies, resulting from germline mutations that affect the RAS-MAPK signaling pathway. Both are associated with increased risk for neurodevelopmental and psychiatric conditions, yet few studies have used structured diagnostic interviews to compare their psychiatric comorbidities. Methods: We conducted clinician-administered DSM-5 diagnostic assessments (KSADS) in 123 children with RASopathies (NF1 = 29, NSSD = 94; ages 5–15). Diagnosis prevalence was compared within each group and to population-based estimates. Results: Psychiatric diagnoses were highly prevalent, at 79.3% in NF1 and 76.6% in NSSD, with ADHD (NF1 = 72.4%, NSSD = 51.1%) and anxiety disorders (NF1 = 37.9% and NSSD = 43.6%) being the most common, rates substantially higher than those reported in general population estimates. Behavioral and sleep disorders were identified in approximately 25% of both groups. Notably, social anxiety disorder was identified in 14.9% of NSSD but not in NF1. Full-scale IQ did not significantly differ by diagnosis status. Specific anxiety disorders, elimination disorders, obsessive–compulsive disorder, and post-traumatic stress disorder were characterized, expanding the known psychiatric phenotype of RASopathies. Conclusions: Children with NF1 and NSSD demonstrate similarly high rates of ADHD, anxiety, and behavioral disorders compared to the general population; in addition, we report sleep disorders in NSSD and characterize psychiatric disorders not previously described in RASopathies. The shared psychiatric profiles may reflect the common effect of RAS-MAPK pathway dysregulation on psychiatric outcomes. These findings highlight the need for early, syndrome-informed mental health screening and intervention in the clinical care of individuals with RASopathies. Full article

(This article belongs to the Special Issue Phenotypic Variability of Genetic Diseases in Children)

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22 pages, 1846 KiB

Open AccessArticle

Structural and Genetic Diversity of Lysis Modules in Bacteriophages Infecting the Genus Streptococcus

by Mathilde Saint-Jean, Olivier Claisse, Claire Le Marrec and Johan Samot

Genes 2025, 16(7), 842; https://doi.org/10.3390/genes16070842 - 19 Jul 2025

Viewed by 274

Abstract

Background/Objectives: Bacteriophages infecting the genus Streptococcus play a crucial role in microbial ecology and have potential applications in biotechnology and medicine. Despite their importance, significant gaps remain in our understanding of their lysis modules. This study aims to address these deficiencies by [...] Read more.

Background/Objectives: Bacteriophages infecting the genus Streptococcus play a crucial role in microbial ecology and have potential applications in biotechnology and medicine. Despite their importance, significant gaps remain in our understanding of their lysis modules. This study aims to address these deficiencies by analyzing the genomic diversity and lysis module organization in Streptococcus phages. Methods: A search was conducted in the NCBI RefSeq database to identify phage genomes infecting Streptococcus. A representative panel was selected based on taxonomic diversity. Lysis modules were annotated and visualized, functional domains in endolysins were identified, and holins were characterized. Results: A total of 205 phage genomes were retrieved from the NCBI RefSeq database, of which 185 complete genomes were analyzed. A subset of 34 phages was selected for in-depth analysis, ensuring the representation of taxonomic diversity. The lysis modules were annotated and visualized, revealing five distinct organizations. Among the 256 identified endolysins, 25 distinct architectural organizations were observed, with amidase activity being the most prevalent. Holins were classified into 9 of the 74 families listed in the Transporter Classification Database, exhibiting one to three transmembrane domains. Conclusions: This study provides insights into the structural diversity of lysis modules in Streptococcus phages, paving the way for future research and potential biotechnological applications. Full article

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

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14 pages, 846 KiB

Open AccessArticle

Uncovering Allele-Specific Expression Patterns Associated with Sea Lice (Caligus rogercresseyi) Burden in Atlantic Salmon

by Pablo Cáceres, Paulina López, Carolina Araya, Daniela Cichero, Liane N. Bassini and José M. Yáñez

Genes 2025, 16(7), 841; https://doi.org/10.3390/genes16070841 - 19 Jul 2025

Viewed by 342

Abstract

Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain [...] Read more.

Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain unclear. Methods: two sea lice challenge trials were conducted, achieving high infestation rates (47.5% and 43.5%). A total of 85 fish, selected based on extreme phenotypes for lice burden (42 low, 43 high), were subjected to transcriptomic analysis. Differential gene expression was integrated with allele-specific expression (ASE) analysis to uncover cis-regulatory variation influencing host response. Results: Sixty genes showed significant ASE (p < 0.05), including 33 overexpressed and 27 underexpressed. Overexpressed ASE genes included Keratin 15, Collagen IV/V, TRIM16, and Angiopoietin-1-like, which are associated with epithelial integrity, immune response, and tissue remodeling. Underexpressed ASE genes such as SOCS3, CSF3R, and Neutrophil cytosolic factor suggest individual variation in cytokine signaling and oxidative stress pathways. Conclusions: several ASE genes co-localized with previously identified QTLs for sea lice resistance, indicating that cis-regulatory variants contribute to phenotypic differences in parasite susceptibility. These results highlight ASE analysis as a powerful tool to identify functional regulatory elements and provide valuable candidates for selective breeding and genomic improvement strategies in aquaculture. Full article

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

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19 pages, 259 KiB

Open AccessArticle

Dietary and Genetic Aspects of Polycystic Ovary Syndrome (PCOS) in Polish Women—Part II: Association of CYP19, FTO, MC4R and INSR Gene Polymorphisms with Clinical Symptoms of PCOS

by Karolina Nowosad, Małgorzata Ostrowska, Paweł Glibowski, Katarzyna Iłowiecka and Wojciech Koch

Genes 2025, 16(7), 840; https://doi.org/10.3390/genes16070840 - 18 Jul 2025

Viewed by 490

Abstract

Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial disorder influenced by both environmental and genetic factors. The aim of this study was to evaluate associations between selected polymorphisms (CYP19, INSR, FTO, MC4R) and the clinical manifestations of PCOS [...] Read more.

Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial disorder influenced by both environmental and genetic factors. The aim of this study was to evaluate associations between selected polymorphisms (CYP19, INSR, FTO, MC4R) and the clinical manifestations of PCOS in a Polish female population. Methods: A total of 50 women (25 with PCOS and 25 healthy controls) were included. Genetic variants were identified using Polymerase Chain Reaction (PCR)-based methods. The frequencies of genotypes and alleles were compared between groups. Clinical symptoms such as irregular menstruation, hirsutism, acne, androgenetic alopecia, and overweight were assessed in relation to genotype. Results: No significant differences were found in genotype distributions for CYP19, FTO, INSR, or MC4R between PCOS and control groups. The MC4R polymorphisms showed deviations from Hardy–Weinberg equilibrium, possibly reflecting population-specific effects. Conclusions: Although most analyzed variants were not directly associated with PCOS in this cohort, the observed link between INSR rs1799817 and acne suggests a role in androgen-related symptoms. These findings contribute new insights to the genetic background of PCOS in Polish women and support the need for further studies combining genetic and phenotypic data in diverse populations. Full article

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

13 pages, 2351 KiB

Open AccessArticle

Transcriptomic Profiling Reveals Gene Expression Changes in Mouse Liver Tissue During Alveolar Echinococcosis

by Xiongying Zhang, Qing Zhang, Na Liu, Jia Liu, Huixia Cai, Cunzhe Zhao, Kemei Shi, Wen Lei, Wanli Ma, Shuai Guo, Wei Wang, Xiao Ma and Mei Wang

Genes 2025, 16(7), 839; https://doi.org/10.3390/genes16070839 - 18 Jul 2025

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Abstract

Background/Objectives: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, poses a significant global health concern. Primarily affecting regions in the northern hemisphere, such as northwest China, which are vital for animal husbandry, it often results in severe hepatic impairment in the host. However, [...] Read more.

Background/Objectives: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, poses a significant global health concern. Primarily affecting regions in the northern hemisphere, such as northwest China, which are vital for animal husbandry, it often results in severe hepatic impairment in the host. However, there remains a dearth of knowledge concerning changes in gene expression profiles during the progression of AE. In this study, we employed transcriptome sequencing (RNA sequencing, RNA-Seq) to detect alterations in gene expression profiles in the liver tissues of mice with AE. Our aims were to understand the transcriptome differences in the liver during E. multilocularis infection and to explore the molecular mechanisms underlying the early progression of this disease. Methods: We established a mouse model of AE by intraperitoneally injecting protoscoleces of E. multilocularis. All the inoculated mice were randomly divided into four groups. Liver tissues were collected at 6, 12, 19, and 25 weeks after inoculation. Paired non-infected mouse-derived liver tissues were used as controls, and transcriptome sequencing was carried out. Results: A total of 629 differentially expressed genes (DEGs) were identified. Among them, 370 genes were upregulated and 259 genes were downregulated. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were significantly associated with immune system modulation, the cell cycle, and the fibrosis process during the pathological changes. Additionally, weighted gene co-expression network analysis (WGCNA) identified several genes, including CCNA2, BIRC5, KIF2C, OTC, TLR2, and NCKAP1L. These hub genes involved in immunoinflammatory processes may be related to E. multilocularis larvae infection. Conclusions: The findings of this research provide a theoretical foundation for a more in-depth understanding of the molecular mechanisms of AE. They offer valuable insights into the molecular mechanisms and potential key factors involved in the pathogenesis of this disease. Full article

(This article belongs to the Special Issue Utilizing High-Throughput Sequencing and Deep Learning to Uncover Disease Epigenetic Mechanisms)

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8 pages, 613 KiB

Open AccessCase Report

Homozygous DHCR7 p.Val330Met Variant Associated with Mild Non-Syndromic Intellectual Disability and Elevated Serum 7-Dehydrocholesterol Levels in Two Siblings

by Lukas Hackl, Edda Haberlandt, Thomas Müller, Susanne Piribauer, Dorota Garczarczyk-Asim, Thomas Zöggeler, Daniela Karall, Johannes Zschocke and Andreas R. Janecke

Genes 2025, 16(7), 838; https://doi.org/10.3390/genes16070838 - 18 Jul 2025

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Abstract

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith–Lemli–Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2–3 [...] Read more.

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith–Lemli–Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2–3 toe syndactyly. Additional congenital malformations may be present in SLOS, and broad clinical variability has been recognized in SLOS. Rarely, biallelic pathogenic DHCR7 variants were reported with low-normal and normal intelligence quotient (IQ) and development. We report here a pair of siblings with mild global developmental delay, infrequent epileptic seizures, and elevated serum 7-DHC levels, associated with the homozygous DHCR7 variant c.988G>A (p.Val330Met). Remarkably, neither sibling displayed congenital anomalies nor dysmorphisms. Quattro-exome sequencing performed for global delay and mild ID in both siblings did not identify other ID causes. c.988G>A affects a highly conserved amino acid and displays a relatively high global population allele frequency of 0.04%, with absence of homozygotes from the population database gnomADv4.1.0. Our observation leads us to suggest that DHCR7 variant c.988G>A and other DHCR7 variants might be generally considered as underlying non-syndromic ID. Full article

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

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14 pages, 2355 KiB

Open AccessArticle

Rainbow Trout (Oncorhynchus mykiss) Spleen-Derived Bioactive Compounds Suppress Pro-Inflammatory Gene Networks via NF-κB Pathway Modulation

by Do-Yeon Kim, Woo-Sung Choi, Ju-Hee Park, Seoghyun Kim, Jinyoung Park, Woohyun Song, Heejung Yang, Han-Heom Na and Keun-Cheol Kim

Genes 2025, 16(7), 837; https://doi.org/10.3390/genes16070837 - 18 Jul 2025

Viewed by 283

Abstract

Background: Natural products are key sources of anti-inflammatory agents, yet the potential of fish visceral extracts remains largely unexplored. This study evaluated the anti-inflammatory activity of a spleen extract from rainbow trout (Oncorhynchus mykiss). Methods: A crude spleen extract [...] Read more.

Background: Natural products are key sources of anti-inflammatory agents, yet the potential of fish visceral extracts remains largely unexplored. This study evaluated the anti-inflammatory activity of a spleen extract from rainbow trout (Oncorhynchus mykiss). Methods: A crude spleen extract and its four solvent fractions were tested in LPS-stimulated RAW264.7 macrophages. Nitric oxide production and expression of iNOS, COX-2, and cytokines were assessed by qRT-PCR and Western blotting. The most active fraction, OSB (n-butanol layer), was further analyzed for its effects on NF-κB signaling, macrophage polarization, and ROS generation. Results: The crude spleen extract significantly reduced NO production and downregulated iNOS and COX-2 expression at both the transcriptional and translational levels. Among the four fractions, the OSB fraction exhibited the most potent and consistent anti-inflammatory effects. OSB markedly suppressed LPS-induced expression of iNOS, COX-2, and pro-inflammatory cytokines, while enhancing anti-inflammatory cytokines. Mechanistic analyses demonstrated that OSB inhibited NF-κB activation by preventing the nuclear translocation of the p65 subunit. Additionally, OSB attenuated LPS-induced ROS production and reduced the expression of M1 macrophage markers, indicating inhibition of M1 polarization. Conclusions: The OSB fraction from rainbow trout spleen exhibits potent anti-inflammatory activity by modulating the NF-κB pathway and suppressing M1 macrophage polarization, suggesting its potential as a natural therapeutic agent. Full article

(This article belongs to the Special Issue 15th Anniversary of Genes: Feature Papers in the “Molecular Genetics and Genomics” Section)

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23 pages, 15440 KiB

Open AccessArticle

Diversity and Correlation Analysis of Differential Amino Acid Metabolites and Dominant Endophytic Bacteria in Lycium chinense Fruits at Different Stages

by Chongxin Yin, Huichun Xie, Xiaoli Yang, Lianyu Zhou, Guigong Geng and Feng Qiao

Genes 2025, 16(7), 836; https://doi.org/10.3390/genes16070836 - 18 Jul 2025

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Abstract

Background: Lycium chinense has been acknowledged for its substantial nutritional benefits. The “Mengqi No.1” variety of L. chinense is known for its high yield and exceptional quality. Methods: We screened twenty dominant endophytic bacterial genera based on OTUs from L. [...] Read more.

Background: Lycium chinense has been acknowledged for its substantial nutritional benefits. The “Mengqi No.1” variety of L. chinense is known for its high yield and exceptional quality. Methods: We screened twenty dominant endophytic bacterial genera based on OTUs from L. chinense fruits during three developmental stages. Results: Forty-three differential amino acid metabolites were selected from L. chinense fruits. Five endophytic bacteria (Enterococcus, Escherichia-Shigella, Bacteroides, Pseudomonas, and Bacillus) were dominant genera in green fruit (GF, 16–19 days after flowering), color-changing fruit (CCF, 22–25 days after flowering), and red-ripe fruit (RRF, 31–34 days after flowering). Four endophytic bacterial genera (Enterococcus, Bacillus, Pseudomonas, and Rhodanobacter) showed positive correlation with twenty different amino acid metabolites and negative correlation with seven different amino acid metabolites. Conclusions: Five genes (AST1, ltaE1, TAT1, SHMT2, and SHMT3) indicated positive correlation with seventeen different amino acid metabolites and negative correlation with eight different amino acid metabolites. AST1 gene had a major role in regulating arginine biosynthesis (ko00220); ltaE1, SHMT2, and SHMT3 genes were major in regulating glycine, serine, and threonine metabolism (ko00260); and TAT1 gene had a major role in regulating tyrosine metabolism (ko00350). These findings offer insights into the relationship between amino acid synthesis and endophytic bacteria in L. chinense fruits. Full article

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

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13 pages, 987 KiB

Open AccessArticle

Clinical and Genetic Characteristics of Senior-Loken Syndrome Patients in Korea

by Jae Ryong Song, Sangwon Jung, Kwangsic Joo, Hoon Il Choi, Yoon Jeon Kim and Se Joon Woo

Genes 2025, 16(7), 835; https://doi.org/10.3390/genes16070835 - 17 Jul 2025

Viewed by 324

Abstract

Background/Objectives: Senior-Loken syndrome (SLS) is a rare autosomal recessive renal–retinal disease caused by mutations in 10 genes. This study aimed to review the ophthalmic findings, renal function, and genotypes of Korean SLS cases. Methods: We retrospectively reviewed 17 genetically confirmed SLS [...] Read more.

Background/Objectives: Senior-Loken syndrome (SLS) is a rare autosomal recessive renal–retinal disease caused by mutations in 10 genes. This study aimed to review the ophthalmic findings, renal function, and genotypes of Korean SLS cases. Methods: We retrospectively reviewed 17 genetically confirmed SLS patients in Korea, including 9 newly identified cases and 8 previously reported. Comprehensive ophthalmologic evaluations and renal assessments were conducted. Genetic testing was performed using whole-genome sequencing (WGS), whole-exome sequencing (WES), or Sanger sequencing. Results: Among the 17 patients, patients with NPHP1 mutations were most common (35.3%), followed by those with NPHP4 (29.4%), IQCB1 (NPHP5, 29.4%), and SDCCAG8 (NPHP10, 5.9%) mutations. Patients with NPHP1 mutations showed retinitis pigmentosa (RP) sine pigmento and preserved central vision independent of renal deterioration. Patients with NPHP4 mutations showed early renal dysfunction. Two patients aged under 20 maintained relatively good visual function, but older individuals progressed to severe retinopathy. Patients with IQCB1 mutations were generally prone to early and severe retinal degeneration, typically manifesting as Leber congenital amaurosis (LCA) (three patients), while two patients exhibited milder RP sine pigmento with preserved central vision. Notably, two out of five (40.0%) maintained normal renal function at the time of diagnosis, and both had large deletions in IQCB1. The patient with SDCCAG8 mutation exhibited both end-stage renal disease and congenital blindness due to LCA. Wide-field fundus autofluorescence (AF) revealed perifoveal and peripapillary hypoAF with a perifoveal hyperAF in younger patients across genotypes. Patients under 20 years old showed relatively preserved central vision, regardless of the underlying genetic mutation. Conclusions: The clinical manifestation of renal and ocular impairment demonstrated heterogeneity among Korean SLS patients according to causative genes, and the severity of renal dysfunction and visual decline was not correlated. Therefore, simultaneous comprehensive evaluations of both renal and ocular function should be performed at the initial diagnosis to guide timely intervention and optimize long-term outcomes. Full article

(This article belongs to the Special Issue Study of Inherited Retinal Diseases—Volume II)

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17 pages, 5077 KiB

Open AccessArticle

Genomic Features and Tissue Expression Profiles of the Tyrosinase Gene Family in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

by Yanchao Liu, Pan Liu, Tong Ren, Yang Gao, Ziman Wang, Junxian Zhu, Chen Chen, Liqin Ji, Xiaoyou Hong, Xiaoli Liu, Chengqing Wei, Xinping Zhu, Zhangjie Chu and Wei Li

Genes 2025, 16(7), 834; https://doi.org/10.3390/genes16070834 - 17 Jul 2025

Viewed by 290

Abstract

In farmed animals, body color is not only an ecological trait but also an important trait that influences the commercial value of the animals. Melanin plays an important role in the formation of body color in animals, while the tyrosinase (TYR) gene family is [...] Read more.

In farmed animals, body color is not only an ecological trait but also an important trait that influences the commercial value of the animals. Melanin plays an important role in the formation of body color in animals, while the tyrosinase (TYR) gene family is a group of key enzymes that regulate melanogenesis. The Chinese soft-shelled turtle (Pelodiscus sinensis) is one of the most important reptiles in freshwater aquaculture. However, the potential role of the TYR gene family in the body color formation of P. sinensis remains unclear. This study aimed to investigate the expression and conservation of the TYR gene family in relation to body color variation in P. sinensis. Three core members of this gene family were identified from the P. sinensis genome. Following identification, the genomic features were analyzed. They shared similar physicochemical properties and conserved domains. Chromosome mapping showed that the three genes of P. sinensis were all located on the autosomes, while phylogenetic and collinearity analysis suggested that the protein functions of the three genes in the studied species were highly conserved. Amino acid sequence alignment indicated high conservation among the three TYR gene family proteins (TYR, TYRP1, and DCT) in multiple critical regions, particularly in their hydrophobic N-/C-terminal regions and cysteine/histidine-rich conserved domains. The qRT-PCR revealed that the TYR and DCT genes were highly expressed in the eyes of individuals with different body colors. The expression levels of TYR and TYRP1 genes in the skin were significantly higher in dark-colored individuals than in light-colored ones (p < 0.05). These results will lay the groundwork for functional studies and breeding programs targeting color traits in aquaculture. Full article

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

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14 pages, 2957 KiB

Open AccessArticle

Patchy Phylogenetic Distribution and Poor Translational Adaptation of a Nested ORF in the Mammalian Mitochondrial cytb Gene

by Sheng-Lin Shi, Dan-Tong Li and Yan-Qun Liu

Genes 2025, 16(7), 833; https://doi.org/10.3390/genes16070833 - 17 Jul 2025

Viewed by 246

Abstract

Background: The mammalian mitochondrial genome has long been considered to encode only 13 proteins. However, a recent study identified a nested alternative open reading frame (nAltORF) within the primate mitochondrial cytb gene, which we designate ncytb, that is reportedly translated in the [...] Read more.

Background: The mammalian mitochondrial genome has long been considered to encode only 13 proteins. However, a recent study identified a nested alternative open reading frame (nAltORF) within the primate mitochondrial cytb gene, which we designate ncytb, that is reportedly translated in the cytosol using the standard genetic code. This discovery challenges conventional understanding and raises questions about the prevalence, conservation, and translational adaptation of such ORFs. Methods: This study conducted a comprehensive bioinformatic analysis of nested ncytb genes in 289 primate and 380 rodent mitochondrial cytb sequences. Results: Nested ncytb genes meeting the criteria (>150 codons, standard genetic code) were identified in only 10.73% of primate and 20.53% of rodent species, suggesting a patchy phylogenetic distribution. While their encoded proteins showed homology to the previously reported protein encoded by the Homo sapiens nested ncytb gene, overall amino acid conservation was low, and characteristic protein domains or signal peptides were generally not predicted. Crucially, the Kozak consensus sequences surrounding the putative start codons of these ncytb genes were exclusively “weak” or “adequate”, with none classified as “strong” or “optimal”. Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) analyses of the nested ncytb genes revealed neither significant adaptation nor deoptimization to the codon usage of nuclear and mitochondrial genes. Furthermore, cosine similarity analysis indicated that ncytb genes exhibit significantly lower codon usage similarity to both nuclear and mitochondrial gene sets compared to their host cytb genes. Conclusions: These findings collectively suggest that while ncytb genes exist in some mammals, their inconsistent presence, weak translational initiation signals, and lack of adaptation to cytosolic codon usage characterize them as dispensable genetic elements rather than core functional genes. Full article

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

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18 pages, 7084 KiB

Open AccessArticle

Analysis of Key miRNA/mRNA Functional Axes During Host Dendritic Cell Immune Response to Mycobacterium tuberculosis Based on GEO Datasets

by Qian Gao, Shuangshuang Bao, Yaqi Sun, Kaixin Zhou and Yan Lin

Genes 2025, 16(7), 832; https://doi.org/10.3390/genes16070832 - 17 Jul 2025

Viewed by 321

Abstract

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology [...] Read more.

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

(This article belongs to the Section Bioinformatics)

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12 pages, 1279 KiB

Open AccessArticle

Discovery of Germplasm Resources and Molecular Marker-Assisted Breeding of Oilseed Rape for Anticracking Angle

by Cheng Zhu, Zhi Li, Ruiwen Liu and Taocui Huang

Genes 2025, 16(7), 831; https://doi.org/10.3390/genes16070831 - 17 Jul 2025

Viewed by 314

Abstract

Introduction: Scattering of kernels due to angular dehiscence is a key bottleneck in mechanized harvesting of oilseed rape. Materials and Methods: In this study, a dual-track “genotype–phenotype” screening strategy was established by innovatively integrating high-throughput KASP molecular marker technology and a standardized random [...] Read more.

Introduction: Scattering of kernels due to angular dehiscence is a key bottleneck in mechanized harvesting of oilseed rape. Materials and Methods: In this study, a dual-track “genotype–phenotype” screening strategy was established by innovatively integrating high-throughput KASP molecular marker technology and a standardized random collision phenotyping system for the complex quantitative trait of angular resistance. Results: Through the systematic evaluation of 634 oilseed rape hybrid progenies, it was found that the KASP marker S12.68, targeting the cleavage resistance locus (BnSHP1) on chromosome C9, achieved a 73.34% introgression rate (465/634), which was significantly higher than the traditional breeding efficiency (<40%). Phenotypic characterization screened seven excellent resources with cracking resistance index (SRI) > 0.6, of which four reached the high resistance standard (SRI > 0.8), including the core materials NR21/KL01 (SRI = 1.0) and YuYou342/KL01 (SRI = 0.97). Six breeding intermediate materials (44.7–48.7% oil content, mycosphaerella resistance MR grade or above) were created, combining high resistance to chipping and excellent agronomic traits. For the first time, it was found that local germplasm YuYou342 (non-KL01-derived line) was purely susceptible at the S12.68 locus (SRI = 0.86), but its angiosperm vascular bundles density was significantly increased by 37% compared with that of the susceptible material 0911 (p < 0.01); and the material 187308 (SRI = 0.78), although purely susceptible at S12.68, had a 2.8-fold downregulation in expression of the angiosperm-related gene, BnIND1, and a 2.8-fold downregulation of expression of the angiosperm-related gene, BnIND1. expression was significantly downregulated 2.8-fold (q < 0.05), indicating the existence of a novel resistance mechanism independent of the primary effector locus. Conclusions: The results of this research provide an efficient technical platform and breakthrough germplasm resources for oilseed rape crack angle resistance breeding, which is of great practical significance for promoting the whole mechanized production. Full article

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

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12 pages, 3331 KiB

Open AccessArticle

Oral Undifferentiated Pleomorphic Sarcoma: A Novel SPECC1L::TERT Gene Fusion and a Comprehensive Literature Review

by Mario Della Mura, Joana Sorino, Eugenio Maiorano, Gerardo Cazzato, Anna Colagrande, Alfonso Manfuso, Concetta Caporusso, Chiara Copelli and Eliano Cascardi

Genes 2025, 16(7), 830; https://doi.org/10.3390/genes16070830 - 17 Jul 2025

Viewed by 310

Abstract

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare, high-grade soft-tissue sarcoma characterized by a patternless proliferation of bizarre pleomorphic tumor cells lacking identifiable lineage differentiation. Its occurrence in the oral cavity is exceptionally uncommon and poses significant diagnostic challenges due to its morphological [...] Read more.

Background: Undifferentiated pleomorphic sarcoma (UPS) is a rare, high-grade soft-tissue sarcoma characterized by a patternless proliferation of bizarre pleomorphic tumor cells lacking identifiable lineage differentiation. Its occurrence in the oral cavity is exceptionally uncommon and poses significant diagnostic challenges due to its morphological overlap with a wide spectrum of other malignancies. Material and Methods: We report a novel case of oral UPS in a 54-year-old woman, characterized by an exceptionally large size and a rapidly progressive clinical course. The diagnostic evaluation included clinical, radiological, histopathological, immunohistochemical, and molecular analyses conducted within a multidisciplinary framework. A comprehensive review of the literature on oral UPS was also performed. Results: The patient underwent an aggressive demolitive surgical approach due to the extent of the lesion. Molecular analysis revealed a previously unreported SPECC1L::TERT gene fusion. The literature review highlighted the rarity of oral UPS, its geographic predilection for Central and East Asia, possible associations with traumatic events, and its heterogeneous clinical and histopathological presentations. Conclusions: This case underscores the critical importance of a thorough diagnostic workup to ensure the accurate diagnosis and appropriate management of this rare and aggressive tumor. Multidisciplinary evaluation is essential, especially in anatomically complex and diagnostically challenging presentations such as oral UPS. Full article

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

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20 pages, 2008 KiB

Open AccessArticle

Transcriptomic Profiling of Gastric Cancer Reveals Key Biomarkers and Pathways via Bioinformatic Analysis

by Ipek Balikci Cicek and Zeynep Kucukakcali

Genes 2025, 16(7), 829; https://doi.org/10.3390/genes16070829 - 16 Jul 2025

Viewed by 393

Abstract

Background/Objectives: Gastric cancer (GC) remains a significant global health burden due to its high mortality rate and frequent diagnosis at advanced stages. This study aimed to identify reliable diagnostic biomarkers and elucidate molecular mechanisms underlying GC by integrating transcriptomic data from independent platforms [...] Read more.

Background/Objectives: Gastric cancer (GC) remains a significant global health burden due to its high mortality rate and frequent diagnosis at advanced stages. This study aimed to identify reliable diagnostic biomarkers and elucidate molecular mechanisms underlying GC by integrating transcriptomic data from independent platforms and applying machine learning techniques. Methods: Two transcriptomic datasets from the Gene Expression Omnibus were analyzed: GSE26899 (microarray, n = 108) as the discovery dataset and GSE248612 (RNA-seq, n = 12) for validation. Differential expression analysis was conducted using limma and DESeq2, selecting genes with |log2FC| > 1 and adjusted p < 0.05. The top 200 differentially expressed genes (DEGs) were used to develop machine learning models (random forest, logistic regression, neural networks). Functional enrichment analyses (GO, KEGG, Hallmark) were applied to explore relevant biological pathways. Results: In GSE26899, 627 DEGs were identified (201 upregulated, 426 downregulated), with key genes including CST1, KIAA1199, TIMP1, MSLN, and ATP4A. The random forest model demonstrated excellent classification performance (AUC = 0.952). GSE248612 validation yielded 738 DEGs. Cross-platform comparison confirmed 55.6% concordance among core genes, highlighting CST1, TIMP1, KRT17, ATP4A, CHIA, KRT16, and CRABP2. Enrichment analyses revealed involvement in ECM–receptor interaction, PI3K-Akt signaling, EMT, and cell cycle. Conclusions: This integrative transcriptomic and machine learning framework effectively identified high-confidence biomarkers for GC. Notably, CST1, TIMP1, KRT16, and ATP4A emerged as consistent, biologically relevant candidates with strong diagnostic performance and potential clinical utility. These findings may aid early detection strategies and guide future therapeutic developments in gastric cancer. Full article

(This article belongs to the Special Issue Machine Learning in Cancer and Disease Genomics)

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12 pages, 2078 KiB

Open AccessArticle

Four Mitochondrial Genomes of Buprestinae (Coleoptera: Buprestidae) and Phylogenetic Analyses

by Yingying Li, Jieqiong Wang, Bowen Ouyang, Zhonghua Wei and Aimin Shi

Genes 2025, 16(7), 828; https://doi.org/10.3390/genes16070828 - 16 Jul 2025

Viewed by 304

Abstract

Background: The family Buprestidae is one of the largest families in Coleoptera; however, the number of reported mitochondrial genomes for this family is limited. Methods: In this study, mitogenomes of Chrysobothris violacea, C. shirakii, Buprestis fairmairei, and Phaenops yin were sequenced, [...] Read more.

Background: The family Buprestidae is one of the largest families in Coleoptera; however, the number of reported mitochondrial genomes for this family is limited. Methods: In this study, mitogenomes of Chrysobothris violacea, C. shirakii, Buprestis fairmairei, and Phaenops yin were sequenced, assembled, and annotated. The mitogenomes of Chrysobothris, Phaenops, and Buprestis are reported for the first time. Results: The mitogenomes of Chrysobothris violacea, C. shirakii, and Phaenops yin are complete, while the mitogenome of Buprestis fairmairei is partial, lacking trnV and 12S genes. The AT-skew of these four mitogenomes is positive (0.02–0.09). Among the protein-coding genes, the Ka/Ks ratio for cox1 is the lowest (0.05), and the nucleotide diversity for nd6 is the highest. Conclusions: The phylogenetic trees based on mitogenome sequences suggest that the target genus Chrysobothris is sister to Phaenops, and the target genus Buprestis is sister to (Melanophila + (Chrysobothris + Phaenops)) clade. The results of this study will provide mitogenomic data for further research on the mitogenome and phylogeny of Buprestidae. Full article

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

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26 pages, 1270 KiB

Open AccessArticle

Boosting Genomic Prediction Transferability with Sparse Testing

by Osval A. Montesinos-López, Jose Crossa, Paolo Vitale, Guillermo Gerard, Leonardo Crespo-Herrera, Susanne Dreisigacker, Carolina Saint Pierre, Iván Delgado-Enciso, Abelardo Montesinos-López and Reka Howard

Genes 2025, 16(7), 827; https://doi.org/10.3390/genes16070827 - 16 Jul 2025

Viewed by 291

Abstract

Background/Objectives: Improving sparse testing is essential for enhancing the efficiency of genomic prediction (GP). Accordingly, new strategies are being explored to refine genomic selection (GS) methods under sparse testing conditions. Methods: In this study, a sparse testing approach was evaluated, specifically in the [...] Read more.

Background/Objectives: Improving sparse testing is essential for enhancing the efficiency of genomic prediction (GP). Accordingly, new strategies are being explored to refine genomic selection (GS) methods under sparse testing conditions. Methods: In this study, a sparse testing approach was evaluated, specifically in the context of predicting performance for tested lines in untested environments. Sparse testing is particularly practical in large-scale breeding programs because it reduces the cost and logistical burden of evaluating every genotype in every environment, while still enabling accurate prediction through strategic data use. To achieve this, we used training data from CIMMYT (Obregon, Mexico), along with partial data from India, to predict line performance in India using observations from Mexico. Results: Our results show that incorporating data from Obregon into the training set improved prediction accuracy, with greater effectiveness when the data were temporally closer. Across environments, Pearson’s correlation improved by at least 219% (in a testing proportion of 50%), while gains in the percentage of matching in top 10% and 20% of top lines were 18.42% and 20.79%, respectively (also in a testing proportion of 50%). Conclusions: These findings emphasize that enriching training data with relevant, temporally proximate information is key to enhancing genomic prediction performance; conversely, incorporating unrelated data can reduce prediction accuracy. Full article

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

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3 pages, 144 KiB

Open AccessEditorial

Editorial for the Special Issue “Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding”

by Xiukai Cao

Genes 2025, 16(7), 826; https://doi.org/10.3390/genes16070826 - 16 Jul 2025

Viewed by 226

Abstract

The landscape of livestock breeding has dramatically shifted with the rise of molecular genetics, offering unprecedented insights into the genomic underpinnings of complex traits in domesticated animals [...] Full article

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

12 pages, 1781 KiB

Open AccessArticle

Detecting Methylation Changes Induced by Prime Editing

by Ronin Joshua S. Cosiquien, Isaiah J. Whalen, Phillip Wong, Ryan J. Sorensen, Anala V. Shetty, Shun-Qing Liang and Clifford J. Steer

Genes 2025, 16(7), 825; https://doi.org/10.3390/genes16070825 - 15 Jul 2025

Viewed by 257

Abstract

While prime editing offers improved precision compared to traditional CRISPR-Cas9 systems, concerns remain regarding potential off-target effects, including epigenetic changes such as DNA methylation. In this study, we investigated whether prime editing induces aberrant CpG methylation patterns. Whole-genome bisulfite sequencing revealed overall methylation [...] Read more.

While prime editing offers improved precision compared to traditional CRISPR-Cas9 systems, concerns remain regarding potential off-target effects, including epigenetic changes such as DNA methylation. In this study, we investigated whether prime editing induces aberrant CpG methylation patterns. Whole-genome bisulfite sequencing revealed overall methylation similarity between Cas9-edited, and PE2-edited cells. However, localized epigenetic changes were observed, particularly in CpG islands and exon regions. The PE2-edited group showed a higher proportion of differentially methylated regions (DMRs) in some coding sequences compared to controls and Cas9-edited samples. Notably, CpG island methylation reached 0.18% in the PE2 vs. Cas9 comparison, indicating a higher susceptibility of these regulatory elements to epigenetic alterations by prime editing. Molecular function analyses including Gene Ontology and KEGG pathway analyses further revealed enrichment in molecular functions related to transcriptional regulation and redox activity in PE2-edited cells. These findings suggest that prime editing, while precise, may introduce subtle but functionally relevant methylation changes that could influence gene expression and cellular pathways. In summary, prime editing can induce localized DNA methylation changes in human cells, particularly within regulatory and coding regions. Understanding these epigenetic consequences is critical for the development of safer and more effective therapeutic applications of genome editing technologies. Full article

(This article belongs to the Special Issue Gene Editing Techniques for Neurodegenerative Diseases)

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12 pages, 5644 KiB

Open AccessArticle

A Subset of HOX Genes Negatively Correlates with HOX/PBX Inhibitor Target Gene Expression and Is Associated with Apoptosis, DNA Repair, and Metabolism in Prostate Cancer

by Richard Morgan, Christopher Smith and Hardev Pandha

Genes 2025, 16(7), 824; https://doi.org/10.3390/genes16070824 - 15 Jul 2025

Viewed by 317

Abstract

Background/Objectives: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to [...] Read more.

Background/Objectives: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including Fos, DUSP1, and ATF3, which are otherwise repressed by HOX/PBX binding. Methods: We analyzed publicly available transcriptomic data in the R2 platform. Results: We show that a specific subgroup of HOX genes is negatively correlated with Fos, DUSP1, and ATF3 expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of HOX genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of HOX expression in normal peripheral blood cells. Conclusions: Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer. Full article

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

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14 pages, 12948 KiB

Open AccessArticle

Phylogenetic Analyses and Plastome Comparison to Confirm the Taxonomic Position of Ligusticum multivittatum (Apiaceae, Apioideae)

by Changkun Liu, Boni Song, Feng Yong, Chengdong Xu, Quanying Dong, Xiaoyi Wang, Chao Sun and Zhenji Wang

Genes 2025, 16(7), 823; https://doi.org/10.3390/genes16070823 - 14 Jul 2025

Viewed by 266

Abstract

Background: Ligusticum L. plants exhibit significant morphological variation in leaves, flowers, bracteoles and mericarps, thus the classifications of members for the genus have always been controversial. Among them, the taxonomic problem of Ligusticum multivittatum Franch. is the most prominent, which has not been [...] Read more.

Background: Ligusticum L. plants exhibit significant morphological variation in leaves, flowers, bracteoles and mericarps, thus the classifications of members for the genus have always been controversial. Among them, the taxonomic problem of Ligusticum multivittatum Franch. is the most prominent, which has not been sufficiently resolved so far. Methods: to clarify the taxonomic position of Ligusticum multivittatum, we performed phylogenetic analyses based on plastome data and ITS sequences. Meanwhile, we conducted comprehensively comparative plastome analyses between Ligusticum multivittatum and fifteen Ligusticopsis species. Results: Both analyses robustly supported that Ligusticum multivittatum nested in genus Ligusticopsis Leute and formed a clade with fifteen Ligusticopsis species, belonged to the Selineae tribe, which was distant from the type species of Ligusticum (Ligusticum scoticum), located in the Acronema clade.The comparative results showed that sixteen plastomes were highly similar and conservative in genome structure, size, gene content and arrangement, codon bias, SSRs and SC/IR. These findings imply that Ligusticum multivittatum is a member of Ligusticopsis, which was further verified by their shared morphological characters: stem base clothed in fibrous remnant sheaths, white petals, pinnate bracteoles, dorsally compressed mericarps with slightly prominent dorsal ribs, winged lateral ribs and numerous vittae in the commissure and in each furrow. Therefore, combining with the evidences of phylogenetic analyses, plastome comparison and morphological features, we affirmed that Ligusticum multivittatum indeed belonged to Ligusticopsis and transformed it into Ligusticopsis conducted by Pimenov was reasonable. Conclusions: Our study not only confirms the classification of Ligusticum multivittatum by integrating evidences, but also provides a reference for resolving taxonomy of contentious taxa. Full article

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

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19 pages, 4493 KiB

Open AccessArticle

Integrating Imaging and Genomics in Amelogenesis Imperfecta: A Novel Diagnostic Approach

by Tina Leban, Aleš Fidler, Katarina Trebušak Podkrajšek, Alenka Pavlič, Tine Tesovnik, Barbara Jenko Bizjan, Blaž Vrhovšek, Robert Šket and Jernej Kovač

Genes 2025, 16(7), 822; https://doi.org/10.3390/genes16070822 - 14 Jul 2025

Viewed by 343

Abstract

Background/Objectives: Amelogenesis imperfecta (AI) represents a heterogeneous group of inherited disorders affecting the quality and quantity of dental enamel, making clinical diagnosis challenging. This study aimed to identify genetic variants in Slovenian patients with non-syndromic AI and to evaluate enamel morphology using radiographic [...] Read more.

Background/Objectives: Amelogenesis imperfecta (AI) represents a heterogeneous group of inherited disorders affecting the quality and quantity of dental enamel, making clinical diagnosis challenging. This study aimed to identify genetic variants in Slovenian patients with non-syndromic AI and to evaluate enamel morphology using radiographic parameters. Methods: Whole exome sequencing (WES) was performed on 24 AI patients and their families. Panoramic radiographs (OPTs) were analyzed using Fiji ImageJ to assess crown dimensions, enamel angle (EA), dentine angle (DA), and enamel–dentine mineralization ratio (EDMR) in lower second molar buds, compared to matched controls (n = 24). Two observers independently assessed measurements, and non-parametric tests compared EA, DA, and EDMR in patients with and without disease-causing variants (DCVs). Statistical models, including bootstrap-validated random forest and logistic regression, assessed variable influences. Results: DCVs were identified in ENAM (40% of families), AMELX (15%), and MMP20 (10%), including four novel variants. AI patients showed significant enamel deviations with high reproducibility, particularly in hypomineralized and hypoplastic regions. DA and EDMR showed significant correlations with DCVs (p < 0.01). A bootstrap-validated random forest model yielded a 90% (84.0–98.0%) AUC-estimated predictive power. Conclusions: These findings highlight a novel and reproducible radiographic approach for detecting developmental enamel defects in AI and support its diagnostic potential. Full article

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

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18 pages, 7687 KiB

Open AccessArticle

Construction of Gene Regulatory Networks Based on Spatial Multi-Omics Data and Application in Tumor-Boundary Analysis

by Yiwen Du, Kun Xu, Siwen Zhang, Lanming Chen, Zhenhao Liu and Lu Xie

Genes 2025, 16(7), 821; https://doi.org/10.3390/genes16070821 - 13 Jul 2025

Viewed by 701

Abstract

Background/Objectives: Cell–cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN). [...] Read more.

Background/Objectives: Cell–cell communication (CCC) is a critical process within the tumor microenvironment, governing regulatory interactions between cancer cells and other cellular subpopulations. Aiming to improve the accuracy and completeness of intercellular gene-regulatory network inference, we constructed a novel spatial-resolved gene-regulatory network framework (spGRN). Methods: Firstly, the spatial multi-omics data of colorectal cancer (CRC) patients were analyzed. We precisely located the tumor boundaries and then systematically constructed the spGRN framework to study the network regulation. Subsequently, the key signaling molecules obtained by the spGRN were identified and further validated by the spatial-proteomics dataset. Results: Through the constructed spatial gene regulatory network, we found that in the communication with malignant cells, the highly expressed ligands LIF and LGALS3BP and receptors IL6ST and ITGB1 in fibroblasts can promote tumor proliferation, and the highly expressed ligands S100A8/S100A9 in plasma cells play an important role in regulating inflammatory responses. Further, validation of the key signaling molecules by the spatial-proteomics dataset highlighted the role of these genes in mediating the regulation of boundary-related cells. Furthermore, we applied the spGRN to publicly available single-cell and spatial-transcriptomics datasets from three other cancer types. The results demonstrate that ITGB1 and its target genes FOS/JUN were commonly expressed in all four cancer types, indicating their potential as pan-cancer therapeutic targets. Conclusion: the spGRN was proven to be a useful tool to select signal molecules as potential biomarkers or valuable therapeutic targets. Full article

(This article belongs to the Special Issue Single-Cell and Spatial Multi-Omics in Human Diseases)

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16 pages, 1534 KiB

Open AccessArticle

Clinician-Based Functional Scoring and Genomic Insights for Prognostic Stratification in Wolf–Hirschhorn Syndrome

by Julián Nevado, Raquel Blanco-Lago, Cristina Bel-Fenellós, Adolfo Hernández, María A. Mori-Álvarez, Chantal Biencinto-López, Ignacio Málaga, Harry Pachajoa, Elena Mansilla, Fe A. García-Santiago, Pilar Barrúz, Jair A. Tenorio-Castaño, Yolanda Muñoz-GªPorrero, Isabel Vallcorba and Pablo Lapunzina

Genes 2025, 16(7), 820; https://doi.org/10.3390/genes16070820 - 12 Jul 2025

Viewed by 393

Abstract

Background/Objectives: Wolf–Hirschhorn syndrome (WHS; OMIM #194190) is a rare neurodevelopmental disorder, caused by deletions in the distal short arm of chromosome 4. It is characterized by developmental delay, epilepsy, intellectual disability, and distinctive facial dysmorphism. Clinical presentation varies widely, complicating prognosis and [...] Read more.

Background/Objectives: Wolf–Hirschhorn syndrome (WHS; OMIM #194190) is a rare neurodevelopmental disorder, caused by deletions in the distal short arm of chromosome 4. It is characterized by developmental delay, epilepsy, intellectual disability, and distinctive facial dysmorphism. Clinical presentation varies widely, complicating prognosis and individualized care. Methods: We assembled a cohort of 140 individuals with genetically confirmed WHS from Spain and Latin-America, and developed and validated a multidimensional, Clinician-Reported Outcome Assessment (ClinRO) based on the Global Functional Assessment of the Patient (GFAP), derived from standardized clinical questionnaires and weighted by HPO (Human Phenotype Ontology) term frequencies. The GFAP score quantitatively captures key functional domains in WHS, including neurodevelopment, epilepsy, comorbidities, and age-corrected developmental milestones (selected based on clinical experience and disease burden). Results: Higher GFAP scores are associated with worse clinical outcomes. GFAP showed strong correlations with deletion size, presence of additional genomic rearrangements, sex, and epilepsy severity. Ward’s clustering and discriminant analyses confirmed GFAP’s discriminative power, classifying over 90% of patients into clinically meaningful groups with different prognoses. Conclusions: Our findings support GFAP as a robust, WHS-specific ClinRO that may aid in stratification, prognosis, and clinical management. This tool may also serve future interventional studies as a standardized outcome measure. Beyond its clinical utility, GFAP also revealed substantial social implications. This underscores the broader socioeconomic burden of WHS and the potential value of GFAP in identifying high-support families that may benefit from targeted resources and services. Full article

(This article belongs to the Special Issue Molecular Basis of Rare Genetic Diseases)

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17 pages, 7594 KiB

Open AccessArticle

Uridine Kinase-like Protein (GhUKL4) Positively Regulates Resistance to Verticillium Wilt in Cotton

by Baimei Cheng, Yanmeng Sun, Xiaohui Sang, Jianhua Lu, Pei Zhao, Wei Chen, Yunlei Zhao and Hongmei Wang

Genes 2025, 16(7), 819; https://doi.org/10.3390/genes16070819 - 12 Jul 2025

Viewed by 256

Abstract

Background: Verticillium wilt (VW), caused by the fungal pathogen Verticillium dahliae, is a destructive disease that severely compromises cotton yield and fiber quality. Pyrimidine nucleotides, as essential metabolites and nucleic acid components, play critical roles in plant development and stress responses. However, [...] Read more.

Background: Verticillium wilt (VW), caused by the fungal pathogen Verticillium dahliae, is a destructive disease that severely compromises cotton yield and fiber quality. Pyrimidine nucleotides, as essential metabolites and nucleic acid components, play critical roles in plant development and stress responses. However, genes involved in pyrimidine metabolism, especially their roles in disease resistance, remain largely uncharacterized in plants. Methods: Ghir_D05G039120, a gene encoding uridine kinase, shown to be associated with VW resistance in our previous study, was cloned and named as GhUKL4. The differential expression of GhUKL4 between the resistant and susceptible cultivars at multiple time points post-inoculation with V. dahliae was analyzed by quantitative real-time PCR (qRT-PCR), and the uracil phosphoribosyl transferase (UPRT) and uridine 5′-monophosphate kinase (UMPK) domains were verified by analyzing the amino acid sequences of GhUKL4. The role of GhUKL4 in the defense against VW infection was estimated by silencing GhUKL4 in the resistant and susceptible cultivars using virus-induced gene silencing (VIGS) analysis. Results: There were significant differences in the expression level of Ghir_D05G039120/ GhUKL4 among resistant and susceptible cotton lines. GhUKL4 contains UPRTase and UMPK domains, and there was one SNP between the resistant and susceptible cultivars in its 3′-UTR region. The silencing of GhUKL4 reduced cotton’s resistance to VW through mediating hormone signaling (JA) and oxidative stress (ROS) pathways. Conclusions: GhUKL4, encoding UMPK and UPRTase domain proteins, is a new regulatory factor associated with VW resistance in Gossypium hirsutum through fine-tuning JA-signalling and ROS bursting. Full article

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

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Genes, Volume 16, Issue 7 (July 2025) – 127 articles

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