Genes

18 pages, 3132 KiB

Open AccessArticle

Comparative and Phylogenetic Analysis of the Complete Chloroplast Genomes of Lithocarpus Species (Fagaceae) in South China

by Shi Shi, Ziyan Zhang, Xinhao Lin, Linjing Lu, Keyi Fu, Miaoxin He, Shiou Yih Lee, Hui Yin and Jingwei Yu

Genes 2025, 16(6), 616; https://doi.org/10.3390/genes16060616 - 22 May 2025

Abstract

Background/Objectives: In South China, Lithocarpus species dominate mixed evergreen broadleaf forests, forming symbiotic relationships with ectomycorrhizal fungi and serving as food resources for diverse fauna, including frugivorous birds and mammals. The limited understanding of chloroplast genomes in this genus restricts our insights [...] Read more.

Background/Objectives: In South China, Lithocarpus species dominate mixed evergreen broadleaf forests, forming symbiotic relationships with ectomycorrhizal fungi and serving as food resources for diverse fauna, including frugivorous birds and mammals. The limited understanding of chloroplast genomes in this genus restricts our insights into its species diversity. This study investigates the chloroplast genome (cp genome) sequences from seven Lithocarpus species, aims to elucidate their structural variation, evolutionary relationships, and functional gene content to provide effective support for future genetic conservation and breeding efforts. Methods: We isolated total DNA from fresh leaves and sequenced the complete cp genomes of these samples. To develop a genomic resource and clarify the evolutionary relationships within Lithocarpus species, comparative chloroplast genome studies and phylogenetic investigations were performed. Results: All studied species exhibited a conserved quadripartite chloroplast genome structure, with sizes ranging from 161,495 to 163,880 bp. Genome annotation revealed 130 functional genes and a GC content of 36.72–37.76%. Codon usage analysis showed a predominance of leucine-encoding codons. Our analysis identified 322 simple sequence repeats (SSRs), which were predominantly palindromic in structure (82.3%). All eight species exhibited the same 19 SSR categories in similar proportions. Eight highly variable regions (ndhF, ycf1, trnS-trnG-exon1, trnk(exon1)-rps16(exon2), rps16(exon2), rbcL-accD, and ccsA-ndh) have been identified, which could be valuable as molecular markers in future studies on the population genetics and phylogeography of this genus. The phylogeny tree provided critical insights into the evolutionary trajectory of Fagaceae, suggesting that Lithocarpus was strongly supported as monophyletic, while Quercus was inferred to be polyphyletic, showing a significant cytonuclear discrepancy. Conclusions: We characterized and compared the chloroplast genome features across eight Lithocarpus species, followed by comprehensive phylogenetic analyses. These findings provide critical insights for resolving taxonomic uncertainties and advancing systematic research in this genus. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptive Evolution in Trees)

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16 pages, 1251 KiB

Open AccessArticle

The Association Between Dexmedetomidine and Bradycardia: An Analysis of FDA Adverse Event Reporting System (FAERS) Data and Transcriptomic Profiles

by Robert Morris, Suguna Aishwarya Kuppa, Xinran Zhu, Kun Bu, Weiru Han and Feng Cheng

Genes 2025, 16(6), 615; https://doi.org/10.3390/genes16060615 - 22 May 2025

Abstract

Background/Objectives: Bradycardia, an uncharacteristically low heart rate below 60 bpm, is a commonly reported adverse drug event (ADE) in individuals administered dexmedetomidine for sedation. Dexmedetomidine is frequently used as a sedative and analgesic for both intubated and non-intubated patients due to its low [...] Read more.

Background/Objectives: Bradycardia, an uncharacteristically low heart rate below 60 bpm, is a commonly reported adverse drug event (ADE) in individuals administered dexmedetomidine for sedation. Dexmedetomidine is frequently used as a sedative and analgesic for both intubated and non-intubated patients due to its low risk of respiratory depression. The purpose of this study was to further characterize the safety profile of dexmedetomidine using safety reports collected from the FDA Adverse Event Reporting System (FAERS) and transcriptomic data. Methods: Association rule mining was used to both identify additional ADEs that presented concurrently with bradycardia in patients sedated with dexmedetomidine, as well as to characterize potential drug–drug interactions (DDIs). Furthermore, public transcriptomic data were analyzed to identify differentially expressed genes that may elucidate the genetic drivers of elevated bradycardia risk in those administered dexmedetomidine. Results: Bradycardia was the most frequently reported ADE for individuals administered dexmedetomidine. Other cardiovascular-related ADEs commonly associated with bradycardia included syncope (lift = 4.711), loss of consciousness (lift = 3.997), cardiac arrest (lift = 2.850), and hypotension (lift = 2.770). Several possible DDIs were identified, including Lactated Ringer’s solution (lift = 5.441), bupivacaine (lift = 2.984), and risperidone (lift = 2.434), which may elevate bradycardia risk. Finally, eight genes related to cardiac muscle contraction were identified as possible regulators of dexmedetomidine-induced bradycardia, including COX5B, COX6A2, COX8B, MYH7, MYH6, MYL2, UQCRQ, and UQCR11 in mouse cardiac cells. Conclusions: Key clinical takeaways include the co-presentation of multiple cardiovascular ADEs, including cardiac arrest, hypotension, and syncope, alongside dexmedetomidine-associated bradycardia. Furthermore, several possible DDIs with dexmedetomidine were also identified. Full article

(This article belongs to the Section Bioinformatics)

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20 pages, 1389 KiB

Open AccessReview

Psychosocial Factors Involved in Genetic Testing for Rare Diseases: A Scoping Review

by Samantha Strasser, Isabella R. McDonald, Melissa K. Uveges, Sharlene Hesse-Biber, Jordan Keels, Neil Smith and Andrew A. Dwyer

Genes 2025, 16(6), 614; https://doi.org/10.3390/genes16060614 - 22 May 2025

Abstract

Background/Objectives: Rare diseases are predominantly genetic in etiology and characterized by a prolonged ‘diagnostic odyssey’. Advances in genetic testing (GT) have helped shorten the time to diagnosis for rare/undiagnosed conditions. We aimed to synthesize the evidence on psychosocial factors related to GT [...] Read more.

Background/Objectives: Rare diseases are predominantly genetic in etiology and characterized by a prolonged ‘diagnostic odyssey’. Advances in genetic testing (GT) have helped shorten the time to diagnosis for rare/undiagnosed conditions. We aimed to synthesize the evidence on psychosocial factors related to GT for rare diseases to inform more person-centered approaches to care. Methods: We conducted a systematic literature search in six databases using structured terms (September 2024). Retrieved articles underwent independent dual review. Data were extracted and collated in tables for analysis. Thematic analysis was used to identify promoters/barriers to GT for patients and families. Findings were validated by a patient advocate and were reported using PRISMA-ScR guidelines. Synthesized findings were mapped to the Theory of Planned Behavior to inform intervention development. Results: Of 1730 retrieved articles, 32 were included for data extraction/synthesis. Studies employed qualitative (n = 19), quantitative (n = 10), and mixed-methods (n = 3) approaches. Nearly all (29/32, 91%) were non-interventional, reporting on decision-making cognitions/processes (19/32, 59%), attitudes/preferences (15/32, 47%), psychosocial impact (6/32, 19%), and knowledge/awareness (4/32, 8%) of pre-conception/prenatal/diagnostic GT and carrier screening. Promoters included understanding GT, ending the diagnostic odyssey, actionable outcomes, personal/family history, altruism, and reproductive decision-making. Barriers included logistical (e.g., distance, cost), psychological burden, perceived lack of benefit, and discrimination/social stigma concerns. Conclusions: Some psychosocial factors related to GT for rare diseases overlap with those in literature on GT for common conditions. Identified factors represent targets for theory-informed, person-centered interventions to support high-quality GT decisions that are informed and aligned with patient/family values and preferences. Full article

(This article belongs to the Special Issue Genetic Counseling, Genomics, Genetic Education)

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20 pages, 2917 KiB

Open AccessArticle

Heterorhabditis bacteriophora Extracellular Vesicles Alter the Innate Immune Signaling in Drosophila melanogaster

by Duarte Toubarro, Eric Kenney, Christa Heryanto, Sreeradha Mallick, Nelson Simões and Ioannis Eleftherianos

Genes 2025, 16(6), 613; https://doi.org/10.3390/genes16060613 - 22 May 2025

Abstract

Background: Heterorhabditis bacteriophora entomopathogenic nematodes are commonly used in agricultural practices for the biological control of insect pests. These parasites are also used in basic research for unveiling the molecular basis of nematode parasitism in relation to the insect anti-nematode response. We [...] Read more.

Background: Heterorhabditis bacteriophora entomopathogenic nematodes are commonly used in agricultural practices for the biological control of insect pests. These parasites are also used in basic research for unveiling the molecular basis of nematode parasitism in relation to the insect anti-nematode response. We have recently shown that H. bacteriophora excreted–secreted products reduce the expression of the antimicrobial peptide gene Diptericin in Drosophila melanogaster, which increases fly mortality due to enhanced propagation of the mutualistic bacteria Photorhabdus luminescens. However, the effect of entomopathogenic nematode extracellular vesicles (EVs) on the insect host defense remains unknown. Methods: Here, we injected adult flies with H. bacteriophora EVs and used quantitative RT-PCR together with gene-specific primers to analyze the activity of immune-related signaling pathways. Results: We found that H. bacteriophora EVs are lethal to Drosophila melanogaster, and they downregulate the expression of Attacin, Cecropin, and Prophenoloxidase 3 in adult flies. Conclusions: These findings build on previous knowledge and strengthen the notion that H. bacteriophora entomopathogenic nematodes release a variety of effector molecules to modify the insect’s innate immune signaling. This information is important because it contributes toward clarifying the molecular interplay between entomopathogenic nematode components and the host’s innate immune system. Full article

(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)

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9 pages, 298 KiB

Open AccessReview

Molecular Genomics of Oral Submucous Fibrosis: A Narrative Review

by Vasileios Zisis, Stefanos Zisis, Christina Charisi, Konstantinos Poulopoulos, Aristeidis Sarkisian and Athanasios Poulopoulos

Genes 2025, 16(6), 612; https://doi.org/10.3390/genes16060612 - 22 May 2025

Abstract

Background: Oral Submucous Fibrosis (OSMF) is a chronic, progressive condition characterized by the fibrosis of the oral mucosa, often associated with the habitual consumption of areca nut and tobacco, leading to significant morbidity. Despite its prevalent occurrence in many parts of the world, [...] Read more.

Background: Oral Submucous Fibrosis (OSMF) is a chronic, progressive condition characterized by the fibrosis of the oral mucosa, often associated with the habitual consumption of areca nut and tobacco, leading to significant morbidity. Despite its prevalent occurrence in many parts of the world, the underlying genetic and molecular mechanisms remain poorly understood, highlighting a critical need for research into its molecular genomics. The aim of this literature review is to investigate the molecular genomics of Oral Submucous Fibrosis by analyzing the relevant literature of the past decade. Methods: The search was conducted using MEDLINE (National Library of Medicine)-PubMed, focusing on the period 2015–2025 using the following keywords: Molecular Genomics AND Oral Submucous Fibrosis. This was followed by a manual search, and references were used to identify relevant articles. Results: A total of 12 articles were included in our review according to our inclusion criteria, which illustrated the importance of TGF-β, Wnt inhibitory factor-1, CypA, Hsp-70 1B, Calreticulin, Lumican, Enolase 1, MMP-2, IGF-1R, XIST, Epigallocatechin-3-gallate, Von Hippel-Lindau, and MUC1 and 4. Conclusions: Understanding the molecular pathogenesis of OSMF involves examining the molecular interactions and the roles of specific proteins. Advanced genomic technologies have opened new frontiers in the study of OSMF. As research in OSMF continues to evolve, emerging interdisciplinary approaches may provide therapeutic strategies, aiming to improve management outcomes for the patients. Full article

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

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18 pages, 3747 KiB

Open AccessArticle

The Complete Chloroplast Genome of Idesia polycarpa and Comparative Analysis of Related Species

by Xueqian Fu, Jie Luo, Yuan Guo, Dalan Feng, Yifei Deng, Mi Kuang, Houlin Zhou, Xia Liu and Chong Sun

Genes 2025, 16(5), 611; https://doi.org/10.3390/genes16050611 - 21 May 2025

Abstract

Background/Objectives: The oil grape (Idesia polycarpa), often called the “golden tree”, is an essential woody plant valued for its edible oil. Although its economic significance is recognized, the specifics of its chloroplast genome and evolutionary connections remain unclear. This study sequenced [...] Read more.

Background/Objectives: The oil grape (Idesia polycarpa), often called the “golden tree”, is an essential woody plant valued for its edible oil. Although its economic significance is recognized, the specifics of its chloroplast genome and evolutionary connections remain unclear. This study sequenced the chloroplast genome of I. polycarpa and performed a comparative analysis of its genome structure, genetic diversity, and phylogenetics using chloroplast data from related species. Methods: In this study, we sequenced and annotated the whole chloroplast genome of I. polycarpa via GISEQ-500 sequencing and de novo assembly. Results: The chloroplast genome of I. polycarpa exhibits a typical tetrad structure, with a length of 155,899 bp and a GC content of 36.78%. It comprises 130 unique genes, including 85 coding genes, 37 tRNAs, and eight rRNAs, showing notable conservation in gene composition and arrangement compared to closely related species. However, the inverted repeat region boundaries are narrower. Phylogenetic analysis showed strong relationships among I. polycarpa, Bennettiodendron brevipes, Poliothyrsis sinensis, Itoa orientalis, and Carrierea calycina within the Salicaceae family. Additionally, positive selection analysis revealed that rpl16, ycf1, rps18, and rpl22 are under significant selective pressure in related species, likely linked to adaptations for photosynthesis and environmental responses. Conclusions: This research provides vital molecular foundations for the conservation, classification, and enhancement of I. polycarpa germplasm resources, advancing the study of adaptive evolutionary mechanisms and broadening the genomic database for I. polycarpa. Full article

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

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16 pages, 5161 KiB

Open AccessArticle

Isolation and Activity Evaluation of Callus-Specific Promoters in Rice (Oryza sativa L.)

by Xiaojiao Ma and Chuanyin Wu

Genes 2025, 16(5), 610; https://doi.org/10.3390/genes16050610 - 21 May 2025

Abstract

Background/Objectives: In crop genetic engineering, morphogenic genes have attracted increasing attention, given their ability to facilitate the transformation of a broad range of otherwise nontransformable cultivars. However, few callus-specific promoters have been identified to date that can be employed to avoid the adverse [...] Read more.

Background/Objectives: In crop genetic engineering, morphogenic genes have attracted increasing attention, given their ability to facilitate the transformation of a broad range of otherwise nontransformable cultivars. However, few callus-specific promoters have been identified to date that can be employed to avoid the adverse effects resulting from the ectopic expression of morphogenic genes on shoot regeneration and growth. Methods: A set of potential callus-specific genes were initially selected based on publicly available data. These genes were then screened using quantitative real-time polymerase chain reaction (qPCR), followed by promoter activity evaluation using a transgenic approach with the GUS gene serving as a reporter. Results: Of the 24 evaluated promoters, 12 were verified as being callus-specific using qPCR. Five genes (Os11g0295900, Os10g0207500, Os01g0300000, Os02g0252200, and Os04g0488100) were chosen, and their promoters were cloned. Based on GUS staining, the pOsTDL1B (Os10g0207500) promoter showed strong callus-specific expression, pOsEDC (Os01g0300000) was a medium-level callus-specific promoter, and pOsDLN53 (Os02g0252200) was strictly callus-specific, although its activity was low. Quantification of GUS activity indicated that all three pOsTDL1B:GUS transgenic lines exhibited strong callus specificity relative to the various tissues tested. Conclusions: A callus-specific promoter was identified that can be used to drive the expression of morphogenic genes in crop transformation. Full article

(This article belongs to the Topic Genetic Engineering in Agriculture)

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12 pages, 1682 KiB

Open AccessArticle

Functional and Bioinformatic Analysis of PDX2 from Ginkgo biloba

by Yifan Xiao, Zhi Feng, Zhi Yao, Hailan Jiang, Yiqiang Wang and Meng Li

Genes 2025, 16(5), 609; https://doi.org/10.3390/genes16050609 - 21 May 2025

Abstract

Background: The PDX2 gene serves as a critical catalytic component in vitamin B6 (VB6) biosynthesis pathways and plays pivotal regulatory roles in plant growth. Methods: To investigate the metabolic regulation of PDX2 (GbPDX2) from Ginkgo biloba in VB6 biosynthesis [...] Read more.

Background: The PDX2 gene serves as a critical catalytic component in vitamin B6 (VB6) biosynthesis pathways and plays pivotal regulatory roles in plant growth. Methods: To investigate the metabolic regulation of PDX2 (GbPDX2) from Ginkgo biloba in VB6 biosynthesis during kernel development, we successfully cloned this gene and conducted systematic expression profiling through qRT-PCR across multiple tissues and developmental stages. Results: Bioinformatic characterization revealed that GbPDX2 contains a 765-bp coding sequence encoding a 254-amino acid polypeptide. The encoded protein displays typical hydrophilic properties (average hydrophobicity index: −0.32) and was predicted to be an unstable cytosolic protein (instability index: 45.7) lacking signal peptides or transmembrane domains with cytoplasmic localization. Phylogenetic analysis demonstrated that GbPDX2’s closest evolutionary relationship was with its ortholog in Picea sitchensis, which had an amino acid sequence similarity of 83.7% with spruce PsPDX2. Tissue-specific expression analysis revealed a gradient expression profile of Kernel > Exocarp > Leaves > Stems > Roots. The expression level in kernels was significantly higher than that in other tissues (19.7 times that in roots, 8.3 times that in stems, and 5.9 times that in leaves; p < 0.01), with peak transcript levels observed in mature kernels. HPLC quantification established a strong positive correlation between GbPDX2 expression dynamics and VB6 accumulation patterns during kernel maturation (r = 0.92, p < 0.01), and the peak period of VB6 reached 288.9 ± 7.1 μg/g. Conclusions: Our findings provide the first experimental evidence that GbPDX2 spatiotemporally regulates VB6 biosynthesis in ginkgo kernels, offering novel insights into the evolutionary adaptation of vitamin metabolism in gymnosperms. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Adaptive Evolution in Trees)

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16 pages, 15842 KiB

Open AccessArticle

Analysis of Codon Usage Bias of 30 Chloroplast Genomes in Ulva (Ulvophyceae, Chlorophyta)

by Jiao Fang, Liming Qin, Hongni Liu and Zhangfeng Hu

Genes 2025, 16(5), 608; https://doi.org/10.3390/genes16050608 - 21 May 2025

Abstract

Background: Ulva is a globally distributed genus with ecological and economic significance, yet the codon usage bias of the Ulva chloroplast genome remains poorly understood. Methods: We assessed the Ulva chloroplast genome codon usage patterns and their drivers by analyzing 30 genomes across [...] Read more.

Background: Ulva is a globally distributed genus with ecological and economic significance, yet the codon usage bias of the Ulva chloroplast genome remains poorly understood. Methods: We assessed the Ulva chloroplast genome codon usage patterns and their drivers by analyzing 30 genomes across 16 Ulva species. Results: The nucleotide composition analysis demonstrated that Ulva chloroplast genomes are rich in A/T, and prefer to use codons that ended with A/T. The relative synonymous codon usage analysis suggested that related species have similar codon usage patterns. A total of 25 high-frequency codons and 7–14 optimal codons were identified in these chloroplast genomes. The ENC values ranged from 31.40 to 32.76, all of which are less than 35, illustrating a strong codon bias of the Ulva genus. Our comparative analyses suggested that natural selection played the main role in the formation of the codon usage bias. Furthermore, the correlation analysis indicated that an influence of the base composition and gene expression levels on the codon usage bias. Conclusions: This study provides the first comprehensive analysis of the codon usage patterns in Ulva chloroplast genomes, improving our understanding of the genetics and evolution of these economically and ecologically important macroalgae. Full article

(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)

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21 pages, 4726 KiB

Open AccessArticle

Comparative Analysis of the Genetic Composition of Minorities in the Carpathian Basin Through Genome-Wide Autosomal Data

by András Szabó, Katalin Sümegi, Zsolt Bánfai, Kinga Hadzsiev, Ferenc Gallyas, Attila Miseta, Miklós Kásler and Béla Melegh

Genes 2025, 16(5), 607; https://doi.org/10.3390/genes16050607 - 21 May 2025

Abstract

Background/Objectives: The Carpathian Basin is a genetically and culturally diverse region shaped by complex historical migrations and various ethnic groups. While studies based on Y-chromosomal and mitochondrial DNA have provided valuable insights into the genetic diversity of these populations, genome-wide autosomal SNP data [...] Read more.

Background/Objectives: The Carpathian Basin is a genetically and culturally diverse region shaped by complex historical migrations and various ethnic groups. While studies based on Y-chromosomal and mitochondrial DNA have provided valuable insights into the genetic diversity of these populations, genome-wide autosomal SNP data remain underutilized in understanding the genetic structure of these groups. This study presents the first genome-wide autosomal SNP-based analysis of key Hungarian-speaking ethnic groups in the region, focusing on admixture patterns and the extent of preserved historical genetic components. Methods: We analyzed genome-wide autosomal SNP data from 597 individuals representing several ethnic groups in the Carpathian Basin. Standard population genetic methods were applied to assess genetic structure, admixture and differentiation, with comparisons to broader European reference populations. Results: Most ethnic groups displayed genetic affinities with Eastern European populations, consistent with historical and geographical proximity. The Swabian group, of German descent, exhibited a distinct Western European genetic component, likely due to historical isolation. Transylvanian populations appeared relatively homogeneous, indicating a shared ancestral background. In contrast, Csangos showed distinct sub-clusters, suggesting population isolation and distinct histories. Overall, genetic homogeneity characterizes the region, though certain isolated groups retain distinct ancestral signatures. Conclusions: Autosomal SNP analysis revealed mild overall genetic structuring among Carpathian Basin ethnic groups. However, historical isolation has preserved unique genetic components in specific groups, highlighting the value of genome-wide data in uncovering fine-scale population structure. These findings contribute to a deeper understanding of regional genetic diversity, which has implications for both population history and health-related genetic research. Full article

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

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14 pages, 1752 KiB

Open AccessArticle

Deciphering the First Mitochondrial Genome of the Liolophura Pilsbry, 1893 Genus: An Extensive Phylogenetic Study Within the Chitonidae Family

by Qianqian Zhou, Zhiyong Liu, Weifeng Dong, Bingpeng Xing, Site Luo and Peng Xiang

Genes 2025, 16(5), 606; https://doi.org/10.3390/genes16050606 - 20 May 2025

Abstract

Background: The Polyplacophora class, which includes all chitons, is distinguished by its unique eight-piece interlocking armor, showcasing a vast diversity in marine environments. However, the detailed evolutionary relationships within the Chitonidae family remain largely unknown. The mitochondrial genome is essential for understanding [...] Read more.

Background: The Polyplacophora class, which includes all chitons, is distinguished by its unique eight-piece interlocking armor, showcasing a vast diversity in marine environments. However, the detailed evolutionary relationships within the Chitonidae family remain largely unknown. The mitochondrial genome is essential for understanding these relationships, but there has been a significant lack of such genomic information, especially for the Liolophura genus. Methods: We generated the first mitogenome of Liolophura japonica by assembling Illumina reads with GetOrganelle, polishing with Pilon, annotating genes with MitoZ and MITOS2, and inferring phylogeny from 13 concatenated protein-coding genes (PCGs) using MAFFT and IQ-TREE. Results: The mitogenome is 15,209 base pairs long and includes 13 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs. The mitogenome exhibited a slight AT bias common in Chitonidae and showcased structural uniqueness with no control region found. Notably, all protein-coding genes demonstrated evidence of purifying selection, with Ka/Ks ratios below 1, highlighting evolutionary conservation. Phylogenetic analysis reveals a close relationship between L. japonica, Acanthopleura loochooana Broderip & Sowerby 1829, and Acanthopleura vaillantii Rochebrune, 1882, potentially warranting future taxonomic re-evaluation. This research emphasizes the crucial role of mitochondrial genomes in mollusk phylogeny and sets the stage for advanced genetic studies within this group. Conclusions: The significance of this study lies in its contribution to understanding the mitochondrial genome of L. japonica, a key species within the Polyplacophora class. By analyzing its mitogenome, we aim to enhance our understanding of evolutionary processes in chitons and other mollusks. Full article

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

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24 pages, 8896 KiB

Open AccessArticle

Systems Genetics Reveals the Gene Regulatory Mechanisms of Arrb2 in the Development of Autism Spectrum Disorders

by Junyu Xia, Akhilesh K. Bajpai, Yamei Liu, Lele Yu, Yating Dong, Feng Li, Fuxue Chen, Lu Lu and Shini Feng

Genes 2025, 16(5), 605; https://doi.org/10.3390/genes16050605 - 20 May 2025

Abstract

Background: Autism spectrum disorder (ASD) involves complex interactions between genetic and environmental factors. Recent studies suggest that dysregulation of β-arrestin2 (Arrb2) in the central nervous system is linked to ASD. However, its specific mechanisms remain unknown. Methods: This study employs a [...] Read more.

Background: Autism spectrum disorder (ASD) involves complex interactions between genetic and environmental factors. Recent studies suggest that dysregulation of β-arrestin2 (Arrb2) in the central nervous system is linked to ASD. However, its specific mechanisms remain unknown. Methods: This study employs a systems genetics approach to comprehensively investigate Arrb2 in multiple brain tissues, including the amygdala, cerebellum, hippocampus, and prefrontal cortex, using BXD recombinant inbred (RI) strains. In addition, genetic variance analysis, correlation analysis, expression quantitative trait loci (eQTL) mapping, and functional annotation were used to identify the key downstream targets of Arrb2, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB). Results: Arrb2 exhibited expression variations across the four brain regions in BXD mice. eQTL mapping revealed that Arrb2 is cis-regulated, and increased Arrb2 expression levels were significantly correlated with ASD-like symptoms, such as impaired social interactions and abnormal learning and memory. Furthermore, protein–protein interaction (PPI) network analysis, tissue correlation, functional relevance to autism, and differential expression identified eight downstream candidate genes regulated by Arrb2. The experimental results demonstrated that deletion of Arrb2 led to the downregulation of Myh9, Dnmt1, and Brd4 expression, along with protein kinase A (PKA)-induced hyperactivation of Synapsin I. These findings suggest that Arrb2 may contribute to the pathogenesis of autism by modulating the expression of these genes. Conclusions: This study highlights the role of Arrb2 in ASD pathogenesis and identifies Myh9, Dnmt1, and Brd4 as key downstream regulators. These findings provide new insights into the molecular mechanisms of ASD and pave the way for novel therapeutic targets. Full article

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

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16 pages, 1455 KiB

Open AccessArticle

Multimorbidity Through the Lens of the Eye: Pathogenic Variants for Multiple Systemic Disorders Found in an Autosomal Dominant Congenital Cataract Cohort

by Vanita Berry, Manav B. Ponnekanti, Nancy Aychoua, Alex Ionides, Chrysanthi Tsika, Roy A. Quinlan and Michel Michaelides

Genes 2025, 16(5), 604; https://doi.org/10.3390/genes16050604 - 20 May 2025

Abstract

Background: This paper will identify the potential genetic causes of multimorbidity associated with autosomal dominant congenital cataract (ADCC). Methods: Whole exome sequencing (WES) was performed on 13 individuals affected with ADCC. Subsequent bioinformatic analyses identified variants with deleterious pathogenicity scores. Results: Disease-causing variants [...] Read more.

Background: This paper will identify the potential genetic causes of multimorbidity associated with autosomal dominant congenital cataract (ADCC). Methods: Whole exome sequencing (WES) was performed on 13 individuals affected with ADCC. Subsequent bioinformatic analyses identified variants with deleterious pathogenicity scores. Results: Disease-causing variants were identified in 8 genes already linked to cataract (CHMP4B, CRYAA, CRYBA1, CRYGD, CYP21A2, GJA8, OPA1, and POMGNT1), but variants previously associated with systemic disorders were also found in a further 11 genes (ACTL9, ALDH18A1, CBS, COL4A3, GALT, LRP5, NOD2, PCK2, POMT2, RSPH4A, and SMO). All variants were identified via pipeline data analysis, prioritising rare coding variants using Kaviar and the Genome Aggregation Database. The following ADCC-associated non-ocular phenotypes were identified in four patients in the cohort: (i) Horner’s pupils, vaso-vagal syncope, and paroxysmal orthostatic tachycardia syndrome; (ii) reduced kidney function and high cholesterol; (iii) hypertension, high cholesterol, and kidney stones; and (iv) grade 1 spondylolysis. Conclusions: We report 11 novel genes identified in an ADCC patient cohort associated with systemic disorders found, along with 8 known cataract-causing genes. Our findings broaden the spectrum of potentially cataract-associated genes and their related lens phenotypes, as well as evidence multimorbidities in four patients, highlighting the importance of careful multisystem phenotyping following genetic analysis. Full article

(This article belongs to the Special Issue Advances in Medical Genetics)

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17 pages, 4095 KiB

Open AccessArticle

Case Study: Genetic and In Silico Analysis of Familial Pancreatitis

by Yash Sharma and Deborah J. Good

Genes 2025, 16(5), 603; https://doi.org/10.3390/genes16050603 - 20 May 2025

Abstract

Background/Objectives: Chronic pancreatitis (CP) is a progressive inflammatory condition of the pancreas that leads to irreversible changes in pancreatic structure. The pancreatic α and β cells secrete hormones such as insulin and glucagon into the bloodstream. The pancreatic acinar cells secrete digestive enzymes [...] Read more.

Background/Objectives: Chronic pancreatitis (CP) is a progressive inflammatory condition of the pancreas that leads to irreversible changes in pancreatic structure. The pancreatic α and β cells secrete hormones such as insulin and glucagon into the bloodstream. The pancreatic acinar cells secrete digestive enzymes that break down macromolecules. When these digestive enzymes do not function properly, maldigestion, malabsorption, and malnutrition may result. Presented here is a case study of an individual newly diagnosed with chronic pancreatitis, along with a genetic analysis of his son and an in-silico analysis of two of the variant proteins. Methods: This study was conducted using human subjects, namely, the proband (father) and his son. Medical genetic testing of the proband (father) identified the presence of two variants in the cystic fibrosis transmembrane receptor gene (CFTR): variant rs213950, resulting in a single amino acid change (p. Val470Met), and variant rs74767530, a nonsense variant (Arg1162Ter) with known pathogenicity for cystic fibrosis. Medical testing also revealed an additional missense variant, rs515726209 (Ala73Thr), in the CTRC gene. Cheek cell DNA was collected from both the proband and his son to determine the inheritance pattern and identify any additional variants. A variant in the human leukocyte antigen (rs7454108), which results in the HLA-DQ8 haplotype, was examined in both the proband and his son due to its known association with autoimmune disease, a condition also linked to chronic pancreatitis. In silico tools were subsequently used to examine the impact of the identified variants on protein function. Results: Heterozygosity for all variants originally identified through medical genetic testing was confirmed in the proband and was absent in the son. Both the proband and his son were found to have the DRB1*0301 (common) haplotype for the HLA locus. However, the proband was also found to carry a linked noncoding variant, rs2647088, which was absent in the son. In silico analysis of variant rs213950 (Val470Met) in CFTR and rs515726209 (Ala73Thr) in CTRC revealed distinct changes in predicted ligand binding for both proteins, which may affect protein function and contribute to the development of CP. Conclusions: This case study of a proband and his son provides additional evidence for a polygenic inheritance pattern in CP. The results also highlight new information on the role of the variants on protein function, suggesting additional testing of ligand binding for these variants should be done to confirm the functional impairments. Full article

(This article belongs to the Special Issue Molecular Discoveries, Clinical Diagnostics, and Personalized Treatments for Human Genetic Diseases)

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15 pages, 3459 KiB

Open AccessArticle

Unraveling the Transcriptomic Profiles of Large and Small Donkey Follicles

by Yanping Wang, Zihao Gao, Qiang Zhang, Xuchuan Guo, Wei Xia, Xinli Gu and Weibin Zeng

Genes 2025, 16(5), 602; https://doi.org/10.3390/genes16050602 - 20 May 2025

Abstract

Background: The diameter of mature follicles in donkeys is several times larger than in cattle and sheep, but the key genes responsible for maintaining follicular development and preventing apoptosis remain unclear. Methods: This study observed the process of donkey follicular development using ultrasound [...] Read more.

Background: The diameter of mature follicles in donkeys is several times larger than in cattle and sheep, but the key genes responsible for maintaining follicular development and preventing apoptosis remain unclear. Methods: This study observed the process of donkey follicular development using ultrasound and analyzed the changes in common reproductive hormones in serum. Granulosa cells (GCs) were collected from large (mature follicles, diameter ≥ 37 mm) and small (atretic follicles, diameter 10–25 mm) follicles for sequencing to screen differentially expressed genes (DEGs) and signaling pathways influencing the development of mature follicles. The roles of selected genes were further validated in in vitro cultured GCs. Results: Donkey follicles exhibited rapid growth 5–7 days before ovulation, reaching maturity at a diameter of 37 mm. The maximum diameter of ovulatory follicles was approximately 40.7 mm, while non-ovulatory follicles began to undergo atresia when reaching about 25 mm. Serum reproductive hormone levels aligned with follicular developmental status. RNA sequencing identified 3291 DEGs between large and small follicles, with KEGG analysis highlighting enrichment in the PI3K-Akt signaling pathway, focal adhesion, amoebiasis, and cancer pathways. Lentiviral overexpression and interference assays targeting the DEGs EMCN and SYT12 revealed that EMCN positively regulates FOXO3, a key gene in the PI3K-Akt pathway. Conclusions: The EMCN gene in mature donkey follicles regulates FOXO3 in the PI3K-Akt signaling pathway, potentially inhibiting apoptosis in follicular granulosa cells and sustaining follicular development until ovulation. This study provides insights into the mechanisms underlying follicular development in donkeys. Full article

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

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13 pages, 923 KiB

Open AccessArticle

Transcriptomic Approach in Understanding Fabry Nephropathy: A Review of the Literature and Proof-of-Concept

by Nika Breznik, Tina Levstek, Bojan Vujkovac, Andreja Cokan Vujkovac and Katarina Trebušak Podkrajšek

Genes 2025, 16(5), 601; https://doi.org/10.3390/genes16050601 - 19 May 2025

Abstract

Background/Objectives: Fabry nephropathy (FN) is a progressive complication of Fabry disease that significantly affects patient outcomes. However, the molecular mechanisms underlying FN are not yet fully understood. Recent advances in transcriptomics have opened new perspectives for the identification of early changes in gene [...] Read more.

Background/Objectives: Fabry nephropathy (FN) is a progressive complication of Fabry disease that significantly affects patient outcomes. However, the molecular mechanisms underlying FN are not yet fully understood. Recent advances in transcriptomics have opened new perspectives for the identification of early changes in gene expression associated with the development and progression of the disease. Methods: This study includes a systematic review of transcriptomic findings in chronic kidney disease, with a particular focus on FN, and presents a proof-of-concept RNA sequencing analysis of peripheral blood samples from six Fabry patients with progressive nephropathy and six age- and sex-matched control subjects. Results: The analysis identified 41 differentially expressed genes (DEGs), all of which were upregulated in Fabry patients. Enrichment analysis revealed significant involvement in immune-related pathways, including neutrophil degranulation, interferon, and cytokine signaling. Cell type enrichment revealed that neutrophils and other immune cells are key players in this process. Conclusions: These results suggest that immune and inflammatory mechanisms play a central role in the pathogenesis of FN. The identified DEGs are involved in pro-fibrotic signaling and immune system activation and shed light on possible mechanisms underlying fibrosis, podocyte injury, and kidney damage. This study contributes to a deeper understanding of FN and may facilitate in the identification of early biomarkers for diagnosis and disease monitoring. Full article

(This article belongs to the Section Genetic Diagnosis)

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22 pages, 1670 KiB

Open AccessReview

Signaling Pathways in Gliomas

by Paulina Stachyra and Ludmiła Grzybowska-Szatkowska

Genes 2025, 16(5), 600; https://doi.org/10.3390/genes16050600 - 19 May 2025

Abstract

Changes in cell signaling pathways, which in normal conditions determine the maintenance of cell homeostasis and the correctness of its basic processes, may cause the transformation of a normal cell into a cancer cell. Alterations in cellular metabolism leading to oncogenesis are considered [...] Read more.

Changes in cell signaling pathways, which in normal conditions determine the maintenance of cell homeostasis and the correctness of its basic processes, may cause the transformation of a normal cell into a cancer cell. Alterations in cellular metabolism leading to oncogenesis are considered to be a hallmark of cancer cells. Therefore, a thorough understanding of cellular enzymes affecting metabolism and respiration, as well as intracellular pathways connected with them, seems crucial. These changes may be both prognostic and predictive factors, especially in terms of using molecularly targeted therapies. Aberrations in the pathways responsible for cell growth and angiogenesis are considered particularly important in the process of oncogenesis. Gliomas are the most common primary malignant tumors of the brain. The most important molecular disorders determining their particularly malignant nature are aberrations in the pathways responsible for cell growth and angiogenesis, such as the PI3K/Akt or RAS/MAPK/ERK signaling pathway, as well as excessive activity of enzymes, like hexokinases, which play a key role in glycolysis, autophagy, and apoptosis. The multitude of alterations detected in glioma cells, high heterogeneity, and the immunosuppressive environment within the tumor are the main features causing failures in the attempts to implement modern therapies. Full article

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

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18 pages, 10821 KiB

Open AccessArticle

Combined Analysis of Transcriptomes and Metabolomes Reveals That MeJA-Mediated Flavonoid Biosynthesis Is Crucial for Pigment Deposition in Naturally Colored Green Cotton Fibers

by Shuangquan Xie, Kailu Chen, Rui Tang, Xuechi Li, Yuxin Wei, Yijie Cheng, Shouwu Tang, Wengang Chen, Quanliang Xie, Zhuang Meng, Asigul Ismayil, Xiang Jin, Fei Wang, Haifeng Liu and Hongbin Li

Genes 2025, 16(5), 599; https://doi.org/10.3390/genes16050599 - 19 May 2025

Abstract

Background: Green cotton fibers (GCFs) are valued for their natural coloration and eco-friendly properties, but their pigmentation mechanisms remain unclear, limiting their wider application in the textile industry. This study aims to uncover the key regulatory genes and metabolic pathways involved in [...] Read more.

Background: Green cotton fibers (GCFs) are valued for their natural coloration and eco-friendly properties, but their pigmentation mechanisms remain unclear, limiting their wider application in the textile industry. This study aims to uncover the key regulatory genes and metabolic pathways involved in GCF coloration. Methods: We conducted transcriptome and metabolome profiling of green and white cotton fibers at different developmental stages to identify differences in gene expression and metabolite accumulation related to pigmentation. Results: Transcript analysis revealed significant enrichment in α-linolenic acid metabolism, flavonoid biosynthesis and phenylpropane metabolism pathways during late pigmentation stages. Key genes in methyl jasmonate (MeJA) biosynthesis and flavonoid biosynthesis (LOX, JMT, ANS, C4H, DFR, F3H) were upregulated. The MYB transcription factor showed the most significant increase during fiber development. Metabolomic analysis identified 12 metabolites that accumulated specifically in green fibers. MeJA treatment promoted the expression of MYB genes and flavonoid biosynthesis genes (DFRs, ANSs, F3H, C4H), as well as the accumulation of Luteolin, Gallocatechin, Cyanidin and Chrysanthemum metabolites. Conclusions: Our study demonstrates that MeJA-mediated flavonoid biosynthesis, regulated by MYB transcription factors, is the central pathway controlling pigment deposition in GCFs. These findings provide valuable insights for developing improved colored cotton materials. Full article

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

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9 pages, 1066 KiB

Open AccessCase Report

The Expression of a Germline Fusion Gene Involving a Protein-Coding and a Long Non-Coding RNA Gene Results in Severe Brain Malformations

by Lukas Kaufmann, Christine Beichler, Jasmin Blatterer, Ingrid Janisch, Bence Csapó, Elisabeth Schreiner, Sarah Verheyen, Jochen B. Geigl and Christian Windpassinger

Genes 2025, 16(5), 598; https://doi.org/10.3390/genes16050598 - 18 May 2025

Abstract

In the present study, an exceptional germline gene fusion involving the protein-coding MN1 gene and the long non-coding RNA (lncRNA) gene CPMER was detected as the genetic cause of severe cerebral abnormalities with unfavorable prognosis in a male fetus at 14 weeks of [...] Read more.

In the present study, an exceptional germline gene fusion involving the protein-coding MN1 gene and the long non-coding RNA (lncRNA) gene CPMER was detected as the genetic cause of severe cerebral abnormalities with unfavorable prognosis in a male fetus at 14 weeks of gestation. Quantitative and qualitative RNA analyses indicate the expression of C-terminally truncated MN1 proteins. MN1 proteins lacking the C-terminal amino acids have been previously described to cause an ultra-rare syndrome with brain malformations due to a gain-of-function effect. To the best of our knowledge, this is the first study reporting a germline gene fusion of a protein-coding gene and an lncRNA gene linked to a functional, but neomorphic, protein associated with severe phenotypic abnormalities. The results of our study are not only relevant for the genotype–phenotype correlation of MN1 but should especially raise awareness for potentially disease-associated protein expressions in germline gene fusions involving lncRNAs. Full article

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

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