Genes

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

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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

Viewed by 262

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

Viewed by 206

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

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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

Viewed by 621

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

Viewed by 259

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

Viewed by 308

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

Viewed by 293

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

Viewed by 355

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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Graphical abstract

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

Viewed by 361

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

Viewed by 343

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

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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

Viewed by 308

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

Viewed by 318

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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10 pages, 2006 KiB

Open AccessArticle

RiceReceptor: The Cell-Surface and Intracellular Immune Receptors of the Oryza Genus

by Baihui Jin, Jian Dong, Xiaolong Hu, Na Li, Xiaohua Li, Dawei Long and Xiaoni Wu

Genes 2025, 16(5), 597; https://doi.org/10.3390/genes16050597 - 18 May 2025

Viewed by 345

Abstract

Introduction: Rice, a cornerstone of global food security, faces escalating demands for enhanced yield and disease resistance. We collected 300 high-quality genomes, representing both cultivated (Oryza sativa indica, O. sativa japonica, and O. sativa aus) and wild species ( [...] Read more.

Introduction: Rice, a cornerstone of global food security, faces escalating demands for enhanced yield and disease resistance. We collected 300 high-quality genomes, representing both cultivated (Oryza sativa indica, O. sativa japonica, and O. sativa aus) and wild species (O. rufipogon, O. glaberrima, and O. barthii). Methods: Leveraging HMMER, NLR-Annotator, and OrthoFinder, we systematically identified 148,077 leucine-rich repeat (LRR) and 143,459 nucleotide-binding leucine-rich repeat (NLR) genes, with LRR receptor-like kinases (LRR-RLKs) dominating immune receptor proportions, followed by coiled-coil domain containing (CNL)-type NLRs and LRR receptor-like proteins (LRR-RLPs). Results: Benchmarking Universal Single-Copy Orthologs (BUSCO) assessments confirmed robust genome quality (average score: 94.78). Strikingly, 454 TIR-NB-LRR (TNL) genes—typically rare in monocots—were detected, challenging prior assumptions. Phylogenetic analysis with Arabidopsis TNLs highlighted five O. glaberrima genes clustering with dicot TNLs; these genes featured truncated PLN03210 motifs fused to nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC) and LRR domains. Conclusions: By bridging structural genomics, evolutionary dynamics, and domestication-driven adaptation, this work provides a foundation for targeted breeding strategies and advances functional studies of plant immunity in rice. Full article

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

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15 pages, 7958 KiB

Open AccessArticle

ABA-Insensitive 5 (ABI5) Is Involved in ABA-Induced Dormancy via Activating PavCIG1/2 Expression in Sweet Cherries

by Jiyuan Wang, Li Wang, Muhammad Usman, Jie Zhu, Songtao Jiu, Ruie Liu and Caixi Zhang

Genes 2025, 16(5), 596; https://doi.org/10.3390/genes16050596 - 18 May 2025

Viewed by 285

Abstract

Background/Objectives: In perennial plants, developing floral buds survive winter through entering a dormant state, which is induced by low temperature and abscisic acid (ABA). ABA performs vital functions in the dormancy process. ABA-insensitive 5 (ABI5) transcription factor is a key regulator in the [...] Read more.

Background/Objectives: In perennial plants, developing floral buds survive winter through entering a dormant state, which is induced by low temperature and abscisic acid (ABA). ABA performs vital functions in the dormancy process. ABA-insensitive 5 (ABI5) transcription factor is a key regulator in the ABA signaling pathway. However, little is known about the regulation of ABI5 in the winter dormancy of sweet cherries. Methods: We identified the sweet cherry ABI5 gene and its expression changes using gene cloning and qRT-PCR. Additionally, we validated the interaction between PavABI5 and PavCIG1/2 using Yeast One-Hybrid and Dual-Luciferase Assays. Results: In this study, we identified a basic leucine zipper (bZIP) family gene ABI5 from the sweet cherry, which was closely related to PduABI5 from Prunus dulcis, PpABI5 from Prunus persica, PmABI5 from Prunus mume, and ParABI5 from Prunus armeniaca, through phylogenetic tree analysis. The seasonal expression pattern showed that the PavABI5 level was increased during the winter dormancy stage and induced by exogenous ABA. Specifically, we found that the expression of cherry cold-induced genes (PavCIG1/2) was positively correlated with PavABI5 expression. Furthermore, PavABI5 directly bound to the ABRE elements in the PavCIG1/2 promoters to activate their expression. We further confirmed that the dormancy-associated MADS-box (DAM) genes DAM4 and DAM5 function downstream of the ABA signaling pathway to regulate bud dormancy in sweet cherries. Conclusions: Our findings suggest a putative regulatory model of ABA-mediated bud-dormancy with PavABI5. Full article

(This article belongs to the Section Genes & Environments)

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18 pages, 3532 KiB

Open AccessArticle

Transcriptomic Profiling of Paulownia fortunei (Seem.) Hemsl. Roots in Response to Chromium and Copper Stress

by Jiang Su, Xinfeng Pan, Kanghua Xian, Chuanming Fu, Jinxiang He, Baojun Liu, Jinhan Sang and Ningzhen Huang

Genes 2025, 16(5), 595; https://doi.org/10.3390/genes16050595 - 18 May 2025

Viewed by 333

Abstract

Background: Soil heavy metal pollution by chromium (Cr) and copper (Cu) is a global environmental concern. Methods: This study evaluated Cr/Cu accumulation in Paulownia fortunei tissues and analyzed its root transcriptome under Cr and Cu stress to elucidate molecular response mechanisms. Results: Findings [...] Read more.

Background: Soil heavy metal pollution by chromium (Cr) and copper (Cu) is a global environmental concern. Methods: This study evaluated Cr/Cu accumulation in Paulownia fortunei tissues and analyzed its root transcriptome under Cr and Cu stress to elucidate molecular response mechanisms. Results: Findings revealed significantly higher Cr and Cu accumulation capacity in roots compared to stems and leaves. Transcriptome sequencing identified 6017 and 2265 differentially expressed genes (DEGs) under Cr and Cu stress, respectively. These DEGs were primarily involved in redox reactions, stress responses, transcriptional regulation, transmembrane transport, and metabolism. Quantitative PCR of 20 selected genes validated dynamic expression changes under stress. Weighted Gene Co-expression Network Analysis (WGCNA) identified distinct co-expression modules associated with Cr and Cu. Hub gene analysis implicated Pfo_020668 and Pfo_019190 in Cr response, while Pfo_010312 and Pfo_000197 may enhance Cu tolerance via cell wall polysaccharide synthesis regulation. Pathways related to pyruvate metabolism and proteasome were significantly enriched under Cr stress, whereas amino acid metabolism pathways were prominent under Cu stress. Conclusions: Differentially expressed transporter genes suggest potential roles in heavy metal uptake and transport. This transcriptomic analysis provides novel insights into P. fortunei’s molecular responses to Cr and Cu stress, offering a foundation for utilizing this species in soil phytoremediation efforts. Full article

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

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12 pages, 3115 KiB

Open AccessArticle

The First Mitochondrial Genome of Family Xylococcidae (Hemiptera, Coccomorpha) and Its Phylogenetic Implications

by Xiaxia Zhao, Yuang Li, Han Xu and Sanan Wu

Genes 2025, 16(5), 594; https://doi.org/10.3390/genes16050594 - 17 May 2025

Viewed by 317

Abstract

Background: The mitochondrial genome has been used for understanding higher-level phylogenetic relationships within Coccomorpha. we sequenced and analyzed the first mitochondrial genome of Xylococcus castanopsis Wu & Huang, 2017 to elucidate its genomic features and phylogenetic position. Methods: The complete mitogenome was assembled [...] Read more.

Background: The mitochondrial genome has been used for understanding higher-level phylogenetic relationships within Coccomorpha. we sequenced and analyzed the first mitochondrial genome of Xylococcus castanopsis Wu & Huang, 2017 to elucidate its genomic features and phylogenetic position. Methods: The complete mitogenome was assembled using NOVOPlasty and annotated with MITOS. We analyzed genome organization, codon usage, and tRNA structures. Phylogenetic relationships were reconstructed using 13 protein-coding genes from 19 scale insect species with Bayesian Inference and Maximum Likelihood methods. Result: The mitochondrial genome is 16,363 bp in size and contains the typical 37 mitochondrial genes, with an A + T content of 89.2%. All protein-coding genes start with the ATN and end with TAA/TAG or a single T- residue. Sixteen tRNAs exhibit the typical cloverleaf structure, while the remaining six lack either the dihydrouridine (DHU) or TΨC (T) arm. Gene rearrangements occur only in individual tRNAs and transpositions between the gene clusters trnS2-ND1 and trnL1-rrnL-trnV-rrnS. Phylogenetic analysis consistently place Xylococcidae as a sister group to all scale insects except Matsucoccidae. Conclusions: This study provides the first complete mitogenome for Xylococcidae, revealing characteristic gene rearrangements. Phylogenetic reconstruction resolves the phylogenetic position of Xylococcidae as a distinct lineage sister to all scale insects except Matsucoccidae, providing critical evolutionary insights. Full article

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

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25 pages, 4439 KiB

Open AccessArticle

Genetic Diversity and Metabolic Profile of Tibetan Medicinal Plant Saussurea obvallata

by Shengnan Zhang, Sujuan Wang, Shiyan Wang, Hao Su and Ji De

Genes 2025, 16(5), 593; https://doi.org/10.3390/genes16050593 - 17 May 2025

Viewed by 314

Abstract

Background/Objectives: Saussurea obvallata (DC.) Edgew., Asteraceae, is a traditional medicinal herbnative to the Qinghai–Tibet Plateau (QTP). Pharmacological investigationshave validated its pharmacological effects in anti-tumor, anti-inflammatory, heat-clearing, detoxifying, and analgesia. S. obv is presently facing habitat fragmentation and population decline. Therefore, we analyzed its [...] Read more.

Background/Objectives: Saussurea obvallata (DC.) Edgew., Asteraceae, is a traditional medicinal herbnative to the Qinghai–Tibet Plateau (QTP). Pharmacological investigationshave validated its pharmacological effects in anti-tumor, anti-inflammatory, heat-clearing, detoxifying, and analgesia. S. obv is presently facing habitat fragmentation and population decline. Therefore, we analyzed its genetic and chemical diversity to provide a scientific basis for the conservation and sustainable use of S. obv. Methods: Seven populations of S. obv were sampled from Xizang, China. The genetic diversity was analyzed using inter-simple sequence repeat (ISSR) markers, and metabolites were identified by ultra-high-performance liquid chromatography-tandem-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). Correlation analysis among genetic diversity, differential metabolites, and climatic factors were performed by R. Results: The genetic diversity among and within populations were both lowly and significantly correlated with geographical distance, showing a decreasing trend from east to west of the QTP. A total of 110 compounds were identified, including flavonoids, phenylpropanoids, lipids, fatty acids, terpenoids, alkaloids, etc. The metabolite contents among populations varied greatly and were related to environmental factors, mainly annual mean temperature and temperature fluctuation. The genetic diversity had little effect on the metabolic differences. Conclusions: These findings provided valuable baseline information for the conservation and pharmacological utilization of S. obv. Meanwhile, further research is necessary for the efficacy evaluation of anti-inflammatory, anti-tumor, radiation protection, and scar removal both in vitro and in vivo. Full article

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

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14 pages, 719 KiB

Open AccessArticle

Pharmacogenetic Profiling of Genes Associated with Outcomes of Chemotherapy in Omani Healthy Controls

by Nahad Al-Mahrouqi, Nada Al Shuaili, Shoaib Al-Zadjali, Anoopa Pullanhi, Hamida Al-Barwani, Aida Al-Kindy, Hadeel Al-Sharqi, Khalid Al-Baimani, Mansour Al-Moundhri and Bushra Salman

Genes 2025, 16(5), 592; https://doi.org/10.3390/genes16050592 - 17 May 2025

Viewed by 378

Abstract

Background/Objectives: Pharmacogenomic screening plays a crucial role in optimizing chemotherapy outcomes and minimizing toxicity. Characterizing the baseline distribution of genetic variants in specific populations is essential to inform the prioritization of drug–gene combinations for clinical implementation. The objective of this study was to [...] Read more.

Background/Objectives: Pharmacogenomic screening plays a crucial role in optimizing chemotherapy outcomes and minimizing toxicity. Characterizing the baseline distribution of genetic variants in specific populations is essential to inform the prioritization of drug–gene combinations for clinical implementation. The objective of this study was to investigate the distribution of pharmacogenetic variants in 36 genes related to the fluoropyrimidine (FP) pathway among healthy Omani individuals, forming a foundation for future studies in cancer patients receiving FP-based chemotherapy. Methods: Ninety-eight healthy Omani participants aged ≥18 years were recruited at the Sultan Qaboos Comprehensive Cancer Care and Research Center. Whole-blood samples were collected, and genomic DNA was extracted. Targeted next-generation sequencing was performed using a custom Ion AmpliSeq panel covering coding exons and splice-site regions of 36 genes involved in FP metabolism and response. Results: A total of 999 variants were detected across the 36 genes, with 63.3% being heterozygous. The ABCC4 gene had the highest mutation frequency (76 mutations), while DHFR and SMUG1 had the lowest (<10 mutations). In DPYD, four functionally significant variants were found at frequencies ranging from 1 to 8.2% of the population. Missense mutations were also observed in MTHFR and UGT1A1. Three actionable variants in DPYD and MTHFR, associated with 5-fluorouracil and/or capecitabine response, were identified. Additionally, 27 novel single-nucleotide polymorphisms of unknown clinical significance were detected. Conclusions: This study reveals key pharmacogenetic variants in the Omani population, underscoring the importance of integrating pharmacogenomic testing into routine care to support safer, more personalized chemotherapy in the region. Full article

(This article belongs to the Section Pharmacogenetics)

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19 pages, 1706 KiB

Open AccessArticle

Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis

by David Ruiz-Ramos, José Jaime Martínez-Magaña, Isela Esther Juárez-Rojop, Germán Alberto Nolasco-Rosales, Fernanda Sosa-Hernández, Juan Daniel Cruz-Castillo, Josefa Cavazos, Adriana Callejas, Patricia Zavaleta-Ramírez, José Antonio Zorrilla-Dosal, Nuria Lanzagorta, Humberto Nicolini, Janitza L. Montalvo-Ortiz, David C. Glahn and Alma Delia Genis-Mendoza

Genes 2025, 16(5), 591; https://doi.org/10.3390/genes16050591 - 17 May 2025

Viewed by 330

Abstract

Background: Psychosis is one of the leading causes of disability worldwide. Individuals with early-onset psychosis (EOP) tend to experience a worse prognosis and shorter life expectancy. The etiology of EOP remains unclear, but epigenetic mechanisms are known to serve as the interface between [...] Read more.

Background: Psychosis is one of the leading causes of disability worldwide. Individuals with early-onset psychosis (EOP) tend to experience a worse prognosis and shorter life expectancy. The etiology of EOP remains unclear, but epigenetic mechanisms are known to serve as the interface between environmental exposures and biological processes to better understand its etiology. Objectives: We characterized the sociodemographic and clinical characteristics, as well as genome-wide epigenetic markers, in Mexican patients with EOP. Methods: We estimated epigenetic age, performed an epigenome-wide association study, and finally developed an epigenetic risk score (MRS) to predict manifestations of psychosis. Results: We found that patients with EOP have a higher epigenetic age using Wu’s clock (p = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, p = 0.046), global functioning (Wu’s clock, p = 0.027), and psychiatric admissions (DNAmTL, p = 0.038). In addition, we observed that a reduction in years of schooling is associated with an increase on epigenetic age (Levine’s clock, β = 5.07, p = 0.001). In our epigenome-wide association study, we identified eight CpGs associated with EOP. Noteworthy, a psychosis-methylation risk score (EOP-MRS) was associated with panic disorder (β = 1.36, p = 0.03), as well as auditory (β = 1.28, p = 0.04) and visual (β = 1.22, p = 0.04) hallucinations. Conclusions: Years of education have an impact on epigenetic age. Additionally, our study suggests associations of DNA methylation with EOP. Finally, we developed an MRS that associates clinical manifestations of psychosis. Full article

(This article belongs to the Section Neurogenomics)

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Graphical abstract

54 pages, 1175 KiB

Open AccessReview

Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy

by Pierre Bougnères and Catherine Le Stunff

Genes 2025, 16(5), 590; https://doi.org/10.3390/genes16050590 - 17 May 2025

Viewed by 537

Abstract

Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding the transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, the same ABCD1 mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal [...] Read more.

Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding the transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, the same ABCD1 mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal cord axonopathy starting in middle-aged adults. The accumulation of undegraded VLCFA in glial cell membranes and myelin has long been thought to be the central mechanism of X-ALD. Methods: This review discusses studies in mouse and drosophila models that have modified our views of X-ALD pathogenesis. Results: In the Abcd1 knockout (KO) mouse that mimics the spinal cord disease, the late manifestations of axonopathy are rapidly reversed by ABCD1 gene transfer into spinal cord oligodendrocytes (OLs). In a peroxin-5 KO mouse model, the selective impairment of peroxisomal biogenesis in OLs achieves an almost perfect phenocopy of cerebral ALD. A drosophila knockout model revealed that VLCFA accumulation in glial myelinating cells causes the production of a toxic lipid able to poison axons and activate inflammatory cells. Other mouse models showed the critical role of OLs in providing energy substrates to axons. In addition, studies on microglial changing substates have improved our understanding of neuroinflammation. Conclusions: Animal models supporting a primary role of OLs and axonal pathology and a secondary role of microglia allow us to revisit of X-ALD mechanisms. Beyond ABCD1 mutations, pathogenesis depends on unidentified contributors, such as genetic background, cell-specific epigenomics, potential environmental triggers, and stochasticity of crosstalk between multiple cell types among billions of glial cells and neurons. Full article

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

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11 pages, 237 KiB

Open AccessArticle

Association Between Genetically Predicted Memory and Self-Reported Foreign Language Proficiency

by Meruert B. Yerdenova, Gaukhar K. Datkhabayeva, Manzura K. Zholdassova, Altyngul T. Kamzanova, Zukhra M. Sadvakassova, Amal Bouzid, Poorna Manasa Bhamidimarri, Rifat Hamoudi, Ekaterina A. Semenova, Andrey K. Larin, Nikolay A. Kulemin, Edward V. Generozov, Tim Rees, Almira M. Kustubayeva and Ildus I. Ahmetov

Genes 2025, 16(5), 589; https://doi.org/10.3390/genes16050589 - 17 May 2025

Viewed by 488

Abstract

Background: Foreign language proficiency is a complex trait that reflects an individual’s ability to effectively understand and use a non-native language, shaped by both genetic and environmental factors. The aim of this study was to establish the relationship between genetically determined memory capacity [...] Read more.

Background: Foreign language proficiency is a complex trait that reflects an individual’s ability to effectively understand and use a non-native language, shaped by both genetic and environmental factors. The aim of this study was to establish the relationship between genetically determined memory capacity and self-reported foreign language proficiency in 129 children (63 males, 66 females, age 14.2 ± 3.9) and 128 adults (90 males, 38 females, age 29.8 ± 8.2). Methods: Seven single nucleotide polymorphisms (SNPs) previously linked with memory function were used in a polygenic analysis (CAMTA1 rs4908449, CLSTN2 rs6439886, COMT rs4680, CPEB3 rs11186856, SCN1A rs10930201, SNAP25 rs3746544, and WWC1 rs17070145). Self-reported foreign language proficiency was evaluated using a single-item question. Children’s level of immersion in foreign languages was divided into three categories: linguistic school, non-linguistic school with extra foreign language courses, and non-linguistic school without additional foreign language courses. Results: We found that genetically predicted memory capacity (i.e., number of memory-increasing alleles) was positively associated with self-reported foreign language proficiency in children (p = 0.0078 adjusted for age, sex, ethnicity, verbal IQ, and level of immersion in foreign languages). When combined, genetically predicted memory capacity, age, sex, ethnicity, verbal IQ, and level of immersion in foreign languages explained 31.5% (p < 0.0001) of the variance in children’s self-reported foreign language proficiency. The association between genetically predicted memory capacity and self-reported foreign language proficiency was replicated in adults (p = 0.0158 adjusted for age, sex, and ethnicity). Conclusions: Foreign language proficiency may partly depend on the presence of a high number of memory-increasing alleles in both children and adults. Full article

(This article belongs to the Section Neurogenomics)

11 pages, 858 KiB

Open AccessCase Report

Cumulative Effects of Genetic Variants Detected in a Child with Early-Onset Non-Syndromic Obesity Due to SIM-1 Gene Mutation

by Giovanni Luppino, Malgorzata Wasniewska, Mara Giordano, Giorgia Pepe, Letteria Anna Morabito, Debora Porri, Tommaso Aversa and Domenico Corica

Genes 2025, 16(5), 588; https://doi.org/10.3390/genes16050588 - 17 May 2025

Viewed by 349

Abstract

Background: Single-minded homolog 1 (SIM1) gene mutations with autosomal dominant inheritance have been related to hyperphagia and early-onset severe obesity. SIM1 is implicated in the development of hypothalamic nuclei, which play a crucial role in energy homeostasis. The development of melanocortin [...] Read more.

Background: Single-minded homolog 1 (SIM1) gene mutations with autosomal dominant inheritance have been related to hyperphagia and early-onset severe obesity. SIM1 is implicated in the development of hypothalamic nuclei, which play a crucial role in energy homeostasis. The development of melanocortin neural circuits in the hypothalamus is promoted by other factors such as Semaphorine 3 (SEMA3) and its receptors, such as PLXNA1-4 and NRP1-2. Loss-of-function across multiple SEMA3/NRP/PLXNA genes can collectively contribute to obesity onset. Case Description: A 3-year-old male was referred for the first time to Outpatient pediatric endocrinology due to early-onset and progressive severe obesity and hyperphagia. He presented neurobehavior disorders and partial diabetes insipidus. At age 6, the child was diagnosed with obesity-related complications, including hyperinsulinemia, impaired glucose tolerance, hypercholesterolemia, hepatic steatosis, and hypovitaminosis. The NGS analysis revealed four variants related to obesity: SIM1, SEMA3C, PLXNA4, and CREBBP gene mutations. Conclusions: The case presents the association of SIM-1 gene mutation with other obesity-related variants. The interactive and cumulative effects of the identified variants could coexist in the determination of severe obesity through abnormalities in the development and function of hypothalamic melanocortin circuits related to energy homeostasis. Although the pathogenic mutation of the SIM1 gene plays the main role, the complex clinical picture may be related to the possible cumulative effect of the other genetic mutations. Full article

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

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15 pages, 1375 KiB

Open AccessArticle

Comparative Transcriptome Analysis Elucidates the Desiccation Stress Adaptation in Sargassum muticum

by Wei Cao, Mingyi Zhang, Nan Wu, Yanxin Zheng, Xiaodong Li, Haiying Han, Tao Yu, Zhongxun Wu, Pei Qu and Bo Li

Genes 2025, 16(5), 587; https://doi.org/10.3390/genes16050587 - 16 May 2025

Viewed by 289

Abstract

Background/Objectives: Desiccation profoundly influences the distribution and abundance of intertidal seaweeds, necessitating robust molecular adaptations. Sargassum muticum is a brown seaweed inhabiting intertidal rocky substrates. During low tides, this species undergoes periodic aerial exposure. Such environmental conditions necessitate robust physiological mechanisms to mitigate [...] Read more.

Background/Objectives: Desiccation profoundly influences the distribution and abundance of intertidal seaweeds, necessitating robust molecular adaptations. Sargassum muticum is a brown seaweed inhabiting intertidal rocky substrates. During low tides, this species undergoes periodic aerial exposure. Such environmental conditions necessitate robust physiological mechanisms to mitigate desiccation stress. Yet, the molecular basis of this adaptation remains poorly understood. Methods: To investigate desiccation-responsive genes and elucidate the underlying mechanisms of adaptation, we exposed S. muticum to 6 h of controlled desiccation stress in sterilized ceramic trays, simulating natural tidal conditions, and performed comparative transcriptome analysis using RNA-seq on the Illumina NovaSeq 6000 platform. Results: High-quality sequencing identified 66,192 unigenes, with 1990 differentially expressed genes (1399 upregulated and 591 downregulated). These differentially expressed genes (DEGs) were categorized into regulatory genes—including mitogen-activated protein kinase (MAPK), calmodulin, elongation factor, and serine/threonine-protein kinase—and functional genes, such as heat shock protein family members (HSP20, HSP40, and HSP70), tubulin (TUBA and TUBB), and endoplasmic reticulum homeostasis-related genes (protein disulfide-isomerase A6, calreticulin, and calnexin). Gene Ontology (GO) enrichment highlighted upregulated DEGs in metabolic processes like glutathione metabolism, critical for oxidative stress mitigation, while downregulated genes were linked to transport functions, such as ammonium transport, suggesting reduced nutrient uptake during dehydration. KEGG pathway analysis revealed significant enrichment in “protein processing in endoplasmic reticulum” and “MAPK signaling pathway-plant”, implicating endoplasmic reticulum stress response and conserved signaling cascades in desiccation adaptation. Validation via qRT-PCR confirmed consistent expression trends for key genes, reinforcing the reliability of transcriptomic data. Conclusions: These findings suggest that S. muticum undergoes extensive biological adjustments to mitigate desiccation stress, highlighting candidate pathways for future investigations into recovery and tolerance mechanisms. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Molecular Genetics and Genomics—2nd Edition)

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13 pages, 2257 KiB

Open AccessArticle

Genetic Diversity Among Wild and Cultured Bighead Carp (Hypophthalmichthys nobilis) in the Middle Yangtze River by Microsatellite Markers

by Junru Wang, Qi Lei, Hanjun Jiang, Jun Liu, Xiaomu Yu, Xusheng Guo and Jingou Tong

Genes 2025, 16(5), 586; https://doi.org/10.3390/genes16050586 - 16 May 2025

Viewed by 184

Abstract

Background: Bighead carp (Hypophthalmichthys nobilis), a vital species in China’s freshwater ecosystems and aquaculture, has experienced significant population declines due to habitat degradation and intensive farming. Methods: In this study, eight polymorphic microsatellite markers were utilized to examine the genotypes and [...] Read more.

Background: Bighead carp (Hypophthalmichthys nobilis), a vital species in China’s freshwater ecosystems and aquaculture, has experienced significant population declines due to habitat degradation and intensive farming. Methods: In this study, eight polymorphic microsatellite markers were utilized to examine the genotypes and genetic diversity of 320 individuals of bighead carp populations located in the middle Yangtze River. This included four wild populations (ZX, DTH, SS, WH) and six cultured populations (HH, XZ, CH, QC, CD, HG). Results: Wild populations exhibited significantly higher genetic diversity (mean Na = 12.25 ± 0.63, Ho = 0.802 ± 0.063) than cultured groups (mean Na = 8.85 ± 1.21, He = 0.779 ± 0.032). Low differentiation (Fst < 0.05) among wild populations indicated high connectivity with low genetic structure, whereas cultured populations CH and HG showed moderate-to-high differentiation (Fst = 0.156–0.293). Bayesian analysis (K = 7) revealed a distinct clustering of wild populations, while cultured stocks exhibited admixed genetic ancestries. Bottleneck tests confirmed recent genetic bottlenecks in three cultured populations. Conclusions: Wild bighead carp populations retain a critical genetic diversity, serving as reservoirs for conservation, while intensive aquaculture practices threaten genetic integrity through allele loss and inbreeding. Full article

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

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11 pages, 368 KiB

Open AccessReview

Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies

by Mario Škarica, Gyula Acsadi and Sasha A. Živković

Genes 2025, 16(5), 585; https://doi.org/10.3390/genes16050585 - 15 May 2025

Viewed by 299

Abstract

Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH [...] Read more.

Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders. Full article

(This article belongs to the Section Neurogenomics)

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24 pages, 418 KiB

Open AccessSystematic Review

Understanding Glycogen Storage Disease Type IX: A Systematic Review with Clinical Focus—Why It Is Not Benign and Requires Vigilance

by Egidio Candela, Giulia Montanari, Andrea Zanaroli, Federico Baronio, Rita Ortolano, Giacomo Biasucci and Marcello Lanari

Genes 2025, 16(5), 584; https://doi.org/10.3390/genes16050584 - 15 May 2025

Viewed by 373

Abstract

Background/Objectives: Glycogen storage disease type IX (GSD IX) is a group of inherited metabolic disorders caused by phosphorylase kinase deficiency affecting the liver or muscle. Despite being relatively common among GSDs, GSD IX remains underexplored. Methods: A systematic review of GSD IX was [...] Read more.

Background/Objectives: Glycogen storage disease type IX (GSD IX) is a group of inherited metabolic disorders caused by phosphorylase kinase deficiency affecting the liver or muscle. Despite being relatively common among GSDs, GSD IX remains underexplored. Methods: A systematic review of GSD IX was conducted per PRISMA guidelines using SCOPUS and PubMed, registered with PROSPERO. Inclusion focused on human clinical studies published up to 31 December 2024. Results: A total of 400 patients with GSD IX were analyzed: 274 IXa (mean age at diagnosis 5.1 years), 72 IXc (mean age at diagnosis 4.9 years), 39 IXb (mean age at diagnosis 4.2 years), and 15 IXd (mean age at diagnosis 44.9 years). Hepatomegaly was commonly reported in types IXa, IXb, and especially IXc (91.7%), but was rare in IXd. Elevated transaminases were frequently observed in types IXa, IXb, and particularly IXc, while uncommon in IXd. Fasting hypoglycemia was occasionally observed in types IXa and IXb, more frequently in IXc (52.7%), and was not reported in IXd. Growth delay or short stature was observed in a substantial proportion of patients with types IXa (43.8%), IXb, and IXc, but was rare in IXd. Muscle involvement was prominent in IXd, with all patients showing elevated CPK (mean 1011 U/L). Neurological involvement was infrequently reported in types IXa and IXc. Conclusions: This systematic review includes the most extensive clinical case history of GSD IX described in the literature. The clinical spectrum of GSD IX varies widely among subtypes, with IXc being the most aggressive. While liver forms are generally present in early childhood, muscle-type IXd shows delayed onset and milder symptoms, often leading to diagnostic delays. For diagnosis, it is essential not to underestimate key clinical features such as hepatic involvement and hypoglycemia in a child under 5 years of age. Other manifestations, including the as-yet unexplored systemic involvement of bone and kidney, remain insufficiently understood and require further investigation. Next-generation sequencing has improved diagnostic precision over traditional biopsy. Dietary management, including uncooked cornstarch, Glycosade^®, and high-protein intake, remains the cornerstone of treatment. However, there is a paucity of well-designed, evidence-based studies to determine the most effective therapeutic approach. Despite its historically perceived benign course, the broad phenotypic variability of GSD IX, including progressive liver involvement and potential neurological complications, highlights its substantial clinical relevance and underscores the need for accurate diagnostic classification and long-term multidisciplinary follow-up. Full article

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

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22 pages, 2546 KiB

Open AccessArticle

Genome-Wide Association Studies and Candidate Genes for Egg Production Traits in Layers from an F₂ Crossbred Population Produced Using Two Divergently Selected Chicken Breeds, Russian White and Cornish White

by Natalia A. Volkova, Michael N. Romanov, Alan Yu. Dzhagaev, Polina V. Larionova, Ludmila A. Volkova, Alexandra S. Abdelmanova, Anastasia N. Vetokh, Darren K. Griffin and Natalia A. Zinovieva

Genes 2025, 16(5), 583; https://doi.org/10.3390/genes16050583 - 15 May 2025

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Abstract

Background/Objectives: Finding single nucleotide polymorphisms (SNPs) and candidate genes that influence the expression of key traits is essential for genomic selection and helps improve the efficiency of poultry production. Here, we aimed to conduct a genome-wide association study (GWAS) for egg production [...] Read more.

Background/Objectives: Finding single nucleotide polymorphisms (SNPs) and candidate genes that influence the expression of key traits is essential for genomic selection and helps improve the efficiency of poultry production. Here, we aimed to conduct a genome-wide association study (GWAS) for egg production traits in an F₂ resource population of chickens (Gallus gallus). Methods: The examined F₂ population was produced by crossing two divergently selected breeds with contrasting phenotypes for egg performance traits, namely Russian White (of higher egg production) and Cornish White (of lower egg production). Sampled birds (n = 142) were genotyped using the Illumina Chicken 60K SNP iSelect BeadChip. Results: In the course of the GWAS analysis, we were able to clarify significant associations with phenotypic traits of interest and economic value by using 47,432 SNPs after the genotype dataset was filtered. At the threshold p < 1.06 × 10⁻⁶, we found 23 prioritized candidate genes (PCGs) associated with egg weight at the age of 42–52 weeks (FGF14, GCK), duration of egg laying (CNTN4), egg laying cycle (SAMD12) and egg laying interval (PHF5A, AKR1B1, CALD1, ATP7B, PIK3R4, PTK2, PRKCE, FAT1, PCM1, CC2D2A, BMS1, SEMA6D, CDH13, SLIT3, ATP10B, ISCU, LRRC75A, LETM2, ANKRD24). Moreover, two SNPs were co-localized within the FGF14 gene. Conclusions: Based on our GWAS findings, the revealed SNPs and candidate genes can be used as genetic markers for egg weight and other performance characteristics in chickens to attain genetic enhancement in production and for further genomic selection. Full article

(This article belongs to the Special Issue Genetic Breeding of Poultry)

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14 pages, 641 KiB

Open AccessReview

Genetic Aspects of Tooth Agenesis

by Clarissa Modafferi, Ilaria Tucci, Francesco Maria Bogliardi, Elena Gimondo, Pietro Chiurazzi, Elisabetta Tabolacci and Cristina Grippaudo

Genes 2025, 16(5), 582; https://doi.org/10.3390/genes16050582 - 15 May 2025

Viewed by 387

Abstract

Tooth agenesis is among the most prevalent congenital anomalies affecting human dentition, characterized by the developmental absence of one or more teeth. This condition may be present in either syndromic or non-syndromic forms, with significant implications for oral function, aesthetics, and craniofacial development. [...] Read more.

Tooth agenesis is among the most prevalent congenital anomalies affecting human dentition, characterized by the developmental absence of one or more teeth. This condition may be present in either syndromic or non-syndromic forms, with significant implications for oral function, aesthetics, and craniofacial development. This narrative review aims to provide a comprehensive overview of tooth agenesis, defining its classification, genetic underpinnings, epidemiological aspects, phenotypic features, and therapeutic approaches. Recent advances in genetic research have identified numerous causative genes, notably EDA, MSX1, WNT10A, and PAX9, each associated with specific patterns of missing teeth and involved in isolated and/or syndromic forms. Additionally, genes such as TSPEAR, LRP6, PITX2, and GREM2 contribute to varying degrees of severity and tooth distribution, often blurring the lines between syndromic and isolated cases. The genotype-phenotype correlations underscore the complexity of the underlying molecular pathways involved in odontogenesis. From a therapeutic perspective, the management of tooth agenesis requires a multidisciplinary approach, often involving orthodontic, prosthetic, and surgical interventions tailored to the severity of tooth loss and patient age. Early diagnosis represents a crucial role in treatment planning, facilitating timely intervention during growth and enhancing long-term outcomes. In conclusion, tooth agenesis remains a complex clinical condition with a strong genetic basis. A patient-centered and interdisciplinary strategy is essential to address both functional and psychosocial needs. 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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Genes, Volume 16, Issue 5 (May 2025) – 141 articles

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