Genes

17 pages, 8644 KiB

Open AccessArticle

Comparative Chloroplast Genomics and Codon Usage Bias Analysis in Hevea Genus

by Yang Yang, Xueyang Liu, Lixia He, Zhenhua Li, Boxuan Yuan, Fengyan Fang, Mei Wang, Aifang Li, Cheng Liu, Minmin He, Shugang Hui, Wenda Wang and Xuchu Wang

Genes 2025, 16(2), 201; https://doi.org/10.3390/genes16020201 - 6 Feb 2025

Abstract

Objectives: This study investigates the cpDNA sequences from six Hevea species, aiming to explore their genomic characteristics, gene content, and genetic relationships. The objectives include understanding the structure of these genomes, identifying potential gene rearrangements, and providing insights into genetic improvement and conservation [...] Read more.

Objectives: This study investigates the cpDNA sequences from six Hevea species, aiming to explore their genomic characteristics, gene content, and genetic relationships. The objectives include understanding the structure of these genomes, identifying potential gene rearrangements, and providing insights into genetic improvement and conservation strategies for the Hevea genus. Methods: cpDNA sequences from six Hevea species were sequenced and analyzed. Genome sizes, GC content, gene encoding potential, and structural integrity were assessed. Simple sequence repeats (SSRs) and codon usage were analyzed, with a focus on optimal codons and their frequency. Phylogenetic analysis was conducted to determine the genetic relationships within the Hevea genus. Results: The cpDNAs from the six species exhibited genome sizes ranging from 161,093 bp to 161,254 bp, with GC content between 35.72% and 35.75%. Each genome contained 91 to 92 protein-coding genes, with the infA gene consistently present. No significant gene rearrangements were detected, and SSR analysis revealed mono-repeats primarily composed of A/T bases. Codon usage analysis indicated that leucine is predominantly encoded by the UUA codon, and 31 optimal codons were identified, mainly ending in A or U. Phylogenetic analysis clarified the genetic relationships among the species. Conclusions: The study provides detailed insights into the cpDNA characteristics of Hevea species, highlighting stable genome structures, conserved genes, and specific patterns of codon usage. These findings are valuable for conservation efforts, genetic improvement strategies, and the sustainable use of Hevea germplasm. Full article

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

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13 pages, 2339 KiB

Open AccessArticle

Genome-Wide In Silico Analysis of Leucine-Rich Repeat R-Genes in Perilla citriodora: Classification and Expression Insights

by Seon-Hwa Bae, Yedomon Ange Bovys Zoclanclounon, Gyu-Hwang Park, Jun-Dae Lee and Tae-Ho Kim

Genes 2025, 16(2), 200; https://doi.org/10.3390/genes16020200 - 6 Feb 2025

Viewed by 142

Abstract

Background: Resistance (R) genes are crucial for defending Perilla against pathogens like anthracnose, downy mildew, and phytophthora blight. Nucleotide-binding site leucine-rich repeat (NBS-LRR) genes, the largest R-gene family, play a central role in immunity. This study aimed to identify and [...] Read more.

Background: Resistance (R) genes are crucial for defending Perilla against pathogens like anthracnose, downy mildew, and phytophthora blight. Nucleotide-binding site leucine-rich repeat (NBS-LRR) genes, the largest R-gene family, play a central role in immunity. This study aimed to identify and characterize NBS-LRR genes in P. citriodora ‘Jeju17’. Methods: Previously conducted genome-wide data for ‘Jeju17’ were analyzed in silico to identify NBS-LRR genes. Results: A total of 535 NBS-LRR genes were identified, with clusters on chromosomes 2, 4, and 10. A unique RPW8-type R-gene was located on chromosome 7. Conclusions: This study provides insights into the NBS-LRR gene family in ‘Je-ju17’, highlighting its role in disease resistance and evolutionary dynamics. By identifying can-didate R-genes, this research supports breeding programs to develop disease-resistant cultivars and improves our understanding of plant immunity. Full article

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

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15 pages, 1602 KiB

Open AccessReview

The Current State of Breast Cancer Genetics in Populations of African Ancestry

by Sarah Elisabeth Santos Cupertino, Ana Carolina Aparecida Gonçalves, Claudemira Vieira Gusmão Lopes, Daniela Fiori Gradia and Marcia Holsbach Beltrame

Genes 2025, 16(2), 199; https://doi.org/10.3390/genes16020199 - 6 Feb 2025

Viewed by 196

Abstract

Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those [...] Read more.

Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those focused on BRCA1 and BRCA2 genes, have revealed population-specific variations in BC susceptibility. Despite efforts to investigate BC genetics in African and African-descendant populations, research remains limited compared to studies conducted in populations of European descent. Socioeconomic factors further compound the challenges faced by marginalized populations, influencing disease outcomes and treatment efficacy. This review explores the BC literature in African and African-descendant populations, highlighting population-specific genetic variants associated with the disease’s subtypes, treatment response, and disease evolution. Limited sample sizes and lack of data on genetic ancestry hinder the development of precise risk stratification and treatment strategies. Efforts to expand research, improve data collection, and enhance genetic analyses in diverse populations are crucial steps toward addressing racial disparities and advancing BC care on a global scale. Full article

(This article belongs to the Special Issue Human Genome Diversity: History and Health)

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13 pages, 1156 KiB

Open AccessArticle

The POLG Variant c.678G>C; p.(Gln226His) Is Associated with Mitochondrial Abnormalities in Fibroblasts Derived from a Patient Compared to a First-Degree Relative

by Imra Mantey, Felix Langerscheidt, Çağla Çakmak-Durmaz, Naomi Baba, Katharina Burghardt, Mert Karakaya and Hans Zempel

Genes 2025, 16(2), 198; https://doi.org/10.3390/genes16020198 - 5 Feb 2025

Viewed by 225

Abstract

Background: The nuclear-encoded enzyme polymerase gamma (Pol-γ) is crucial in the replication of the mitochondrial genome (mtDNA), which in turn is vital for mitochondria and hence numerous metabolic processes and energy production in eukaryotic cells. Variants in the POLG gene, which encodes [...] Read more.

Background: The nuclear-encoded enzyme polymerase gamma (Pol-γ) is crucial in the replication of the mitochondrial genome (mtDNA), which in turn is vital for mitochondria and hence numerous metabolic processes and energy production in eukaryotic cells. Variants in the POLG gene, which encodes the catalytic subunit of Pol-γ, can significantly impair Pol-γ enzyme function. Pol-γ-associated disorders are referred to as POLG-spectrum disorders (POLG-SDs) and are mainly autosomal-recessively inherited. Clinical manifestations include muscle weakness and fatigue, and severe forms of the disease can lead to premature death in infancy, childhood, and early adulthood, often associated with seizures, liver failure, or intractable epilepsy. Here, we analyzed fibroblasts from a compound heterozygous patient with the established pathogenic variant c.2419C>T; p.(Arg807Cys) and a previously undescribed variant c.678G>C; p.(Gln226His) with a clinical manifestation compatible with POLG-SDs, sensory ataxic neuropathy, and infantile muscular atrophy. We conducted a battery of functional studies for Pol-γ and mitochondrial dysfunction on the patient’s fibroblasts, to test whether the novel variant c.678G>C; p.(Gln226His) may be causative in human disease. Aims/Methods: We analyzed skin-derived fibroblasts in comparison to a first-degree relative (the mother of the patient), an asymptomatic carrier harboring only the established c.2419C>T; p.(Arg807Cys) mutation. Assessments of mitochondrial function included measurements of mtDNA content, mRNA levels of mitochondrial genes, mitochondrial mass, and mitochondrial morphology. Case Presentation and Results: A 13-year-old male presented with symptoms starting at three years of age, including muscle weakness and atrophy in the lower extremities and facial muscles, which later extended to the upper limbs, voice, and back muscles, without further progression. The patient also reported fatigue and muscle pain after physical activity, with no sensory deficits. Extensive diagnostic tests such as electromyography, nerve conduction studies, muscle biopsy, and MRI were unremarkable. Exome sequencing revealed that he carried the compound heterozygous variants in POLG c.678G>C; p.(Gln226His) and c.2419C>T; p.(Arg807Cys), but no other potential genetic pathogenic causes. In comparison to a first-degree relative (his mother) who only carried the c.2419C>T; p.(Arg807Cys) pathogenic mutation, in vitro analyses revealed a significant reduction in mtDNA content (~50%) and mRNA levels of mtDNA-encoded proteins. Mitochondrial mass was reduced by approximately 20%, and mitochondrial interconnectivity within cells was impaired, as determined by fluorescence microscopy and mitochondrial staining. Conclusions: Our findings suggest that the c.678G>C; p.(Gln226His) variant, in conjunction with the c.2419C>T; p.(Arg807Cys) mutation, may compromise mtDNA replication and mitochondrial function and could result in clinically significant mitochondriopathy. As this study is based on one patient compared to a first-degree relative (but with an identical mitochondrial genome), the pathogenicity of c.678G>C; p.(Gln226His) of POLG should be confirmed in future studies, in particular, in conjunction with other POLG-variants. Full article

(This article belongs to the Special Issue Molecular Genetics of Neurodegenerative Diseases and Neuromuscular Diseases)

18 pages, 1762 KiB

Open AccessArticle

Effects of Combined Transcriptome and Metabolome Analysis Training on Athletic Performance of 2-Year-Old Trot-Type Yili Horses

by Liping Yang, Pengcheng Li, Xinxin Huang, Chuankun Wang, Yaqi Zeng, Jianwen Wang, Xinkui Yao and Jun Meng

Genes 2025, 16(2), 197; https://doi.org/10.3390/genes16020197 - 4 Feb 2025

Viewed by 220

Abstract

Objectives: Training is essential for enhancing equine athletic performance, but the genetic mechanisms that regulate athletic performance are unknown. Therefore, this paper aims to identify candidate genes and metabolic pathways for the effects of training on equine athletic performance through multi-omics analyses. Methods: [...] Read more.

Objectives: Training is essential for enhancing equine athletic performance, but the genetic mechanisms that regulate athletic performance are unknown. Therefore, this paper aims to identify candidate genes and metabolic pathways for the effects of training on equine athletic performance through multi-omics analyses. Methods: The experiment selected 12 untrained trot-type Yili horses, which underwent a 12-week professional training program. Blood samples were collected at rest before training (BT) and after training (AT). Based on their race performance, whole blood and serum samples from 4 horses were chosen for transcriptomic and metabolomic analyses. Results: The race performance of the horses is dramatically improved in the AT period compared to the BT (p < 0.01) period. The transcriptome analysis identified a total of 57 differentially expressed genes, which were significantly enriched in pathways related to circadian entrainment, steroid hormone biosynthesis, chemokine signaling, and cholinergic synapses (p < 0.05). Additionally, metabolomic analysis revealed 121 differentially identified metabolites, primarily enriched in metabolic pathways such as histidine metabolism, purine metabolism, and the PI3K-Akt signaling pathway. The integration of transcriptomic and metabolomic analyses uncovered five shared pathways, and further combined pathway analyses identified eight differentially expressed genes that correlate with 19 differentially identified metabolites. Conclusions: The current findings will contribute to establishing a theoretical framework for investigating the molecular mechanisms of genes associated with the impact of training on equine athletic performance. Additionally, these results will serve as a foundation for enhancing the athletic capabilities of trot-type Yili horses. Full article

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

22 pages, 1500 KiB

Open AccessArticle

Molecular Review of Suspected Alport Syndrome Patients—A Single-Centre Experience

by Paulina Halat-Wolska, Elżbieta Ciara, Michał Pac, Łukasz Obrycki, Dorota Wicher, Katarzyna Iwanicka-Pronicka, Ewelina Bielska, Beata Chałupczyńska, Dorota Siestrzykowska, Grażyna Kostrzewa, Piotr Stawiński, Rafał Płoski, Mieczysław Litwin and Krystyna Chrzanowska

Genes 2025, 16(2), 196; https://doi.org/10.3390/genes16020196 - 4 Feb 2025

Viewed by 376

Abstract

Background: Alport syndrome (AS) is a clinically and genetically heterogeneous glomerulopathy resulting from pathogenic variants in COL4A3, COL4A4, and COL4A5. Genetic diagnosis is increasingly being conducted using next-generation sequencing (NGS). Methods: Within eight years, we examined a group of 247 Polish individuals [...] Read more.

Background: Alport syndrome (AS) is a clinically and genetically heterogeneous glomerulopathy resulting from pathogenic variants in COL4A3, COL4A4, and COL4A5. Genetic diagnosis is increasingly being conducted using next-generation sequencing (NGS). Methods: Within eight years, we examined a group of 247 Polish individuals and found in total 138 unrelated probands suspected with AS based on clinical course, laboratory findings, and/or family history, as well as the total of 109 family members. We applied a targeted NGS panel to identify the genetic spectrum of AS. Known and novel variants were revealed, and detailed evaluation was performed according to ACMG/AMP guidelines to classify them as pathogenic/likely pathogenic/VUS changes. Identified genotypes were compared with clinical manifestations: hematuria, proteinuria, chronic kidney disease, sensorineural hearing impairment, ocular abnormalities, and hypertension. Results: The molecular background was established in 109/138 probands. Overall, 79 different COL4A3-COL4A5 changes (56 known and 23 novel) were revealed. About 97% were SNVs, and only two COL4A5 CNVs were identified. In total, 11 recurrent COL4A3-COL4A5 variants were observed, including the most frequent COL4A5:p.Gly624Asp, accounting for 31% of X-linked AS. Conclusions: The use of NGS panel has shown considerable promise in the field of AS, increasing diagnostic rate to 79% and reducing time to diagnosis. The phenotype-driven gene panel, specific for genetic diseases in the pediatric population, is an affordable alternative to WGS and WES, offering comparable diagnostic efficacy and supporting its implementation as a first-line genetic test in rare diseases, including AS. Based on the obtained genotype–phenotype correlation, we assessed that NGS allows us to avoid invasive renal biopsy in AS diagnosis. It provides AS confirmation/exclusion, atypical AS identification, symptomatic/asymptomatic monoallelic COL4A3-COL4A5 carrier (especially COL4A5 females) determination, and inheritance pattern establishment. AS diagnosis confirmation enables clinical course prediction and is crucial for the early introduction of renoprotective treatment with renin–angiotensin–aldosterone system blockade, aimed at slowing the disease progression and estimating the risk in family members, which is important for genetic counselling. Full article

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

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11 pages, 3412 KiB

Open AccessArticle

Maternal and Parent-of-Origin Gene–Environment Effects on the Etiology of Orofacial Clefting

by Nikola Rasevic, Joseph Bastasic, Michele Rubini, Mohan R. Rakesh, Kelly M. Burkett, Debashree Ray, Peter A. Mossey, Borut Peterlin, Mohammad Faisal J. Khan, Amin Ravaei, Luca Autelitano, Maria C. Meazzini, Julian Little and Marie-Hélène Roy-Gagnon

Genes 2025, 16(2), 195; https://doi.org/10.3390/genes16020195 - 4 Feb 2025

Viewed by 275

Abstract

Background/Objectives: We investigated maternal and parent-of-origin (PoO) gene-environment interaction effects on the risk of nonsyndromic orofacial clefts for two maternal environmental factors: periconceptional smoking and folic acid supplementation. Methods: Genome-wide single nucleotide polymorphisms (SNPs) genotypes and TopMed-imputed genotypes were obtained for case-parent triads [...] Read more.

Background/Objectives: We investigated maternal and parent-of-origin (PoO) gene-environment interaction effects on the risk of nonsyndromic orofacial clefts for two maternal environmental factors: periconceptional smoking and folic acid supplementation. Methods: Genome-wide single nucleotide polymorphisms (SNPs) genotypes and TopMed-imputed genotypes were obtained for case-parent triads from the EUROCRAN and ITALCLEFT studies. Candidate regions were selected around target SNPs from a previous genome-wide association study, resulting in 12 (726 SNPs) and 11 regions (730 SNPs) for maternal and PoO effects, respectively. Log-linear models were used to analyze 404 case-parent triads and 40 case-parent dyads. p-values were combined across regions. Results: None of the interactions reached statistical significance after correction for the number of regions tested. Nominally significant (pooled p-values < 0.05) interactions pointed to regions in or close to genes LRRC7 (maternal gene-folate interaction), NCKAP5 (PoO-smoking interaction), and IFT43 and GPATCH2L (PoO-folate interaction). Conclusions: Our results suggested that the genetic effects in or around these genes were heightened under periconceptional exposure to tobacco or no folic acid supplementation. The involvement of these genes in orofacial cleft development, in conjunction with environmental exposures, should be further studied. Full article

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

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13 pages, 535 KiB

Open AccessReview

Narrative Review of Genetic and Immunological Mechanisms Involved in the Pathogenesis of Kimura’s Disease: New Therapeutic Targets

by Antonella Loperfido, Carlo Cavaliere, Bruno Fionda, Gianluca Bellocchi, Simonetta Masieri and Marco Caminati

Genes 2025, 16(2), 194; https://doi.org/10.3390/genes16020194 - 4 Feb 2025

Viewed by 271

Abstract

Kimura’s disease (KD) is a rare, chronic inflammatory disorder that predominantly affects young men of East Asian descent. It is characterized by painless solid masses primarily localized to the deep subcutaneous tissues of the head and neck, eosinophilia, and elevated serum immunoglobulin E [...] Read more.

Kimura’s disease (KD) is a rare, chronic inflammatory disorder that predominantly affects young men of East Asian descent. It is characterized by painless solid masses primarily localized to the deep subcutaneous tissues of the head and neck, eosinophilia, and elevated serum immunoglobulin E (IgE). While the exact cause remains unclear, the pathogenesis is thought to involve dysregulated immune responses, particularly those mediated by T-helper cells 2 (Th2), eosinophils, and IgE production. Advances in molecular biology have suggested that genetic factors play a significant role in the development and progression of this chronic inflammatory condition. Recent studies have implicated several genes and immune pathways in its development, and understanding these genetic components may provide insights into better diagnostic tools and therapeutic strategies for KD. In this regard, biological therapies, by targeting the immune mechanisms underlying KD, have been used to treat this challenging condition with promising results, contributing to a better understanding of the pathogenesis of this rare disorder. The aim of this study was to review the literature concerning the genetic factors and immune mechanisms that contribute to the pathogenesis of KD, with a special focus on the role of biological therapies. Full article

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

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18 pages, 3208 KiB

Open AccessArticle

GRM1 as a Candidate Gene for Buffalo Fertility: Insights from Genome-Wide Association Studies and Its Role in the FOXO Signaling Pathway

by Wangchang Li, Haiying Zheng, Duming Cao, Anqin Duan, Liqing Huang, Chao Feng and Chunyan Yang

Genes 2025, 16(2), 193; https://doi.org/10.3390/genes16020193 - 4 Feb 2025

Viewed by 234

Abstract

Background: Water buffaloes represent a crucial genetic resource for the global dairy industry, yet enhancements in their production performance remain relatively constrained. The advent of advanced sequencing technologies, coupled with genome-wide association studies (GWASs), has significantly boosted the potential for breeding superior-quality water [...] Read more.

Background: Water buffaloes represent a crucial genetic resource for the global dairy industry, yet enhancements in their production performance remain relatively constrained. The advent of advanced sequencing technologies, coupled with genome-wide association studies (GWASs), has significantly boosted the potential for breeding superior-quality water buffalo. Methods: An integrated genomic analysis was performed on sequencing data from 100 water buffaloes, utilizing the high-quality UOA_WB_1 genome assembly as a reference. This study particularly emphasized reproduction-related traits, with a focus on age at first calving (AFC). Results: Our analysis revealed two significant single-nucleotide polymorphisms (SNPs). Based on these genetic markers, the GRM1 gene was identified as a candidate gene. This gene shows substantial involvement in various reproduction-associated pathways, including the FOXO signaling pathway, calcium signaling pathway, and estrogen signaling pathway. Conclusions: The identification of GRM1 as a candidate gene provides a robust theoretical basis for molecular breeding strategies aimed at enhancing fertility in water buffaloes. These findings offer critical scientific support for optimizing breeding programs, thereby improving overall production efficiency. Full article

(This article belongs to the Special Issue Buffalo Genetics and Genomics)

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19 pages, 2891 KiB

Open AccessArticle

Unveiling Photoperiod-Responsive Regulatory Networks in Tropical Maize Through Transcriptome Analysis

by Tianhui Zheng, Jinge Bo, Jing Wang, Siyuan Li, Haonan Li, Mengyao Liu, Hongbin Niu, Thanhliem Nguyen, Yanhui Chen and Juan Sun

Genes 2025, 16(2), 192; https://doi.org/10.3390/genes16020192 - 4 Feb 2025

Viewed by 242

Abstract

Background/Objectives: Maize (Zea mays L.), a crop of worldwide importance, owes its adaptability to diverse environments to its genetic variation. However, tropical maize exhibits intrinsic photoperiod sensitivity, limiting its adaptability to temperate regions. Photoperiod sensitivity significantly affects the flowering time and other [...] Read more.

Background/Objectives: Maize (Zea mays L.), a crop of worldwide importance, owes its adaptability to diverse environments to its genetic variation. However, tropical maize exhibits intrinsic photoperiod sensitivity, limiting its adaptability to temperate regions. Photoperiod sensitivity significantly affects the flowering time and other agronomic traits, but the underlying molecular mechanisms remain poorly understood. In this study, the aim is to elucidate the transcriptional regulatory networks mediating photoperiod responses in tropical maize inbred line Su65, providing insights into improving photoperiod adaptability. Methods: RNA-seq analysis was carried out to investigate photoperiod-responsive genes and pathways in tropical line Su65 exposed to varying photoperiod conditions. Differential expression analysis, functional enrichment, and the construction of protein–protein interaction (PPI) networks were carried out to investigate transcriptional dynamics. Additionally, qRT-PCR was employed to confirm the expression patterns of key candidate genes and generate detailed temporal expression profiles. Results: A total of 1728 differentially expressed genes (DEGs) were identified, with significant enrichment in pathways such as stress responses, redox homeostasis, and secondary metabolite biosynthesis. A set of new key hub genes (such as Zm00001d048531, Zm00001d018821, Zm00001d034892, etc.) were identified through PPI network analysis. Temporal expression profiling of ZmPHYB1, ZmPHYC1, ZmFKF2, ZmGI2, and ZmPRR37a, the key genes involved in circadian rhythms, revealed distinct regulatory patterns of photoperiod-sensitive genes at different time points, highlighting their roles in flowering time regulation and developmental transitions. Conclusions: In this study, critical molecular networks underlying photoperiod sensitivity in tropical maize are uncovered and a foundation is provided for improving photoperiod adaptability through genetic improvement. By integrating RNA-seq and qRT-PCR, the research offers valuable insights into transcriptional dynamics and their role in maize development under photoperiodic regulation. Full article

(This article belongs to the Special Issue Genetic and Genomic Studies of Crop Breeding)

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40 pages, 1989 KiB

Open AccessArticle

Evaluation of Prenatal Transportation Stress on DNA Methylation (DNAm) and Gene Expression in the Hypothalamic–Pituitary–Adrenal (HPA) Axis Tissues of Mature Brahman Cows

by Audrey L. Earnhardt-San, Emilie C. Baker, Kubra Z. Cilkiz, Rodolfo C. Cardoso, Noushin Ghaffari, Charles R. Long, Penny K. Riggs, Ronald D. Randel, David G. Riley and Thomas H. Welsh, Jr.

Genes 2025, 16(2), 191; https://doi.org/10.3390/genes16020191 - 4 Feb 2025

Viewed by 217

Abstract

Background/Objectives: The experience of prenatal stress results in various physiological disorders due to an alteration of an offspring’s methylome and transcriptome. The objective of this study was to determine whether PNS affects DNA methylation (DNAm) and gene expression in the stress axis tissues [...] Read more.

Background/Objectives: The experience of prenatal stress results in various physiological disorders due to an alteration of an offspring’s methylome and transcriptome. The objective of this study was to determine whether PNS affects DNA methylation (DNAm) and gene expression in the stress axis tissues of mature Brahman cows. Methods: Samples were collected from the paraventricular nucleus (PVN), anterior pituitary (PIT), and adrenal cortex (AC) of 5-year-old Brahman cows that were prenatally exposed to either transportation stress (PNS, n = 6) or were not transported (Control, n = 8). The isolated DNA and RNA samples were, respectively, used for methylation and RNA-Seq analyses. A gene ontology and KEGG pathway enrichment analysis of each data set within each sample tissue was conducted with the DAVID Functional Annotation Tool. Results: The DNAm analysis revealed 3, 64, and 99 hypomethylated and 2, 93, and 90 hypermethylated CpG sites (FDR < 0.15) within the PVN, PIT, and AC, respectively. The RNA-Seq analysis revealed 6, 25, and 5 differentially expressed genes (FDR < 0.15) in the PVN, PIT, and AC, respectively, that were up-regulated in the PNS group relative to the Control group, as well as 24 genes in the PIT that were down-regulated. Based on the enrichment analysis, several developmental and cellular processes, such as maintenance of the actin cytoskeleton, cell motility, signal transduction, neurodevelopment, and synaptic function, were potentially modulated. Conclusions: The methylome and transcriptome were altered in the stress axis tissues of mature cows that had been exposed to prenatal transportation stress. These findings are relevant to understanding how prenatal experiences may affect postnatal neurological functions. Full article

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

9 pages, 760 KiB

Open AccessArticle

FOXP2 Expression and Oral Feeding Success in Preterm Infants: Sex 2 Differences

by Leonardo Henrique Ferreira Gomes, Andressa Brito Marques, Isabel Cristina de Meireles Dias, Daniela Prado Cunha, Hellen Porto Pimenta, Letícia da Cunha Guida, Sabrina Lopes Lucena and Adriana Duarte Rocha

Genes 2025, 16(2), 190; https://doi.org/10.3390/genes16020190 - 4 Feb 2025

Viewed by 365

Abstract

Background: The FOXP2 gene, crucial for speech and motor functions, exhibits sex-specific expression differences. In premature infants, elevated FOXP2 expression, particularly in females, correlates with improved oral feeding readiness, indicating the potential for enhancing neonatal care. Objective: This study investigates FOXP2 gene expression [...] Read more.

Background: The FOXP2 gene, crucial for speech and motor functions, exhibits sex-specific expression differences. In premature infants, elevated FOXP2 expression, particularly in females, correlates with improved oral feeding readiness, indicating the potential for enhancing neonatal care. Objective: This study investigates FOXP2 gene expression in premature newborns across five feeding stages using salivary RNA, focusing on sex differences and their impact on oral feeding readiness to refine neonatal clinical protocols. Methods: FOXP2 expression was analyzed using RT-qPCR and the ΔΔCt method across five feeding stages in 45 premature newborns using saliva-derived RNA (n = 225). Results: FOXP2 expression increased significantly through feeding stages, especially in full oral feeding. Female infants showed consistently higher expression levels than males, with 58% higher expression by stage 5. Significant sex differences were apparent from stage 2. Conclusions: FOXP2 expression impacts neuromuscular coordination and feeding readiness in preterm infants. The sex differences suggest that FOXP2 could serve as a non-invasive biomarker for predicting oral feeding readiness, potentially improving clinical outcomes. Perspectives: FOXP2 gene expression correlates with better oral feeding readiness in premature infants and may serve as a non-invasive biomarker to improve neonatal care. The study could enhance neonatal care, leading to improved outcomes and reduced hospital stays for preterm infants. Full article

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

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18 pages, 3504 KiB

Open AccessArticle

Fluctuating Genetic Influences at Three Different Stages of Development of Dental Arches: A Complex System

by Toby Hughes, Zuliani Mahmood, Jamal Giri, Grant Townsend and Alan Henry Brook

Genes 2025, 16(2), 189; https://doi.org/10.3390/genes16020189 - 3 Feb 2025

Viewed by 408

Abstract

Background/Objectives: The development of dental arches is a complex adaptive system with interactions between genetic and environmental factors. At different developmental stages, the relative contribution of these factors varies. The aims of this project were to identify the longitudinal changes of dental [...] Read more.

Background/Objectives: The development of dental arches is a complex adaptive system with interactions between genetic and environmental factors. At different developmental stages, the relative contribution of these factors varies. The aims of this project were to identify the longitudinal changes of dental arches in the primary, mixed and permanent dentition stages, using curve fitting methods on serial dental casts, and to investigate the contribution of the genotype to dental arch development. Methods: Longitudinal dental records from 125 monozygotic same-sex twin pairs, 89 dizygotic same-sex twin pairs, and 49 opposite-sex dizygotic twin pairs were used. Standardized model photographs were collected, and key landmarks were digitized. Fourth-order orthogonal polynomials were applied to the Cartesian data. Descriptive statistics were calculated, and structural equation models were developed to analyze the individual polynomial coefficients. The final models employed a genetic simplex framework, enabling the evaluation of how genetic and environmental influences changed over time. These changes were examined both quantitatively (e.g., variations in heritability) and qualitatively (e.g., the influence of different genes at various stages). Results: In the primary dentition, arches were typically parabolic, while in the permanent dentition, they tended to be more square-shaped. Asymmetry made a minor contribution to variation across all stages of development. Genetic analysis revealed that a core group of genes influenced arch shape over time, though their impact varied. Additionally, some genes were specific to certain developmental stages, with their relative contributions differing significantly. Notably, there was evidence of sexual heterogeneity in arch shape, particularly in the permanent dentition. Heritability was consistently high, both at individual developmental stages and throughout the overall developmental process. Conclusions: The degree of genetic influence at each developmental stage was substantial but it fluctuated between the primary, mixed, and permanent dentition stages. Full article

(This article belongs to the Special Issue The CranioFacial Biology Group at the University of Adelaide Collection: Genetic, Epigenetic and Environmental Factors in Complex Adaptive Systems, Multilayer Complex Interactive Networks, and Multiple Models During Oral Development)

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14 pages, 1523 KiB

Open AccessReview

The p12 Subunit Choreographs the Regulation and Functions of Two Forms of DNA Polymerase δ in Mammalian Cells

by Dazhong Xu, Selvaraj Ayyamperumal, Sufang Zhang, Jinjin Chen, Ernest Y. C. Lee and Marietta Y. W. T. Lee

Genes 2025, 16(2), 188; https://doi.org/10.3390/genes16020188 - 3 Feb 2025

Viewed by 417

Abstract

There are two forms of DNA polymerase δ in human cells, Pol δ4 and Pol δ3, which differ based on their possession of the p12 subunit. The degradation of p12 has emerged as an important regulatory mechanism that controls the generation of Pol [...] Read more.

There are two forms of DNA polymerase δ in human cells, Pol δ4 and Pol δ3, which differ based on their possession of the p12 subunit. The degradation of p12 has emerged as an important regulatory mechanism that controls the generation of Pol δ3. The underlying importance of this system lies in the altered enzymatic properties of the two forms of Pol δ engendered by the influence of p12. We briefly review how the balance of these two forms is regulated through the degradation of p12. We focus on the roles of Pol δ4, whose cellular functions are less well known. This is significant because recent studies show that this is the form engaged in the homology-dependent repair of double-strand breaks. We consider new horizons for future research into this system and their potential involvement in tumorigenesis. Full article

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15 pages, 2865 KiB

Open AccessArticle

Transcriptomic Analysis Reveals Patterns of Expression of Stage-Specific Genes in Early Apis cerana Embryos

by Runlang Su, Yuhui Chen, Rui Zhu, Guiling Ding, Kun Dong, Mao Feng and Jiaxing Huang

Genes 2025, 16(2), 187; https://doi.org/10.3390/genes16020187 - 3 Feb 2025

Viewed by 358

Abstract

Background/Objectives: Apis cerana development is described as comprising four stages: embryo, larva, pupa, and adult. There are significant differences between workers and drones in terms of physiological functions and social roles, and the formation of the organ primordia occurs during the embryonic stage. [...] Read more.

Background/Objectives: Apis cerana development is described as comprising four stages: embryo, larva, pupa, and adult. There are significant differences between workers and drones in terms of physiological functions and social roles, and the formation of the organ primordia occurs during the embryonic stage. Therefore, the objective of this study is to investigate the differential expression of and alternative splicing of genes in worker and drone embryos and to explain their unique developmental patterns. Methods: Long-read sequencing (PacBio Iso-Seq) and short-read sequencing (Illumina RNA-Seq) were used to investigate worker and drone embryo gene expression differences in A. cerana across five developmental points (12, 24, 36, 48, and 60 h). Results: The study identified 59,254 common isoforms, with 5744 and 5106 isoforms specific to worker and drone embryos, respectively. Additionally, a new transcript of the csd gene was identified. The number of differentially expressed genes (3391) and differential splicing events (470 genes) peaked at the 24-h embryonic stage. Differential splicing events of csd, dsx, and Y-y were observed in the worker and drone embryos. Conclusions: The gene expression results indicated that the 24-h embryonic point is a critical period for the expression of genes related to developmental and behavioral differences between workers and drones. The findings provide a theoretical basis for future research on the developmental differences between workers and drones. Full article

(This article belongs to the Special Issue Genetics and Genomics of Bee)

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16 pages, 5136 KiB

Open AccessArticle

Analysis of the Codon Usage Bias Pattern in the Chloroplast Genomes of Chloranthus Species (Chloranthaceae)

by Jisi Zhang and Miao Feng

Genes 2025, 16(2), 186; https://doi.org/10.3390/genes16020186 - 2 Feb 2025

Viewed by 500

Abstract

Background: The codon preference of chloroplast genomes not only reflects mutation patterns during the evolutionary processes of species but also significantly affects the efficiency of gene expression. This characteristic holds significant scientific importance in the application of chloroplast genetic engineering and the genetic [...] Read more.

Background: The codon preference of chloroplast genomes not only reflects mutation patterns during the evolutionary processes of species but also significantly affects the efficiency of gene expression. This characteristic holds significant scientific importance in the application of chloroplast genetic engineering and the genetic improvement of species. Chloranthus, an ancestral angiosperm with significant economic, medicinal, and ornamental value, belongs to the basal angiosperms. However, the codon usage patterns among Chloranthus species have remained unclear. Methods: To investigate codon usage bias and its influencing factors in Chloranthus chloroplast genomes, we utilized CodonW, CUSP, and SPSS software to analyze the chloroplast genomes of seven Chloranthus species. Results: In this study, we reported and characterized the complete chloroplast genome of the Chinese endemic species Chloranthus angustifolius. The phylogenetic tree based on the whole chloroplast genomes showed that C. angustifolius is sister to Chloranthus fortunei, and the genus Chloranthus is divided into two major clades, consistent with previous studies. Our results revealed that the GC content at different codon positions across all seven Chloranthus species was less than 50%, with GC1 > GC2 > GC3. Additionally, the average effective number of codons (ENC) values exceeded 45. A total of 10 shared optimal codons were identified, nine of which end with A or U. PR2-plot, ENC-plot, and neutrality plot analyses indicated that natural selection primarily influenced codon usage bias in the chloroplast genomes of Chloranthus. Conclusions: We newly obtained the chloroplast genome of C. angustifolius and proposed that natural selection played a key role in codon usage patterns in Chloranthus species. These findings contribute to our understanding of evolutionary history and genetic diversity within this genus. Full article

(This article belongs to the Special Issue Molecular Adaptation and Evolutionary Genetics in Plants)

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18 pages, 878 KiB

Open AccessReview

Integrating Machine Learning-Based Approaches into the Design of ASO Therapies

by Jamie Leckie and Toshifumi Yokota

Genes 2025, 16(2), 185; https://doi.org/10.3390/genes16020185 - 2 Feb 2025

Viewed by 617

Abstract

Rare diseases impose a significant burden on affected individuals, caregivers, and healthcare systems worldwide. Developing effective therapeutics for these small patient populations presents substantial challenges. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach that targets the underlying genetic cause of disease [...] Read more.

Rare diseases impose a significant burden on affected individuals, caregivers, and healthcare systems worldwide. Developing effective therapeutics for these small patient populations presents substantial challenges. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach that targets the underlying genetic cause of disease at the RNA level. Several ASOs have gained FDA approval for the treatment of genetic conditions, including use in personalized N-of-1 trials. However, despite their potential, ASOs often exhibit limited clinical efficacy, and optimizing their design is a complex process influenced by numerous factors. Machine learning-based platforms, including eSkip-Finder and ASOptimizer, have been developed to address these challenges by predicting optimal ASO sequences and chemical modifications to enhance efficacy. eSkip-Finder focuses on exon-skipping applications, while ASOptimizer aims to optimize ASOs for RNA degradation. Preliminary in vitro results have demonstrated the promising predictive power of these platforms. However, limitations remain, including their generalizability to alternative targets and gaps in their consideration of all factors influencing ASO efficacy and safety. Continued advancements in machine learning models, alongside efforts to incorporate additional features affecting ASO efficacy and safety, hold significant promise for the field. These platforms have the potential to streamline ASO development, reduce associated costs, and improve clinical outcomes, positioning machine learning as a key tool in the future of ASO therapeutics. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2024)

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17 pages, 8146 KiB

Open AccessArticle

Characterization and Expression Analysis of the bHLH Gene Family During Developmental Stages and Under Various Abiotic Stresses in Sanghuangporus baumii

by Ruipeng Liu, Tingting Sun, Pengyu Du, Zengcai Liu, Yawei Li, Xinyu Tong and Li Zou

Genes 2025, 16(2), 184; https://doi.org/10.3390/genes16020184 - 2 Feb 2025

Viewed by 397

Abstract

Background: Basic helix–loop–helix (bHLH) transcription factors (TFs) widely exist in eukaryotic organisms and play a key role in plant growth and development in response to environmental stresses. Sanghuangporus baumii, an important medicinal mushroom known for its anticancer properties, has limited research on [...] Read more.

Background: Basic helix–loop–helix (bHLH) transcription factors (TFs) widely exist in eukaryotic organisms and play a key role in plant growth and development in response to environmental stresses. Sanghuangporus baumii, an important medicinal mushroom known for its anticancer properties, has limited research on the bHLH gene family. Methods: This research utilized the genomic data from S. baumii to identify bHLH family members, and their gene structure, conserved motifs, and phylogenetic relationship were characterized. Additionally, we conducted an analysis of promoter cis-elements and predicted protein interaction networks. We also examined the expression profiles of bHLH genes during different developmental stages and in response to four abiotic stresses: heat, cold, oxidative stress, and heavy metal exposure. Finally, we overexpressed the candidate gene SbbHLH3 in yeast to assess its tolerance to these different stress conditions. Results: A total of 12 SbbHLH genes were identified in S. baumii, and the members of the bHLH gene family displayed a variety of physicochemical characteristics, reflecting their diverse array of functions. Based on homology, the SbbHLH proteins are more closely related to those found in Lentinula edodes and Pleurotus ostreatus. The analysis of promoter cis-elements showed that SbbHLHs contain several elements associated with abiotic stress response, and a network prediction identified 28 bHLH-interacting proteins. Expression pattern analysis revealed that most SbbHLH genes exhibited a positive response to different developmental stages and abiotic stresses. Notably, the overexpression of SbbHLH3 significantly enhanced stress tolerance in yeast. Conclusions: This study provides a comprehensive assessment of the bHLH family in S. baumii, delivering new genetic resources for breeding resistant varieties. Full article

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

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17 pages, 3776 KiB

Open AccessArticle

Molecular Markers Specific for the Pseudomonadaceae Genera Provide Novel and Reliable Means for the Identification of Other Pseudomonas Strains/spp. Related to These Genera

by Bashudev Rudra and Radhey S. Gupta

Genes 2025, 16(2), 183; https://doi.org/10.3390/genes16020183 - 2 Feb 2025

Viewed by 328

Abstract

Background/Objectives: Taxon-specific conserved signature indels (CSIs) exhibit a strong predictive ability of being found in other members of specific taxa/genera. Recently, multiple exclusively shared CSIs were identified for several newly described Pseudomonadaceae genera (viz. Aquipseudomonas, Atopomonas, Caenipseudomonas, Chryseomonas Ectopseudomonas, [...] Read more.

Background/Objectives: Taxon-specific conserved signature indels (CSIs) exhibit a strong predictive ability of being found in other members of specific taxa/genera. Recently, multiple exclusively shared CSIs were identified for several newly described Pseudomonadaceae genera (viz. Aquipseudomonas, Atopomonas, Caenipseudomonas, Chryseomonas Ectopseudomonas, Geopseudomonas, Halopseudomonas, Metapseudomonas, Phytopseudomonas, Serpens, Stutzerimonas, Thiopseudomonas, and Zestomonas). This study examines the potential applications of these CSIs for identifying other Pseudomonas spp. (strains) related to these genera. Methods: This work utilized the AppIndels.com server, which uses information regarding the presence of known taxon-specific CSIs in a genome for predicting its taxonomic affiliation. For this purpose, sequence information for different CSIs specific for the Pseudomonadaceae species/genera were added to the server’s database. Results: The AppIndels server was used to predict the taxonomic affiliation of 1972 genomes of unclassified Pseudomonas spp. (strains/isolates). Based upon finding a significant number of CSIs matching a specific taxon, the AppIndels server made positive predictions regarding the taxonomic affiliation of 299 examined genomes into the following clades/genera: Pseudomonas sensu stricto clade (46), Pseudomonas aeruginosa (64), Ectopseudomonas (46), Chryseomonas (32), Stutzerimonas (31), Metapseudomonas (22), Aquipseudomonas (21), Phytopseudomonas (17), Halopseudomonas (9), Geopseudomonas (4), Thiopseudomonas (3), Serpens (2), and Caenipseudomonas and Zestomonas (1 each). Phylogenetic studies confirmed that the taxonomic predictions by the server were 100% accurate. Conclusions: Our results demonstrate that the CSIs specific for Pseudomonadaceae species/genera, in conjunction with the AppIndels server, provides a novel and useful tool for identifying other species/strains affiliated with these species/genera. Phylogenetic studies suggest that many examined Pseudomonas strains constitute novel species in the indicated genera. Full article

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

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10 pages, 923 KiB

Open AccessArticle

MLH1 Methylation Status and Microsatellite Instability in Patients with Colorectal Cancer

by Manuel Alejandro Rico-Méndez, Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Jesús Arturo Hernández-Sandoval, Anahí González-Mercado, Melva Gutiérrez-Angulo, José Geovanni Romero-Quintana, Jesús Alonso Valenzuela-Pérez, Ruth Ramírez-Ramírez, Beatriz Armida Flores-López and José Miguel Moreno-Ortiz

Genes 2025, 16(2), 182; https://doi.org/10.3390/genes16020182 - 2 Feb 2025

Viewed by 356

Abstract

Background/Objectives: The purpose of the current study was to compare the methylation of five regions of the CpG island of MLH1 with the presence of microsatellite instability (MSI) in colorectal cancer (CRC) patients. Methods: The study analyzed 138 CRC tumor samples. DNA extraction [...] Read more.

Background/Objectives: The purpose of the current study was to compare the methylation of five regions of the CpG island of MLH1 with the presence of microsatellite instability (MSI) in colorectal cancer (CRC) patients. Methods: The study analyzed 138 CRC tumor samples. DNA extraction was performed, followed by bisulfite conversion. MLH1 gene methylation was assessed by methylation-specific PCR (MS-PCR), and the resulting fragments were analyzed using polyacrylamide gels. MSI was evaluated using multiplex PCR, and the fragments were run through capillary electrophoresis. R studio (v4.4.1) and SPSS (v29.0) software were used for the statistical analysis, and values of p < 0.05 were considered statistically significant. Results: The study showed 75.4% unmethylated, 21% partially methylated, and 3.6% fully methylated samples, with region A frequently methylated. MSI was observed in 7.2% of cases (MSI-H: 5.8%, MSI-L: 1.4%). BAT-26 was the most unstable marker. A significant difference between MLH1 methylation and MSI-H (p < 0.01) was identified, but there was no relationship with specific MLH1 regions. Conclusions: No differences were identified when analyzing specific methylation regions in relation to MSI. This study is the first to describe MSI frequency in Mexican patients regardless of age. Full article

(This article belongs to the Special Issue Genetic and Genomic Research on Colorectal Cancer)

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13 pages, 47260 KiB

Open AccessArticle

Transcriptome Analysis Reveals Equine Endometrium’s Gene Expression Profile Around Embryo Fixation

by Tseweendolmaa Ulaangerel, Siqin Mu, Jolanqiqige Sodyelalt, Minna Yi, Bilig Zhao, Asiya Hao, Xin Wen, Baoxiang Han and Gerelchimeg Bou

Genes 2025, 16(2), 181; https://doi.org/10.3390/genes16020181 - 1 Feb 2025

Viewed by 378

Abstract

Background/Objectives: The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: [...] Read more.

Background/Objectives: The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: In this study, the structural and transcriptomic characteristics of endometrial tissue from the fixed and nonfixed sides of 20-day gestation embryos in Mongolian horses were investigated to search for important genes and potential molecular markers associated with the fixation phase of equine embryos. Results: A comparison of the structures of the endometrial tissues of the two sides revealed that the endometrium on the fixed side presented distinctive features, which were characterized mainly by the development of glands on the fixed side compared with those on the nonfixed side. A total of 3987 differentially expressed genes were identified in the transcriptome, among which 1931 genes were highly expressed on the fixed side of the embryo, including CDH1, DRA, DQB, CLND2, BOLA-DQB, CLDN10, PTGER2, and PTGFR. The differentially expressed genes were enriched in biological processes such as cell adhesion, morphogenesis, NOD signaling, and vitamin uptake, as well as prostatic hormones. Conclusions: These results suggest that equine embryo fixation may depend at least on the regulation of prostaglandins and the establishment of cellular connections. This provides a foundation for exploring the molecular mechanisms of key genes and pathways related to equine embryo fixation and offers new insights into feeding management and the monitoring of mares in the early stages of pregnancy. Full article

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

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20 pages, 3701 KiB

Open AccessArticle

miRNA Signatures as Predictors of Therapy Response in Castration-Resistant Prostate Cancer: Insights from Clinical Liquid Biopsies and 3D Culture Models

by Jonathan Puente-Rivera, Stephanie I. Nuñez-Olvera, Verónica Fernández-Sánchez, Monica Alethia Cureño-Díaz, Erika Gómez-Zamora, Estibeyesbo Said Plascencia-Nieto, Elisa Elvira Figueroa-Angulo and María Elizbeth Alvarez-Sánchez

Genes 2025, 16(2), 180; https://doi.org/10.3390/genes16020180 - 1 Feb 2025

Viewed by 414

Abstract

Background/Objectives: Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to [...] Read more.

Background/Objectives: Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to investigate the potential of microRNAs (miRNAs) as biomarkers for predicting therapeutic response in CRPC patients. Methods: We performed miRNA and mRNA expression analyses using publicly available datasets and applied 3D cell culture models to replicate more physiologically relevant tumor conditions. Genetic analysis techniques were employed on publicly available data, and expression profiles from 3D cell culture models were examined. Results: Eighteen miRNAs with differential expression were identified between patients who responded favorably to abiraterone therapy (responders) and those with advanced CRPC (non-responders). Specifically, miRNAs such as hsa-miR-152-3p and hsa-miR-34a-3p were found to be associated with critical pathways, including TGF-β signaling and P53, which are linked to therapeutic resistance. Several miRNAs were identified as potential predictors of treatment efficacy, including therapies like abiraterone. Conclusions: These results indicate that miRNAs could serve as non-invasive biomarkers for predicting therapeutic outcomes, facilitating a more personalized approach to CRPC treatment. This study provides a novel perspective on treatment strategies for CRPC, emphasizing the role of miRNAs in improving therapeutic precision and efficacy in this complex disease. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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18 pages, 2989 KiB

Open AccessArticle

Genetic Diversity Analysis and Comprehensive Evaluation of “M82” in EMS-Mutagenized Tomato

by Yanchao Yang, Zhanming Tan, Shuang Liang, Wei Cheng, Yihuan Sun, Yunxia Cheng, Yu Song, Yongming Wang, Jialong Wu and Qi Wang

Genes 2025, 16(2), 179; https://doi.org/10.3390/genes16020179 - 1 Feb 2025

Viewed by 310

Abstract

Background: Ethyl methyl sulfonate (EMS) mutagenesis is widely used because of its advantages of inducing point mutations and no need for genetic transformation. To identify germplasm resources of processed tomatoes with superior comprehensive traits suitable for cultivation in Xinjiang. Methods: In this study, [...] Read more.

Background: Ethyl methyl sulfonate (EMS) mutagenesis is widely used because of its advantages of inducing point mutations and no need for genetic transformation. To identify germplasm resources of processed tomatoes with superior comprehensive traits suitable for cultivation in Xinjiang. Methods: In this study, tomato seeds were treated with 2% EMS reagent for 12 h, 21 quality traits and 20 quantitative traits of 33 processed tomatoes derived from EMS-mutagenized“M82”were evaluated. Results: The results indicated that for traits such as hypocotyl color, growth habit, plant type, leaf type, and leaf shape, the range of quantitative trait variation was 8.45–37.25%, with a genetic diversity index ranging from 1.25 to 2.07. Conclusions: Cluster analysis of quantitative traits categorized the 33 EMS-mutagenized “M82” processed tomato resources into five groups: Group I contained 22 robust germplasm samples; Group II consisted of a single potential high-quality germplasm; Group III comprised five germplasm with a small and extreme plant type; Group IV included four high-yield germplasm; and Group V represented one moderate, conventional germplasm. Raw data from 15 quantitative traits across the 33 accessions were standardized using the “extreme method” to extract six comprehensive factors. The top 10 germplasm resources based on the comprehensive score were 76, 137, 97, 102, 19, 104, 21, 108, 17, and 147. It provides some theoretical basis for realizing the high-yield and high-quality cultivation and variety breeding of processed tomatoes in Xinjiang. Full article

(This article belongs to the Special Issue Genes and Genomics of Plants Under Abiotic Stresses)

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18 pages, 4427 KiB

Open AccessArticle

An Actively Homing Insertion Element in a Phage Methylase Contains a Hidden HNH Endonuclease

by Danielle Arsenault, Sophia P. Gosselin and Johann Peter Gogarten

Genes 2025, 16(2), 178; https://doi.org/10.3390/genes16020178 - 1 Feb 2025

Viewed by 393

Abstract

Background/Objectives: The ShiLan domain was previously identified as an insertion sequence in a phage DNA methylase gene that exhibited similar evolutionary patterns to that of an active intein or self-splicing intron but could not be identified as either. It produces no internal [...] Read more.

Background/Objectives: The ShiLan domain was previously identified as an insertion sequence in a phage DNA methylase gene that exhibited similar evolutionary patterns to that of an active intein or self-splicing intron but could not be identified as either. It produces no internal stop codons when read in frame with its host methylase gene, leading to the thought that it may not be an intron and rather be an abnormal type of intein. However, the sequence has no detectable self-splicing domains, which are essential for intein persistence, as preventing an intein from successfully splicing is often detrimental to proper host protein function. Methods: The analysis of alternate open reading frames for the full nucleotide sequence of this insertion element revealed the insertion to be an out-of-frame histidine-asparagine-histidine (HNH) endonuclease. A GTG start codon is located 18 bp into the insertion, and a TAA stop codon within the last four bases of the insertion (TAAC). When this frame is read, an HNH endonuclease is revealed. In-depth computational analysis could not retrieve support for this element being any known type of self-splicing element, neither intein nor intron. When read in-frame with the methylase gene, this insertion is predicted to take on a looping structure that may be able to avoid interference with the DNA methylase activity. We performed searches for sequences similar in nature to the inserted out-of-frame HNH and found several in other phages and prokaryotes. We present our survey of these out-of-frame endonuclease insertion elements as well as some speculation on how these endonucleases are getting translated to facilitate their homing activity. Conclusions: These findings expand our understanding of the possible arrangements for and prevalence of unorthodox mobile genetic elements and overlapping open reading frames in phages. Full article

(This article belongs to the Section Viral Genomics)

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19 pages, 1210 KiB

Open AccessReview

Understanding Heritable Variation Among Hosts in Infectious Diseases Through the Lens of Twin Studies

by Maria K. Smatti, Hadi M. Yassine, Hamdi Mbarek and Dorret I. Boomsma

Genes 2025, 16(2), 177; https://doi.org/10.3390/genes16020177 - 1 Feb 2025

Viewed by 418

Abstract

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of [...] Read more.

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of heritability on the proneness as well as infection- and vaccine-induced immune responses have been documented for multiple infections, including tuberculosis, malaria, leprosy, otitis media, polio, mumps, measles, rubella, influenza, hepatitis B, and human papillomavirus infections, and recently, SARS-CoV-2. The current data show the heritable aspect in nearly all infections considered. In this contribution, we review and discuss human twin studies on the heritability of host characteristics in liability and response to IDs. This review emphasizes the importance of considering factors such as sex, disease stages, and disease presentation when assessing heritability and argues that the classical twin design provides a unique circumstance for exploring the genetic contribution as twins share levels of maternal antibodies, ancestral background, often the dates and number of vaccine doses, differences in vaccines’ manufacturing and storage, age, family environment, and other exposures. Additionally, we highlight the value of twin studies and the usefulness of combining the twin model with contemporary genomics technologies and advanced statistical tools to grasp a comprehensive and nuanced understanding of heritability in IDs. Full article

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

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12 pages, 635 KiB

Open AccessCase Report

The Arg99Gln Substitution in HNRNPC Is Associated with a Distinctive Clinical Phenotype Characterized by Facial Dysmorphism and Ocular and Cochlear Anomalies

by Luigi Chiriatti, Manuela Priolo, Roberta Onesimo, Mattia Carvetta, Chiara Leoni, Alessandro Bruselles, Francesca Clementina Radio, Camilla Cappelletti, Marco Ferilli, Daniela Ricci, Marcello Niceta, Viviana Cordeddu, Andrea Ciolfi, Cecilia Mancini, Giuseppe Zampino and Marco Tartaglia

Genes 2025, 16(2), 176; https://doi.org/10.3390/genes16020176 - 1 Feb 2025

Viewed by 336

Abstract

Background/Objectives: Heterozygous variants in the heterogeneous nuclear ribonucleoprotein C gene (HNRNPC) have recently been reported to cause intellectual developmental disorder-74 (MRD74), a neurodevelopmental disorder with no recurrent diagnostic handles. Affected individuals show variable, non-specific, and subtle dysmorphic features. The degree of [...] Read more.

Background/Objectives: Heterozygous variants in the heterogeneous nuclear ribonucleoprotein C gene (HNRNPC) have recently been reported to cause intellectual developmental disorder-74 (MRD74), a neurodevelopmental disorder with no recurrent diagnostic handles. Affected individuals show variable, non-specific, and subtle dysmorphic features. The degree of developmental delay (DD)/intellectual disability (ID) is also wide, ranging from mild to severe. The mutational spectrum is relatively broad with exon deletions and splice site and frameshift variants distributed along the entire length of the gene leading to HNRNPC loss of function. Only two missense changes located within the RNA-binding motif (RBM) and adjacent linker region of the more abundant isoform (Arg64Trp and Arg99Gln) have been described. Notably, the Arg99Gln amino acid substitution was reported in a subject presenting with a more complex and unique clinical phenotype characterized by distinctive facial features, DD/ID, cochlear aplasia, and bilateral colobomatous microphthalmia, suggesting the possible occurrence of phenotypic heterogeneity. Results: Here, we report the second individual carrying the Arg99Gln change in HNRNPC and having clinical features with a significant overlap with the peculiar phenotype of the previously described subject, supporting the occurrence of a genotype–phenotype correlation. Conclusions: Due to the concomitant occurrence of ocular and cochlear involvement as recognizable diagnostic handles, we propose that the HNRNPC^Arg99Gln-related phenotype should be considered as a potential differential diagnosis in subjects with ID and major signs of CHARGE syndrome not fulfilling the minimum criteria for a clinical diagnosis. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2024)

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13 pages, 4519 KiB

Open AccessArticle

Transcriptional Regulatory Network of the Embryonic Diapause Termination Process in Artemia

by Bin Wang, Zhen He, Mingzhi Zhang, Ruiqi Zhang, Zhentao Song, Anqi Li and Tong Hao

Genes 2025, 16(2), 175; https://doi.org/10.3390/genes16020175 - 1 Feb 2025

Viewed by 352

Abstract

Artemia is a typical animal used for the study of the diapause mechanism. The research on the regulation mechanism of diapause mainly focuses on the occurrence and maintenance of diapause. There are few studies on the mechanism of embryonic pause termination (EDT), especially [...] Read more.

Artemia is a typical animal used for the study of the diapause mechanism. The research on the regulation mechanism of diapause mainly focuses on the occurrence and maintenance of diapause. There are few studies on the mechanism of embryonic pause termination (EDT), especially for its transcriptional regulation mechanism. This study integrated transcriptional regulatory data from ATAC-seq and gene expression data from RNA-seq to explore the transcriptional regulatory mechanisms involved in the EDT process. Through integrated analysis, four important transcription factors (TFs), SVP, MYC, RXR, and SMAD6, were found to play a role in the EDT process, in which SVP, MYC, and RXR were upregulated, while SMAD6 was downregulated in the EDT stage. Through co-expression analysis, a transcription regulatory network for these four TFs was constructed and the functions of the TFs were analyzed. The expression of the TFs was further verified by RT-qPCR. Through functional analysis, SVP was found to be predominantly involved in cell adhesion and signal transduction. MYC probably played a role in protein binding. RXR may function in the process of RNA binding and the transfer of phosphorus-containing groups. Smad6 regulated the signal transduction, cell adhesion, and oxidation–reduction processes. The expression of the key TFs was verified by RT-qPCR. The results of this work provide important clues for the mechanism of transcriptional regulation in the EDT process of Artemia. Full article

(This article belongs to the Special Issue Genetic and Genomic Studies of Marine Animals)

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15 pages, 23444 KiB

Open AccessArticle

Construction of the Red Swamp Crayfish (Procambarus clarkii) Family Selection Population and Whole Genome Sequencing to Screen WIPFI Candidate Genes Related to Growth

by Xing Tian, Xiudan Yuan, Zhigang He, Weiguo Li, Jinlong Li, Yong He, Shiming Deng, Jiarong Guo, Miaoquan Fang and Dongwu Wang

Genes 2025, 16(2), 174; https://doi.org/10.3390/genes16020174 - 31 Jan 2025

Viewed by 423

Abstract

Background/Objectives: Procambarus clarkii is an important freshwater aquaculture species in China which has the characteristics of rich nutrition and delicious taste. However, the expansion of aquaculture scale, germplasm degradation, and other problems that have become increasingly prominent seriously restrict the sustainable development [...] Read more.

Background/Objectives: Procambarus clarkii is an important freshwater aquaculture species in China which has the characteristics of rich nutrition and delicious taste. However, the expansion of aquaculture scale, germplasm degradation, and other problems that have become increasingly prominent seriously restrict the sustainable development of the crayfish industry. Genetic improvement is an urgent need for the crayfish aquaculture industry, and selective breeding is an important way to improve the crayfish varieties. Methods: We established full-sibling family populations of the red swamp crayfish and performed whole-genome resequencing of the F3 family-selected red swamp crayfish population and wild red swamp crayfish populations from four regions of Hunan Province (Nanx, Mil, Caish, and Wangc). Results: The results showed that there was a clear separation between the wild population and the family population, and the decline rate was slightly faster in the wild population than that of the family breeding population. There was local gene flow between family populations, as well as gene flow between Mil, Caish, and families. In addition, 52 SNP loci related to body weight traits were identified by genome-wide association analysis, and the candidate gene WIPF1 related to growth was screened out. Conclusions: We established a line selection population of red swamp crayfish and obtained more stable candidate lines. In addition, this study identified Wiskott–Aldrich syndrome protein-interacting protein family member 1 (WIPF1) as a candidate gene related to body weight for the first time. The results provide a theoretical basis for exploring the growth mechanism of P. clarkii and carrying out in-depth genetic improvement. Full article

(This article belongs to the Special Issue Genetics and Genomics Applied to Aquatic Animal Science—2nd Edition)

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18 pages, 17704 KiB

Open AccessArticle

Terrestrial Adaptation in Chelonoidis vicina as Revealed Based on Analysis of the Complete Mitochondrial Genome

by Yao Chen, Xibao Wang, Xiaoyang Wu, Yongquan Shang, Qinguo Wei, Haotian Cai, Weilai Sha, Yan Qi, Shuli Liu and Honghai Zhang

Genes 2025, 16(2), 173; https://doi.org/10.3390/genes16020173 - 30 Jan 2025

Viewed by 479

Abstract

Background/Objectives: Mitochondrial genomes are widely used in phylogenetics and evolutionary and ecological research. Methods: In this study, the newest mitochondrial genome of Chelonoidis vicina was assembled and annotated. The comparative mitochondrial genome and selection pressure analyses were used to examine the terrestrial adaptive [...] Read more.

Background/Objectives: Mitochondrial genomes are widely used in phylogenetics and evolutionary and ecological research. Methods: In this study, the newest mitochondrial genome of Chelonoidis vicina was assembled and annotated. The comparative mitochondrial genome and selection pressure analyses were used to examine the terrestrial adaptive evolution characteristics of C. vicina and other terrestrial reptiles. Results: The results reveal that the mitochondrial genome of the tortoise C. vicina is consistent with that of other tortoise species, comprising 13 protein-coding genes (PCGs), 2 rRNAs, 22 tRNAs, and 1 noncoding control region (CR). The analysis of selection pressure reveals the presence of positive selection sites in the COX2, COX3, Cytb, ND3, ND4, ND4L, ND5, and ND6 genes of terrestrial reptiles. Of these, the COX2 and ND3 genes exhibited faster evolutionary rates. The mitochondrial genome structure of C. vicina is consistent with that of different terrestrial reptiles. The positive selection sites of COX2 and ND3 in terrestrial reptiles are closely related to a change in mitochondrial energy metabolism, which is possibly related to terrestrial adaptability. Conclusions: The results of this study provide new insights into the adaptive evolution of C. vicina to terrestrial niches from a mitogenomic perspective, as well as genetic resources for the protection of C. vicina. Full article

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

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19 pages, 3451 KiB

Open AccessArticle

Type 1 Diabetes Risk Variants Reduce Beta Cell Function

by Wiktoria Ratajczak, Angus G. Jones, Sarah D. Atkinson and Catriona Kelly

Genes 2025, 16(2), 172; https://doi.org/10.3390/genes16020172 - 29 Jan 2025

Viewed by 513

Abstract

Introduction: The variants rs10517086 and rs1534422 are predictive of type 1 diabetes mellitus (T1DM) development and poor residual β cell function within the first year of diagnosis. However, the mechanism by which risk is conferred is unknown. We explored the impact of both [...] Read more.

Introduction: The variants rs10517086 and rs1534422 are predictive of type 1 diabetes mellitus (T1DM) development and poor residual β cell function within the first year of diagnosis. However, the mechanism by which risk is conferred is unknown. We explored the impact of both variants on β cell function in vitro and assessed their relationship with C-peptide in people with T1DM and type 2 diabetes mellitus (T2DM). Methods: Using CRISPR/Cas9, the variants were introduced into a β cell line (BRIN-BD11) and a T cell line (Jurkat cells) from which the conditioned media was applied to otherwise healthy β cells to model the inflammatory environment associated with these variants. Results: Both variants significantly reduced glucose-stimulated insulin secretion, increased production of pro-inflammatory cytokines and reduced expression of several β cell markers and transcription factors (KCNJ11, KCNQ1, SCL2A2, GCK, NKX6.1, Pdx1 NGN3). However, HNF1A was significantly upregulated in the presence of both variants. We subsequently silenced HNF1A in variant expressing BRIN-BD11 cells using siRNA and found that gene expression profiles were normalised. Induction of each variant significantly increased expression of the lncRNAs they encode, which was normalised upon HNF1A silencing. Analysis of the DARE (Diabetes Alliance for Research in England) study revealed an association of rs10517086_A genotype with C-peptide in 153 individuals with T1DM, but not in 417 people with T2DM. Conclusions: These data suggest that rs1534422 and rs10517086 exert multiple insults on the β cell through excessive upregulation of HNF1A and induction of pro-inflammatory cytokines, and highlight their utility as prognostic markers of β cell function. Full article

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

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Genes, Volume 16, Issue 2 (February 2025) – 92 articles

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