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Genes, Volume 16, Issue 2 (February 2025) – 80 articles

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18 pages, 3504 KiB  
Article
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 (registering DOI) - 3 Feb 2025
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  
Review
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
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  
Article
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 7
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  
Article
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 368
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  
Review
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 287
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  
Article
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 274
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  
Article
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 224
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  
Article
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 216
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  
Article
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 269
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  
Article
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 302
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  
Article
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 221
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  
Article
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 230
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  
Review
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 303
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  
Case 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 225
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 HNRNPCArg99Gln-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  
Article
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 279
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  
Article
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 361
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  
Article
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 437
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  
Article
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 464
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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11 pages, 466 KiB  
Article
The Relationship of the Pathogenic Variant rs721048 in the Intron of the EHBP1 Gene with the Development of Prostate Cancer and Colorectal Cancer in the Kazakh Population
by Marina Romanova, Saltanat Abdikerim, Kaisar Dauyey, Ziyo Gassanov, Nurlan Baltayev, Shyngys Satymbayev, Aigul Zhunussova, Dilyara Kaidarova and Gulnur Zhunussova
Genes 2025, 16(2), 171; https://doi.org/10.3390/genes16020171 - 28 Jan 2025
Viewed by 492
Abstract
Background: Prostate cancer (PC) is one of the most common oncological diseases among men. Up to 20% of PC cases are associated with hereditary risks or syndromes. The impact of common variants, particularly EHBP1 c.1185+30064G>A rs721048, on developing PC and other malignancies remains [...] Read more.
Background: Prostate cancer (PC) is one of the most common oncological diseases among men. Up to 20% of PC cases are associated with hereditary risks or syndromes. The impact of common variants, particularly EHBP1 c.1185+30064G>A rs721048, on developing PC and other malignancies remains unclear. There are also no data on the frequency of this variant in the Kazakh population or its association with PC, nor its potential connection with other malignancies, particularly colorectal cancer (CRC). Methods: We utilized the TruSight Cancer Sequencing Panel to assess pathological genomic variants in 72 male patients with histologically verified aggressive PC and 119 patients of Kazakh nationality with histologically confirmed CRC compared to the control group. Results: A variant in the intron of the EHBP1 gene c.1185+30064G>A rs721048 was identified in 18 patients (25%) out of 72 with PC, while in the control group of 41 healthy males, the rs721048 variant was found in only 4 (9.8%) individuals. In the CRC group, rs721048 was detected in 17 cases (14.2%) and eight control individuals (10%). Conclusions: The frequency of the EHBP1 c.1185+30064G>A rs721048 variant in the PC group was significantly higher (p < 0.05) than in healthy males of Kazakh nationality. Identifying EHBP1 c.1185+30064G>A among the male population of Kazakhstan will help form the high-risk groups for PC to prevent the development of malignant neoplasms. The presence of rs721048 was not significantly associated with the risk of developing CRC in our study. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 1803 KiB  
Article
Long Noncoding RNAs Responding to Ethanol Stress in Yeast Seem Associated with Protein Synthesis and Membrane Integrity
by Amanda Piveta Schnepper, Agatha M. S. Kubo, Camila Moreira Pinto, Ramon Hernany Martins Gomes, Matheus Naia Fioretto, Luís Antonio Justulin, Aline M. M. Braz, Marjorie de Assis Golim, Rejane M. T. Grotto and Guilherme Targino Valente
Genes 2025, 16(2), 170; https://doi.org/10.3390/genes16020170 - 28 Jan 2025
Viewed by 966
Abstract
Background/Objectives: Translation and the formation of membraneless organelles are linked mechanisms to promote cell stress surveillance. LncRNAs responsive to ethanol stress transcr_9136 of the SEY6210 strain and transcr_10027 of the BY4742 strain appear to act on tolerance to ethanol in these strains. Here, [...] Read more.
Background/Objectives: Translation and the formation of membraneless organelles are linked mechanisms to promote cell stress surveillance. LncRNAs responsive to ethanol stress transcr_9136 of the SEY6210 strain and transcr_10027 of the BY4742 strain appear to act on tolerance to ethanol in these strains. Here, we investigate whether the ethanol responsiveness of transcr_9136 and transcr_10027 and their role in ethanol stress are associated with protein biogenesis and membraneless organelle assembly. Methods: SEY6210 transcr_9136∆ and BY4742 transcr_10027∆ and their wild-type counterparts were subjected to their maximum ethanol-tolerant stress. The expression of the transcr_9136, transcr_10027, ILT1, RRP1, 27S, 25S, TIR3, and FAA3 genes was accessed by qPCR. The level of DCP1a, PABP, and eIF4E proteins was evaluated by Western blotting. Bioinformatics analyses allowed us to check whether transcr_9136 may regulate the expression of RRP1 and predict the interaction between transcr_10027 and Tel1p. The cell death rate of SEY6210 strains under control and ethanol stress conditions was assessed by flow cytometry. Finally, we evaluated the total protein yield of all strains analyzed. Results: The results demonstrated that transcr_9136 of SEY6210 seems to control the expression of RRP1 and 27S rRNA and reduce the general translation. Furthermore, transcr_9136 seems to act on cell membrane integrity. Transcr_10027 of BY4742 appears to inhibit processing body formation and induce a general translation level. Conclusions: This is the first report on the effect of lncRNAs on yeast protein synthesis and new mechanisms of stress-responsive lncRNAs in yeast, with potential industrial applications such as ethanol production. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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12 pages, 4045 KiB  
Article
Analysis of Short Tandem Repeat Expansions in a Cohort of 12,496 Exomes from Patients with Neurological Diseases Reveals Variable Genotyping Rate Dependent on Exome Capture Kits
by Clarissa Rocca, David Murphy, Chris Clarkson, Matteo Zanovello, Delia Gagliardi, Queen Square Genomics, Rauan Kaiyrzhanov, Javeria Alvi, Reza Maroofian, Stephanie Efthymiou, Tipu Sultan, Jana Vandrovcova, James Polke, Robyn Labrum, Henry Houlden and Arianna Tucci
Genes 2025, 16(2), 169; https://doi.org/10.3390/genes16020169 - 28 Jan 2025
Viewed by 503
Abstract
Background/Objectives: Short tandem repeat expansions are the most common cause of inherited neurological diseases. These disorders are clinically and genetically heterogeneous, such as in myotonic dystrophy and spinocerebellar ataxia, and they are caused by different repeat motifs in different genomic locations. Major advances [...] Read more.
Background/Objectives: Short tandem repeat expansions are the most common cause of inherited neurological diseases. These disorders are clinically and genetically heterogeneous, such as in myotonic dystrophy and spinocerebellar ataxia, and they are caused by different repeat motifs in different genomic locations. Major advances in bioinformatic tools used to detect repeat expansions from short read sequencing data in the last few years have led to the implementation of these workflows into next generation sequencing pipelines in healthcare. Here, we aimed to evaluate the clinical utility of analysing repeat expansions through exome sequencing in a large cohort of genetically undiagnosed patients with neurological disorders. Methods: We here analyse 27 disease-causing DNA repeats found in the coding, intronic and untranslated regions in 12,496 exomes in patients with a range of neurogenetic conditions. Results: We identified—and validated by polymerase chain reaction—29 repeat expansions across a range of loci, 48% (n = 14) of which were diagnostic. We then analysed the genotyping performance across all repeat loci and found that, despite high coverage in most repeats in coding regions, some loci had low genotyping rates, such as those that cause spinocerebellar ataxia 2 (ATXN2, 0.1–8.4%) and Huntington disease (HTT, 0.2–58.2%), depending on the capture kit. Conversely, while most intronic repeats were not genotyped, we found a high genotyping rate in the intronic locus that causes spinocerebellar ataxia 36 (NOP56, 30.1–98.3%) and in the one that causes myotonic dystrophy type 1 (DMPK, myotonic dystrophy type 1). Conclusions: We show that the key factors that influence the genotyping rate of repeat expansion loci analysis are the sequencing read length and exome capture kit. These results provide important information about the performance of exome sequencing as a genetic test for repeat expansion disorders. Full article
(This article belongs to the Special Issue Molecular Genetics of Neurodegenerative Diseases and Neuromuscular Diseases)
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14 pages, 632 KiB  
Article
Association of BMP15 and GDF9 Gene Polymorphisms with Litter Size in Hu Sheep
by Yuting Zhang, Haitao Wang, Tingting Li, Na Zhang, Jieran Chen, Hengqian Yang, Shiyu Peng, Runlin Ma, Daxiang Wang, Qiuyue Liu and Yuanyuan Wang
Genes 2025, 16(2), 168; https://doi.org/10.3390/genes16020168 - 28 Jan 2025
Viewed by 305
Abstract
(1) Background: Litter size is one of the most important economic traits of sheep. The FecB locus has been extensively studied due to its significant impact on litter size in Hu sheep, and BMP15 and GDF9 have also been reported as major genes [...] Read more.
(1) Background: Litter size is one of the most important economic traits of sheep. The FecB locus has been extensively studied due to its significant impact on litter size in Hu sheep, and BMP15 and GDF9 have also been reported as major genes associated with litter size in sheep. This study aimed to identify variants of BMP15 and GDF9 and perform an association analysis of these variants with litter size in the Hu sheep breed. (2) Methods: In this study, exons of the BMP15 and GDF9 genes were fully sequenced to identify polymorphisms in Hu sheep. Population genetic parameters and haplotype frequencies were estimated, and an association analysis between these polymorphic loci and litter size was performed. Additionally, the protein structures of the wild-type and mutated BMP15 and GDF9 genes were predicted. (3) Results: The polymorphisms of the BMP15 and GDF9 genes were investigated within their exon regions, revealing mutations at four previously reported sites: BMP15 c.31_33CTTdel and GDF9 (G2, G3, and G4) in Hu sheep, with no novel variants were detected. Genetic analysis indicated that the GDF9-G3 and GDF9-G4 loci have low polymorphisms, whereas the BMP15 c.31_33CTTdel and the GDF9-G2 locus are moderately polymorphic. The mutation sites in the BMP15 and GDF9 genes were under Hardy–Weinberg equilibrium. Association analysis revealed that the BMP15 c.31_33CTTdel and GDF9 (G2, G3, and G4) mutations are not associated with litter size in Hu sheep. Protein structure prediction indicated that the mutations in BMP15 and GDF9 resulted in alterations to their tertiary structures. (4) Conclusions: In this study, four reported mutations in the BMP15 and GDF9 genes can also be detected in the Hu sheep breed. In these mutations, the G2 and G3 mutations of GDF9 did not alter the amino acid sequence, while the BMP15 c.31_33CTTdel mutation and the GDF9 G4 mutation resulted in protein structure alteration. Furthermore, the BMP15 c.31_33CTTdel mutation and the GDF9 mutations (G2, G3, G4) were associated with an increased tendency in litter size. However, no significant difference was observed (p > 0.05). This study provides valuable insights for improving the lambing performance of Hu sheep. Full article
(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)
5 pages, 160 KiB  
Editorial
Editorial for the Special Issue: Bioinformatics and Computational Biology for Cancer Prediction and Prognosis
by Garrett M. Dancik and Spiros A. Vlahopoulos
Genes 2025, 16(2), 167; https://doi.org/10.3390/genes16020167 - 28 Jan 2025
Viewed by 393
Abstract
Cancer is a global health concern, with approximately 20 million new cancer cases diagnosed worldwide each year [...] Full article
(This article belongs to the Special Issue Bioinformatics and Computational Biology for Cancer Prediction and Prognosis)
21 pages, 2311 KiB  
Article
The Potential Role of Brassica napus Metallothioneins in Salt Stress and Interactions with Plant Growth-Promoting Bacteria
by Agnieszka Mierek-Adamska, Wioleta Tylman-Mojżeszek, Agnieszka Pawełek, Milena Kulasek and Grażyna B. Dąbrowska
Genes 2025, 16(2), 166; https://doi.org/10.3390/genes16020166 - 28 Jan 2025
Viewed by 384
Abstract
Background/Objectives: Plant metallothioneins (MTs) are low-molecular-weight proteins involved in heavy metal binding and response to stress conditions. This work aimed to analyse canola (Brassica napus L.) MTs (BnMT1-4) response to salinity and plant interaction with bacteria. Methods: (1) We tested [...] Read more.
Background/Objectives: Plant metallothioneins (MTs) are low-molecular-weight proteins involved in heavy metal binding and response to stress conditions. This work aimed to analyse canola (Brassica napus L.) MTs (BnMT1-4) response to salinity and plant interaction with bacteria. Methods: (1) We tested germination and canola growth and development in the presence of sodium chloride and bacteria Serratia plymuthica; (2) We analysed phytohormones content using LC-MS/MS; (3) We identified in silico cis-regulatory elements in promoters of BnMT1-4 genes; and (4) we investigated BnMT1-4 genes’ expression in B. napus. Results: Under saline conditions, canola germination and plant growth were notably inhibited, whereas inoculation of seeds with S. plymuthica significantly stimulated the analysed physiological traits of B. napus. The content of auxin, abscisic acid, jasmonates, gibberellins, and salicylic acid in B. napus was significantly affected by salinity and modulated by S. plymuthica presence. The promoter regions of the BnMT1-4 genes contain numerous regulatory elements controlled by light, hormones, and various stresses. Interestingly, the expression of BnMT1-3 genes was down-regulated under salt stress, while BnMT4 transcript levels increased strongly at the highest salt concentrations with and without S. plymuthica present. Conclusions: The results show that BnMT genes are differently affected by salinity and bacteria S. plymuthica and significantly correlate with particular phytohormones content in canola tissues, confirming the diversified functions of MTs in plant responses to changing environment. Full article
(This article belongs to the Section Genes & Environments)
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12 pages, 2838 KiB  
Article
Col5a3 Likely Promotes Adipogenesis of 3T3-L1 Through Oxidative Phosphorylation
by Sheng Wen, Ruimin Ren, Hanhao Yuan, Ning Gao, Jun He and Yuebo Zhang
Genes 2025, 16(2), 165; https://doi.org/10.3390/genes16020165 - 27 Jan 2025
Viewed by 297
Abstract
Background: A recent study reported that a deficiency of Col5a3 reduces dermal fat. However, the regulatory mechanism of the Col5a3 gene on adipose deposition remains unclear. Methods: In this study, we assessed the effects of Col5a3 interference on the proliferation and differentiation of [...] Read more.
Background: A recent study reported that a deficiency of Col5a3 reduces dermal fat. However, the regulatory mechanism of the Col5a3 gene on adipose deposition remains unclear. Methods: In this study, we assessed the effects of Col5a3 interference on the proliferation and differentiation of 3T3-L1 preadipocytes through CCK-8, EdU staining, cell cycle detection, RT-qPCR, Western blot, a triglyceride assay, and Oil Red O staining. RNA-seq was then performed on differentiated adipocytes to identify key differentially expressed genes (DEGs) and signaling pathways. Results: Col5a3 interference significantly promoted the proliferation of 3T3-L1 cells but inhibited their differentiation. RNA-seq analysis identified 368 DEGs, with the most significant enrichment observed in the oxidative phosphorylation pathway. Conclusion: This study demonstrates the regulatory role of Col5a3 in the proliferation and differentiation of preadipocytes, identifying various genes regulated by Col5a3 in adipogenesis. We speculate that Col5a3 may influence adipogenesis through the oxidative phosphorylation pathway in 3T3-L1 cells. The findings help gain a better understanding of the molecular mechanisms underlying fat deposition and obesity-related metabolic diseases. Full article
(This article belongs to the Section Animal Genetics and Genomics)
17 pages, 841 KiB  
Article
The Association of Genetic Variants Within the Type XII Collagen and Tenascin C Genes with Knee Joint Laxity Measurements
by Samantha Beckley, Roopam Dey, Shaun Stinton, Willem van der Merwe, Thomas Branch, Alison V. September, Michael Posthumus and Malcolm Collins
Genes 2025, 16(2), 164; https://doi.org/10.3390/genes16020164 - 27 Jan 2025
Viewed by 387
Abstract
Background/Objectives: Types I, V, and XI collagen gene variants have been reported to associate with measurements of knee joint laxity and/or absolute knee ligament length changes. Type XII collagen and tenascin C are also ligament structural proteins whose expression is regulated by mechanical [...] Read more.
Background/Objectives: Types I, V, and XI collagen gene variants have been reported to associate with measurements of knee joint laxity and/or absolute knee ligament length changes. Type XII collagen and tenascin C are also ligament structural proteins whose expression is regulated by mechanical loading. This study investigated whether COL12A1 and TNC variants are associated with knee laxity and/or ligament length changes. Methods: Genu recurvatum, anterior–posterior tibial translation, external–internal tibial rotation, and ligament length changes were measured in 128 healthy participants. They were genotyped for COL12A1 (rs970547) and TNC (rs1061494, rs2104772, rs1138545). Results: Both the COL12A1 AA and TNC rs1061494 TT genotypes were associated with decreased external (p = 0.007, p = 0.010) and internal (p = 0.025, p = 0.002) rotation, as well as slack (p = 0.033, p = 0.014), in the dominant leg. Both genotypes, together with sex, weight, and/or COL1A1 genotypes, explained 26% and 32% of the variance in external and internal rotation, respectively. The TNC genotype, sex, and BMI explained 23% of the variance in slack. The COL12A1 AA and the TNC rs1061494 TT genotypes were associated with smaller changes in the MCL (aMCL: COL12A1 p = 0.009, TNC p = 0.045; iMCL: COL12A1 p = 0.004, TNC p = 0.043; pMCL: COL12A1 p = 0.003, TNC p = 0.067; aDMCL: COL12A1 p = 0.007, TNC p = 0.020; pDMCL: COL12A1 p = 0.007, TNC p = 0.023) and/or LCL (COL12A1 p = 0.652, TNC p = 0.049) lengths within the dominant knee. The TNC rs1061494 CC genotype was associated with larger changes in the non-dominant anterior (p = 0.021) and posterior (p < 0.001) ACL bundle lengths. Conclusions: These findings suggest that COL12A1 and TNC variants are associated with internal–external tibial rotation and knee ligament length changes in healthy individuals. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
19 pages, 5197 KiB  
Article
Genome-Wide Association Studies for Lactation Performance in Buffaloes
by Wangchang Li, Henggang Li, Chunyan Yang, Haiying Zheng, Anqin Duan, Liqing Huang, Chao Feng, Xiaogan Yang and Jianghua Shang
Genes 2025, 16(2), 163; https://doi.org/10.3390/genes16020163 - 27 Jan 2025
Viewed by 358
Abstract
Background: Buffaloes are considered an indispensable genetic resource for dairy production. However, improvements in lactation performance have been relatively limited. Advances in sequencing technology, combined with genome-wide association studies, have facilitated the breeding of high-quality buffalo. Methods: We conducted an integrated [...] Read more.
Background: Buffaloes are considered an indispensable genetic resource for dairy production. However, improvements in lactation performance have been relatively limited. Advances in sequencing technology, combined with genome-wide association studies, have facilitated the breeding of high-quality buffalo. Methods: We conducted an integrated analysis of genomic sequencing data from 120 water buffalo, the high-quality water buffalo genome assembly designated as UOA_WB_1, and milk production traits, including 305-day milk yield (MY), peak milk yield (PM), total protein yield (PY), protein percentage (PP), fat percentage (FP), and total milk fat yield (FY). Results: The results identified 56 significant SNPs, and based on these markers, 54 candidate genes were selected. These candidate genes were significantly enriched in lactation-related pathways, such as the cAMP signaling pathway (ABCC4), TGF-β signaling pathway (LEFTY2), Wnt signaling pathway (CAMK2D), and metabolic pathways (DGAT1). Conclusions: These candidate genes (e.g., ABCC4, LEFTY2, CAMK2D, DGAT1) provide a substantial theoretical foundation for molecular breeding to enhance milk production in buffaloes. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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14 pages, 17803 KiB  
Article
Differential Expression of tRNA-Derived Small RNA Markers of Antidepressant Response and Functional Forecast of Duloxetine in MDD Patients
by Xiaoyan Wang, Ming Gao, Jing Song, Miaolong Li, Yu Chen, Yingfang Lv, Wei Jia and Bingbing Wan
Genes 2025, 16(2), 162; https://doi.org/10.3390/genes16020162 - 27 Jan 2025
Viewed by 436
Abstract
Background/Objectives: Duloxetine, despite being a leading treatment option for major depressive disorder (MDD), exhibits a relatively low adequate response rate when used as a monotherapy, and the fundamental molecular mechanisms remain largely elusive. tRNA-derived small RNA (tsRNA) is a particularly interesting and new [...] Read more.
Background/Objectives: Duloxetine, despite being a leading treatment option for major depressive disorder (MDD), exhibits a relatively low adequate response rate when used as a monotherapy, and the fundamental molecular mechanisms remain largely elusive. tRNA-derived small RNA (tsRNA) is a particularly interesting and new class of molecules that is becoming increasingly noticeable for investigation. Methods: We integrated small RNA sequencing with bioinformatics approaches to dissect the expression profiles of tsRNAs and decipher their functional roles post-duloxetine treatment. Subsequently, molecular docking experiments were carried out to validate the potential functions. Results: Ten tsRNAs significantly changed in the duloxetine response group after an 8-week therapy. Correlation analyses revealed that these tsRNAs predominantly interacted with miRNAs across multiple biological pathways and processes, such as the ECM-receptor interaction and B cell activation. Molecular docking analysis corroborated the binding capabilities of duloxetine with key proteins associated with ECM1 and BAFF, respectively. Conclusions: The identified changes in tsRNAs can precisely mirror the response of duloxetine in MDD treatment, offering novel insights into the underlying mechanisms of duloxetine action. Full article
(This article belongs to the Special Issue Pharmacogenetics of Psychiatric Diseases)
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10 pages, 384 KiB  
Systematic Review
NETest and Gastro-Entero-Pancreatic Neuroendocrine Tumors: Still Far from Routine Clinical Application? A Systematic Review
by Roberta Elisa Rossi and Anna La Salvia
Genes 2025, 16(2), 161; https://doi.org/10.3390/genes16020161 - 27 Jan 2025
Viewed by 445
Abstract
Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are the most prevalent subgroup among NETs and include heterogeneous tumors characterized by different clinical behavior and prognosis. The NETest is a tool based on real-time PCR combined with deep learning strategies to specifically identify tumors with [...] Read more.
Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are the most prevalent subgroup among NETs and include heterogeneous tumors characterized by different clinical behavior and prognosis. The NETest is a tool based on real-time PCR combined with deep learning strategies to specifically identify tumors with a neuroendocrine genotype. Despite the promising results achieved regarding its utility in the field of GEP-NETs, the NETest has not yet entered into routine clinical practice. Methods: We performed a systematic review aimed at summarizing available evidence on the application of the NETest in both the diagnosis and the prognostic stratification of GEP-NETs. Results: We identified five studies evaluating the diagnostic role of the NETest and nine studies evaluating its prognostic value. The NETest emerged as a reliable biomarker for GEP-NET diagnosis with an accuracy higher than 90%, regardless of tumor stage and grade. However, according to some studies, the NETest showed a low specificity, mainly attributed to interferences with other gastro-intestinal malignancies. In terms of prognostic value, the NETest correlated with the detection of residual disease after surgery in six studies. The NETest was also associated with patients’ survival outcomes, namely progression-free survival (PFS) and overall survival (OS) in three studies. Conclusions: According to current systematic review, the value of the NETest both for diagnosis and for prognosis of GEP-NET emerged as robust across different studies. Further prospective analysis on larger GEP-NET series is encouraged to validate this tool, improving patients’ diagnosis, management, and follow-up. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Article
Evaluation of Pan-Cancer Immune Heterogeneity Based on DNA Methylation
by Yang Zhou, Jiebiao Liu, Bowen Shi, Te Ma, Peishen Yu, Ji Li, Yue Gu and Yan Zhang
Genes 2025, 16(2), 160; https://doi.org/10.3390/genes16020160 - 26 Jan 2025
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Abstract
Abstract: Background/Objectives: The heterogeneity of the tumor immune microenvironment is a key determinant of tumor oncogenesis. This study aims to evaluate the composition of seven immune cells across 5323 samples from 14 cancers using DNA methylation data. Methods: A deconvolution algorithm was [...] Read more.
Abstract: Background/Objectives: The heterogeneity of the tumor immune microenvironment is a key determinant of tumor oncogenesis. This study aims to evaluate the composition of seven immune cells across 5323 samples from 14 cancers using DNA methylation data. Methods: A deconvolution algorithm was proposed to estimate the composition of seven immune cells using 1256 immune cell population-specific methylation genes. Based on the immune infiltration features of seven immune cell fractions, 42 subtypes of 14 tumors (2–5 subtypes per tumor) were identified. Results: Significant differences in immune cells between subtypes were revealed for each cancer. The study found that the methylation values of the selected specific sites correlated with gene expression in most tumor subtypes. Immune infiltration results were integrated with phenotypic data, including survival data and tumor stages, revealing significant correlations between immune infiltration and phenotypes in some tumors. Subtypes with high proportions of CD4+ T cells, CD8+ T cells, CD56+ NK cells, CD19+ B cells, CD14+ monocytes, neutrophils, and eosinophils were identified, with subtype counts of 9, 24, 22, 13, 19, 9, and 11, respectively. Additionally, 2412 differentially expressed genes between these subtypes and normal tissues were identified. Pathway enrichment analysis revealed that these genes were mainly enriched in pathways related to drug response and chemical carcinogens. Differences in ESTIMATE scores for subtypes of seven tumors and TIDE scores for eight tumors were also observed. Conclusions: This study demonstrates the intra-tumor and inter-tumor immune heterogeneity of pan-cancer through DNA methylation analysis, providing assistance for tumor diagnosis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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