Genes

18 pages, 5921 KiB

Open AccessArticle

Functional Equivalence of Insulin and IGF-1 in the In Vitro Culture of Chicken Primordial Germ Cells

by Xin Liu, Jun Wu, Yixiu Peng, Guangzheng Liu, Kai Jin, Yingjie Niu, Jiuzhou Song, Wei Han, Guohong Chen, Bichun Li and Qisheng Zuo

Genes 2025, 16(5), 481; https://doi.org/10.3390/genes16050481 - 24 Apr 2025

Abstract

Background: Chicken Primordial Germ Cells (PGCs) are one of the few germ cells that can be cultured for a long time in vitro, but challenges remain such as low culture efficiency and unclear roles of nutrient factors and signaling pathways. Method: In this [...] Read more.

Background: Chicken Primordial Germ Cells (PGCs) are one of the few germ cells that can be cultured for a long time in vitro, but challenges remain such as low culture efficiency and unclear roles of nutrient factors and signaling pathways. Method: In this study, protein kinase B (AKT) pathway activator insulin-like growth factor 1 (IGF-1) was screened for its ability to promote cell proliferation by transcriptome results using various inhibitors of pathway activation. The effects of IGF-1 on PGCs were evaluated through EdU assays, qRT-PCR, flow cytometry, and migration experiments. Results: This study systematically examined the effects of insulin and IGF-1 on the proliferation, cell cycle, ferroptosis, migration capacity, and establishment efficiency of PGCs. The findings demonstrated that IGF-1 exhibited comparable effects to insulin and could effectively replace insulin in PGC culture systems. Conclusions: The research results are expected to provide a solid theoretical basis for optimizing the chicken PGC cultivation system and promoting its practical application. Full article

(This article belongs to the Special Issue Developmental Biology and Genetics in Chicken Embryo Germ Cell)

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19 pages, 18553 KiB

Open AccessArticle

Transcriptomic Analysis of Leaves from Two Maize Hybrids Under Heat Stress During the Early Generative Stage

by Siqi Zhang, Lei Sun, Chunhong Ma, Dajin Xu, Bo Jiao, Jiao Wang, Fushuang Dong, Fan Yang, Shuo Zhou, Qing Yang and Pu Zhao

Genes 2025, 16(5), 480; https://doi.org/10.3390/genes16050480 - 24 Apr 2025

Abstract

Background: High temperatures during the early generative stage significantly threaten maize productivity, yet the molecular basis of heat tolerance remains unclear. Methods: To elucidate the molecular mechanisms of heat tolerance in maize, two hybrids—ZD309 (heat-tolerant) and XY335 (heat-sensitive)—were selected for integrated transcriptomic and [...] Read more.

Background: High temperatures during the early generative stage significantly threaten maize productivity, yet the molecular basis of heat tolerance remains unclear. Methods: To elucidate the molecular mechanisms of heat tolerance in maize, two hybrids—ZD309 (heat-tolerant) and XY335 (heat-sensitive)—were selected for integrated transcriptomic and physiological analyses. The plants were subjected to high-temperature treatments (3–5 °C above ambient field temperature) for 0, 1, 3, 5, and 7 days, with controls grown under natural conditions. Physiological indices, including Superoxide dismutase (SOD) activity, and proline (PRO), malondialdehyde (MDA), soluble sugar, and protein content, were measured. Results: Transcriptome analysis identified 1595 differentially expressed genes (DEGs) in XY335 (509 up- and 1086 down-regulated) and 1526 DEGs in ZD309 (863 up- and 663 down-regulated), with the most pronounced changes occurring on day 5. Key DEGs in XY335 were enriched in galactose metabolism and carbohydrate catabolism, whereas ZD309 exhibited rapid activation of oxidative stress and cell wall integrity pathways. Mfuzz time-series analysis categorized DEGs from XY335 and ZD309 into six clusters each. Weighted gene co-expression network analysis (WGCNA) identified 10 hub genes involved in ubiquitin thioesterase activity and RNA modification, suggesting protein-level regulatory roles. Conclusions: This study reveals distinct transcriptional dynamics between heat-tolerant and heat-sensitive varieties, providing candidate genes for breeding thermotolerant maize and advancing our understanding of heat stress responses during critical reproductive stages. Full article

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

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14 pages, 8990 KiB

Open AccessArticle

Molecular Cloning and Heterologous Expression of the Mitochondrial ATP6 Gene from Kenaf (Hibiscus cannabinus) in Tobacco (Nicotiana tabacum)

by Bangbang Huang, Meiling Wei, Rongchang Wei, Wenhuan Hou, Xingfu Tang, Yanhong Zhao, Xiaofang Liao and Ruiyang Zhou

Genes 2025, 16(5), 479; https://doi.org/10.3390/genes16050479 - 23 Apr 2025

Abstract

Background: The aim of this study was to develop a genetic transformation system to construct an overexpression vector for the mitochondrial gene atp6 in tobacco, thereby providing a foundation to investigate the functional roles of mitochondrial genes in this species. Methods: A full-length [...] Read more.

Background: The aim of this study was to develop a genetic transformation system to construct an overexpression vector for the mitochondrial gene atp6 in tobacco, thereby providing a foundation to investigate the functional roles of mitochondrial genes in this species. Methods: A full-length coding sequence (CDS) of the atp6 gene from a sterile line was cloned, along with the mitochondrial leader peptide sequence of atp2-1 from tobacco, using cDNA from kenaf UG93A anthers as a template. An overexpression vector for plants was constructed by employing In-Fusion technology, and wild-type tobacco plants were transformed via Agrobacterium-mediated transformation. Transgenic tobacco plants were then subjected to resistance screening and PCR validation. Results: The overexpression vector PBI121-atp2-1-atp6-EGFP, which includeds the mitochondrial leader peptide sequence, was successfully constructed. PCR validation using two pairs of primers targeting different sites on the overexpression vector confirmed the stable expression of the target gene in six transgenic tobacco plants (H1, H3, H4, H5, H7, and H8) via both primer pairs. A phenotypic analysis and iodine–potassium iodide (I₂-KI) staining of pollen grains from transgenic tobacco plants revealed the presence of shriveled and malformed pollen grains with reduced viability. These findings suggest that the atp6A gene, including the mitochondrial signal peptide, induces pollen abortion in tobacco. Conclusions: The genetic transformation system developed for the vector overexpressing the atp6 mitochondrial gene from kenaf provides a valuable framework to investigate the molecular regulatory mechanisms underlying the role of the atp6 gene in kenaf cytoplasmic male sterility (CMS). Full article

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

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21 pages, 1323 KiB

Open AccessReview

Autism Spectrum Disorder: Genetic Mechanisms and Inheritance Patterns

by Ilaria La Monica, Maria Rosaria Di Iorio, Antonia Sica, Francesca Rufino, Chiara Sotira, Lucio Pastore and Barbara Lombardo

Genes 2025, 16(5), 478; https://doi.org/10.3390/genes16050478 - 23 Apr 2025

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that first develops in early childhood and is characterized by restricted interests, activities, and behaviors, as well as difficulties with social interactions and communication. ASD arises from a complex interaction between environmental factors and genetic [...] Read more.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that first develops in early childhood and is characterized by restricted interests, activities, and behaviors, as well as difficulties with social interactions and communication. ASD arises from a complex interaction between environmental factors and genetic inheritance, influenced by epigenetic mechanisms. With an estimated heritability of 70–90%, ASD is highly familial, indicating that genetic factors play a significant role in its development. This shows how hundreds of genetic variants contribute to ASD, whose risk effects are highly variable and are often related to other conditions; these genetic alterations are at different levels, which include single gene mutations, monogenic disorders, genomic variants, and chromosomal abnormalities. Copy number variants (CNVs) appear to contribute significantly to understanding the pathogenesis of this complex disease. In some cases, single CNVs in genomic DNA are pathogenic and causative, supporting the hypothesis that some sporadic cases of ASD may result from rare mutations with significant clinical impact. However, in many cases, there are common genomic variants that increase the risk of developing ASD but are insufficient by themselves to determine an ASD phenotype, and rare genomic variants, of various sizes, inherited from a parent or de novo, that can be associated with the ASD phenotype. Therefore, the aim of this review is to deepen the concept of ASD inheritance through the two-hit theory of CNVs, in which the concomitant presence of two alterations could determine the clinical phenotypes, the concept of incomplete penetrance for inherited CNVs with pathogenic clinical significance, and the presence of compound heterozygosity. These aspects represent important mechanisms underlying the pathogenesis of autism, contributing to a better elucidation for the understanding of the genetic contribution to the ASD phenotype. Full article

(This article belongs to the Special Issue Genetic Insights into Neurodevelopmental Disorders)

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19 pages, 9027 KiB

Open AccessArticle

Phylogenetic Insights into the Evolutionary History of the RSPO Gene Family in Metazoa

by Jia Cheng, Ling Yang, Shiping Wang, Kaiyong Luo, Senlin Luo, Yang Dong, Ya Ning and Weibin Wang

Genes 2025, 16(5), 477; https://doi.org/10.3390/genes16050477 - 23 Apr 2025

Abstract

Background: The RSPO gene family encodes secreted glycoproteins that are rich in cysteine, which generally serve as activators of the Wnt signaling pathway in animals. Four types of this family have been identified in a few model species. However, the evolution of [...] Read more.

Background: The RSPO gene family encodes secreted glycoproteins that are rich in cysteine, which generally serve as activators of the Wnt signaling pathway in animals. Four types of this family have been identified in a few model species. However, the evolution of the family remains unclear. Methods: In this study, we identified a total of 1496 RSPO homologs through an extensive survey of the RSPO genes in 430 animals. Gene family clustering and phylogenetic analysis identified four major subtypes of the family (RSPO1–RSPO4) and clarified their distribution of copy number in different species. Results and Conclusions: Members of the RSPO4 subfamily that were closest to ancestral forms existed in both Deuterostomes and Protostomates, and we speculate that representatives of this subfamily already existed in Urbilatera, the last common ancestor of Deuterostomes. Particularly, in some RSPO3 subtypes of Actinopterygii (ray-finned fishes), an FU repeated motif with three conserved cysteines was identified. Further conservative analysis of amino acids and alignment of tertiary protein structure revealed the potential functional sites for each subgroup. The results provide insight into the phylogenetic relationships and evolutionary patterns of conserved motifs of RSPO family genes in animal kingdoms, which will guide further studies on the biological functions of RSPO in other non-model species. Full article

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

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18 pages, 8196 KiB

Open AccessArticle

Genome-Wide Screening of the MYB Genes in Coptis chinensis and Their Roles in Growth, Development, and Heavy Metal Resistance

by Yang Yang, Jingmao You and Xuebo Hu

Genes 2025, 16(5), 476; https://doi.org/10.3390/genes16050476 - 23 Apr 2025

Abstract

Background: Coptis chinensis is a traditional medicinal plant rich in bioactive compounds like berberine, known for its antibacterial, anti-inflammatory, and antioxidant properties. This study aims to analyze the MYB transcription factor family in C. chinensis to better understand their roles in plant [...] Read more.

Background: Coptis chinensis is a traditional medicinal plant rich in bioactive compounds like berberine, known for its antibacterial, anti-inflammatory, and antioxidant properties. This study aims to analyze the MYB transcription factor family in C. chinensis to better understand their roles in plant growth, development, metabolism, and stress responses. Methods: We employed bioinformatics to conduct a genome-wide identification of MYB genes in C. chinensis, followed by analyses of physicochemical properties, phylogenetic relationships, gene structures, chromosomal localization, conserved motifs, cis-acting elements, and expression patterns. Results were validated using qRT-PCR. Results: A total of 129 CcMYB genes were identified across nine chromosomes. Phylogenetic analysis categorized these genes into 19 subgroups, notably highlighting the S6 subgroup, which lacks counterparts in Arabidopsis. Comparative genomics revealed segmental duplication among gene pairs. Transcriptomic analysis indicated that CcMYB21, CcMYB40, CcMYB105, and CcMYB116 had high expression levels in stems. Importantly, CcMYB94 expression significantly increased under cadmium stress, suggesting its role in stress regulation. Conclusions: This study offers a comprehensive analysis of the MYB gene family in C. chinensis, underscoring the significance of MYB transcription factors in enhancing the plant’s medicinal value and stress tolerance, particularly against cadmium exposure. These insights pave the way for further exploration of specific MYB genes to improve stress resilience in C. chinensis. Full article

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

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14 pages, 1031 KiB

Open AccessCase Report

Example of Intrafamilial Clinical Polymorphism in a Family with Osteogenesis Imperfecta

by Varvara A. Galkina, Tatyana A. Vasilyeva, Inna S. Tebieva, Zolina K. Getoeva, Andrey V. Marakhonov, Vitaly V. Kadyshev, Sergey I. Kutsev and Rena A. Zinchenko

Genes 2025, 16(5), 475; https://doi.org/10.3390/genes16050475 - 23 Apr 2025

Abstract

Background/Objectives: According to the International Classification of Hereditary Skeletal Diseases (2019), osteogenesis imperfecta (OI) is classified as a disorder resulting from impaired formation of the cortical layer density of diaphyses and metaphyseal modeling. OI comprises a heterogeneous group of genetic diseases, with [...] Read more.

Background/Objectives: According to the International Classification of Hereditary Skeletal Diseases (2019), osteogenesis imperfecta (OI) is classified as a disorder resulting from impaired formation of the cortical layer density of diaphyses and metaphyseal modeling. OI comprises a heterogeneous group of genetic diseases, with most cases inherited in an autosomal dominant manner, while others follow autosomal recessive or X-linked recessive inheritance patterns. Accurate DNA testing is essential for precise medical and genetic counseling, ensuring reliable prognostic assessments for patients’ descendants and siblings. As part of a medical genetic study of the population of the Republic of the North Ossetia Alania, specifically in the Mozdok district, specialists from the Laboratory of Genetic Epidemiology at the Research Centre for Medical Genetics (RCMG) examined a family with 13 affected individuals with OI across four generations. Methods: A comprehensive clinical assessment was performed, followed by molecular genetic analysis using whole-exome sequencing (WES). Segregation analysis within the family was conducted via Sanger sequencing. Results: Clinical evaluation suggested a diagnosis of OI, which was subsequently confirmed by genetic testing. The severity and spectrum of symptoms varied considerably among affected family members and were influenced by age and specific nuclear family lineage. Molecular analysis in the proband identified a heterozygous pathogenic variant in the COL1A1 gene variant (c.1243C>T, p.(Arg415*)), confirming a diagnosis of OI type IV. The variant was found to co-segregate with the disease within the family. Conclusions: Molecular diagnosis enabled precise risk assessment for affected offspring in family members with mild phenotypic manifestations. Additionally, pediatric patients were referred for standard bisphosphonate therapy to manage the condition effectively. Full article

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

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13 pages, 1289 KiB

Open AccessArticle

Analysis of Selected Eye Disorders in a Group of Predisposed Breeds of Dogs: Molecular Diagnostics of Collie Eye Anomaly and Progressive Retinal Atrophy

by Jaroslav Bučan, Beáta Holečková, Martina Galdíková, Jana Halušková and Viera Schwarzbacherová

Genes 2025, 16(5), 474; https://doi.org/10.3390/genes16050474 - 23 Apr 2025

Abstract

Background: Two hereditary eye disorders that are frequently observed in Collies and related breeds are Collie Eye Anomaly (CEA) and Progressive Retinal Atrophy (PRA). The main symptom of CEA is choroidal hypoplasia. It is associated with a 7.8 kb deletion in intron 4 [...] Read more.

Background: Two hereditary eye disorders that are frequently observed in Collies and related breeds are Collie Eye Anomaly (CEA) and Progressive Retinal Atrophy (PRA). The main symptom of CEA is choroidal hypoplasia. It is associated with a 7.8 kb deletion in intron 4 of the NHEJ1 gene located on chromosome CFA7. Rod–cone dysplasia 3 (RCD3), an early-onset form of PRA, is associated with mutations in the PDE6A gene. Methods: Molecular diagnostic techniques were used in this study to identify genetic mutations linked to CEA and RCD3-type PRA in a subset of dog breeds. Australian Shepherds (n = 29), Border Collies (n = 9), Longhaired Collies (n = 27), and Shetland Sheepdogs (n = 10) provided a total of 75 DNA samples. Samples were collected by buccal swab or blood draw, and PCR and real-time PCR methods were used for processing. Results: Of the dogs in the studied breeds, 31 had the NHEJ1 gene mutation linked to CEA. Among these, 15 were homozygous recessive (affected), while 16 were heterozygous (carriers). None of the samples had any mutations in the PDE6A gene associated with RCD3-type PRA. Conclusions: Effective identification of carriers and affected individuals for CEA was made possible by PCR-based genetic testing, confirming its value in early diagnosis and breed control. Although the RCD3 form of PRA has not been previously reported in Collies or Australian Shepherds, it was included in our analysis due to the genetic relatedness among herding breeds and the potential presence of undetected carriers resulting from historical crossbreeding. Full article

(This article belongs to the Special Issue Genetics in Retinal Diseases—2nd Edition)

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19 pages, 402 KiB

Open AccessArticle

Enhancing Prognostic Signatures in Glioblastoma with Feature Selection and Regularised Cox Regression

by Beatriz N. Leitão, André Veríssimo, Alexandra M. Carvalho and Susana Vinga

Genes 2025, 16(5), 473; https://doi.org/10.3390/genes16050473 - 23 Apr 2025

Abstract

Background: Glioblastoma is a highly aggressive brain tumour with poor survival outcomes, highlighting the need for reliable prognostic models. Developing robust and interpretable prognostic signatures is critical for improving patient stratification and guiding therapy. This study explored the integration of machine learning feature [...] Read more.

Background: Glioblastoma is a highly aggressive brain tumour with poor survival outcomes, highlighting the need for reliable prognostic models. Developing robust and interpretable prognostic signatures is critical for improving patient stratification and guiding therapy. This study explored the integration of machine learning feature selection with regularised Cox regression to construct prognostic gene signatures for glioblastoma patients. Methods: We combined the Boruta algorithm and Random Survival Forests (RSFs) with regularised Cox regression, along with network-based regularisation techniques (HubCox and OrphanCox), to develop interpretable prognostic signatures for stratifying high- and low-risk glioblastoma patients. Using mRNA-seq and survival data from The Cancer Genome Atlas (TCGA), we developed predictive models following WHO-2021 glioma guidelines. Results: Integrating Boruta or RSF with regularised Cox regression improved the performance and interpretability. Boruta increased the concordance indexes (C-indexes) by 0.030 and 0.013 for LASSO and Elastic Net, respectively, while significantly reducing the feature numbers. RSF similarly enhanced the performance and feature reduction. The genes Lysyl Oxidase Like 1 (LOXL1) and Insulin Like Growth Factor Binding Protein 6 (IGFBP6) were consistently selected and linked to glioma survival, emphasising their clinical significance. The network-based methods demonstrated superior survival probability prediction (lower Integrated Brier Score), although with lower C-index values, highlighting limitations in ranking the survival times. To evaluate the generalisability, external validation using the Chinese Glioma Genome Atlas (CGGA) confirmed that a multigene signature derived from the most consistently selected genes significantly stratified the patients by risk. Conclusions: This study underscored the utility of combining machine learning feature selection with survival analysis to enhance prognostic modelling while balancing predictive performance and interpretability. Full article

(This article belongs to the Section Bioinformatics)

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15 pages, 1917 KiB

Open AccessArticle

Clinical Relevance of IFT140 Loss-of-Function Variants in Development of Renal Cysts

by Carlotta Pia Cristalli, Sara Calabrese, Luca Caramanna, Andrea Pietra, Giulia Vitetta, Bianca De Nicolo, Elena Bonora, Giulia Severi, Soara Menabò, Simona Ferrari, Francesca Ciurli, Valeria Aiello, Irene Capelli, Andrea Pasini, Irene Alberici, Roberto Pillon, Claudio La Scola, Cesare Rossi, Francesca Montanari and Claudio Graziano

Genes 2025, 16(5), 472; https://doi.org/10.3390/genes16050472 - 22 Apr 2025

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, affecting approximately 1 in 1000 individuals. This genetically heterogeneous condition is primarily caused by monoallelic pathogenic or likely pathogenic variants in the PKD1 and PKD2 genes, accounting for 78% [...] Read more.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, affecting approximately 1 in 1000 individuals. This genetically heterogeneous condition is primarily caused by monoallelic pathogenic or likely pathogenic variants in the PKD1 and PKD2 genes, accounting for 78% and 15% of typical cases, respectively. Recently, the application of NGS methods has led to the identification of additional genes associated with ADPKD, which have been incorporated into routine diagnostic testing for detecting phenocopies of the disease. Methods: In this study, targeted NGS (tNGS) analysis of the main cystogenes associated with classic and atypical ADPKD was performed in a cohort of 218 patients clinically diagnosed with cystic nephropathies. Results: Genetic testing identified variants in 175 out of 218 cases (80.3%). Among these, 133 probands (76%) harbored likely pathogenic or pathogenic variants in one or more genes of the panel, while 42 individuals (24%) had a variant of unknown significance (VUS). Specifically, one or more class 4/5 variants in PKD1, PKD2, or both were identified in 111 (83.5%) probands. Remarkably, a pathogenic variant in the IFT140 gene was identified in 14 index cases (8% of positive individuals, 6.4% of the global cohort): 10 distinct loss-of-function (LoF) variants were identified (including four frameshift variants, four nonsense variants, and two splice site defects); one individual carried a second IFT140 missense variant classified as VUS. Furthermore, five affected family members were found to carry a P/LP LoF variant in IFT140. Conclusions: Our data support that IFT140 heterozygous IFT140 LoF variants result in an atypical, mild form of ADPKD, consisting of bilateral kidney cysts and renal functional decline at older ages. Furthermore, we describe the second pediatric patient with a mild form of ADPKD due to an IFT140 variant and discuss hyperuricemia as a previously unappreciated feature of this condition. Full article

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

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18 pages, 3042 KiB

Open AccessArticle

RNA-Seq of Chicken Embryo Liver Reveals Transcriptional Pathways Influenced by Egg Formaldehyde Treatment

by Mustafa Özdemir, Ghulam Asghar Sajid, Selma Büyükkılıç Beyzi, Mehmet Kızılaslan, Yunus Arzık, Servet Yalçın, Stephen N. White and Mehmet Ulas Cinar

Genes 2025, 16(5), 471; https://doi.org/10.3390/genes16050471 - 22 Apr 2025

Abstract

Background/Objectives: Hatchery fumigation is recognized as a crucial step to control microbial bloom in the environment, and formaldehyde is one of the most widely used disinfectants to ensure successful hatchability and healthy production. While many of the benefits are thought to be derived [...] Read more.

Background/Objectives: Hatchery fumigation is recognized as a crucial step to control microbial bloom in the environment, and formaldehyde is one of the most widely used disinfectants to ensure successful hatchability and healthy production. While many of the benefits are thought to be derived from disinfectant properties, it is possible that additional host gene and genetic pathway modulation could contribute to these outcomes. The current study aimed to capture the in ovo transcriptional response of liver tissue to formaldehyde treatment. Methods: Chick embryos were subjected to formaldehyde fumigation treatment for 25 min at 24–25 °C and 75% relative humidity, keeping a control group as untreated. On the 18th day of incubation at 37.8 °C and 58–63% humidity, eggs were broken, and liver tissue was obtained for RNA isolation, cDNA library preparation, and RNA sequencing. Results: Bioinformatics analysis revealed 908 significant differentially expressed genes (DEGs), among which 814 were known genes and 94 were novel genes. A total of 672 DEGs were upregulated, whereas 236 genes were downregulated in response to FA treatment. Of the 94 novel genes, 80 were upregulated. Key DEGs, associated QTLs, and transcription factors were involved in immuno-inflammatory responses, oxidative stress, epigenetic modification, and cellular adaptation-related activities. Further research should focus on biological validation of key DEGs to clarify their roles, pathways, and relationships to FA treatment. Conclusions: Overall, these findings (1) provide critical molecular detail as a first step towards genetic selection to improve formaldehyde treatment response and effectiveness, and (2) provide DEG signatures for FA treatment as a reference against which to compare other interventions to achieve hatchability and production benefits. Full article

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

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14 pages, 3508 KiB

Open AccessArticle

Genetic Editing of Tomato Golgi-Localized Nucleotide Sugar Transporter 1.1 Promotes Immunity Against Phytophthora infestans

by Peize He, Yanling Cai, Yanzi Wang, Zhiqing Wang, Yaqing Lyu, Tao Li, Xingtan Zhang and Shaoqun Zhou

Genes 2025, 16(4), 470; https://doi.org/10.3390/genes16040470 - 21 Apr 2025

Abstract

Background: Functional alleles of host plant susceptibility genes (S genes) can exacerbate the severity of diseases by enhancing pathogen compatibility. Genetic editing of the targeted host S genes has demonstrated remarkable efficacy in conferring broad-spectrum resistance across multiple crop species. We have previously [...] Read more.

Background: Functional alleles of host plant susceptibility genes (S genes) can exacerbate the severity of diseases by enhancing pathogen compatibility. Genetic editing of the targeted host S genes has demonstrated remarkable efficacy in conferring broad-spectrum resistance across multiple crop species. We have previously identified a Golgi-localized Nucleotide Sugar Transporter 1 homolog (SlGONST1.1) in the host plant Solanum lycopersicum as a susceptibility gene towards late blight caused by Phytophthora infestans. Methods: In this study, we performed a detailed characterization of tissue-specific and P. infestans-inducible expression patterns of this gene, and the subcellular localization of its encoded protein product. Results: Similar to phenotypes of two reported Slgonst1.1 edited lines, two newly generated genetically edited lines of SlGONST1.1 demonstrated enhanced resistance against P. infestans without obvious growth and developmental abnormality. Phytohormonal quantifications and reactive oxygen species measurements showed that an Slgonst1.1 line had lower constitutive abscisic acid contents and depleted reactive oxygen species burst induced by pathogen-associated molecular pattern. Further comparative transcriptomic analyses revealed that the expression of defense-related genes is disproportionally up-regulated in the Slgonst1.1 line. Conclusions: In summary, our findings confirmed SlGONST1.1 as a functional host susceptibility gene towards late blight and shed light on the potential molecular mechanism underlying its function. Full article

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

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11 pages, 238 KiB

Open AccessArticle

Clinical-Genetic Approach to Conditions with Macrocephaly and ASD/Behaviour Abnormalities: Variants in PTEN and PPP2R5D Are the Most Recurrent Gene Mutations in a Patient-Oriented Diagnostic Strategy

by Federica Francesca L’Erario, Annalisa Gazzellone, Ilaria Contaldo, Chiara Veredice, Marina Carapelle, Anna Gloria Renzi, Clarissa Modafferi, Marta Palucci, Pino D’Ambrosio, Elena Sonnini, Lorenzo Loberti, Arianna Panfili, Emanuela Lucci Cordisco, Pietro Chiurazzi, Valentina Trevisan, Chiara Leoni, Giuseppe Zampino, Maria Grazia Pomponi, Daniela Orteschi, Marcella Zollino and Giuseppe Marangi Show full author list Hide full author list

Genes 2025, 16(4), 469; https://doi.org/10.3390/genes16040469 - 20 Apr 2025

Abstract

Background: Macrocephaly can be a component manifestation of several monogenic conditions, in association with intellectual disability/developmental delay (ID/DD) behaviour abnormalities, including autism spectrum disorders (ASD), and variable additional features. On the other hand, idiopathic ASD can present with developmental delay and macrocephaly. Methods: [...] Read more.

Background: Macrocephaly can be a component manifestation of several monogenic conditions, in association with intellectual disability/developmental delay (ID/DD) behaviour abnormalities, including autism spectrum disorders (ASD), and variable additional features. On the other hand, idiopathic ASD can present with developmental delay and macrocephaly. Methods: We carried out a retrospective analysis of a cohort of 78 patients who were tested from February 2017 to December 2024 by high-throughput sequencing of a panel of 27 genes (ABCC9, AKT1, AKT2, AKT3, BRWD3, DIS3L2, DNMT3A, EZH2, GPC3, GPC4, HERC1, MED12, MTOR, NFIA, NFIX, NSD1, PDGFRB, PIK3CA, PIK3R1, PIK3R2, PPP2R1A, PPP2R5D, PTEN, RAB39B, RNF135, SETD2, and TBC1D7) because of neurodevelopmental impairment, including ID/DD, ASD/behaviour abnormalities associated with macrocephaly, mimicking to a large extent idiopathic ASD. Results: Pathogenic variants leading to the diagnosis of monogenic conditions were detected in 22 patients (28%), including NSD1 (2), PTEN (16), and PPP2R5D (4). Distinctive of the PTEN-associated phenotype were true macrocephaly (100%), ASD or behaviour abnormalities (92%), mild/borderline ID (79%), and no facial dysmorphisms. Typical of the PPP2R5D-associated phenotype were relative macrocephaly (75%), a few unspecific peculiar facial characteristics (50%), and a more variable presentation of the neurodevelopmental phenotype. Conclusions: Pathogenic variants in PTEN and PPP2R5D are the most recurrent gene mutations in a patient-oriented procedure for the genetic diagnosis of apparently idiopathic ASD and behaviour abnormalities associated with macrocephaly. The clinical applicability of the presented diagnostic strategy is discussed. Full article

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

22 pages, 12266 KiB

Open AccessArticle

Physiological and Transcriptomic Analyses Unveil the Preservation Mechanism of Streptomyces albulus Ah11601 Fermentation Broth on ‘Shine Muscat’ Grapes

by Chao-Tian Lv, Huan Li and Ri-Mao Hua

Genes 2025, 16(4), 468; https://doi.org/10.3390/genes16040468 - 19 Apr 2025

Abstract

Background/Objectives: Grapes (Vitis vinifera), particularly ‘Shine Muscat’, are prone to postharvest quality loss mainly due to poor storage tolerance. Actinomycetes are microbial resources that produce secondary metabolites that exhibit notable functional properties. Methods: This study explored the use of Streptomyces albulus [...] Read more.

Background/Objectives: Grapes (Vitis vinifera), particularly ‘Shine Muscat’, are prone to postharvest quality loss mainly due to poor storage tolerance. Actinomycetes are microbial resources that produce secondary metabolites that exhibit notable functional properties. Methods: This study explored the use of Streptomyces albulus Ah11601 fermentation broth (SFB) as a postharvest treatment to preserve ‘Shine Muscat’ grape quality during 6 days of room temperature storage using physiological, transcriptomic, and bioinformatics analyses to elucidate the underlying regulatory mechanism. Results: The results demonstrated that, compared to the control group stored at room temperature (25 °C) for 6 days (6D), the SFB-treated group (T6D) presented a significant delay in the decrease in fruit hardness and vitamin C content. Further investigations revealed that the 6D treatment significantly elevated lipoxygenase activity, MDA content, O₂⁻ generation rate, and H₂O₂ levels. In addition, both the 6D and T6D treatments significantly increased the activities of SOD and APX. Functional enrichment analysis revealed that the upregulated DEGs in the 6D group were predominantly enriched in pathways such as phenylpropanoid biosynthesis; flavonoid biosynthesis; phenylalanine metabolism; and stilbenoid, diarylheptanoid, and gingerol biosynthesis. The downregulated DEGs were enriched primarily in the endoplasmic reticulum protein processing pathway. In the T6D group, the upregulated DEGs were predominantly enriched in the zeatin biosynthesis pathway. In addition, significant alterations in the expression of genes associated with the ethylene and abscisic acid signaling pathways were detected. Conclusions: In conclusion, SFB treatment effectively mitigated the deterioration of the postharvest quality of ‘Shine Muscat’ grapes by preserving the cellular redox balance, regulating cytokinin and ethylene biosynthesis, and optimizing the regulation of ethylene and abscisic acid signaling. Full article

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

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12 pages, 10633 KiB

Open AccessReview

Splenic Diffuse Red Pulp Small B-Cell Lymphoma with Overlapping Clinical and Immunophenotypic Features with Hairy Cell Leukaemia: A Case Report and a Review of the Literature

by Mirette Hanna, Michola Trus and Erica DiMaria

Genes 2025, 16(4), 467; https://doi.org/10.3390/genes16040467 - 19 Apr 2025

Abstract

Background: Splenic B-cell lymphomas and leukaemias include hairy cell leukaemia, splenic marginal zone lymphoma, splenic diffuse red pulp small B-cell lymphoma, and splenic B-cell lymphoma/leukaemia with prominent nucleoli. The main diagnostic challenge is to differentiate between splenic B-cell lymphomas and leukaemias due to [...] Read more.

Background: Splenic B-cell lymphomas and leukaemias include hairy cell leukaemia, splenic marginal zone lymphoma, splenic diffuse red pulp small B-cell lymphoma, and splenic B-cell lymphoma/leukaemia with prominent nucleoli. The main diagnostic challenge is to differentiate between splenic B-cell lymphomas and leukaemias due to highly overlapping clinical, morphologic, and phenotypic features in the absence of splenectomies for diagnostic purposes. Case presentation: We describe a case of a 78-year-old woman who presented with weight loss and was subsequently found to have pancytopenia, lymphocytosis, and splenomegaly. Peripheral blood smear showed a homogenous population of small- to medium-sized lymphocytes having oval nuclei, condensed chromatin, and villous cytoplasmic projections. Bone marrow showed B-cell infiltrate in a predominantly intrasinusoidal pattern. Except for cyclin D1 and BRAF, the immunophenotype was similar to that of hairy cell leukaemia. This was further supported by the lack of BRAF p.V600E mutation by polymerase chain reaction. A diagnosis of splenic diffuse red pulp small B-cell lymphoma was thus favored based on the lack of cyclin D1 expression and pattern of infiltration in the bone marrow biopsy. Conclusions: Awareness of this infrequent clinical presentation and immunophenotype of splenic diffuse red pulp small B-cell lymphoma is crucial for diagnosis and devising appropriate therapeutic strategies for the patient. Full article

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

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22 pages, 5264 KiB

Open AccessArticle

miR-143-3p Promotes T_SCM Differentiation and Inhibits Progressive T Cell Differentiation via Inhibiting ABL2 and PAG1

by Wenkai Shi, Jieming Hu, Hongqiong Wang, Huishan Zhong, Wenfeng Zhang, Jinquan Wang, Hongwei Shao, Han Shen, Huaben Bo, Changli Tao and Fenglin Wu

Genes 2025, 16(4), 466; https://doi.org/10.3390/genes16040466 - 19 Apr 2025

Abstract

Background: Adoptive cell therapy (ACT), including CAR-T and TCR-T therapies, shows promise for cancer treatment, depending on infused T cell expansion, persistence and activity. We previously characterized four T-cell subsets (T_N, T_SCM, T_CM and T_EM) and [...] Read more.

Background: Adoptive cell therapy (ACT), including CAR-T and TCR-T therapies, shows promise for cancer treatment, depending on infused T cell expansion, persistence and activity. We previously characterized four T-cell subsets (T_N, T_SCM, T_CM and T_EM) and their miRNA profiles. Objectives: This study investigates miR-143-3p’s role in T cell differentiation. Methods: Using qPCR, we analyzed miR-143-3p expression. Target genes were validated by dual-luciferase assays. Functional assays assessed differentiation markers, proliferation, apoptosis and cytokine secretion. Results: miR-143-3p was upregulated in early-differentiated T_SCM but downregulated during progression. We confirmed ABL2 and PAG1 as direct targets suppressed by miR-143-3p. Overexpression increased early markers (LEF1, CCR7 and CD62L) while decreasing late markers (EOMES, KLRG1 and CD45RO). It also enhanced proliferation, reduced apoptosis and suppressed cytokine secretion. Conclusions: miR-143-3p promotes T_SCM differentiation and inhibits progressive differentiation by targeting ABL2/PAG1, suggesting new ACT optimization strategies. Full article

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

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30 pages, 2870 KiB

Open AccessReview

Barth Syndrome: TAFAZZIN Gene, Cardiologic Aspects, and Mitochondrial Studies—A Comprehensive Narrative Review

by Consolato M. Sergi

Genes 2025, 16(4), 465; https://doi.org/10.3390/genes16040465 (registering DOI) - 18 Apr 2025

Abstract

Barth syndrome (BTHS) is inherited through an X-linked pattern. The gene is located on Xq28. Male individuals who inherit the TAFAZZIN pathogenic variant will have the associated condition, while female individuals who inherit the TAFAZZIN pathogenic variant generally do not experience the condition. [...] Read more.

Barth syndrome (BTHS) is inherited through an X-linked pattern. The gene is located on Xq28. Male individuals who inherit the TAFAZZIN pathogenic variant will have the associated condition, while female individuals who inherit the TAFAZZIN pathogenic variant generally do not experience the condition. There are several organs that may be affected, but striking is the cardiological involvement. Cardiovascular disease, which may be the trigger starting the diagnostic procedure in a proband, may include a range of diseases from a severely dilated heart to a hypertrophic heart in the spectrum of anomalies encountered. Left ventricular non-compaction of the heart is also occasionally encountered. This cardiac event may reveal the prognosis of the affected patients. In this narrative review, we highlight the gene’s characteristics, the reactome, the cardiological features of the cardiovascular disease observed in patients affected with BTHS, emphasize the most current studies on BTHS cardiomyopathy, and delineate the biological underlying mechanisms supporting the proposal of new therapeutic options. Full article

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13 pages, 1729 KiB

Open AccessArticle

Novel Truncating Variants in PODXL Represent a New Entity to Be Explored Among Podocytopathies

by José María García-Aznar, María Lara Besada-Cerecedo, Cristina Castro-Alonso, Milagros Sierra Carpio, Miquel Blasco, Borja Quiroga, Michal Červienka, Ricardo Mouzo, Roser Torra, Alberto Ortiz and Patricia de Sequera

Genes 2025, 16(4), 464; https://doi.org/10.3390/genes16040464 - 18 Apr 2025

Abstract

Background/Objectives: Podocalyxin is a sialoprotein mainly expressed in the kidney cortex and lung tissue, which has been described as a component of the podocyte glycocalyx. This protein promotes the reorganization of the podocyte cytoskeleton, as well as the morphogenesis and differentiation of nascent [...] Read more.

Background/Objectives: Podocalyxin is a sialoprotein mainly expressed in the kidney cortex and lung tissue, which has been described as a component of the podocyte glycocalyx. This protein promotes the reorganization of the podocyte cytoskeleton, as well as the morphogenesis and differentiation of nascent podocytes, actively participating in glomerular filtration. Previous research has suggested that PODXL haploinsufficiency leads to podocytopathy with development of focal segmental glomerulosclerosis, a disorder that has been demonstrated in Podxl-deficient animal models and proposed as a primary cause in human families affected by this condition. However, only a few families have been reported, which limits the understanding about the spectrum of phenotype and prognosis of the disease. Methods: We performed high-throughput sequencing in a cohort of young adults with CKD, describing the clinical scenario of those who harbored truncating variants in the PODXL gene and testing the families for detected variants. Results: The PODXL gene exhibited a slight deviation in loss intolerance probability and moderate deviation in the observed/expected ratio of variation, which is typically observed in dominant genes with age-dependent incomplete penetrance or variable expression. We reported four novel truncating variants in the PODXL gene, along with a collection of previously published monoallelic truncating variants. Conclusions: These findings further support evidence about genetic defects in the PODXL gene associated with a new molecular entity of podocytopathy with adult onset. Additionally, the nucleotide sequence of PODXL contains particularities that require careful analysis to interpret the effect of the variants detected in this gene. Full article

(This article belongs to the Section Genetic Diagnosis)

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16 pages, 11711 KiB

Open AccessArticle

The Solute Carrier Superfamily as Therapeutic Targets in Pancreatic Ductal Adenocarcinoma

by Sang Yeon Cho, Hyuk Soo Eun, Jaejeung Kim, Yun Dam Ko, Woo Sun Rou and Jong Seok Joo

Genes 2025, 16(4), 463; https://doi.org/10.3390/genes16040463 - 18 Apr 2025

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC), a challenging and malignant cancer, primarily originates from the exocrine cells of the pancreas. The superfamily of solute carrier (SLC) transporters, consisting of more than 450 proteins divided into 65 families, is integral to various cellular processes and [...] Read more.

Background: Pancreatic ductal adenocarcinoma (PDAC), a challenging and malignant cancer, primarily originates from the exocrine cells of the pancreas. The superfamily of solute carrier (SLC) transporters, consisting of more than 450 proteins divided into 65 families, is integral to various cellular processes and represents a promising target in precision oncology. As therapeutic targets, SLC transporters are explored through an integrative analysis. Materials and Methods: The expression profiles of SLCs were systematically analyzed using mRNA data from The Cancer Genome Atlas (TCGA) and protein data from the Human Protein Atlas (HPA). Survival analysis was examined to evaluate the prognostic significance of SLC transporters for overall survival (OS) and disease-specific survival (DSS). Genetic alterations were examined using cBioPortal, while structural studies were performed with AlphaFold and AlphaMissense to predict functional impacts. Furthermore, Gene Set Enrichment Analysis (GSEA) was carried out to identify oncogenic pathways linked to SLC transporter expression. Results: SLC transporters were significantly upregulated in tumors relative to normal tissues. Higher expression levels of SLC39A10 (HR = 1.89, p = 0.0026), SLC22B5 (HR = 1.84, p = 0.0042), SLC55A2 (HR = 2.15, p = 0.00023), and SLC30A6 (HR = 1.90, p = 0.003) were strongly associated with unfavorable OS, highlighting their connection to poor prognosis in PDAC. GSEA highlighted that these four transporters are significantly involved in key oncogenic pathways, such as epithelial–mesenchymal transition (EMT), TNF-α signaling, and angiogenesis. Conclusions: The study identifies four SLCs as therapeutic targets in PDAC, highlighting their crucial role in essential metabolic pathways. These findings lay the groundwork for developing next-generation metabolic anti-cancer treatment to improve survival for PDAC patients. Full article

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

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