Genes

12 pages, 1022 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Studies Revealed Several Candidate Genes of Meat Productivity in Saryarka Fat-Tailed Coarse-Wool Sheep Breed

by Kairat Dossybayev, Makpal Amandykova, Ainur Orakbayeva, Sholpan Adylkanova, Altynay Kozhakhmet, Kanagat Yergali, Temirlan Kulboldin, Beibit Kulataev and Aibyn Torekhanov

Genes 2024, 15(12), 1549; https://doi.org/10.3390/genes15121549 - 29 Nov 2024

Cited by 5 | Viewed by 1463

Abstract

Background: Saryarka sheep belong to fat-tailed coarse-wool sheep breed. This breed is distinguished by increased meat productivity while being competitive in young lamb production. Live weight and body indices are relevant data for assessing sheep body constitution, which directly affects the breeding characteristics [...] Read more.

Background: Saryarka sheep belong to fat-tailed coarse-wool sheep breed. This breed is distinguished by increased meat productivity while being competitive in young lamb production. Live weight and body indices are relevant data for assessing sheep body constitution, which directly affects the breeding characteristics and meat productivity of animals. Objectives: This study aimed to find associations with SNPs and nine phenotypic characteristics of the Saryarka fat-tailed coarse-wool sheep breed including live weight and eight body indices (wither height, rump height, bicoastal diameter, body depth, body length, rump width, heart girth, and cannon bone circumference), and find candidate genes related to these characteristics. Methods: A total of 100 animals from the Karaganda region of Kazakhstan were used in this study. Live weight and eight body indices of sheep were measured using tape and electronic scales. The blood samples of the animals were used for DNA extraction. DNA samples were genotyped with the OvineSNP50 Genotyping BeadChip and analyzed using GWAS. Statistically significant SNPs were identified for each characteristic trait referencing the genome of Ovis aries (Oar_v3.1) using BioMart. Results: The GWAS results demonstrated a substantial chromosomal-level correlation between 32 chromosome-wide significant and suggestively significant SNPs in the studied sheep breed. Overall, seven SNPs located in seven different genes were revealed as candidates for live weight and four body indices: s20793.1 SNP in the IGFBP6 gene for live weight, OAR4_54217431.1 SNP in the ST7 gene for bicoastal diameter, s25229.1 in the SCD5 gene, and s01175.1 SNP in the DTNBP1 gene for rump width, OAR2_175574781.1 SNP in the KYNU gene for heart girth, and OAR1_209022621.1 SNP in the FGF12 gene and s15415.1 SNP in the FTO gene for cannon bone circumference. Some of these genes were previously reported to be involved in body constitution and fat deposit in other sheep breeds. Conclusions: The results of the present study open up new opportunities for targeted sheep breeding for meat and fat productivity. Full article

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

► Show Figures

Figure 1

13 pages, 7132 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of Peroxidase (PRX) Gene Family in Cucumber

by Weirong Luo, Junjun Liu, Wenchen Xu, Shenshen Zhi, Xudong Wang and Yongdong Sun

Genes 2024, 15(10), 1245; https://doi.org/10.3390/genes15101245 - 25 Sep 2024

Cited by 2 | Viewed by 1263

Abstract

Background: The Peroxidase (PRX) gene family is essential for plant growth and significantly contributes to defense against stresses. However, information about PRX genes in cucumber (Cucumis sativus L.) remains limited. Methods: In this present study, CsPRX genes were [...] Read more.

Background: The Peroxidase (PRX) gene family is essential for plant growth and significantly contributes to defense against stresses. However, information about PRX genes in cucumber (Cucumis sativus L.) remains limited. Methods: In this present study, CsPRX genes were identified and characterized using bioinformatics analysis. The expression pattern analysis of CsPRX genes were examined utilizing the RNA-seq data of cucumber from public databases and real-time quantitative PCR (qRT-PCR) analysis. Results: Here, we identified 60 CsPRX genes and mapped them onto seven chromosomes of cucumber. The CsPRX proteins exhibited the presence of 10 conserved motifs, with motif 8, motif 2, motif 5, and motif 3 consistently appearing across all 60 CsPRX protein sequences, indicating the conservation of CsPRX proteins. Furthermore, RNA-seq analysis revealed that differential expression of CsPRX genes in various tissues. Notably, a majority of the CsPRX genes exhibited significantly higher expression levels in the root compared to the other plant tissues, suggesting a potential specialization of these genes in root function. In addition, qRT-PCR analysis for four selected CsPRX genes under different stress conditions indicated that these selected CsPRX genes demonstrated diverse expression levels when subjected to NaCl, CdCl₂, and PEG treatments, and the CsPRX17 gene was significantly induced by NaCl, CdCl₂, and PEG stresses, suggesting a vital role of the CsPRX17 gene in response to environmental stresses. Conclusions: These findings will contribute valuable insights for future research into the functions and regulatory mechanisms associated with CsPRX genes in cucumber. Full article

(This article belongs to the Special Issue Molecular Biology of Crop Abiotic Stress Resistance)

► Show Figures

Figure 1

32 pages, 4213 KiB

Open AccessEditor’s ChoiceReview

The Past, Present, and Future of Plant Activators Targeting the Salicylic Acid Signaling Pathway

by Misbah Naz, Dongqin Zhang, Kangcen Liao, Xulong Chen, Nazeer Ahmed, Delu Wang, Jingjiang Zhou and Zhuo Chen

Genes 2024, 15(9), 1237; https://doi.org/10.3390/genes15091237 - 23 Sep 2024

Cited by 8 | Viewed by 3919

Abstract

Plant activators have emerged as promising alternatives to conventional crop protection chemicals for managing crop diseases due to their unique mode of action. By priming the plant’s innate immune system, these compounds can induce disease resistance against a broad spectrum of pathogens without [...] Read more.

Plant activators have emerged as promising alternatives to conventional crop protection chemicals for managing crop diseases due to their unique mode of action. By priming the plant’s innate immune system, these compounds can induce disease resistance against a broad spectrum of pathogens without directly inhibiting their proliferation. Key advantages of plant activators include prolonged defense activity, lower effective dosages, and negligible risk of pathogen resistance development. Among the various defensive pathways targeted, the salicylic acid (SA) signaling cascade has been extensively explored, leading to the successful development of commercial activators of systemic acquired resistance, such as benzothiadiazole, for widespread application in crop protection. While the action sites of many SA-targeting activators have been preliminarily mapped to different steps along the pathway, a comprehensive understanding of their precise mechanisms remains elusive. This review provides a historical perspective on plant activator development and outlines diverse screening strategies employed, from whole-plant bioassays to molecular and transgenic approaches. We elaborate on the various components, biological significance, and regulatory circuits governing the SA pathway while critically examining the structural features, bioactivities, and proposed modes of action of classical activators such as benzothiadiazole derivatives, salicylic acid analogs, and other small molecules. Insights from field trials assessing the practical applicability of such activators are also discussed. Furthermore, we highlight the current status, challenges, and future prospects in the realm of SA-targeting activator development globally, with a focus on recent endeavors in China. Collectively, this comprehensive review aims to describe existing knowledge and provide a roadmap for future research toward developing more potent plant activators that enhance crop health. Full article

(This article belongs to the Special Issue Genetic Insights into Plant-Pathogen Interactions)

► Show Figures

Figure 1

11 pages, 1540 KiB

Open AccessEditor’s ChoiceReview

The Desmoplakin Phenotype Spectrum: Is the Inflammation the “Fil Rouge” Linking Myocarditis, Arrhythmogenic Cardiomyopathy, and Uncommon Autoinflammatory Systemic Disease?

by Saverio D’Elia, Adriano Caputo, Francesco Natale, Enrica Pezzullo, Giuseppe Limongelli, Paolo Golino, Giovanni Cimmino and Francesco S. Loffredo

Genes 2024, 15(9), 1234; https://doi.org/10.3390/genes15091234 - 22 Sep 2024

Cited by 3 | Viewed by 2907

Abstract

Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific [...] Read more.

Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific cause remains unidentified. Recent research has highlighted the potential role of genetic susceptibility in the development of myocarditis (and in some cases the development of inflammatory dilated cardiomyopathy, i.e., the condition in which there is chronic inflammation (>3 months) and left ventricular dysfunction\dilatation), with several studies indicating a correlation between myocarditis and genetic backgrounds. Notably, pathogenic genetic variants linked to dilated or arrhythmic cardiomyopathy are found in 8–16% of myocarditis patients. Genetic predispositions can lead to recurrent myocarditis and a higher incidence of ventricular arrhythmias and heart failure. Moreover, the presence of DSP mutations has been associated with distinct pathological patterns and clinical outcomes in arrhythmogenic cardiomyopathy (hot phases). The interplay between genetic factors and environmental triggers, such as viral infections and physical stress, is crucial in understanding the pathogenesis of myocarditis. Identifying these genetic markers can improve the diagnosis, risk stratification, and management of patients with myocarditis, potentially guiding tailored therapeutic interventions. This review aims to synthesize current knowledge on the genetic underpinnings of myocarditis, with an emphasis on desmoplakin-related arrhythmogenic cardiomyopathy, to enhance clinical understanding and inform future research directions. Full article

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

► Show Figures

Figure 1

17 pages, 9424 KiB

Open AccessEditor’s ChoiceArticle

Flavonoid Synthesis Pathway Response to Low-Temperature Stress in a Desert Medicinal Plant, Agriophyllum Squarrosum (Sandrice)

by Pengshu Zhao, Xia Yan, Chaoju Qian, Guorong Ma, Xingke Fan, Xiaoyue Yin, Yuqiu Liao, Tingzhou Fang, Shanshan Zhou, Ibrahim Awuku and Xiao-Fei Ma

Genes 2024, 15(9), 1228; https://doi.org/10.3390/genes15091228 - 20 Sep 2024

Cited by 9 | Viewed by 1889

Abstract

Background/Objectives: Agriophyllum squarrosum (L.) Moq. (A. squarrosum), also known as sandrice, is an important medicinal plant widely distributed in dunes across all the deserts of China. Common garden trials have shown content variations in flavonoids among the ecotypes of sandrice, [...] Read more.

Background/Objectives: Agriophyllum squarrosum (L.) Moq. (A. squarrosum), also known as sandrice, is an important medicinal plant widely distributed in dunes across all the deserts of China. Common garden trials have shown content variations in flavonoids among the ecotypes of sandrice, which correlated with temperature heterogeneity in situ. However, there have not been any environmental control experiments to further elucidate whether the accumulation of flavonoids was triggered by cold stress; Methods: This study conducted a four-day ambient 4 °C low-temperature treatment on three ecotypes along with an in situ annual mean temperature gradient (Dulan (DL), Aerxiang (AEX), and Dengkou (DK)); Results: Target metabolomics showed that 12 out of 14 flavonoids in sandrice were driven by cold stress. Among them, several flavonoids were significantly up-regulated, such as naringenin and naringenin chalcone in all three ecotypes; isorhamnetin, quercetin, dihydroquercetin, and kaempferol in DL and AEX; and astragalin in DK. They were accompanied by 19 structural genes of flavonoid synthesis and 33 transcription factors were markedly triggered by cold stress in sandrice. The upstream genes, AsqAEX006535−CHS, AsqAEX016074−C4H, and AsqAEX004011−4CL, were highly correlated with the enrichment of naringenin, which could be fine-tuned by AsqAEX015868−bHLH62, AsqAEX001711−MYB12, and AsqAEX002220−MYB1R1; Conclusions: This study sheds light on how desert plants like sandrice adapt to cold stress by relying on a unique flavonoid biosynthesis mechanism that regulating the accumulation of naringenin. It also supports the precise development of sandrice for the medicinal industry. Specifically, quercetin and isorhamnetin should be targeted for development in DL and AEX, while astragalin should be precisely developed in DK. Full article

(This article belongs to the Special Issue Molecular Genetics and Multi-omics in Medicinal Plants)

► Show Figures

Figure 1

16 pages, 1402 KiB

Open AccessEditor’s ChoiceReview

Research Progress on miRNAs and Artificial miRNAs in Insect and Disease Resistance and Breeding in Plants

by Zengfeng Ma, Jianyu Wang and Changyan Li

Genes 2024, 15(9), 1200; https://doi.org/10.3390/genes15091200 - 12 Sep 2024

Cited by 9 | Viewed by 2624

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that are expressed in a tissue- and temporal-specific manner during development. They have been found to be highly conserved during the evolution of different species. miRNAs regulate the expression of several genes in various organisms, with some [...] Read more.

MicroRNAs (miRNAs) are small, non-coding RNAs that are expressed in a tissue- and temporal-specific manner during development. They have been found to be highly conserved during the evolution of different species. miRNAs regulate the expression of several genes in various organisms, with some regulating the expression of multiple genes with similar or completely unrelated functions. Frequent disease and insect pest infestations severely limit agricultural development. Thus, cultivating resistant crops via miRNA-directed gene regulation in plants, insects, and pathogens is an important aspect of modern breeding practices. To strengthen the application of miRNAs in sustainable agriculture, plant endogenous or exogenous miRNAs have been used for plant breeding. Consequently, the development of biological pesticides based on miRNAs has become an important avenue for future pest control methods. However, selecting the appropriate miRNA according to the desired target traits in the target organism is key to successfully using this technology for pest control. This review summarizes the progress in research on miRNAs in plants and other species involved in regulating plant disease and pest resistance pathways. We also discuss the molecular mechanisms of relevant target genes to provide new ideas for future research on pest and disease resistance and breeding in plants. Full article

(This article belongs to the Special Issue Plant Small RNAs: Biogenesis and Functions)

► Show Figures

Figure 1

12 pages, 491 KiB

Open AccessEditor’s ChoiceArticle

DTVF: A User-Friendly Tool for Virulence Factor Prediction Based on ProtT5 and Deep Transfer Learning Models

by Jiawei Sun, Hongbo Yin, Chenxiao Ju, Yongheng Wang and Zhiyuan Yang

Genes 2024, 15(9), 1170; https://doi.org/10.3390/genes15091170 - 5 Sep 2024

Cited by 3 | Viewed by 2226

Abstract

Virulencefactors (VFs) are key molecules that enable pathogens to evade the immune systems of the host. These factors are crucial for revealing the pathogenic processes of microbes and drug discovery. Identification of virulence factors in microbes become an important problem in the field [...] Read more.

Virulencefactors (VFs) are key molecules that enable pathogens to evade the immune systems of the host. These factors are crucial for revealing the pathogenic processes of microbes and drug discovery. Identification of virulence factors in microbes become an important problem in the field of bioinformatics. To address this problem, this study proposes a novel model DTVF (Deep Transfer Learning for Virulence Factor Prediction), which integrates the ProtT5 protein sequence extraction model with a dual-channel deep learning model. In the dual-channel deep learning model, we innovatively integrate long short-term memory (LSTM) with convolutional neural networks (CNNs), creating a novel integrated architecture. Furthermore, by incorporating the attention mechanism, the accuracy of VF detection was significantly enhanced. We evaluated the DTVF model against other excellent-performing models in the field. DTVF demonstrates superior performance, achieving an accuracy rate of 84.55% and an AUROC of 92.08% on the benchmark dataset. DTVF shows state-of-the-art performance in this field, surpassing the existing models in nearly all metrics. To facilitate the use of biologists, we have also developed an interactive web-based user interface version of DTVF based on Gradio. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

11 pages, 433 KiB

Open AccessEditor’s ChoiceArticle

Feeding and Nutritional Key Features of Crisponi/Cold-Induced Sweating Syndrome

by Roberta Onesimo, Elisabetta Sforza, Federica Palermo, Valentina Giorgio, Chiara Leoni, Donato Rigante, Valentina Trevisan, Cristiana Agazzi, Domenico Limongelli, Francesco Proli, Eliza Maria Kuczynska, Laura Crisponi, Giangiorgio Crisponi and Giuseppe Zampino

Genes 2024, 15(9), 1109; https://doi.org/10.3390/genes15091109 - 23 Aug 2024

Cited by 2 | Viewed by 1637

Abstract

Feeding difficulties are constantly present in patients with Crisponi/cold-induced sweating syndrome type 1 (CS/CISS1). The aim of our study was to describe their prevalence and evolution from birth to adult age. We performed an observational study at the Department of Life Sciences and [...] Read more.

Feeding difficulties are constantly present in patients with Crisponi/cold-induced sweating syndrome type 1 (CS/CISS1). The aim of our study was to describe their prevalence and evolution from birth to adult age. We performed an observational study at the Department of Life Sciences and Public Health, Rome. Fourteen patients were included in this study (six M; mean age: 18 years; SD: 10.62 years; median age: 15 years; age range: 6–44 years); six were adults (43%). Data on oral motor abilities from birth were collected. Meal duration, presence of swallowing reflex, dysphagia symptoms, difficulty chewing, and drooling management were assessed. At birth, all patients needed enteral feeding. Introduction of solid food was postponed beyond the age of 18 months in 43% of patients. During childhood and adolescence, mealtime was characterized by increased duration (43%) accompanied by fatigue during chewing (43%), food spillage from the nasal cavities (21%), sialorrhea (86%), and poor/reduced appetite (57%). A mature rotatory chewing skill was never achieved. This report expands the phenotype description of CS/CISS1 and also improves the overall management and prevention of complications in this ultra-rare disease. Full article

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

► Show Figures

Figure 1

20 pages, 28009 KiB

Open AccessEditor’s ChoiceArticle

Integration of Bioinformatics and Machine Learning to Identify CD8+ T Cell-Related Prognostic Signature to Predict Clinical Outcomes and Treatment Response in Breast Cancer Patients

by Baoai Wu, Longpeng Li, Longhui Li, Yinghua Chen, Yue Guan and Jinfeng Zhao

Genes 2024, 15(8), 1093; https://doi.org/10.3390/genes15081093 - 19 Aug 2024

Cited by 2 | Viewed by 2286

Abstract

The incidence of breast cancer (BC) continues to rise steadily, posing a significant burden on the public health systems of various countries worldwide. As a member of the tumor microenvironment (TME), CD8+ T cells inhibit cancer progression through their protective role. This study [...] Read more.

The incidence of breast cancer (BC) continues to rise steadily, posing a significant burden on the public health systems of various countries worldwide. As a member of the tumor microenvironment (TME), CD8+ T cells inhibit cancer progression through their protective role. This study aims to investigate the role of CD8+ T cell-related genes (CTRGs) in breast cancer patients. Methods: We assessed the abundance of CD8+ T cells in the TCGA and METABRIC datasets and obtained CTRGs through WGCNA. Subsequently, a prognostic signature (CTR score) was constructed from CTRGs screened by seven machine learning algorithms, and the relationship between the CTR score and TME, immunotherapy, and drug sensitivity was analyzed. Additionally, CTRGs’ expression in different cells within TME was identified through single-cell analysis and spatial transcriptomics. Finally, the expression of CTRGs in clinical tissues was verified via RT-PCR. Results: The CD8+ T cell-related prognostic signature consists of two CTRGs. In the TCGA and METABRIC datasets, the CTR score appeared to be negatively linked to the abundance of CD8+ T cells, and BC patients with higher risk score show a worse prognosis. The low CTR score group exhibits higher immune infiltration levels, closely associated with inhibiting the tumor microenvironment. Compared with the high CTR score group, the low CTR score group shows better responses to chemotherapy and immune checkpoint therapy. Single-cell analysis and spatial transcriptomics reveal the heterogeneity of two CTRGs in different cells. Compared with the adjacent tissues, CD163L1 and KLRB1 mRNA are downregulated in tumor tissues. Conclusions: This study establishes a robust CD8+ T cell-related prognostic signature, providing new insights for predicting the clinical outcomes and treatment responses of breast cancer patients. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

14 pages, 4279 KiB

Open AccessEditor’s ChoiceArticle

A Comprehensive Systematic Review Coupled with an Interacting Network Analysis Identified Candidate Genes and Biological Pathways Related to Bovine Temperament

by Gilberto Ruiz-De-La-Cruz, Thomas H. Welsh, Jr., Ronald D. Randel and Ana María Sifuentes-Rincón

Genes 2024, 15(8), 981; https://doi.org/10.3390/genes15080981 - 25 Jul 2024

Cited by 2 | Viewed by 1616

Abstract

Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review [...] Read more.

Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to analyze candidate genes related to bovine temperament, using bovine as the population, SNPs and genes as the exposure, and temperament test as the outcome, as principal search terms for population, exposure, and outcome (PEO) categories to define the scope of the search. The search results allowed the selection of 36 articles after removing duplicates and filtering by relevance. One hundred-two candidate genes associated with temperament traits were identified. The genes were further analyzed to construct an interaction network using the STRING database, resulting in 113 nodes and 346 interactions and the identification of 31 new candidate genes for temperament. Notably, the main genes identified were SST and members of the Kelch family. The candidate genes displayed interactions with pathways associated with different functions such as AMPA receptors, hormones, neuronal maintenance, protein signaling, neuronal regulation, serotonin synthesis, splicing, and ubiquitination activities. These new findings demonstrate the complexity of interconnected biological processes that regulate behavior and stress response in mammals. This insight now enables our targeted analysis of these newly identified temperament candidate genes in bovines. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

► Show Figures

Figure 1

11 pages, 5149 KiB

Open AccessEditor’s ChoiceArticle

The Role of IRF9 Upregulation in Modulating Sensitivity to Olaparib and Platinum-Based Chemotherapies in Breast Cancer

by SeokGyeong Choi, Han-Gyu Bae, Dong-Gyu Jo and Woo-Young Kim

Genes 2024, 15(7), 959; https://doi.org/10.3390/genes15070959 - 22 Jul 2024

Cited by 3 | Viewed by 2318

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors [...] Read more.

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors in breast cancer cell lines. Our findings indicated that the interferon (IFN) signaling gene IRF9 was critically involved in modulating sensitivity to these inhibitors. We revealed that the loss of IRF9 leads to increased resistance to the PARP inhibitor in MDA-MB-468 cells, and a similar desensitization was observed in another breast cancer cell line, MDA-MB-231. Further analysis indicated that while the basal expression of IRF9 did not correlate with the response to the PARP inhibitor olaparib, its transcriptional induction was significantly associated with increased sensitivity to the DNA-damaging agent cisplatin in the NCI-60 cell line panel. This finding suggests a mechanistic link between IRF9 induction and cellular responses to DNA damage. Additionally, data from the METABRIC patient tissue study revealed a complex network of IFN-responsive gene expressions postchemotherapy, with seven upregulated genes, including IRF9, and three downregulated genes. These findings underscore the intricate role of IFN signaling in the cellular response to chemotherapy. Collectively, our CRISPR screening data and subsequent bioinformatic analyses suggest that IRF9 is a novel biomarker for sensitivity to DNA-damaging agents, such as olaparib and platinum-based chemotherapeutic agents. Our findings for IRF9 not only enhance our understanding of the genetic basis of drug sensitivity, but also elucidate the role of IRF9 as a critical effector within IFN signaling pathways, potentially influencing the association between the host immune system and chemotherapeutic efficacy. Full article

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

► Show Figures

Figure 1

10 pages, 2029 KiB

Open AccessEditor’s ChoiceArticle

Genetic Variations of MSTN and Callipyge in Tibetan Sheep: Implications for Early Growth Traits

by Kai Zhao, Xue Li, Dehui Liu, Lei Wang, Quanbang Pei, Buying Han, Zian Zhang, Dehong Tian, Song Wang, Jincai Zhao, Bin Huang and Fuqiang Zhang

Genes 2024, 15(7), 921; https://doi.org/10.3390/genes15070921 - 15 Jul 2024

Cited by 3 | Viewed by 1446

Abstract

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin ( [...] Read more.

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study’s results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep. Full article

(This article belongs to the Special Issue Genetics and Breeding in Sheep and Goats)

► Show Figures

Figure 1

17 pages, 1008 KiB

Open AccessEditor’s ChoiceReview

SARS-CoV-2 Genomic Epidemiology Dashboards: A Review of Functionality and Technological Frameworks for the Public Health Response

by Nikita Sitharam, Houriiyah Tegally, Danilo de Castro Silva, Cheryl Baxter, Tulio de Oliveira and Joicymara S. Xavier

Genes 2024, 15(7), 876; https://doi.org/10.3390/genes15070876 - 3 Jul 2024

Cited by 3 | Viewed by 3333

Abstract

During the coronavirus disease 2019 (COVID-19) pandemic, the number and types of dashboards produced increased to convey complex information using digestible visualizations. The pandemic saw a notable increase in genomic surveillance data, which genomic epidemiology dashboards presented in an easily interpretable manner. These [...] Read more.

During the coronavirus disease 2019 (COVID-19) pandemic, the number and types of dashboards produced increased to convey complex information using digestible visualizations. The pandemic saw a notable increase in genomic surveillance data, which genomic epidemiology dashboards presented in an easily interpretable manner. These dashboards have the potential to increase the transparency between the scientists producing pathogen genomic data and policymakers, public health stakeholders, and the public. This scoping review discusses the data presented, functional and visual features, and the computational architecture of six publicly available SARS-CoV-2 genomic epidemiology dashboards. We found three main types of genomic epidemiology dashboards: phylogenetic, genomic surveillance, and mutational. We found that data were sourced from different databases, such as GISAID, GenBank, and specific country databases, and these dashboards were produced for specific geographic locations. The key performance indicators and visualization used were specific to the type of genomic epidemiology dashboard. The computational architecture of the dashboards was created according to the needs of the end user. The genomic surveillance of pathogens is set to become a more common tool used to track ongoing and future outbreaks, and genomic epidemiology dashboards are powerful and adaptable resources that can be used in the public health response. Full article

(This article belongs to the Special Issue Genomics and Bioinformatics in Microbial Science)

► Show Figures

Figure 1

14 pages, 1740 KiB

Open AccessEditor’s ChoiceArticle

Genomic Regions Associated with Resistance to Gastrointestinal Parasites in Australian Merino Sheep

by Brenda Vera, Elly A. Navajas, Pablo Peraza, Beatriz Carracelas, Elize Van Lier and Gabriel Ciappesoni

Genes 2024, 15(7), 846; https://doi.org/10.3390/genes15070846 - 27 Jun 2024

Cited by 3 | Viewed by 2221

Abstract

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination [...] Read more.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic, and phenotypic data. This methodology converts GEBVs into SNP effects. The analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2) and 1700 50K SNP genotypes. The comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21, and 25, and for FEC2 on OAR 5, 6, and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

► Show Figures

Graphical abstract

12 pages, 567 KiB

Open AccessEditor’s ChoiceReview

Preparing for Patient-Customized N-of-1 Antisense Oligonucleotide Therapy to Treat Rare Diseases

by Harry Wilton-Clark, Eric Yan and Toshifumi Yokota

Genes 2024, 15(7), 821; https://doi.org/10.3390/genes15070821 - 21 Jun 2024

Cited by 10 | Viewed by 5564

Abstract

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of [...] Read more.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development and addresses some of the major limitations that previously hindered the development of therapies for rare diseases. Full article

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

► Show Figures

Figure 1

13 pages, 2561 KiB

Open AccessEditor’s ChoiceArticle

A Small Auxin-Up RNA Gene, IbSAUR36, Regulates Adventitious Root Development in Transgenic Sweet Potato

by Yuanyuan Zhou, Aixian Li, Taifeng Du, Zhen Qin, Liming Zhang, Qingmei Wang, Zongyun Li and Fuyun Hou

Genes 2024, 15(6), 760; https://doi.org/10.3390/genes15060760 - 10 Jun 2024

Cited by 6 | Viewed by 1782

Abstract

Small auxin-upregulated RNAs (SAURs), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few SAUR genes [...] Read more.

Small auxin-upregulated RNAs (SAURs), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few SAUR genes are known in the root development of sweet potatoes. In this study, an IbSAUR36 gene was cloned and functionally analyzed. The IbSAUR36 protein was localized to the nucleus and plasma membrane. The transcriptional level of this gene was significantly higher in the pencil root and leaf.This gene was strongly induced by indole-3-acetic acid (IAA), but it was downregulated under methyl-jasmonate(MeJA) treatment. The promoter of IbSAUR36 contained the core cis-elements for phytohormone responsiveness. Promoter β-glucuronidase (GUS) analysis in Arabidopsis showed that IbSAUR36 is highly expressed in the young tissues of plants, such as young leaves, roots, and buds. IbSAUR36-overexpressing sweet potato roots were obtained by an efficient Agrobacterium rhizogenes-mediated root transgenic system. We demonstrated that overexpression of IbSAUR36 promoted the accumulation of IAA, upregulated the genes encoding IAA synthesis and its signaling pathways, and downregulated the genes encoding lignin synthesis and JA signaling pathways. Taken together, these results show that IbSAUR36 plays an important role in adventitious root (AR) development by regulating IAA signaling, lignin synthesis, and JA signaling pathways in transgenic sweet potatoes. Full article

(This article belongs to the Special Issue Advances in Genetic Breeding of Sweetpotato)

► Show Figures

Figure 1

17 pages, 3167 KiB

Open AccessEditor’s ChoiceArticle

Biodiversity of Demersal Fish Communities in the Cosmonaut Sea Revealed by DNA Barcoding Analyses

by Hai Li, Xing Miao, Rui Wang, Yuzhuo Liao, Yilin Wen, Ran Zhang and Longshan Lin

Genes 2024, 15(6), 691; https://doi.org/10.3390/genes15060691 - 26 May 2024

Cited by 4 | Viewed by 1550

Abstract

The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we provided a description of demersal fish diversity in the Cosmonaut Sea by analysing [...] Read more.

The Cosmonaut Sea is one of the least accessed regions in the Southern Ocean, and our knowledge about the fish biodiversity in the region is sparse. In this study, we provided a description of demersal fish diversity in the Cosmonaut Sea by analysing cytochrome oxidase I (COI) barcodes of 98 fish samples that were hauled by trawling during the 37th and 38th Chinese National Antarctic Research Expedition (CHINARE) cruises. Twenty-four species representing 19 genera and 11 families, namely, Artedidraconidae, Bathydraconidae, Bathylagidae, Channichthyidae, Liparidae, Macrouridae, Muraenolepididae, Myctophidae, Nototheniidae, Paralepididae and Zoarcidae, were discriminated and identified, which were largely identical to local fish occurrence records and the general pattern of demersal fish communities at high Antarctic shelf areas. The validity of a barcoding gap failed to be detected and confirmed across all species due to the indicative signals of two potential cryptic species. Nevertheless, DNA barcoding still demonstrated to be a very efficient and sound method for the discrimination and classification of Antarctic fishes. In the future, various sampling strategies that cover all geographic sections and depth strata of the Cosmonaut Sea are encouraged to enhance our understanding of local fish communities, within which DNA barcoding can play an important role in either molecular taxonomy or the establishment of a dedicated local reference database for eDNA metabarcoding analyses. Full article

(This article belongs to the Special Issue DNA Taxonomy, Molecular Phylogeny and Population Genetics of Cartilaginous Fishes and Teleost Fishes)

► Show Figures

Figure 1

30 pages, 6195 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Bioinformatic Investigation of TP53 Dysregulation in Diverse Cancer Landscapes

by Ruby Khan, Bakht Pari and Krzysztof Puszynski

Genes 2024, 15(5), 577; https://doi.org/10.3390/genes15050577 - 30 Apr 2024

Cited by 7 | Viewed by 6261

Abstract

P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic [...] Read more.

P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance (p < 0.05), our analysis reveals the distinct influence of TP53 overexpression on DFS outcomes in PRAD. Additionally, graphical representations of overall survival (OS) underscore the notable disparity in OS duration between tumors exhibiting elevated TP53 expression (depicted by the red line) and those with lower TP53 levels (indicated by the blue line). The hazard ratio (HR) further emphasizes the profound impact of TP53 on overall survival. Moreover, our investigation delves into the intricate TP53 protein network, unveiling genes exhibiting robust positive correlations with TP53 expression across 13 out of 27 cancers. Remarkably, negative correlations emerge with pivotal tumor suppressor genes. This network analysis elucidates critical proteins, including SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, pivotal in regulating cell cycle dynamics, DNA damage response, and transcriptional regulation. Our study underscores the paramount importance of deciphering TP53 dynamics in cancer, providing invaluable insights into tumor behavior, disease-free survival, and potential therapeutic avenues. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology for Cancer Prediction and Prognosis)

► Show Figures

Figure 1

25 pages, 1644 KiB

Open AccessEditor’s ChoiceReview

Insights into Salinity Tolerance in Wheat

by Zechao Zhang, Zelin Xia, Chunjiang Zhou, Geng Wang, Xiao Meng and Pengcheng Yin

Genes 2024, 15(5), 573; https://doi.org/10.3390/genes15050573 - 29 Apr 2024

Cited by 20 | Viewed by 4777

Abstract

Salt stress has a detrimental impact on food crop production, with its severity escalating due to both natural and man-made factors. As one of the most important food crops, wheat is susceptible to salt stress, resulting in abnormal plant growth and reduced yields; [...] Read more.

Salt stress has a detrimental impact on food crop production, with its severity escalating due to both natural and man-made factors. As one of the most important food crops, wheat is susceptible to salt stress, resulting in abnormal plant growth and reduced yields; therefore, damage from salt stress should be of great concern. Additionally, the utilization of land in coastal areas warrants increased attention, given diminishing supplies of fresh water and arable land, and the escalating demand for wheat. A comprehensive understanding of the physiological and molecular changes in wheat under salt stress can offer insights into mitigating the adverse effects of salt stress on wheat. In this review, we summarized the genes and molecular mechanisms involved in ion transport, signal transduction, and enzyme and hormone regulation, in response to salt stress based on the physiological processes in wheat. Then, we surveyed the latest progress in improving the salt tolerance of wheat through breeding, exogenous applications, and microbial pathways. Breeding efficiency can be improved through a combination of gene editing and multiple omics techniques, which is the fundamental strategy for dealing with salt stress. Possible challenges and prospects in this process were also discussed. Full article

(This article belongs to the Special Issue Breeding and Genetics in Wheat)

► Show Figures

Figure 1

12 pages, 1241 KiB

Open AccessEditor’s ChoiceReview

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment

by Malini S. Ramaiyer, Eslam Saad, Irem Kurt and Mostafa A. Borahay

Genes 2024, 15(5), 558; https://doi.org/10.3390/genes15050558 - 27 Apr 2024

Cited by 10 | Viewed by 4596

Abstract

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly [...] Read more.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and “suicide gene therapy” to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options. Full article

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

► Show Figures

Figure 1

13 pages, 1381 KiB

Open AccessEditor’s ChoiceArticle

Resistome, Virulome, and Clonal Variation in Methicillin-Resistant Staphylococcus aureus (MRSA) in Healthy Swine Populations: A Cross-Sectional Study

by Vanessa Silva, Adriana Silva, Raquel Barbero, Mario Romero, Rosa del Campo, Manuela Caniça, Rui Cordeiro, Gilberto Igrejas and Patricia Poeta

Genes 2024, 15(5), 532; https://doi.org/10.3390/genes15050532 - 24 Apr 2024

Cited by 2 | Viewed by 1882

Abstract

This cross-sectional study investigates the methicillin-resistant Staphylococcus aureus (MRSA): its prevalence, antimicrobial resistance, and molecular characteristics in healthy swine populations in central Portugal. A total of 213 samples were collected from pigs on twelve farms, and MRSA prevalence was assessed using selective agar [...] Read more.

This cross-sectional study investigates the methicillin-resistant Staphylococcus aureus (MRSA): its prevalence, antimicrobial resistance, and molecular characteristics in healthy swine populations in central Portugal. A total of 213 samples were collected from pigs on twelve farms, and MRSA prevalence was assessed using selective agar plates and confirmed via molecular methods. Antimicrobial susceptibility testing and whole genome sequencing (WGS) were performed to characterize resistance profiles and genetic determinants. Among the 107 MRSA-positive samples (83.1% prevalence), fattening pigs and breeding sows exhibited notably high carriage rates. The genome of 20 isolates revealed the predominance of the ST398 clonal complex, with diverse spa types identified. Antimicrobial susceptibility testing demonstrated resistance to multiple antimicrobial agents, including penicillin, cefoxitin, and tetracycline. WGS analysis identified a diverse array of resistance genes, highlighting the genetic basis of antimicrobial resistance. Moreover, virulence gene profiling revealed the presence of genes associated with pathogenicity. These findings underscore the significant prevalence of MRSA in swine populations and emphasize the need for enhanced surveillance and control measures to mitigate zoonotic transmission risks. Implementation of prudent antimicrobial use practices and targeted intervention strategies is essential to reducing MRSA prevalence and safeguarding public health. Continued research efforts are warranted to elucidate transmission dynamics and virulence potential, ultimately ensuring food safety and public health protection. Full article

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

► Show Figures

Figure 1

24 pages, 6666 KiB

Open AccessEditor’s ChoiceArticle

Impact of Vanadium–Titanium–Magnetite Mining Activities on Endophytic Bacterial Communities and Functions in the Root Systems of Local Plants

by Zhuang Xiong, Yunfeng Zhang, Xiaodie Chen, Ajia Sha, Wenqi Xiao, Yingyong Luo, Lianxin Peng, Liang Zou and Qiang Li

Genes 2024, 15(5), 526; https://doi.org/10.3390/genes15050526 - 23 Apr 2024

Cited by 13 | Viewed by 1741

Abstract

This study utilized 16S rRNA high-throughput sequencing technology to analyze the community structure and function of endophytic bacteria within the roots of three plant species in the vanadium–titanium–magnetite (VTM) mining area. The findings indicated that mining activities of VTM led to a notable [...] Read more.

This study utilized 16S rRNA high-throughput sequencing technology to analyze the community structure and function of endophytic bacteria within the roots of three plant species in the vanadium–titanium–magnetite (VTM) mining area. The findings indicated that mining activities of VTM led to a notable decrease in both the biodiversity and abundance of endophytic bacteria within the root systems of Eleusine indica and Carex (p < 0.05). Significant reductions were observed in the populations of Nocardioides, concurrently with substantial increments in the populations of Pseudomonas (p < 0.05), indicating that Pseudomonas has a strong adaptability to this environmental stress. In addition, β diversity analysis revealed divergence in the endophytic bacterial communities within the roots of E. indica and Carex from the VTM mining area, which had diverged to adapt to the environmental stress caused by mining activity. Functional enrichment analysis revealed that VTM mining led to an increase in polymyxin resistance, nicotinate degradation I, and glucose degradation (oxidative) (p < 0.05). Interestingly, we found that VTM mining did not notably alter the endophytic bacterial communities or functions in the root systems of Dodonaea viscosa, indicating that this plant can adapt well to environmental stress. This study represents the primary investigation into the influence of VTM mining activities on endophytic bacterial communities and the functions of nearby plant roots, providing further insight into the impact of VTM mining activities on the ecological environment. Full article

(This article belongs to the Special Issue Genomics of Microbial Diversity, Evolution and Function)

► Show Figures

Figure 1

8 pages, 1764 KiB

Open AccessEditor’s ChoiceCase Report

A TMEM63A Nonsense Heterozygous Variant Linked to Infantile Transient Hypomyelinating Leukodystrophy Type 19?

by Dimitra Siori, Dimitrios Vlachakis, Periklis Makrythanasis, Joanne Traeger-Synodinos, Danai Veltra, Afrodite Kampouraki and George P. Chrousos

Genes 2024, 15(5), 525; https://doi.org/10.3390/genes15050525 - 23 Apr 2024

Cited by 3 | Viewed by 2555

Abstract

Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified [...] Read more.

Infantile onset transient hypomyelination (IOTH) is a rare form of leukodystrophy that is associated with transient motor impairment and delayed central nervous system myelination. Here, we report a case of a new mutation in the transmembrane protein 63A (TMEM63A) gene identified using Whole-Exome Sequencing (WES) in an 8.5-year-old boy with clinical symptoms similar to IOTH. The patient exhibited a mild developmental delay, including hypotonia and delayed motor milestones, as well as some notable phenotypic characteristics, such as macrocephaly and macrosomia. Despite the absence of early neuroimaging, genetic testing revealed a paternally inherited variant in TMEM63A (NM_14698.3:c.220A>T;p:(Arg74*)), potentially linked to infantile transient hypomyelinating leukodystrophy type 19. Our findings in this study and the patient’s favorable clinical course underscore the potential for successful myelination even with delayed initiation and may contribute to a better understanding of the genotype–phenotype correlation in IOTH, emphasizing the importance of genetic analysis in unresolved developmental delay cases and providing critical insights for accurate diagnosis, prognosis and potential therapeutic strategies in rare leukodystrophies. Full article

(This article belongs to the Special Issue Head and Neck Genetics)

► Show Figures

Figure 1

11 pages, 2470 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Short-Term Artificial Feed Domestication on the Expression of Oxidative-Stress-Related Genes and Antioxidant Capacity in the Liver and Gill Tissues of Mandarin Fish (Siniperca chuatsi)

by Zhou Zhang, Xiping Yuan, Hao Wu, Jinwei Gao, Jiayu Wu, Zhenzhen Xiong, Zhifeng Feng, Min Xie, Shaoming Li, Zhonggui Xie and Guoqing Zeng

Genes 2024, 15(4), 487; https://doi.org/10.3390/genes15040487 - 12 Apr 2024

Cited by 8 | Viewed by 2019

Abstract

To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification, [...] Read more.

To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification, coagulation, and immune regulation, while the gills are important respiratory organs that are sensitive to changes in the water environment. Therefore, we used the liver and gills of Mandarin fish as research materials. The aim of this study was to investigate the effects of short-term artificial feed domestication on the expression of oxidative stress genes and the changes in oxidative-stress-related enzyme activity in the liver and gills of Mandarin fish. We divided the Mandarin fish into two groups for treatment. The control group was fed with live bait continuously for 14 days, while the experimental group was fed with half artificial feed and half live bait from 0 to 7 days (T-7 d), followed by solely artificial feed from 7 to 14 days (T-14 d). The experimental results showed that there was no difference in the body weight, length, and standard growth rate of the Mandarin fish between the two groups of treatments; after two treatments, there were differences in the expression of genes related to oxidative stress in the gills (keap1, kappa, gsta, gstt1, gstk1, SOD, and CAT) and in the liver (GPx, keap1, kappa, gsta, gstt1, gr, and SOD). In the liver, GPx activity and the content of MDA were significantly upregulated after 7 days of domestication, while in the gills, SOD activity was significantly upregulated after 7 days of domestication and GPx activity was significantly downregulated after 14 days of domestication. These results suggest that artificial feed domestication is associated with oxidative stress. Moreover, these results provide experimental basic data for increasing the production of aquaculture feed for Mandarin fish. Full article

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

► Show Figures

Figure 1

18 pages, 6581 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Changes and Regulatory Networks Associated with Resistance to Mastitis in Xinjiang Brown Cattle

by Dan Wang, Haiyan Yang, Shengchao Ma, Tingting Liu, Mengjie Yan, Mingming Dong, Menghua Zhang, Tao Zhang, Xiaoxue Zhang, Lei Xu, Xixia Huang and Hong Chen

Genes 2024, 15(4), 465; https://doi.org/10.3390/genes15040465 - 7 Apr 2024

Cited by 4 | Viewed by 1745

Abstract

Xinjiang brown cattle are highly resistant to disease and tolerant of roughage feeding. The identification of genes regulating mastitis resistance in Xinjiang brown cattle is a novel means of genetic improvement. In this study, the blood levels of IL-1β, IL-6, IL-10, TNF-α, and [...] Read more.

Xinjiang brown cattle are highly resistant to disease and tolerant of roughage feeding. The identification of genes regulating mastitis resistance in Xinjiang brown cattle is a novel means of genetic improvement. In this study, the blood levels of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in Xinjiang brown cattle with high and low somatic cell counts (SCCs) were investigated, showing that cytokine levels were higher in cattle with high SCCs. The peripheral blood transcriptomic profiles of healthy and mastitis-affected cattle were constructed by RNA-seq. Differential expression analysis identified 1632 differentially expressed mRNAs (DE-mRNAs), 1757 differentially expressed lncRNAs (DE-lncRNAs), and 23 differentially expressed circRNAs (DE-circRNAs), which were found to be enriched in key pathways such as PI3K/Akt, focal adhesion, and ECM-receptor interactions. Finally, ceRNA interaction networks were constructed using the differentially expressed genes and ceRNAs. It was found that keynote genes or mRNAs were also enriched in pathways such as PI3K-Akt, cholinergic synapses, cell adhesion molecules, ion binding, cytokine receptor activity, and peptide receptor activity, suggesting that the key genes and ncRNAs in the network may play an important role in the regulation of bovine mastitis. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

► Show Figures

Figure 1

22 pages, 2125 KiB

Open AccessEditor’s ChoiceReview

PCR in Forensic Science: A Critical Review

by Caitlin McDonald, Duncan Taylor and Adrian Linacre

Genes 2024, 15(4), 438; https://doi.org/10.3390/genes15040438 - 29 Mar 2024

Cited by 16 | Viewed by 17220

Abstract

The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This [...] Read more.

The polymerase chain reaction (PCR) has played a fundamental role in our understanding of the world, and has applications across a broad range of disciplines. The introduction of PCR into forensic science marked the beginning of a new era of DNA profiling. This era has pushed PCR to its limits and allowed genetic data to be generated from trace DNA. Trace samples contain very small amounts of degraded DNA associated with inhibitory compounds and ions. Despite significant development in the PCR process since it was first introduced, the challenges of profiling inhibited and degraded samples remain. This review examines the evolution of the PCR from its inception in the 1980s, through to its current application in forensic science. The driving factors behind PCR evolution for DNA profiling are discussed along with a critical comparison of cycling conditions used in commercial PCR kits. Newer PCR methods that are currently used in forensic practice and beyond are examined, and possible future directions of PCR for DNA profiling are evaluated. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

18 pages, 892 KiB

Open AccessEditor’s ChoiceReview

Innovations in Medicine: Exploring ChatGPT’s Impact on Rare Disorder Management

by Stefania Zampatti, Cristina Peconi, Domenica Megalizzi, Giulia Calvino, Giulia Trastulli, Raffaella Cascella, Claudia Strafella, Carlo Caltagirone and Emiliano Giardina

Genes 2024, 15(4), 421; https://doi.org/10.3390/genes15040421 - 28 Mar 2024

Cited by 13 | Viewed by 3830

Abstract

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of [...] Read more.

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for generating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT integration, with pilot studies and trials revealing each field’s potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex datasets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs. Full article

(This article belongs to the Collection Genetics and Genomics of Rare Disorders)

► Show Figures

Figure 1

18 pages, 301 KiB

Open AccessEditor’s ChoiceReview

Advancements in Viral Gene Therapy for Gaucher Disease

by Akhil Kulkarni, Tiffany Chen, Ellen Sidransky and Tae-Un Han

Genes 2024, 15(3), 364; https://doi.org/10.3390/genes15030364 - 15 Mar 2024

Cited by 12 | Viewed by 5248

Abstract

Gaucher disease, an autosomal recessively inherited lysosomal storage disorder, results from biallelic mutations in the GBA1 gene resulting in deficient activity of the enzyme glucocerebrosidase. In Gaucher disease, the reduced levels and activity of glucocerebrosidase lead to a disparity in the rates of [...] Read more.

Gaucher disease, an autosomal recessively inherited lysosomal storage disorder, results from biallelic mutations in the GBA1 gene resulting in deficient activity of the enzyme glucocerebrosidase. In Gaucher disease, the reduced levels and activity of glucocerebrosidase lead to a disparity in the rates of formation and breakdown of glucocerebroside and glucosylsphingosine, resulting in the accumulation of these lipid substrates in the lysosome. This gives rise to the development of Gaucher cells, engorged macrophages with a characteristic wrinkled tissue paper appearance. There are both non-neuronopathic (type 1) and neuronopathic (types 2 and 3) forms of Gaucher disease, associated with varying degrees of severity. The visceral and hematologic manifestations of Gaucher disease respond well to both enzyme replacement therapy and substrate reduction therapy. However, these therapies do not improve the neuronopathic manifestations, as they cannot cross the blood–brain barrier. There is now an established precedent for treating lysosomal storage disorders with gene therapy strategies, as many have the potential to cross into the brain. The range of the gene therapies being employed is broad, but this review aimed to discuss the progress, advances, and challenges in developing viral gene therapy as a treatment for Gaucher disease. Full article

(This article belongs to the Special Issue Genetics and Genomics of Inherited Metabolic Diseases)

13 pages, 7064 KiB

Open AccessEditor’s ChoiceArticle

A Single-Cell Transcriptome of Bovine Milk Somatic Cells

by Minja Zorc, Mateja Dolinar and Peter Dovč

Genes 2024, 15(3), 349; https://doi.org/10.3390/genes15030349 - 10 Mar 2024

Cited by 10 | Viewed by 3071

Abstract

The production of milk by dairy cows far exceeds the nutritional needs of the calf and is vital for the economical use of dairy cattle. High milk yield is a unique production trait that can be effectively enhanced through traditional selection methods. The [...] Read more.

The production of milk by dairy cows far exceeds the nutritional needs of the calf and is vital for the economical use of dairy cattle. High milk yield is a unique production trait that can be effectively enhanced through traditional selection methods. The process of lactation in cows serves as an excellent model for studying the biological aspects of lactation with the aim of exploring the mechanistic base of this complex trait at the cellular level. In this study, we analyzed the milk transcriptome at the single-cell level by conducting scRNA-seq analysis on milk samples from two Holstein Friesian cows at mid-lactation (75 and 93 days) using the 10× Chromium platform. Cells were pelleted and fat was removed from milk by centrifugation. The cell suspension from each cow was loaded on separate channels, resulting in the recovery of 9313 and 14,544 cells. Library samples were loaded onto two lanes of the NovaSeq 6000 (Illumina) instrument. After filtering at the cell and gene levels, a total of 7988 and 13,973 cells remained, respectively. We were able to reconstruct different cell types (milk-producing cells, progenitor cells, macrophages, monocytes, dendritic cells, T cells, B cells, mast cells, and neutrophils) in bovine milk. Our findings provide a valuable resource for identifying regulatory elements associated with various functions of the mammary gland such as lactation, tissue renewal, native immunity, protein and fat synthesis, and hormonal response. Full article

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

► Show Figures

Figure 1

25 pages, 1834 KiB

Open AccessEditor’s ChoiceReview

Role of Post-Transcriptional Regulation in Learning and Memory in Mammals

by Carlo Maria Di Liegro, Gabriella Schiera, Giuseppe Schirò and Italia Di Liegro

Genes 2024, 15(3), 337; https://doi.org/10.3390/genes15030337 - 5 Mar 2024

Cited by 4 | Viewed by 3113

Abstract

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is [...] Read more.

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system. Full article

(This article belongs to the Special Issue Post-transcriptional Regulation in Mammals)

► Show Figures

Figure 1

17 pages, 2274 KiB

Open AccessEditor’s ChoiceArticle

A Scalable and Robust Chloroplast Genotyping Solution: Development and Application of SNP and InDel Markers in the Maize Chloroplast Genome

by Rui Wang, Yang Yang, Hongli Tian, Hongmei Yi, Liwen Xu, Yuanda Lv, Jianrong Ge, Yikun Zhao, Lu Wang, Shiliang Zhou and Fengge Wang

Genes 2024, 15(3), 293; https://doi.org/10.3390/genes15030293 - 25 Feb 2024

Cited by 7 | Viewed by 2054

Abstract

Maize(Zea mays. L) is a globally important crop, and understanding its genetic diversity is crucial for plant breeding phylogenetic analyses and comparative genetics. While nuclear markers have been extensively used for mapping agriculturally important genes, they are limited in recognizing characteristics, such [...] Read more.

Maize(Zea mays. L) is a globally important crop, and understanding its genetic diversity is crucial for plant breeding phylogenetic analyses and comparative genetics. While nuclear markers have been extensively used for mapping agriculturally important genes, they are limited in recognizing characteristics, such as cytoplasmic male sterility and reciprocal cross hybrids. In this study, we performed next-generation sequencing of 176samples, and the maize cultivars represented five distinct groups. A total of 89 single nucleotide polymorphisms (SNPs) and 11 insertion/deletion polymorphisms (InDels) were identified. To enable high-throughput detection, we successfully amplified and confirmed 49 SNP and InDel markers, which were defined as a Varietal Chloroplast Panel (VCP) using the Kompetitive Allele Specific PCR (KASP). The specific markers provided a valuable tool for identifying chloroplast groups. The verification experiment, focusing on the identification of reciprocal cross hybrids and cytoplasmic male sterility hybrids, demonstrated the significant advantages of VCP markers in maternal inheritance characterization. Furthermore, only a small subset of these markers is needed to provide useful information, showcasing the effectiveness of these markers in elucidating the artificial selection process of elite maize lines. Full article

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

► Show Figures

Figure 1

21 pages, 355 KiB

Open AccessEditor’s ChoiceReview

Genetic Advancements in Infantile Epileptic Spasms Syndrome and Opportunities for Precision Medicine

by Hannah E. Snyder, Puneet Jain, Rajesh RamachandranNair, Kevin C. Jones and Robyn Whitney

Genes 2024, 15(3), 266; https://doi.org/10.3390/genes15030266 - 21 Feb 2024

Cited by 11 | Viewed by 5753

Abstract

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, [...] Read more.

Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored. Full article

(This article belongs to the Special Issue Molecular Genetics of Neurodevelopmental Disorders)

9 pages, 593 KiB

Open AccessEditor’s ChoiceArticle

FecB Was Associated with Litter Size and Follows Mendel’s Laws of Inheritance When It Transited to Next Generation in Suhu Meat Sheep Breeding Population

by Pengwei Su, Yifei Gu, Shanhe Wang, Xiukai Cao, Xiaoyang Lv, Tesfaye Getachew, Yutao Li, Zhenghai Song, Zehu Yuan and Wei Sun

Genes 2024, 15(3), 260; https://doi.org/10.3390/genes15030260 - 20 Feb 2024

Cited by 4 | Viewed by 1817

Abstract

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep [...] Read more.

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep population were tested for FecB using capillary electrophoresis. We combined the lambing records of 473 ewes, the growth trait records of 881 sheep at both the birth and weaning (2-month-old) stages, and the complete genealogical records of 643 lambs to analysis the distribution of FecB in the Suhu meat sheep breeding population, its effect on litter size of ewes, growth and development of lambs, and the inheritance patterns of FecB. The results showed that there were three genotypes of FecB in the Suhu meat sheep population, namely the AA genotype, AG genotype, and GG genotype. FecB in this population has a moderate polymorphism (0.25 < PIC < 0.5), and deviates from Hardy–Weinberg disequilibrium (p < 0.05). The litter size of GG genotype ewes was significantly higher than that with the AG and AA genotypes (p < 0.01). A Chi-square test showed that the inheritance patterns of FecB follows Mendel’s Laws of Inheritance (p > 0.05). An association analysis of different genotypes of FecB with body weight and body size of Suhu meat sheep at birth and weaning revealed that FecB adversely affects the early growth and development of Suhu meat sheep. In summary, FecB can improve the litter size of ewes but it has negative effects on the early growth and survival rate of lambs in sheep. Therefore, FecB test results and feeding management measures should be comprehensively applied to improve the reproductive performance of ewes, the survival rate and production performance of lambs in sheep production, and thus improve the economic benefits of sheep farms. Full article

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

► Show Figures

Figure 1

15 pages, 2734 KiB

Open AccessEditor’s ChoiceArticle

The Complete Mitochondrial Genome of Paeonia lactiflora Pall. (Saxifragales: Paeoniaceae): Evidence of Gene Transfer from Chloroplast to Mitochondrial Genome

by Pan Tang, Yang Ni, Jingling Li, Qianqi Lu, Chang Liu and Jinlin Guo

Genes 2024, 15(2), 239; https://doi.org/10.3390/genes15020239 - 14 Feb 2024

Cited by 10 | Viewed by 2852

Abstract

Paeonia lactiflora (P. lactiflora), a perennial plant renowned for its medicinal roots, provides a unique case for studying the phylogenetic relationships of species based on organelle genomes, as well as the transference of DNA across organelle genomes. In order to investigate [...] Read more.

Paeonia lactiflora (P. lactiflora), a perennial plant renowned for its medicinal roots, provides a unique case for studying the phylogenetic relationships of species based on organelle genomes, as well as the transference of DNA across organelle genomes. In order to investigate this matter, we sequenced and characterized the mitochondrial genome (mitogenome) of P. lactiflora. Similar to the chloroplast genome (cpgenome), the mitogenome of P. lactiflora extends across 181,688 base pairs (bp). Its unique quadripartite structure results from a pair of extensive inverted repeats, each measuring 25,680 bp in length. The annotated mitogenome includes 27 protein-coding genes, 37 tRNAs, 8 rRNAs, and two pseudogenes (rpl5, rpl16). Phylogenetic analysis was performed to identify phylogenetic trees consistent with Paeonia species phylogeny in the APG Ⅳ system. Moreover, a total of 12 MTPT events were identified and 32 RNA editing sites were detected during mitogenome analysis of P. lactiflora. Our research successfully compiled and annotated the mitogenome of P. lactiflora. The study provides valuable insights regarding the taxonomic classification and molecular evolution within the Paeoniaceae family. Full article

(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome—2nd Edition)

► Show Figures

Figure 1

13 pages, 1899 KiB

Open AccessEditor’s ChoiceArticle

The Impact of Cancer-Associated Fibroblasts on the Biology and Progression of Colorectal Carcinomas

by Larissa Maria Henrich, Kristina Greimelmaier, Michael Wessolly, Nick Alexander Klopp, Elena Mairinger, Yvonne Krause, Sophia Berger, Jeremias Wohlschlaeger, Hans-Ulrich Schildhaus, Hideo Andreas Baba, Fabian Dominik Mairinger and Sabrina Borchert

Genes 2024, 15(2), 209; https://doi.org/10.3390/genes15020209 - 6 Feb 2024

Cited by 10 | Viewed by 3634

Abstract

(1) Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Cancer-associated fibroblasts (CAFs) are major components of CRC’s tumour microenvironment (TME), but their biological background and interplay with the TME remain poorly understood. This study investigates CAF biology and its impact [...] Read more.

(1) Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Cancer-associated fibroblasts (CAFs) are major components of CRC’s tumour microenvironment (TME), but their biological background and interplay with the TME remain poorly understood. This study investigates CAF biology and its impact on CRC progression. (2) The cohort comprises 155 cases, including CRC, with diverse localizations, adenomas, inflammations, and controls. Digital gene expression analysis examines genes associated with signalling pathways (MAPK, PI3K/Akt, TGF-β, WNT, p53), while next-generation sequencing (NGS) determines CRC mutational profiles. Immunohistochemical FAP scoring assesses CAF density and activity. (3) FAP expression is found in 81 of 150 samples, prevalent in CRC (98.4%), adenomas (27.5%), and inflammatory disease (38.9%). Several key genes show significant associations with FAP-positive fibroblasts. Gene set enrichment analysis (GSEA) highlights PI3K and MAPK pathway enrichment alongside the activation of immune response pathways like natural killer (NK)-cell-mediated cytotoxicity via CAFs. (4) The findings suggest an interplay between CAFs and cancer cells, influencing growth, invasiveness, angiogenesis, and immunogenicity. Notably, TGF-β, CDKs, and the Wnt pathway are affected. In conclusion, CAFs play a significant role in CRC and impact the TME throughout development. Full article

(This article belongs to the Special Issue Molecular Diagnostics for Cancer Treatment)

► Show Figures

Figure 1

24 pages, 752 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances

by Vincent Zimmern and Berge Minassian

Genes 2024, 15(2), 171; https://doi.org/10.3390/genes15020171 - 27 Jan 2024

Cited by 11 | Viewed by 5716

Abstract

The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe. While each of the disorders is individually rare, they collectively make up a non-trivial portion of the complex epilepsy [...] Read more.

The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe. While each of the disorders is individually rare, they collectively make up a non-trivial portion of the complex epilepsy and myoclonus cases that are seen in tertiary care centers. The last decade has seen substantial progress in our understanding of the pathophysiology, diagnosis, prognosis, and, in select disorders, therapies of these diseases. In this scoping review, we examine English language publications from the past decade that address diagnostic, phenotypic, and therapeutic advances in all PMEs. We then highlight the major lessons that have been learned and point out avenues for future investigation that seem promising. Full article

(This article belongs to the Special Issue Impact of Genetic Testing in Epilepsy and Other Neurological Conditions)

► Show Figures

Figure 1

22 pages, 6400 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive View on the Protein Functions of Porcine Epidemic Diarrhea Virus

by Xin Li, Yiwan Wu, Zhibin Yan, Gen Li, Jun Luo, Shile Huang and Xiaofeng Guo

Genes 2024, 15(2), 165; https://doi.org/10.3390/genes15020165 - 26 Jan 2024

Cited by 10 | Viewed by 5124

Abstract

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the [...] Read more.

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the pig industry. PEDV possesses various crucial structural and functional proteins, which play important roles in viral structure, infection, replication, assembly, and release, as well as in escaping host innate immunity. Over the past few years, there has been progress in the study of PEDV pathogenesis, revealing the crucial role of the interaction between PEDV viral proteins and host cytokines in PEDV infection. At present, the main control measure against PEDV is vaccine immunization of sows, but the protective effect for emerging virus strains is still insufficient, and there is no ideal safe and efficient vaccine. Although scientists have persistently delved their research into the intricate structure and functionalities of the PEDV genome and viral proteins for years, the pathogenic mechanism of PEDV remains incompletely elucidated. Here, we focus on reviewing the research progress of PEDV structural and nonstructural proteins to facilitate the understanding of biological processes such as PEDV infection and pathogenesis. Full article

(This article belongs to the Section Viral Genomics)

► Show Figures

Figure 1

12 pages, 4372 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Studies of Embryogenic Callus Induction Rate in Peanut (Arachis hypogaea L.)

by Dandan Luo, Lei Shi, Ziqi Sun, Feiyan Qi, Hongfei Liu, Lulu Xue, Xiaona Li, Han Liu, Pengyu Qu, Huanhuan Zhao, Xiaodong Dai, Wenzhao Dong, Zheng Zheng, Bingyan Huang, Liuyang Fu and Xinyou Zhang

Genes 2024, 15(2), 160; https://doi.org/10.3390/genes15020160 - 26 Jan 2024

Cited by 5 | Viewed by 1894

Abstract

The capability of embryogenic callus induction is a prerequisite for in vitro plant regeneration. However, embryogenic callus induction is strongly genotype-dependent, thus hindering the development of in vitro plant genetic engineering technology. In this study, to examine the genetic variation in embryogenic callus [...] Read more.

The capability of embryogenic callus induction is a prerequisite for in vitro plant regeneration. However, embryogenic callus induction is strongly genotype-dependent, thus hindering the development of in vitro plant genetic engineering technology. In this study, to examine the genetic variation in embryogenic callus induction rate (CIR) in peanut (Arachis hypogaea L.) at the seventh, eighth, and ninth subcultures (T7, T8, and T9, respectively), we performed genome-wide association studies (GWAS) for CIR in a population of 353 peanut accessions. The coefficient of variation of CIR among the genotypes was high in the T7, T8, and T9 subcultures (33.06%, 34.18%, and 35.54%, respectively), and the average CIR ranged from 1.58 to 1.66. A total of 53 significant single-nucleotide polymorphisms (SNPs) were detected (based on the threshold value −log₁₀(p) = 4.5). Among these SNPs, SNPB03-83801701 showed high phenotypic variance and neared a gene that encodes a peroxisomal ABC transporter 1. SNPA05-94095749, representing a nonsynonymous mutation, was located in the Arahy.MIX90M locus (encoding an auxin response factor 19 protein) at T8, which was associated with callus formation. These results provide guidance for future elucidation of the regulatory mechanism of embryogenic callus induction in peanut. Full article

(This article belongs to the Special Issue Peanut Genetic Breeding and Germplasm Innovation)

► Show Figures

Figure 1

12 pages, 4186 KiB

Open AccessEditor’s ChoiceArticle

The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting

by Wenxin Wang, Wei Li, Dan Zhang, Yongrun Mi, Jingyu Zhang and Guoyang He

Genes 2024, 15(1), 132; https://doi.org/10.3390/genes15010132 - 21 Jan 2024

Cited by 11 | Viewed by 5184

Abstract

Objective: This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Methods: Instrumental variables within ±100 kb of the PCSK9 gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were [...] Read more.

Objective: This study explores the potential causal association between proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and tumor development using Mendelian randomization (MR) based on drug targets. Methods: Instrumental variables within ±100 kb of the PCSK9 gene locus, impacting low-density lipoprotein cholesterol (LDL-C), were utilized for MR analysis. Coronary heart disease (CHD) served as a positive control to validate the causal relationship between PCSK9 inhibitors and various cancers. We employed reverse MR to address the reverse causation concerns. Data from positive controls and tumors were sourced from OpenGWAS. Results: MR analysis suggested a negative causal relationship between PCSK9 inhibitors and both breast and lung cancers (95%CI_{Breast cancer} 0.81~0.99, p = 2.25 × 10⁻²; 95%CI_{Lung cancer} 0.65~0.94, p = 2.55 × 10⁻³). In contrast, a positive causal link was observed with gastric, hepatic, and oral pharyngeal cancers and cervical intraepithelial neoplasia (95%CI_{Gastric cancer} 1.14~1.75, p = 1.88 × 10⁻²; 95%CI_{Hepatic cancer} 1.46~2.53, p = 1.16 × 10⁻²; 95%CI_{Oral cavity and pharyngeal cancer} 4.49~6.33, p = 3.36 × 10⁻⁴; 95%CI_{Carcinoma in situ of cervix uteri} 4.56~7.12, p = 6.91 × 10⁻³), without heterogeneity or pleiotropy (p > 0.05). Sensitivity analyses confirmed these findings. The results of MR of drug targets suggested no causal relationship between PCSK9 inhibitors and bladder cancer, thyroid cancer, pancreatic cancer, colorectal cancer, malignant neoplasms of the kidney (except for renal pelvis tumors), malignant neoplasms of the brain, and malignant neoplasms of the esophagus (p > 0.05). Reverse MR helped mitigate reverse causation effects. Conclusions: The study indicates a divergent causal relationship of PCSK9 inhibitors with certain cancers. While negatively associated with breast and lung cancers, a positive causal association was observed with gastric, hepatic, oral cavity, and pharyngeal cancers and cervical carcinoma in situ. No causal links were found with bladder, thyroid, pancreatic, colorectal, certain kidney, brain, and esophageal cancers. Full article

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

► Show Figures

Graphical abstract

25 pages, 2939 KiB

Open AccessEditor’s ChoiceReview

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

by Luis Alberto Bravo-Vázquez, Sujay Paul, Miriam Guadalupe Colín-Jurado, Luis David Márquez-Gallardo, Luis Germán Castañón-Cortés, Antara Banerjee, Surajit Pathak and Asim K. Duttaroy

Genes 2024, 15(1), 123; https://doi.org/10.3390/genes15010123 - 19 Jan 2024

Cited by 10 | Viewed by 4081

Abstract

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. [...] Read more.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations. Full article

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

► Show Figures

Figure 1

15 pages, 5093 KiB

Open AccessEditor’s ChoiceArticle

Conserved Role of Heterotrimeric G Proteins in Plant Defense and Cell Death Progression

by Parastoo Karimian, Yuri Trusov and Jose Ramon Botella

Genes 2024, 15(1), 115; https://doi.org/10.3390/genes15010115 - 18 Jan 2024

Cited by 5 | Viewed by 2180

Abstract

Programmed cell death (PCD) is a critical process in plant immunity, enabling the targeted elimination of infected cells to prevent the spread of pathogens. The tight regulation of PCD within plant cells is well-documented; however, specific mechanisms remain elusive or controversial. Heterotrimeric G [...] Read more.

Programmed cell death (PCD) is a critical process in plant immunity, enabling the targeted elimination of infected cells to prevent the spread of pathogens. The tight regulation of PCD within plant cells is well-documented; however, specific mechanisms remain elusive or controversial. Heterotrimeric G proteins are multifunctional signaling elements consisting of three distinct subunits, Gα, Gβ, and Gγ. In Arabidopsis, the Gβγ dimer serves as a positive regulator of plant defense. Conversely, in species such as rice, maize, cotton, and tomato, mutants deficient in Gβ exhibit constitutively active defense responses, suggesting a contrasting negative role for Gβ in defense mechanisms within these plants. Using a transient overexpression approach in addition to knockout mutants, we observed that Gβγ enhanced cell death progression and elevated the accumulation of reactive oxygen species in a similar manner across Arabidopsis, tomato, and Nicotiana benthamiana, suggesting a conserved G protein role in PCD regulation among diverse plant species. The enhancement of PCD progression was cooperatively regulated by Gβγ and one Gα, XLG2. We hypothesize that G proteins participate in two distinct mechanisms regulating the initiation and progression of PCD in plants. We speculate that G proteins may act as guardees, the absence of which triggers PCD. However, in Arabidopsis, this G protein guarding mechanism appears to have been lost in the course of evolution. Full article

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

► Show Figures

Figure 1

18 pages, 3455 KiB

Open AccessEditor’s ChoiceArticle

Deciphering the Immune Microenvironment at the Forefront of Tumor Aggressiveness by Constructing a Regulatory Network with Single-Cell and Spatial Transcriptomic Data

by Kun Xu, Dongshuo Yu, Siwen Zhang, Lanming Chen, Zhenhao Liu and Lu Xie

Genes 2024, 15(1), 100; https://doi.org/10.3390/genes15010100 - 15 Jan 2024

Cited by 5 | Viewed by 3882

Abstract

The heterogeneity and intricate cellular architecture of complex cellular ecosystems play a crucial role in the progression and therapeutic response of cancer. Understanding the regulatory relationships of malignant cells at the invasive front of the tumor microenvironment (TME) is important to explore the [...] Read more.

The heterogeneity and intricate cellular architecture of complex cellular ecosystems play a crucial role in the progression and therapeutic response of cancer. Understanding the regulatory relationships of malignant cells at the invasive front of the tumor microenvironment (TME) is important to explore the heterogeneity of the TME and its role in disease progression. In this study, we inferred malignant cells at the invasion front by analyzing single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) data of ER-positive (ER+) breast cancer patients. In addition, we developed a software pipeline for constructing intercellular gene regulatory networks (IGRNs), which help to reduce errors generated by single-cell communication analysis and increase the confidence of selected cell communication signals. Based on the constructed IGRN between malignant cells at the invasive front of the TME and the immune cells of ER+ breast cancer patients, we found that a high expression of the transcription factors FOXA1 and EZH2 played a key role in driving tumor progression. Meanwhile, elevated levels of their downstream target genes (ESR1 and CDKN1A) were associated with poor prognosis of breast cancer patients. This study demonstrates a bioinformatics workflow of combining scRNA-seq and ST data; in addition, the study provides the software pipelines for constructing IGRNs automatically (cIGRN). This strategy will help decipher cancer progression by revealing bidirectional signaling between invasive frontline malignant tumor cells and immune cells, and the selected signaling molecules in the regulatory network may serve as biomarkers for mechanism studies or therapeutic targets. Full article

(This article belongs to the Special Issue Bioinformatics of Disease Research)

► Show Figures

Figure 1

24 pages, 1417 KiB

Open AccessEditor’s ChoiceReview

Effects of Peanut Rust Disease (Puccinia arachidis Speg.) on Agricultural Production: Current Control Strategies and Progress in Breeding for Resistance

by Yu You, Junhua Liao, Zemin He, Muhammad Khurshid, Chaohuan Wang, Zhenzhen Zhang, Jinxiong Mao and Youlin Xia

Genes 2024, 15(1), 102; https://doi.org/10.3390/genes15010102 - 15 Jan 2024

Cited by 10 | Viewed by 4401

Abstract

Peanuts play a pivotal role as an economic crop on a global scale, serving as a primary source of both edible oil and protein. Peanut rust (Puccinia arachidis Speg.) disease constitutes a significant global biotic stress, representing a substantial economic threat to [...] Read more.

Peanuts play a pivotal role as an economic crop on a global scale, serving as a primary source of both edible oil and protein. Peanut rust (Puccinia arachidis Speg.) disease constitutes a significant global biotic stress, representing a substantial economic threat to the peanut industry by inducing noteworthy reductions in seed yields and compromising oil quality. This comprehensive review delves into the distinctive characteristics and detrimental symptoms associated with peanut rust, scrutinizing its epidemiology and the control strategies that are currently implemented. Notably, host resistance emerges as the most favored strategy due to its potential to surmount the limitations inherent in other approaches. The review further considers the recent advancements in peanut rust resistance breeding, integrating the use of molecular marker technology and the identification of rust resistance genes. Our findings indicate that the ongoing refinement of control strategies, especially through the development and application of immune or highly resistant peanut varieties, will have a profound impact on the global peanut industry. Full article

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

► Show Figures

Figure 1

12 pages, 2104 KiB

Open AccessEditor’s ChoiceArticle

PFHxS Exposure and the Risk of Non-Alcoholic Fatty Liver Disease

by Zulvikar Syambani Ulhaq and William Ka Fai Tse

Genes 2024, 15(1), 93; https://doi.org/10.3390/genes15010093 - 13 Jan 2024

Cited by 11 | Viewed by 3074

Abstract

Perfluorohexanesulfonic acid (PFHxS) is a highly prevalent environmental pollutant, often considered to be less toxic than other poly- and perfluoroalkyl substances (PFASs). Despite its relatively lower environmental impact compared to other PFASs, several studies have suggested that exposure to PFHxS may be associated [...] Read more.

Perfluorohexanesulfonic acid (PFHxS) is a highly prevalent environmental pollutant, often considered to be less toxic than other poly- and perfluoroalkyl substances (PFASs). Despite its relatively lower environmental impact compared to other PFASs, several studies have suggested that exposure to PFHxS may be associated with disruptions of liver function in humans. Nevertheless, the precise pathomechanisms underlying PFHxS-induced non-alcoholic fatty liver disease (NAFLD) remain relatively unclear. Therefore, this study applied our previously published transcriptome dataset to explore the effects of PFHxS exposure on the susceptibility to NAFLD and to identify potential mechanisms responsible for PFHxS-induced NAFLD through transcriptomic analysis conducted on zebrafish embryos. Results showed that exposure to PFHxS markedly aggravated hepatic symptoms resembling NAFLD and other metabolic syndromes (MetS) in fish. Transcriptomic analysis unveiled 17 genes consistently observed in both NAFLD and insulin resistance (IR), along with an additional 28 genes identified in both the adipocytokine signaling pathway and IR. These shared genes were also found within the NAFLD dataset, suggesting that hepatic IR may play a prominent role in the development of PFHxS-induced NAFLD. In conclusion, our study suggests that environmental exposure to PFHxS could be a potential risk factor for the development of NAFLD, challenging the earlier notion of PFHxS being safer as previously claimed. Full article

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

► Show Figures

Figure 1

13 pages, 457 KiB

Open AccessEditor’s ChoiceStudy Protocol

Autism Spectrum Disorder with Epilepsy: A Research Protocol for a Clinical and Genetic Study

by Roberto Canitano and Yuri Bozzi

Genes 2024, 15(1), 61; https://doi.org/10.3390/genes15010061 - 31 Dec 2023

Cited by 2 | Viewed by 3941

Abstract

Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting ~1% of people worldwide. Core ASD features present with impaired social communication abilities, repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a series of comorbidities. Among these, epilepsy [...] Read more.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting ~1% of people worldwide. Core ASD features present with impaired social communication abilities, repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a series of comorbidities. Among these, epilepsy is frequently observed. The co-occurrence of ASD and epilepsy is currently thought to result from common abnormal neurodevelopmental pathways, including an imbalanced excitation/inhibition ratio. However, the pathological mechanisms involved in ASD-epilepsy co-morbidity are still largely unknown. Here, we propose a research protocol aiming to investigate electrophysiological and genetic features in subjects with ASD and epilepsy. This study will include a detailed electroencephalographic (EEG) and blood transcriptomic characterization of subjects with ASD with and without epilepsy. The combined approach of EEG and transcriptomic studies in the same subjects will contribute to a novel stratification paradigm of the heterogeneous ASD population based on quantitative gene expression and neurophysiological biomarkers. In addition, our protocol has the potential to indicate new therapeutic options, thus amending the current condition of absence of data and guidelines for the treatment of ASD with epilepsy. Full article

(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2023)

► Show Figures

Figure 1

18 pages, 3505 KiB

Open AccessEditor’s ChoiceArticle

Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer’s Disease

by Natalie A. Tan, Angelica M. Alvarado Carpio, H. Craig Heller and Elsa C. Pittaras

Genes 2024, 15(1), 47; https://doi.org/10.3390/genes15010047 - 28 Dec 2023

Cited by 2 | Viewed by 2328

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of [...] Read more.

Alzheimer’s disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of brain function. TgSwDI is a well-studied transgenic mouse model of AD, but no longitudinal studies have been performed to characterize cognitive deficits or β-amyloid plaque accumulation for use as a baseline reference in future research. Thus, we use behavioral tests (T-Maze, Novel Object Recognition (NOR), Novel Object Location (NOL)) to study long-term and working memory, and immunostaining to study β-amyloid plaque deposits, as well as brain size, in hippocampal, cerebellum, and cortical slices in TgSwDI and wild-type (WT) mice at 3, 5, 8, and 12 months old. The behavioral results show that TgSwDI mice exhibit deficits in their long-term spatial memory starting at 8 months old and in long-term recognition memory at all ages, but no deficits in their working memory. Immunohistochemistry showed an exponential increase in β-amyloid plaque in the hippocampus and cortex of TgSwDI mice over time, whereas there was no significant accumulation of plaque in WT mice at any age. Staining showed a smaller hippocampus and cerebellum starting at 8 months old for the TgSwDI compared to WT mice. Our data show how TgSwDI mice differ from WT mice in their baseline levels of cognitive function and β-amyloid plaque load throughout their lives. Full article

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

► Show Figures

Figure 1

23 pages, 629 KiB

Open AccessEditor’s ChoiceReview

Methodological Considerations in Longitudinal Analyses of Microbiome Data: A Comprehensive Review

by Ruiqi Lyu, Yixiang Qu, Kimon Divaris and Di Wu

Genes 2024, 15(1), 51; https://doi.org/10.3390/genes15010051 - 28 Dec 2023

Cited by 10 | Viewed by 6316

Abstract

Biological processes underlying health and disease are inherently dynamic and are best understood when characterized in a time-informed manner. In this comprehensive review, we discuss challenges inherent in time-series microbiome data analyses and compare available approaches and methods to overcome them. Appropriate handling [...] Read more.

Biological processes underlying health and disease are inherently dynamic and are best understood when characterized in a time-informed manner. In this comprehensive review, we discuss challenges inherent in time-series microbiome data analyses and compare available approaches and methods to overcome them. Appropriate handling of longitudinal microbiome data can shed light on important roles, functions, patterns, and potential interactions between large numbers of microbial taxa or genes in the context of health, disease, or interventions. We present a comprehensive review and comparison of existing microbiome time-series analysis methods, for both preprocessing and downstream analyses, including differential analysis, clustering, network inference, and trait classification. We posit that the careful selection and appropriate utilization of computational tools for longitudinal microbiome analyses can help advance our understanding of the dynamic host–microbiome relationships that underlie health-maintaining homeostases, progressions to disease-promoting dysbioses, as well as phases of physiologic development like those encountered in childhood. Full article

(This article belongs to the Special Issue Statistical Analysis of Microbiome Data: From Methods to Application)

► Show Figures

Figure 1

18 pages, 14236 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptome Analysis of Gene Expression and Regulatory Characteristics Associated with Different Bolting Periods in Spinacia oleracea

by Hao Wu, Zhilong Zhang, Zhiyuan Liu, Qing Meng, Zhaosheng Xu, Helong Zhang, Wei Qian and Hongbing She

Genes 2024, 15(1), 36; https://doi.org/10.3390/genes15010036 - 26 Dec 2023

Cited by 2 | Viewed by 2163

Abstract

Bolting is a symbol of the transition from vegetative to reproductive growth in plants. Late bolting can effectively prolong the commercial value of spinach and is of great importance for spinach breeding. Bolting has complex regulatory networks, and current research on spinach bolting [...] Read more.

Bolting is a symbol of the transition from vegetative to reproductive growth in plants. Late bolting can effectively prolong the commercial value of spinach and is of great importance for spinach breeding. Bolting has complex regulatory networks, and current research on spinach bolting is relatively weak, with specific regulatory pathways and genes unclear. To clarify the regulatory characteristics and key genes related to bolting in spinach, we conducted a comparative transcriptome analysis. In this study, 18 samples from three periods of bolting-tolerant spinach material 12S3 and bolting-susceptible material 12S4 were analyzed using RNA-seq on, resulting in 10,693 differentially expressed genes (DEGs). Functional enrichment and co-expression trend analysis indicated that most DEGs were enriched in the photoperiod pathway, the hormone signaling pathway, and the cutin, suberin, and wax biosynthetic pathways. According to the weighted gene co-expression network analysis (WGCNA), SpFT (SOV4g003400), SOV4g040250, and SpGASA1 (SOV6g017600) were likely to regulate bolting through the gibberellin and photoperiod pathways, and SpELF4 (SOV1g028600) and SpPAT1 (SOV4g058860) caused differences in early and late bolting among different cultivars. These results provide important insights into the genetic control of bolting in spinach and will help elucidate the molecular mechanisms of bolting in leafy vegetables. Full article

(This article belongs to the Special Issue Vegetable Genetic Breeding)

► Show Figures

Figure 1

16 pages, 4389 KiB

Open AccessEditor’s ChoiceReview

Unraveling the Epigenetic Tapestry: Decoding the Impact of Epigenetic Modifications in Hidradenitis Suppurativa Pathogenesis

by Elena Maria Nardacchione, Paola Maura Tricarico, Ronald Moura, Adamo Pio d’Adamo, Ayshath Thasneem, Muhammad Suleman, Angelo Valerio Marzano, Sergio Crovella and Chiara Moltrasio

Genes 2024, 15(1), 38; https://doi.org/10.3390/genes15010038 - 26 Dec 2023

Cited by 8 | Viewed by 2931

Abstract

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, [...] Read more.

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, severity, and clinical course of this disease, although the exact molecular mechanisms are still being explored. Epigenetics is currently emerging as an interesting field of investigation that could potentially shed light on the molecular intricacies underlying HS, but there is much still to uncover on the subject. The aim of this work is to provide an overview of the epigenetic landscape involved in HS. Specifically, in this in-depth review we provide a comprehensive overview of DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs (such as microRNA—miRNA-132, miRNA-200c, miRNA-30a-3p, miRNA-100-5b, miRNA-155-5p, miRNA-338-5p) dysregulation in HS patients. An interesting element of epigenetic regulation in HS is that the persistent inflammatory milieu observed in HS lesional skin could be exacerbated by an altered methylation profile and histone acetylation pattern associated with key inflammatory genes. Deepening our knowledge on the subject could enable the development of targeted epigenetic therapies to potentially restore normal gene expression patterns, and subsequentially ameliorate, or even reverse, the progression of the disease. By deciphering the epigenetic code governing HS, we strive to usher in a new era of personalized and effective interventions for this enigmatic dermatological condition. Full article

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

► Show Figures

Figure 1

12 pages, 2629 KiB

Open AccessEditor’s ChoiceReview

Children with Rare Nager Syndrome—Literature Review, Clinical and Physiotherapeutic Management

by Bożena Anna Marszałek-Kruk, Andrzej Myśliwiec, Anna Lipowicz, Wojciech Wolański, Małgorzata Kulesa-Mrowiecka and Krzysztof Dowgierd

Genes 2024, 15(1), 29; https://doi.org/10.3390/genes15010029 - 24 Dec 2023

Cited by 3 | Viewed by 4709

Abstract

Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare [...] Read more.

Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the SF3B4 gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient’s lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient’s benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures. Full article

(This article belongs to the Special Issue Diagnosis of Rare Genetic Disorders)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI