Genes

15 pages, 2757 KiB

Open AccessArticle

Identification and Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Networks in A2780 Cells Treated with Resveratrol

by Weihua Zhu, Yuanting Zhang, Qianqian Zhou, Cheng Zhen, Herong Huang and Xiaoying Liu

Genes 2024, 15(7), 965; https://doi.org/10.3390/genes15070965 - 22 Jul 2024

Viewed by 526

Abstract

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations [...] Read more.

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations of 0, 10, 25, 50, 75, 100, 150, 200, and 300

μ

M. RNA sequencing (RNA-seq) was performed to analyze the circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) expression spectrum. The differentially expressed genes included 460 circRNAs, 1988 miRNAs, and 1671 mRNAs, and they were subjected to analyses including Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment. We selected signaling pathways enriched in the cell processes by mRNA KEGG, comprehensively analyzed the circRNA-miRNA-mRNA regulatory network, and verified several miRNAs expressed in the regulatory network diagram using the quantitative real-time polymerase chain reaction. The data showed that the cell proliferation of A2780 cells treated with RES for 24 h or 48 h decreased with increasing concentrations of RES. The circRNA-miRNA-mRNA regulatory network that we constructed provides new insights into the ability of RES to inhibit cell proliferation and promote apoptosis in A2780 cells. Full article

(This article belongs to the Section RNA)

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18 pages, 5887 KiB

Open AccessArticle

Phylogenetic and Comparative Genomics Study of Papilionidae Based on Mitochondrial Genomes

by Zhen-Tian Yan, Xiao-Ya Tang, Dong Yang, Zhen-Huai Fan, Si-Te Luo and Bin Chen

Genes 2024, 15(7), 964; https://doi.org/10.3390/genes15070964 - 22 Jul 2024

Viewed by 457

Abstract

Most species of Papilionidae are large and beautiful ornamental butterflies. They are recognized as model organisms in ecology, evolutionary biology, genetics, and conservation biology but present numerous unresolved phylogenetic problems. Complete mitochondrial genomes (mitogenomes) have been widely used in phylogenetic studies of butterflies, [...] Read more.

Most species of Papilionidae are large and beautiful ornamental butterflies. They are recognized as model organisms in ecology, evolutionary biology, genetics, and conservation biology but present numerous unresolved phylogenetic problems. Complete mitochondrial genomes (mitogenomes) have been widely used in phylogenetic studies of butterflies, but mitogenome knowledge within the family Papilionidae is limited, and its phylogeny is far from resolved. In this study, we first report the mitogenome of Byasa confusa from the subfamily Papilioninae of Papilionidae. The mitogenome of B. confusa is 15,135 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region (CR), closely mirroring the genomic structure observed in related butterfly species. Comparative analysis of 77 Papilionidae mitogenomes shows gene composition and order to be identical to that of an ancestral insect, and the AT bias, Ka/Ks, and relative synonymous codon usage (RSCU) are all consistent with that of other reported butterfly mitogenomes. We conducted phylogenetic analyses using maximum-likelihood (ML) and Bayesian-inference (BI) methods, with 77 Papilionidae species as ingroups and two species of Nymphalidae and Lycaenidae as outgroups. The phylogenetic analysis indicated that B. confusa were clustered within Byasa. The phylogenetic trees show the monophyly of the subfamily Papilioninae and the tribes Leptocircini, Papilionini, and Troidini. The data supported the following relationships in tribe level on Papilioninae: (((Troidini + Papilionini) + Teinopalpini) + Leptocircini). The divergence time analysis suggests that Papilionidae originated in the late Creataceous. Overall, utilizing the largest number of Papilionidae mitogenomes sequenced to date, with the current first exploration in a phylogenetic analysis on Papilionidae (including four subfamilies), this study comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny, providing information for further studies on the mitogenome, phylogeny, evolution, and taxonomic revision of the Papilionidae family. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)

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15 pages, 3078 KiB

Open AccessArticle

Liver Transcriptomic Profiles of Ruminant Species Fed Spent Hemp Biomass Containing Cannabinoids

by Agung Irawan and Massimo Bionaz

Genes 2024, 15(7), 963; https://doi.org/10.3390/genes15070963 - 22 Jul 2024

Viewed by 504

Abstract

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appears to be safe with minor effects on the metabolism, including a decrease in circulating cholesterol and increase bilirubinemia, both [...] Read more.

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appears to be safe with minor effects on the metabolism, including a decrease in circulating cholesterol and increase bilirubinemia, both associated with liver metabolism. Those effects could be consequence of the presence of cannabinoids, particularly Δ⁹-tetrahydrocannabinol (THC) and CBD in the SHB. This study aimed to study the transcriptional profile of the liver of dairy cows and lambs fed SHB. Dairy cows received SHB or alfalfa pellet for four weeks of intervention (IP) and four weeks of withdrawal periods (WP). Finishing lambs were fed a control diet (CON), 10% (LH2), or 20% (HH2) SHB for 2 months or 1 month followed by 1-month SHB withdrawal (LH1 and HH1, respectively). RNA sequencing was performed, and the mRNA was annotated using the latest reference genomes. The RNAseq data were filtered, normalized for library size and composition, and statistically analyzed by DESeq2. The bioinformatic analysis was performed by using DAVID, Gene Set Enrichment Analysis (GSEA), and the Dynamic Impact Approach. Using a 0.2 FDR cut-off, we identified only ≤24 differentially expressed genes (DEG) in the liver by feeding SHB in dairy cows and a larger number of DEGs in lambs (from 71 in HH1 vs. CON to 552 in LH1 vs. CON). The KEGG analysis demonstrated that feeding SHB in dairy cows and lambs had relatively minor to moderate metabolic alterations in dairy cows and lambs mainly associated with amino acids and lipid metabolism whereas cholesterol synthesis was overall activated in lambs. GSEA identified activation of the PPAR signaling pathway only in dairy cows. We found an opposite effect on activation of metabolism of drug and xenobiotics by cytochrome P450 enzymes in dairy cows and lambs receiving less SHB but an inhibition in HH2 lambs. Immune system-related pathways were inhibited by feeding SHB in lambs, but the impact was minor. Cumulatively, inclusion of SHB containing cannabinoids in dairy and lambs demonstrate very little effects on the alteration of transcriptomic profile of the liver. Full article

(This article belongs to the Special Issue Livestock Genomics, Genetics and Breeding)

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14 pages, 4077 KiB

Open AccessArticle

Identification of Two Potential Gene Insertion Sites for Gene Editing on the Chicken Z/W Chromosomes

by Gaoyuan Wu, Youchen Liang, Chen Chen, Guohong Chen, Qisheng Zuo, Yingjie Niu, Jiuzhou Song, Wei Han, Kai Jin and Bichun Li

Genes 2024, 15(7), 962; https://doi.org/10.3390/genes15070962 - 22 Jul 2024

Viewed by 505

Abstract

The identification of accurate gene insertion sites on chicken sex chromosomes is crucial for advancing sex control breeding materials. In this study, the intergenic region NC_006127.4 on the chicken Z chromosome and the non-repetitive sequence EE0.6 on the W chromosome were selected as [...] Read more.

The identification of accurate gene insertion sites on chicken sex chromosomes is crucial for advancing sex control breeding materials. In this study, the intergenic region NC_006127.4 on the chicken Z chromosome and the non-repetitive sequence EE0.6 on the W chromosome were selected as potential gene insertion sites. Gene knockout vectors targeting these sites were constructed and transfected into DF-1 cells. T7E1 enzyme cleavage and luciferase reporter enzyme analyses revealed knockout efficiencies of 80.00% (16/20), 75.00% (15/20), and 75.00% (15/20) for the three sgRNAs targeting the EE0.6 site. For the three sgRNAs targeting the NC_006127.4 site, knockout efficiencies were 70.00% (14/20), 60.00% (12/20), and 45.00% (9/20). Gel electrophoresis and high-throughput sequencing were performed to detect potential off-target effects, showing no significant off-target effects for the knockout vectors at the two sites. EdU and CCK-8 proliferation assays revealed no significant difference in cell proliferation activity between the knockout and control groups. These results demonstrate that the EE0.6 and NC_006127.4 sites can serve as gene insertion sites on chicken sex chromosomes for gene editing without affecting normal cell proliferation. Full article

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

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18 pages, 3664 KiB

Open AccessArticle

Uncovering Porphyrin Accumulation in the Tumor Microenvironment

by Swamy R. Adapa, Abdus Sami, Pravin Meshram, Gloria C. Ferreira and Rays H. Y. Jiang

Genes 2024, 15(7), 961; https://doi.org/10.3390/genes15070961 - 22 Jul 2024

Viewed by 451

Abstract

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), [...] Read more.

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed “Porphyrin Overdrive”. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME’s stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease 2024)

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13 pages, 11009 KiB

Open AccessArticle

Molecular Cloning, Characterization, and Function of Insulin-Related Peptide 1 (IRP1) in the Haliotis discus hanna

by Jianfang Huang, Mingcan Zhou, Jianming Chen and Caihuan Ke

Genes 2024, 15(7), 960; https://doi.org/10.3390/genes15070960 - 22 Jul 2024

Viewed by 366

Abstract

Abalone is a popular mollusk in the marine aquaculture industry of China. However, existing challenges, like slow growth, individual miniaturization, and the absence of abundant abalone, have emerged as significant obstacles impeding its long-term progress in aquaculture. Studies have demonstrated that insulin-related peptide [...] Read more.

Abalone is a popular mollusk in the marine aquaculture industry of China. However, existing challenges, like slow growth, individual miniaturization, and the absence of abundant abalone, have emerged as significant obstacles impeding its long-term progress in aquaculture. Studies have demonstrated that insulin-related peptide (IRP) is a crucial factor in the growth of marine organisms. However, limited studies have been conducted on IRP in abalone. This study indicated that the hdh-MIRP1 open reading frame (ORF) was composed of 456 base pairs, which encoded 151 amino acids. Based on the gene expression and immunofluorescence analyses, the cerebral ganglion of Haliotis discus hannai (H. discus hannai) was the primary site of hdh-MIRP1 mRNA expression. Moreover, hdh-MIRP1 expression was observed to be higher in the larger group than in the smaller group abalones. Only single nucleotide polymorphism (SNP) was related to their growth characteristics. However, approximately 82 proteins that may interact with hdh-MIRP1 were identified. The functional enrichment analysis of the 82 genes indicated that hdh-MIRP1 may be involved in the regulation of glucose metabolism and the process of growth. This study established a benchwork for further investigating the role of IRP in the growth of abalone. Full article

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

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11 pages, 5149 KiB

Open AccessArticle

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

Viewed by 458

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)

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43 pages, 2514 KiB

Open AccessReview

Advances in CircRNAs in the Past Decade: Review of CircRNAs Biogenesis, Regulatory Mechanisms, and Functions in Plants

by Dongqin Zhang, Yue Ma, Misbah Naz, Nazeer Ahmed, Libo Zhang, Jing-Jiang Zhou, Ding Yang and Zhuo Chen

Genes 2024, 15(7), 958; https://doi.org/10.3390/genes15070958 - 21 Jul 2024

Viewed by 503

Abstract

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable [...] Read more.

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control. Full article

(This article belongs to the Special Issue Genetic Regulation of Biotic Stress Responses)

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19 pages, 4953 KiB

Open AccessArticle

ECPUB5 Polyubiquitin Gene in Euphorbia characias: Molecular Characterization and Seasonal Expression Analysis

by Faustina Barbara Cannea, Daniela Diana, Rossano Rossino and Alessandra Padiglia

Genes 2024, 15(7), 957; https://doi.org/10.3390/genes15070957 - 21 Jul 2024

Viewed by 503

Abstract

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and [...] Read more.

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and expressed protein in E. characias. Using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) and rapid amplification of cDNA ends (5′/3′-RACE), we reconstructed the entire open reading frame (ORF) and noncoding regions. Our analysis revealed that the polyubiquitin gene encodes five tandemly repeated sequences, each coding for a ubiquitin monomer with amino acid variations in four of the five repeats. In silico studies have suggested functional differences among monomers. Gene expression peaked during the summer, correlating with high temperatures and suggesting a role in heat stress response. Western blotting confirmed the presence of polyubiquitin in the latex and leaf tissues, indicating active ubiquitination processes. These findings enhance our understanding of polyubiquitin’s regulatory mechanisms and functions in E. characias, highlighting its unique structural and functional features. Full article

(This article belongs to the Special Issue Abiotic Stress in Land Plants: Molecular Genetics and Genomics)

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9 pages, 1869 KiB

Open AccessArticle

Rare Variants of the SMN1 Gene Detected during Neonatal Screening

by Maria Akhkiamova, Aleksander Polyakov, Andrey Marakhonov, Sergey Voronin, Elena Saifullina, Zulfiia Vafina, Kristina Michalchuk, Svetlana Braslavskaya, Alena Chukhrova, Nina Ryadninskaya, Sergey Kutsev and Olga Shchagina

Genes 2024, 15(7), 956; https://doi.org/10.3390/genes15070956 - 21 Jul 2024

Viewed by 760

Abstract

During the expanded neonatal screening program conducted in 2023, we analyzed samples obtained from 1,227,130 out of 1,256,187 newborns in the Russian Federation in order to detect 5q spinal muscular atrophy (5q SMA). Within the 253-sample risk group formed based on the results [...] Read more.

During the expanded neonatal screening program conducted in 2023, we analyzed samples obtained from 1,227,130 out of 1,256,187 newborns in the Russian Federation in order to detect 5q spinal muscular atrophy (5q SMA). Within the 253-sample risk group formed based on the results of the first screening stage, 5 samples showed a discrepancy between the examination results obtained via various screening methods and quantitative MLPA (used as reference). The discrepancy between the results was caused by the presence of either a c.835-18C>T intronic variant or a c.842G>C p.(Arg281Thr) missense variant in the SMN1 gene, both of which are located in the region complementary to the sequences of annealing probes for ligation and real-time PCR. Three newborns had the c.835-18C>T variant in a compound heterozygous state with a deletion of exons 7–8 of the SMN1 gene, one newborn with two copies of the SMN1 gene had the same variant in a heterozygous state, and one newborn had both variants—c.835-18C>T and c.842G>C p.(Arg281Thr)—in a compound heterozygous state. Additional examination was carried out for these variants, involving segregation analysis in families, carriage analysis in population cohorts, and RNA analysis. Based on the obtained results, according to the ACMG criteria, the c.835-18C>T intronic variant should be classified as likely benign, and the c.842G>C p.(Arg281Thr) missense substitution as a variant of uncertain clinical significance. All five probands are under dynamic monitoring. No 5q SMA symptoms were detected in these newborns neonatally or during a 1-year follow-up period. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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14 pages, 2146 KiB

Open AccessArticle

Divergence of Phyllosphere Microbial Community Assemblies and Components of Volatile Organic Compounds between the Invasive Sphagneticola trilobata, the Native Sphagneticola calendulacea and Their Hybrids, and Its Implications for Invasiveness

by Hui Zhang, Shanshan Li, Sheng Zhou, Wei Guo, Ping Chen, Yongquan Li and Wei Wu

Genes 2024, 15(7), 955; https://doi.org/10.3390/genes15070955 - 20 Jul 2024

Viewed by 377

Abstract

Closely-related plant groups with distinct microbiomes, chemistries and ecological characteristics represent tractable models to explore mechanisms shaping species spread, competitive dynamics and community assembly at the interface of native and introduced ranges. We investigated phyllosphere microbial communities, volatile organic compound (VOC) compositions, and [...] Read more.

Closely-related plant groups with distinct microbiomes, chemistries and ecological characteristics represent tractable models to explore mechanisms shaping species spread, competitive dynamics and community assembly at the interface of native and introduced ranges. We investigated phyllosphere microbial communities, volatile organic compound (VOC) compositions, and potential interactions among introduced S. trilobata, native S. calendulacea and their hybrid in South China. S. trilobata exhibited higher α diversity but significantly different community composition compared to the native and hybrid groups. However, S. calendulacea and the hybrid shared certain microbial taxa, suggesting potential gene flow or co-existence. The potent antimicrobial VOC profile of S. trilobata, including unique compounds like p-cymene (13.33%), likely contributes to its invasion success. The hybrid’s intermediate microbial and VOC profiles suggest possible consequences for species distribution, genetic exchange, and community assembly in heterogeneous environments. This hybrid deserves further study as both an opportunity for and threat to diversity maintenance. These differentiating yet connected plant groups provide insight into ecological and evolutionary dynamics shaping microbiome structure, species co-occurrence and competitive outcomes during biological exchange and habitat transformation. An interdisciplinary approach combining chemical and microbial ecology may reveal mechanisms underlying community stability and change, informing management of species spread in a globalized world. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

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25 pages, 10990 KiB

Open AccessArticle

Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases

by Vaishnavi Aradhyula, Joshua D. Breidenbach, Bella Z. Khatib-Shahidi, Julia N. Slogar, Sonia A. Eyong, Dhilhani Faleel, Prabhatchandra Dube, Rajesh Gupta, Samer J. Khouri, Steven T. Haller and David J. Kennedy

Genes 2024, 15(7), 954; https://doi.org/10.3390/genes15070954 - 20 Jul 2024

Viewed by 666

Abstract

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce [...] Read more.

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes. Full article

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

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12 pages, 970 KiB

Open AccessReview

The MET Family of Receptor Tyrosine Kinases Promotes a Shift to Pro-Tumor Metabolism

by James C. Davis and Susan E. Waltz

Genes 2024, 15(7), 953; https://doi.org/10.3390/genes15070953 - 20 Jul 2024

Viewed by 564

Abstract

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor [...] Read more.

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor that is implicated in this shift to pro-tumor metabolism. RTKs are important drivers of cancer growth and metastasis. One such family of RTKs is the MET family, which consists of MET and RON (MST1R). The overexpression of either MET or RON has been associated with worse cancer patient prognosis in a variety of tumor types. Both MET and RON signaling promote increased glycolysis by upregulating the expression of key glycolytic enzymes via increased MYC transcription factor activity. Additionally, both MET and RON signaling promote increased cholesterol biosynthesis downstream of glycolysis by upregulating the expression of SREBP2-induced cholesterol biosynthesis enzymes via CTTNB1. These changes in metabolism, driven by RTK activity, provide potential targets in limiting tumor growth and metastasis via pharmacological inhibition or modifications in diet. This review summarizes pro-tumor changes in metabolism driven by the MET family of RTKs. In doing so, we will offer our unique perspective on metabolic pathways that drive worse patient prognosis and provide suggestions for future study. Full article

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

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17 pages, 3069 KiB

Open AccessArticle

Exonic Short Interspersed Nuclear Element Insertion in FAM161A Is Associated with Autosomal Recessive Progressive Retinal Atrophy in the English Shepherd

by Katherine Stanbury, Ellen C. Schofield, Bryan McLaughlin, Oliver P. Forman and Cathryn S. Mellersh

Genes 2024, 15(7), 952; https://doi.org/10.3390/genes15070952 - 20 Jul 2024

Viewed by 2157

Abstract

Progressive retinal atrophies (PRAs) are a genetically heterogeneous group of inherited eye diseases that affect over 100 breeds of dog. The initial clinical sign is visual impairment in scotopic conditions, as a consequence of rod photoreceptor cell degeneration. Photopic vision degeneration then follows, [...] Read more.

Progressive retinal atrophies (PRAs) are a genetically heterogeneous group of inherited eye diseases that affect over 100 breeds of dog. The initial clinical sign is visual impairment in scotopic conditions, as a consequence of rod photoreceptor cell degeneration. Photopic vision degeneration then follows, due to progression of the disease to the cone photoreceptors, and ultimately results in complete blindness. Two full-sibling English Shepherds were diagnosed with PRA at approximately 5 years old and tested clear of all published PRA genetic variants. This study sought to identify the novel PRA-associated variant segregating in the breed. We utilised a combined approach of whole genome sequencing of the probands and homozygosity mapping of four cases and 22 controls and identified a short interspersed nuclear element within an alternatively spliced exon in FAM161A. The XP_005626197.1 c.17929_ins210 variant was homozygous in six PRA cases and heterozygous or absent in control dogs, consistent with a recessive mode of inheritance. The insertion is predicted to extend exon 4 by 39 aberrant amino acids followed by an early termination stop codon. PRA is intractable to treatment, so the development of a genetic screening test, based on the associated variant, is significant, because it provides dog breeders/owners with a means of reducing the frequency of the disease variant within this breed as well as minimising the risk of breeding puppies that will develop this blinding disease. Full article

(This article belongs to the Special Issue Advances in Canine Genetics)

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14 pages, 6380 KiB

Open AccessArticle

Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases

by María Domínguez-Ruiz, Margarita Olarte, Esther Onecha, Irene García-Vaquero, Nancy Gelvez, Greizy López, Manuela Villamar, Matías Morín, Miguel A. Moreno-Pelayo, Carmelo Morales-Angulo, Rubén Polo, Martha L. Tamayo and Ignacio del Castillo

Genes 2024, 15(7), 951; https://doi.org/10.3390/genes15070951 - 19 Jul 2024

Viewed by 358

Abstract

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of [...] Read more.

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype–phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C>T in KARS1, c.475C>T, c.728A>C and c.1012G>A in HARS2, and c.795A>G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence. Full article

(This article belongs to the Section Cytogenomics)

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22 pages, 4152 KiB

Open AccessArticle

Dissecting the Genetic Architecture of Morphological Traits in Sunflower (Helianthus annuus L.)

by Yavuz Delen, Semra Palali-Delen, Gen Xu, Mohamed Neji, Jinliang Yang and Ismail Dweikat

Genes 2024, 15(7), 950; https://doi.org/10.3390/genes15070950 - 19 Jul 2024

Viewed by 475

Abstract

The sunflower (Helianthus annuus L.) is one of the most essential oil crops in the world. Several component traits, including flowering time, plant height, stem diameter, seed weight, and kernel weight, determine sunflower seed and oil yield. Although the genetic mechanisms governing [...] Read more.

The sunflower (Helianthus annuus L.) is one of the most essential oil crops in the world. Several component traits, including flowering time, plant height, stem diameter, seed weight, and kernel weight, determine sunflower seed and oil yield. Although the genetic mechanisms governing the variation of these yield-related traits have been studied using various approaches, genome-wide association studies (GWAS) have not been widely applied to sunflowers. In this study, a set of 342 sunflower accessions was evaluated in 2019 and 2020 using an incomplete randomized block design, and GWAS was conducted utilizing two complementary approaches: the mixed linear model (MLM) and the fixed and random model circulating probability unification (farmCPU) model by fitting 226,779 high-quality SNPs. As a result, GWAS identified a number of trait-associated SNPs. Those SNPs were located close to several genes that may serve as a basis for further molecular characterization and provide promising targets for sunflower yield improvement. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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11 pages, 3336 KiB

Open AccessArticle

Hepatopancreas Transcriptome Analysis of Spinibarbus sinensis to Reveal Different Growth-Related Genes

by Bo Zhou, Leyan Ling, Bin Wang, Fei Yang, Mengdan Hou, Fan Liu, Yu Li, Hui Luo, Wenping He and Hua Ye

Genes 2024, 15(7), 949; https://doi.org/10.3390/genes15070949 - 19 Jul 2024

Viewed by 399

Abstract

Spinibarbus sinensis, also known as Qingbo, is an important economic fish in China. However, the detailed mechanisms underlying its growth are still unknown. To excavate the genes and signaling pathways related to its growth, we compared the transcriptome profiles of the hepatopancreas [...] Read more.

Spinibarbus sinensis, also known as Qingbo, is an important economic fish in China. However, the detailed mechanisms underlying its growth are still unknown. To excavate the genes and signaling pathways related to its growth, we compared the transcriptome profiles of the hepatopancreas tissues of S. sinensis, with two groups of growth rate for evaluation. An average of 66,304,909 and 68,739,585 clean reads were obtained in the fast growth (FG) and slow growth (SG) group, respectively. The differential gene expression analysis results showed that 272 differentially expressed genes (DEGs) were screened between the FG and SG groups, including 101 up-regulated genes and 171 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that GO terms related to metabolic process, organic substance metabolic process, and catalytic activity were enriched, pathway signals related to steroid biosynthesis and protein digestion and absorption were also detected. Meanwhile, the potential key regulatory genes sst2, fndc4, and cckra related to the growth of S. sinensis were screened. Reverse transcript fluorescence quantitative PCR (RT-qPCR) validation of 18 DEGs associated with growth differences showed that the RT-qPCR results were consistent with RNA-seq analysis, and nine genes, stk31, gpr149, angptl1, fstl1, sik1, ror2, nlrc3, pdlim2, and nav2 were significantly expressed in the FG group. bmp1, stc1, gpatch8, sstrt2, s100a1, ktf6, cckar6, sync1, bhlha15, a total of nine genes were significantly expressed in the SG group. This study provides basic information for improving the growth characteristics of S. sinensis and the functional research of candidate genes. Full article

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

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16 pages, 5151 KiB

Open AccessArticle

Transcriptome Analysis Reveals Genes and Pathways Associated with Drought Tolerance of Early Stages in Sweet Potato (Ipomoea batatas (L.) Lam.)

by Peng Cheng, Fanna Kong, Yang Han, Xiaoping Liu and Jiaping Xia

Genes 2024, 15(7), 948; https://doi.org/10.3390/genes15070948 - 19 Jul 2024

Viewed by 455

Abstract

The yield of sweet potato [Ipomoea batatas (L.) Lam] can be easily threatened by drought stress. Typically, early stages like the seedling stage and tuber-root expansion stage are more vulnerable to drought stress. In this study, a highly drought-tolerant sweet potato cultivar [...] Read more.

The yield of sweet potato [Ipomoea batatas (L.) Lam] can be easily threatened by drought stress. Typically, early stages like the seedling stage and tuber-root expansion stage are more vulnerable to drought stress. In this study, a highly drought-tolerant sweet potato cultivar “WanSu 63” was subjected to drought stress at both the seedling stage (15 days after transplanting, 15 DAT) and the tuber-root expansion stage (45 DAT). Twenty-four cDNA libraries were constructed from leaf segments and root tissues at 15 and 45 DAT for Next-Generation Sequencing. A total of 663, 063, and 218 clean reads were obtained and then aligned to the reference genome with a total mapped ratio greater than 82.73%. A sum of 7119, 8811, 5463, and 930 differentially expressed genes were identified from leaves in 15 days (L15), roots in 15 days (R15), leaves in 45 days (L45), and roots in 45 days (R45), respectively, in drought stress versus control. It was found that genes encoding heat shock proteins, sporamin, LEA protein dehydrin, ABA signaling pathway protein gene NCED1, as well as a group of receptor-like protein kinases genes were enriched in differentially expressed genes. ABA content was significantly higher in drought-treated tissues than in the control. The sweet potato biomass declined sharply to nearly one-quarter after drought stress. In conclusion, this study is the first to identify the differentially expressed drought-responsive genes and signaling pathways in the leaves and roots of sweet potato at the seedling and root expansion stages. The results provide potential resources for drought resistance breeding of sweet potato. Full article

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

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11 pages, 2787 KiB

Open AccessArticle

The Missense Variant in the Signal Peptide of α-GLA Gene, c.13 A/G, Promotes Endoplasmic Reticular Stress and the Related Pathway’s Activation

by Sabrina Bossio, Ida Daniela Perrotta, Danilo Lofaro, Daniele La Russa, Vittoria Rago, Renzo Bonofiglio, Rosita Greco, Michele Andreucci, Antonio Aversa, Antonella La Russa and Anna Perri

Genes 2024, 15(7), 947; https://doi.org/10.3390/genes15070947 - 19 Jul 2024

Viewed by 513

Abstract

Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could [...] Read more.

Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway’s activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1β, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband’s PBMC exhibited higher expression of TGFβ 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant’s contribution to cellular and tissue damage. Full article

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

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13 pages, 20689 KiB

Open AccessArticle

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping

by Mario Cuk, Busra Unal, Andjela Bevanda, Connor P. Hayes, McKenzie Walker, Feruza Abraamyan, Robert Beluzic, Kristina Crkvenac Gornik, David Ozretic, Maja Prutki, Qian Nie, Honey V. Reddi and Arezou A. Ghazani

Genes 2024, 15(7), 946; https://doi.org/10.3390/genes15070946 - 19 Jul 2024

Viewed by 530

Abstract

Purpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged [...] Read more.

Purpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2–15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes. Full article

(This article belongs to the Special Issue Precision Medicine and Genetics)

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14 pages, 2145 KiB

Open AccessArticle

Expression Patterns of TGF-β1, TβR-I, TβR-II, and Smad2 Reveal Insights into Heterosis for Growth of Hybrid Offspring between Acanthopagrus schlegelii and Pagrus major

by Xinran Du, Yue Zhao, Jingbo Li, Wenli Xie, Linna Lyu, Shuyin Chen, Chaofeng Jia, Jie Yan and Peng Li

Genes 2024, 15(7), 945; https://doi.org/10.3390/genes15070945 - 19 Jul 2024

Viewed by 492

Abstract

TGF-β1/Smads is a classic signaling pathway, which plays important roles in the development process of organisms. Black porgy Acanthopagrus schlegelii and red porgy Pagrus major are valuable economic fishes, and their hybrid offspring show excellent heterosis traits. Yet the molecular regulation mechanism of [...] Read more.

TGF-β1/Smads is a classic signaling pathway, which plays important roles in the development process of organisms. Black porgy Acanthopagrus schlegelii and red porgy Pagrus major are valuable economic fishes, and their hybrid offspring show excellent heterosis traits. Yet the molecular regulation mechanism of the heterosis traits is less clear. Here, we explored the TGF-β1/Smads pathway’s molecular genetic information for heterosis in A. schlegelii ♂ × P. major ♀ (AP) and A. schlegelii ♀ × P. major ♂ (PA) in terms of growth and development. The mRNA expression levels of TGF-β1, TβR-I, TβR-II, and Smad2 genes in different developmental stages of A. schlegelii were detected. Furthermore, the expression levels of TGF-β1, TβR-I, TβR-II, and Smad2 genes in different tissues of adult (mRNA level) and larva (mRNA and protein level) of A. schlegelii, P. major, and their hybrids were determined by both real-time quantitative PCR and Western blot techniques. The results indicated the ubiquitous expression of these genes in all developmental stages of A. schlegelii and in all tested tissues of A. schlegelii, P. major, and its hybrids. Among them, the mRNA of TGF-β1, TβR-I, and TβR-II genes is highly expressed in the liver, gill, kidney, and muscle of black porgy, red porgy, and their hybrid offspring. There are significant changes in gene and protein expression levels in hybrid offspring, which indirectly reflect hybrid advantage. In addition, there was no correlation between protein and mRNA expression levels of Smad2 protein. The results provide novel data for the differential expression of growth and development genes between the reciprocal hybridization generation of black porgy and red porgy and its parents, which is conducive to further explaining the molecular regulation mechanism of heterosis in the growth and development of hybrid porgy. Full article

(This article belongs to the Special Issue Genetics and Molecular Breeding in Fisheries and Aquaculture)

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15 pages, 3180 KiB

Open AccessReview

MicroRNA166: Old Players and New Insights into Crop Agronomic Traits Improvement

by Zhanhui Zhang, Tianxiao Yang, Na Li, Guiliang Tang and Jihua Tang

Genes 2024, 15(7), 944; https://doi.org/10.3390/genes15070944 - 18 Jul 2024

Viewed by 431

Abstract

MicroRNA (miRNA), a type of non-coding RNA, is crucial for controlling gene expression. Among the various miRNA families, miR166 stands out as a highly conserved group found in both model and crop plants. It plays a key role in regulating a wide range [...] Read more.

MicroRNA (miRNA), a type of non-coding RNA, is crucial for controlling gene expression. Among the various miRNA families, miR166 stands out as a highly conserved group found in both model and crop plants. It plays a key role in regulating a wide range of developmental and environmental responses. In this review, we explore the diverse sequences of MIR166s in major crops and discuss the important regulatory functions of miR166 in plant growth and stress responses. Additionally, we summarize how miR166 interacts with other miRNAs and highlight the potential for enhancing agronomic traits by manipulating the expression of miR166 and its targeted HD-ZIP III genes. Full article

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

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17 pages, 2221 KiB

Open AccessFeature PaperArticle

In Silico Prediction of BRCA1 and BRCA2 Variants with Conflicting Clinical Interpretation in a Cohort of Breast Cancer Patients

by Stefania Stella, Silvia Rita Vitale, Michele Massimino, Federica Martorana, Irene Tornabene, Cristina Tomarchio, Melissa Drago, Giuliana Pavone, Cristina Gorgone, Chiara Barone, Sebastiano Bianca and Livia Manzella

Genes 2024, 15(7), 943; https://doi.org/10.3390/genes15070943 - 18 Jul 2024

Viewed by 487

Abstract

Germline BRCA1/2 alteration has been linked to an increased risk of hereditary breast and ovarian cancer syndromes. As a result, genetic testing, based on NGS, allows us to identify a high number of variants of uncertain significance (VUS) or conflicting interpretation of pathogenicity [...] Read more.

Germline BRCA1/2 alteration has been linked to an increased risk of hereditary breast and ovarian cancer syndromes. As a result, genetic testing, based on NGS, allows us to identify a high number of variants of uncertain significance (VUS) or conflicting interpretation of pathogenicity (CIP) variants. The identification of CIP/VUS is often considered inconclusive and clinically not actionable for the patients’ and unaffected carriers’ management. In this context, their assessment and classification remain a significant challenge. The aim of the study was to investigate whether the in silico prediction tools (PolyPhen-2, SIFT, Mutation Taster and PROVEAN) could predict the potential clinical impact and significance of BRCA1/2 CIP/VUS alterations, eventually impacting the clinical management of Breast Cancer subjects. In a cohort of 860 BC patients, 10.6% harbored BRCA1 or BRCA2 CIP/VUS alterations, mostly observed in BRCA2 sequences (85%). Among them, forty-two out of fifty-five alterations were predicted as damaging, with at least one in silico that used tools. Prediction agreement of the four tools was achieved in 45.5% of patients. Moreover, the highest consensus was obtained in twelve out of forty-two (28.6%) mutations by considering three out of four in silico algorithms. The use of prediction tools may help to identify variants with a potentially damaging effect. The lack of substantial agreement between the different algorithms suggests that the bioinformatic approaches should be combined with the personal and family history of the cancer patients. Full article

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

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21 pages, 595 KiB

Open AccessReview

A Review of Experimental Studies on Natural Chalcone-Based Therapeutic Targeting of Genes and Signaling Pathways in Type 2 Diabetes Complications

by Naser A. Alsharairi

Genes 2024, 15(7), 942; https://doi.org/10.3390/genes15070942 - 18 Jul 2024

Viewed by 594

Abstract

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and β-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the [...] Read more.

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and β-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the cause of increasing mortality. Diabetic nephropathy (DNE), neuropathy (DNU), and retinopathy (DR) are the most common complications of diabetic microangiopathy, while diabetic cardiomyopathy (DCM) and peripheral vascular diseases are the major diabetic macroangiopathy complications. Chalcones (CHs) are in the flavonoid family and are commonly found in certain plant species as intermediate metabolites in the biosynthesis of flavonoids and their derivatives. Natural CHs with different substituents exert diverse therapeutic activities, including antidiabetic ones. However, the therapeutic mechanisms of natural CHs through influencing genes and/or signaling pathways in T2DM complications remain unknown. Therefore, this review summarizes the existing results from experimental models which highlight the mechanisms of natural CHs as therapeutic agents for T2DM complications. Full article

(This article belongs to the Special Issue Omics Studies of Type 2 Diabetes and Diabetes-Related Complications)

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15 pages, 29526 KiB

Open AccessArticle

Genome-Wide Identification and Characterization of CCT Gene Family from Microalgae to Legumes

by Yi Xu, Huiying Yao, Yanhong Lan, Yu Cao, Qingrui Xu, Hui Xu, Dairong Qiao and Yi Cao

Genes 2024, 15(7), 941; https://doi.org/10.3390/genes15070941 - 18 Jul 2024

Viewed by 362

Abstract

The CCT (CO, COL and TOC1) gene family has been elucidated to be involved in the functional differentiation of the products in various plant species, but their specific mechanisms are poorly understood. In the present investigation, we conducted a genome-wide identification and phylogenetic [...] Read more.

The CCT (CO, COL and TOC1) gene family has been elucidated to be involved in the functional differentiation of the products in various plant species, but their specific mechanisms are poorly understood. In the present investigation, we conducted a genome-wide identification and phylogenetic analysis of CCT genes from microalgae to legumes. A total of 700 non-redundant members of the CCT gene family from 30 species were identified through a homology search. Phylogenetic clustering with Arabidopsis and domain conservation analysis categorized the CCT genes into three families. Multiple sequence alignment showed that the CCT domain contains important amino acid residues, and each CCT protein contains 24 conserved motifs, as demonstrated by the motif analysis. Whole-genome/segment duplication, as well as tandem duplication, are considered to be the driving forces in the evolutionary trajectory of plant species. This comprehensive investigation into the proliferation of the CCT gene family unveils the evolutionary dynamics whereby WGD/segment duplication is the predominant mechanism contributing to the expansion of the CCT genes. Meanwhile, the examination of the gene expression patterns revealed that the expression patterns of CCT genes vary in different tissues and at different developmental stages of plants, with high expression in leaves, which is consistent with the molecular regulation of flowering in photosynthesis by CCT. Based on the protein–protein interaction analysis of CCT genes in model plants, we propose that the CCT gene family synergistically regulates plant development and flowering with light-signaling factors (PHYs and PIFs) and MYB family transcription factors. Understanding the CCT gene family’s molecular evolution enables targeted gene manipulation for enhanced plant traits, including optimized flowering and stress resistance. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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19 pages, 8420 KiB

Open AccessArticle

Intraspecific Differentiation of Styrax japonicus (Styracaceae) as Revealed by Comparative Chloroplast and Evolutionary Analyses

by Hao-Zhi Zheng, Wei Dai, Meng-Han Xu, Yu-Ye Lin, Xing-Li Zhu, Hui Long, Li-Li Tong and Xiao-Gang Xu

Genes 2024, 15(7), 940; https://doi.org/10.3390/genes15070940 - 18 Jul 2024

Viewed by 371

Abstract

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. [...] Read more.

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. The results demonstrated that the four chloroplast genomes (157,914–157,962 bp) exhibited a typical quadripartite structure consisting of a large single copy (LSC) region, a small single copy (SSC) region, and a pair of reverse repeats (IRa and IRb), and the structure was highly conserved. DNA polymorphism analysis revealed that three coding genes (infA, psbK, and rpl33) and five intergene regions (petA-psbJ, trnC-petN, trnD-trnY, trnE-trnT, and trnY-trnE) were identified as mutation hotspots. These genetic fragments have the potential to be utilized as DNA barcodes for future identification purposes. When comparing the boundary genes, a small contraction was observed in the IR region of four S. japonicus. Selection pressure analysis indicated positive selection for ycf1 and ndhD. These findings collectively suggest the adaptive evolution of S. japonicus. The phylogenetic structure revealed conflicting relationships among several S. japonicus, indicating divergent evolutionary paths within this species. Our study concludes by uncovering the genetic traits of the chloroplast genome in the differentiation of S. japonicus variety, offering fresh perspectives on the evolutionary lineage of this species. Full article

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

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18 pages, 644 KiB

Open AccessReview

Using Genetics to Investigate Relationships between Phenotypes: Application to Endometrial Cancer

by Kelsie Bouttle, Nathan Ingold and Tracy A. O’Mara

Genes 2024, 15(7), 939; https://doi.org/10.3390/genes15070939 - 18 Jul 2024

Viewed by 597

Abstract

Genome-wide association studies (GWAS) have accelerated the exploration of genotype–phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various phenotypes, focusing [...] Read more.

Genome-wide association studies (GWAS) have accelerated the exploration of genotype–phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various phenotypes, focusing on endometrial cancer, the most prevalent gynecological malignancy in developed nations. Advancements in analytical techniques such as genetic correlation, colocalization, cross-trait locus identification, and causal inference analyses have enabled deeper exploration of associations between different phenotypes, enhancing statistical power to uncover novel genetic risk regions. These analyses have unveiled shared genetic associations between endometrial cancer and many phenotypes, enabling identification of novel endometrial cancer risk loci and furthering our understanding of risk factors and biological processes underlying this disease. The current status of research in endometrial cancer is robust; however, this review demonstrates that further opportunities exist in statistical genetics that hold promise for advancing the understanding of endometrial cancer and other complex diseases. Full article

(This article belongs to the Special Issue Statistical Methods for Genetic Epidemiology)

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12 pages, 3540 KiB

Open AccessArticle

GENet: A Graph-Based Model Leveraging Histone Marks and Transcription Factors for Enhanced Gene Expression Prediction

by Mahdieh Labani, Amin Beheshti and Tracey A. O’Brien

Genes 2024, 15(7), 938; https://doi.org/10.3390/genes15070938 - 18 Jul 2024

Viewed by 436

Abstract

Understanding the regulatory mechanisms of gene expression is a crucial objective in genomics. Although the DNA sequence near the transcription start site (TSS) offers valuable insights, recent methods suggest that analyzing only the surrounding DNA may not suffice to accurately predict gene expression [...] Read more.

Understanding the regulatory mechanisms of gene expression is a crucial objective in genomics. Although the DNA sequence near the transcription start site (TSS) offers valuable insights, recent methods suggest that analyzing only the surrounding DNA may not suffice to accurately predict gene expression levels. We developed GENet (Gene Expression Network from Histone and Transcription Factor Integration), a novel approach that integrates essential regulatory signals from transcription factors and histone modifications into a graph-based model. GENet extends beyond simple DNA sequence analysis by incorporating additional layers of genetic control, which are vital for determining gene expression. Our method markedly enhances the prediction of mRNA levels compared to previous models that depend solely on DNA sequence data. The results underscore the significance of including comprehensive regulatory information in gene expression studies. GENet emerges as a promising tool for researchers, with potential applications extending from fundamental biological research to the development of medical therapies. Full article

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

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15 pages, 721 KiB

Open AccessArticle

Challenges of Preimplantation Genetic Counselling in the Context of Cystic Fibrosis and Other CFTR-Related Disorders: A Monocentric Experience in a Cohort of 92 Couples

by Ugo Sorrentino, Massimo Menegazzo, Ilaria Gabbiato, Davide Calosci, Carlo Federico Zambon and Daniela Zuccarello

Genes 2024, 15(7), 937; https://doi.org/10.3390/genes15070937 - 18 Jul 2024

Viewed by 579

Abstract

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced [...] Read more.

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders. Full article

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

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12 pages, 855 KiB

Open AccessArticle

Validation of Gene Expression Patterns for Oral Feeding Readiness: Transcriptional Analysis of Set of Genes in Neonatal Salivary Samples

by Leonardo Henrique Ferreira Gomes, Andressa Brito Marques, Isabel Cristina de Meireles Dias, Sanny Cerqueira de O. Gabeira, Tamara Rosa Barcelos, Mariana de Oliveira Guimarães, Igor Ribeiro Ferreira, Letícia Cunha Guida, Sabrina Lopes Lucena and Adriana Duarte Rocha

Genes 2024, 15(7), 936; https://doi.org/10.3390/genes15070936 - 18 Jul 2024

Viewed by 451

Abstract

Background: Neonatal health assessment is crucial for detecting and intervening in various disorders. Traditional gene expression analysis methods often require invasive procedures during sample collection, which may not be feasible or ideal for preterm infants. In recent years, saliva has emerged as a [...] Read more.

Background: Neonatal health assessment is crucial for detecting and intervening in various disorders. Traditional gene expression analysis methods often require invasive procedures during sample collection, which may not be feasible or ideal for preterm infants. In recent years, saliva has emerged as a promising noninvasive biofluid for assessing gene expression. Another trend that has been growing is the use of “omics” technologies such as transcriptomics in the analysis of gene expression. The costs for carrying out these analyses and the difficulty of analysis make the detection of candidate genes necessary. These genes act as biomarkers for the maturation stages of the oral feeding issue. Methodology: Salivary samples (n = 225) were prospectively collected from 45 preterm (<34 gestational age) infants from five predefined feeding stages and submitted to RT-qPCR. A better description of the targeted genes and results from RT-qPCR analyses were included. The six genes previously identified as predictive of feeding success were tested. The genes are AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1, along with two reference genes: GAPDH and 18S. RT-qPCR amplification enabled the analysis of the gene expression of AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 in neonatal saliva. Expression results were correlated with the feeding status during sample collection. Conclusions: In summary, the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding and the development of premature infants. Understanding the influence of these genes can provide valuable insights for improving nutritional care and support the development of these vulnerable babies. Evidence suggests that saliva-based gene expression analysis in newborns holds great promise for early detection and monitoring of disease and understanding developmental processes. More research and standardization of protocols are needed to fully explore the potential of saliva as a noninvasive biomarker in neonatal care. Full article

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

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