Genes

13 pages, 1377 KiB

Open AccessEditor’s ChoiceArticle

In Silico CRISPR-Cas-Mediated Base Editing Strategies for Early-Onset, Severe Cone–Rod Retinal Degeneration in Three Crumbs homolog 1 Patients, including the Novel Variant c.2833G>A

by Hoda Shamsnajafabadi, Maria Kaukonen, Julia-Sophia Bellingrath, Robert E. MacLaren and Jasmina Cehajic-Kapetanovic

Genes 2024, 15(5), 625; https://doi.org/10.3390/genes15050625 - 15 May 2024

Cited by 4 | Viewed by 2191

Abstract

Pathogenic variants in the Crumbs homolog 1 (CRB1) gene lead to severe, childhood-onset retinal degeneration leading to blindness in early adulthood. There are no approved therapies, and traditional adeno-associated viral vector-based gene therapy approaches are challenged by the existence of multiple CRB1 isoforms. [...] Read more.

Pathogenic variants in the Crumbs homolog 1 (CRB1) gene lead to severe, childhood-onset retinal degeneration leading to blindness in early adulthood. There are no approved therapies, and traditional adeno-associated viral vector-based gene therapy approaches are challenged by the existence of multiple CRB1 isoforms. Here, we describe three CRB1 variants, including a novel, previously unreported variant that led to retinal degeneration. We offer a CRISPR-Cas-mediated DNA base editing strategy as a potential future therapeutic approach. This study is a retrospective case series. Clinical and genetic assessments were performed, including deep phenotyping by retinal imaging. In silico analyses were used to predict the pathogenicity of the novel variant and to determine whether the variants are amenable to DNA base editing strategies. Case 1 was a 24-year-old male with cone–rod dystrophy and retinal thickening typical of CRB1 retinopathy. He had a relatively preserved central outer retinal structure and a best corrected visual acuity (BCVA) of 60 ETDRS letters in both eyes. Genetic testing revealed compound heterozygous variants in exon 9: c.2843G>A, p.(Cys948Tyr) and a novel variant, c.2833G>A, p.(Gly945Arg), which was predicted to likely be pathogenic by an in silico analysis. Cases 2 and 3 were two brothers, aged 20 and 24, who presented with severe cone–rod dystrophy and a significant disruption of the outer nuclear layers. The BCVA was reduced to hand movements in both eyes in Case 2 and to 42 ETDRS letters in both eyes in Case 3. Case 2 was also affected with marked cystoid macular lesions, which are common in CRB1 retinopathy, but responded well to treatment with oral acetazolamide. Genetic testing revealed two c.2234C>T, p.(Thr745Met) variants in both brothers. As G-to-A and C-to-T variants, all three variants are amenable to adenine base editors (ABEs) targeting the forward strand in the Case 1 variants and the reverse strand in Cases 2 and 3. Available PAM sites were detected for KKH-nSaCas9-ABE8e for the c.2843G>A variant, nSaCas9-ABE8e and KKH-nSaCas9-ABE8e for the c.2833G>A variant, and nSpCas9-ABE8e for the c.2234C>T variant. In this case series, we report three pathogenic CRB1 variants, including a novel c.2833G>A variant associated with early-onset cone–rod dystrophy. We highlight the severity and rapid progression of the disease and offer ABEs as a potential future therapeutic approach for this devastating blinding condition. Full article

(This article belongs to the Special Issue Study of Inherited Retinal Diseases—Volume II)

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10 pages, 1347 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Profiling of Peripheral B Cells in Antibody Positive Sjogren’s Patients Reveals Interferon Signature

by Mehrnaz Maleki-Fischbach, Kelsey Anderson and Evans R. Fernández Pérez

Genes 2024, 15(5), 628; https://doi.org/10.3390/genes15050628 - 15 May 2024

Cited by 3 | Viewed by 1808

Abstract

Background: Sjögren’s disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of [...] Read more.

Background: Sjögren’s disease (SjD) is a common systemic autoimmune disease that affects mainly women. Key pathologic features include the infiltration of exocrine glands by lymphocytes and the activation of B lymphocytes with the production of autoantibodies. We aimed to analyze the transcriptome of circulating B cells from patients with SJD and healthy controls to decipher the B-cell-specific contribution to SJD. Methods: RNA from peripheral blood B cells of five untreated female patients with SjD and positive ANA, positive anti-SSA (both Ro-52 and Ro-60), positive anti-SSB and positive rheumatoid-factor, and five healthy controls was subjected to whole-transcriptome sequencing. A false discovery rate of < 0.1 was applied to define differentially expressed genes (DEG). Results: RNA-sequencing identified 56 up and 23 down DEG. Hierarchal clustering showed a clear separation between the two groups. Ingenuity pathway analysis revealed that these genes may play a role in interferon signaling, chronic mycobacterial infection, and transformation to myeloproliferative disorders. Conclusions: We found upregulated expression of type-I and type-II interferon (IFN)-induced genes, as well as genes that may contribute to other concomitant conditions, including infections and a higher risk of myeloproliferative disorders. This adds insight into the autoimmune process and suggests potential targets for future functional and prognostic studies. Full article

(This article belongs to the Special Issue Autoimmune Disease Genetics Volume II)

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14 pages, 7189 KiB

Open AccessEditor’s ChoiceArticle

DNA Microarray and Bioinformatic Analysis Reveals the Potential of Whale Oil in Enhancing Hair Growth in a C57BL/6 Mice Dorsal Skin Model

by Junko Shibato, Fumiko Takenoya, Ai Kimura, Michio Yamashita, Satoshi Hirako, Randeep Rakwal and Seiji Shioda

Genes 2024, 15(5), 627; https://doi.org/10.3390/genes15050627 - 15 May 2024

Viewed by 2108

Abstract

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde’s [...] Read more.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde’s whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent. Full article

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

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16 pages, 475 KiB

Open AccessEditor’s ChoicePerspective

Deep Learning for Elucidating Modifications to RNA—Status and Challenges Ahead

by Sarah Rennie

Genes 2024, 15(5), 629; https://doi.org/10.3390/genes15050629 - 15 May 2024

Viewed by 2067

Abstract

RNA-binding proteins and chemical modifications to RNA play vital roles in the co- and post-transcriptional regulation of genes. In order to fully decipher their biological roles, it is an essential task to catalogue their precise target locations along with their preferred contexts and [...] Read more.

RNA-binding proteins and chemical modifications to RNA play vital roles in the co- and post-transcriptional regulation of genes. In order to fully decipher their biological roles, it is an essential task to catalogue their precise target locations along with their preferred contexts and sequence-based determinants. Recently, deep learning approaches have significantly advanced in this field. These methods can predict the presence or absence of modification at specific genomic regions based on diverse features, particularly sequence and secondary structure, allowing us to decipher the highly non-linear sequence patterns and structures that underlie site preferences. This article provides an overview of how deep learning is being applied to this area, with a particular focus on the problem of mRNA-RBP binding, while also considering other types of chemical modification to RNA. It discusses how different types of model can handle sequence-based and/or secondary-structure-based inputs, the process of model training, including choice of negative regions and separating sets for testing and training, and offers recommendations for developing biologically relevant models. Finally, it highlights four key areas that are crucial for advancing the field. Full article

(This article belongs to the Special Issue Bioinformatics of RNA Modifications and Epitranscriptome)

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12 pages, 2135 KiB

Open AccessEditor’s ChoiceArticle

Transposable Element Expression Profiles in Premalignant Pigment Cell Lesions and Melanoma of Xiphophorus

by Luca Münch, Frederik Helmprobst, Jean-Nicolas Volff, Domitille Chalopin, Manfred Schartl and Susanne Kneitz

Genes 2024, 15(5), 620; https://doi.org/10.3390/genes15050620 - 14 May 2024

Viewed by 1584

Abstract

Transposable elements (TEs) are characterized by their ability to change their genomic position. Through insertion or recombination leading to deletions and other chromosomal aberrations, they can cause genetic instability. The extent to which they thereby exert regulatory influence on cellular functions is unclear. [...] Read more.

Transposable elements (TEs) are characterized by their ability to change their genomic position. Through insertion or recombination leading to deletions and other chromosomal aberrations, they can cause genetic instability. The extent to which they thereby exert regulatory influence on cellular functions is unclear. To better characterize TEs in processes such as carcinogenesis, we used the well-established Xiphophorus melanoma model. By transcriptome sequencing, we show that an increasing total number in transposons correlates with progression of malignancy in melanoma samples from Xiphophorus interspecific hybrids. Further, by comparing the presence of TEs in the parental genomes of Xiphophorus maculatus and Xiphophorus hellerii, we could show that even in closely related species, genomic location and spectrum of TEs are considerably different. Full article

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

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14 pages, 2200 KiB

Open AccessEditor’s ChoiceArticle

Assessing DNA Degradation through Differential Amplification Efficiency of Total Human and Human Male DNA in a Forensic qPCR Assay

by Elena Chierto, Serena Aneli, Nicola Nocco, Alessia Riem, Martina Onofri, Eugenia Carnevali and Carlo Robino

Genes 2024, 15(5), 622; https://doi.org/10.3390/genes15050622 - 14 May 2024

Cited by 4 | Viewed by 2114

Abstract

The assessment of degradation is crucial for the analysis of human DNA samples isolated from forensic specimens. Forensic quantitative PCR (qPCR) assays can include multiple targets of varying amplicon size that display differential amplification efficiency, and thus different concentrations, in the presence of [...] Read more.

The assessment of degradation is crucial for the analysis of human DNA samples isolated from forensic specimens. Forensic quantitative PCR (qPCR) assays can include multiple targets of varying amplicon size that display differential amplification efficiency, and thus different concentrations, in the presence of degradation. The possibility of deriving information on DNA degradation was evaluated in a forensic qPCR assay not specifically designed to detect DNA fragmentation, the Plexor HY (Promega), by calculating the ratio between the estimated concentrations of autosomal (99 bp) and Y-chromosomal (133 bp) targets (“[Auto]/[Y]”). The [Auto]/[Y] ratio measured in 57 formalin-fixed, paraffin-embedded samples was compared to a quality score (QS) calculated for corresponding STR profiles using quantitative data (allele peak height). A statistically significant inverse correlation was observed between [Auto]/[Y] and QS (R = −0.65, p < 0.001). The [Auto]/[Y] values were highly correlated (R = 0.75, p < 0.001) with the “[Auto]/[D]” values obtained using the PowerQuant (Promega) assay, expressly designed to detect DNA degradation through simultaneous quantification of a short (Auto) and a long (D) autosomal target. These results indicate that it is possible to estimate DNA degradation in male samples through Plexor HY data and suggest an alternative strategy for laboratories lacking the equipment required for the assessment of DNA integrity through dedicated qPCR assays. Full article

(This article belongs to the Special Issue Genetic Tools and Techniques in Forensic Science—an In-Depth Look at the Process of Quantification of Forensic Samples)

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7 pages, 1848 KiB

Open AccessEditor’s ChoiceBrief Report

Identification of Breed-Specific SNPs of Danish Large White Pig in Comparison with Four Chinese Local Pig Breed Genomes

by Xudong Wu, Decai Xiang, Wei Zhang, Yu Ma, Guiying Zhao and Zongjun Yin

Genes 2024, 15(5), 623; https://doi.org/10.3390/genes15050623 - 14 May 2024

Cited by 2 | Viewed by 1477

Abstract

Genetic variation facilitates the evolution, environmental adaptability, and biodiversity of organisms. Danish Large White (LW) pigs have more desirable phenotypes compared with local Chinese pigs, which have difficulty adapting to the modern swine industry. However, the genome-wide mutational differences between these pig breeds [...] Read more.

Genetic variation facilitates the evolution, environmental adaptability, and biodiversity of organisms. Danish Large White (LW) pigs have more desirable phenotypes compared with local Chinese pigs, which have difficulty adapting to the modern swine industry. However, the genome-wide mutational differences between these pig breeds are yet to be evaluated. Therefore, this study aimed to evaluate genomic variation and identify breed-specific SNPs in Danish LW pigs. Here, 43 LW, 15 Diqing Tibetan (DQZ), and 15 Diannan small-ear (DN) pigs whose genomes were re-sequenced with 5× depth were selected. This was followed by a conjoined analysis of our previous resequencing data of 24 Anqing six-end white (AQ) and six Asian wild (SS) pigs. In total, 39,158,378 SNPs and 13,143,989 insertion–deletions were obtained in all breeds. The variation number of LW pigs was the lowest, with 287,194 breed-specific and 1289 non-synonymous SNPs compared with Chinese breeds. Functional analysis of the breed-specific non-synonymous SNPs indicated that these mutations were mainly associated with the reproductive performance, feed intake, and feed conversion ratio of LW pigs. These findings provide a theoretical basis for genetic improvements in the Chinese swine industry. Full article

(This article belongs to the Special Issue Breeding and Genetics of Pig)

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24 pages, 3946 KiB

Open AccessEditor’s ChoiceArticle

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways

by Dumitru Andrei Iacobas and Sanda Iacobas

Genes 2024, 15(5), 621; https://doi.org/10.3390/genes15050621 - 14 May 2024

Viewed by 2197

Abstract

The genetic causes of the differentiated, highly treatable, and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully understood. The mostly accepted PTC etiology blames the altered sequence or/and expression level of certain biomarker genes. However, tumor heterogeneity and the patient’s unique [...] Read more.

The genetic causes of the differentiated, highly treatable, and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully understood. The mostly accepted PTC etiology blames the altered sequence or/and expression level of certain biomarker genes. However, tumor heterogeneity and the patient’s unique set of favoring factors question the fit-for-all gene biomarkers. Publicly accessible gene expression profiles of the cancer nodule and the surrounding normal tissue from a surgically removed PTC tumor were re-analyzed to determine the cancer-induced alterations of the genomic fabrics responsible for major functional pathways. Tumor data were compared with those of standard papillary and anaplastic thyroid cancer cell lines. We found that PTC regulated numerous genes associated with DNA replication, repair, and transcription. Results further indicated that changes of the gene networking in functional pathways and the homeostatic control of transcript abundances also had major contributions to the PTC phenotype occurrence. The purpose to proliferate and invade the entire gland may explain the substantial transcriptomic differences we detected between the cells of the cancer nodule and those spread in homo-cellular cultures (where they need only to survive). In conclusion, the PTC etiology should include the complex molecular mechanisms involved in the remodeling of the genetic information processing pathways. Full article

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

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13 pages, 3567 KiB

Open AccessEditor’s ChoiceArticle

The Effect of Short- and Long-Term Cryopreservation on Chicken Primordial Germ Cells

by Mariam Ibrahim, Ewa Grochowska, Bence Lázár, Eszter Várkonyi, Marek Bednarczyk and Katarzyna Stadnicka

Genes 2024, 15(5), 624; https://doi.org/10.3390/genes15050624 - 14 May 2024

Cited by 6 | Viewed by 1780

Abstract

Primordial germ cells (PGCs) are the precursors of functional gametes and the only cell type capable of transmitting genetic and epigenetic information from generation to generation. These cells offer valuable starting material for cell-based genetic engineering and genetic preservation, as well as epigenetic [...] Read more.

Primordial germ cells (PGCs) are the precursors of functional gametes and the only cell type capable of transmitting genetic and epigenetic information from generation to generation. These cells offer valuable starting material for cell-based genetic engineering and genetic preservation, as well as epigenetic studies. While chicken PGCs have demonstrated resilience in maintaining their germness characteristics during both culturing and cryopreservation, their handling remains a complex challenge requiring further refinement. Herein, the study aimed to compare the effects of different conditions (freezing-thawing and in vitro cultivation) on the expression of PGC-specific marker genes. Embryonic blood containing circulating PGCs was isolated from purebred Green-legged Partridgelike chicken embryos at 14–16 Hamburger–Hamilton (HH) embryonic development stage. The blood was pooled separately for males and females following sex determination. The conditions applied to the blood containing PGCs were as follows: (1) fresh isolation; (2) cryopreservation for a short term (2 days); and (3) in vitro culture (3 months) with long-term cryopreservation of purified PGCs (~2 years). To characterize PGCs, RNA isolation was carried out, followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of specific germ cell markers (SSEA1, CVH, and DAZL), as well as pluripotency markers (OCT4 and NANOG). The investigated genes exhibited consistent expression among PGCs maintained under diverse conditions, with no discernible differences observed between males and females. Notably, the analyzed markers demonstrated higher expression levels in PGCs when subjected to freezing than in their freshly isolated counterparts. Full article

(This article belongs to the Special Issue Poultry Breeding: Genetics and Genomics)

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12 pages, 7308 KiB

Open AccessEditor’s ChoiceArticle

Normal Ovarian Function in Subfertile Mouse with Amhr2-Cre-Driven Ablation of Insr and Igf1r

by Jenna C. Douglas, Nikola Sekulovski, Madison R. Arreola, Yeongseok Oh, Kanako Hayashi and James A. MacLean II

Genes 2024, 15(5), 616; https://doi.org/10.3390/genes15050616 - 12 May 2024

Cited by 2 | Viewed by 1862

Abstract

Insulin receptor signaling promotes cell differentiation, proliferation, and growth which are essential for oocyte maturation, embryo implantation, endometrial decidualization, and placentation. The dysregulation of insulin signaling in women with metabolic syndromes including diabetes exhibits poor pregnancy outcomes that are poorly understood. We utilized [...] Read more.

Insulin receptor signaling promotes cell differentiation, proliferation, and growth which are essential for oocyte maturation, embryo implantation, endometrial decidualization, and placentation. The dysregulation of insulin signaling in women with metabolic syndromes including diabetes exhibits poor pregnancy outcomes that are poorly understood. We utilized the Cre/LoxP system to target the tissue-specific conditional ablation of insulin receptor (Insr) and insulin-like growth factor-1 receptor (Igf1r) using an anti-Mullerian hormone receptor 2 (Amhr2) Cre-driver which is active in ovarian granulosa and uterine stromal cells. Our long-term goal is to examine insulin-dependent molecular mechanisms that underlie diabetic pregnancy complications, and our conditional knockout models allow for such investigation without confounding effects of ligand identity, source and cross-reactivity, or global metabolic status within dams. Puberty occurred with normal timing in all conditional knockout models. Estrous cycles progressed normally in Insr^d/d females but were briefly stalled in diestrus in Igf1r^d/d and double receptor (DKO) mice. The expression of vital ovulatory genes (Lhcgr, Pgr, Ptgs2) was not significantly different in 12 h post-hCG superovulated ovaries in knockout mice. Antral follicles exhibited an elevated apoptosis of granulosa cells in Igf1r^d/d and DKO mice. However, the distribution of ovarian follicle subtypes and subsequent ovulations was normal in all insulin receptor mutants compared to littermate controls. While ovulation was normal, all knockout lines were subfertile suggesting that the loss of insulin receptor signaling in the uterine stroma elicits implantation and decidualization defects responsible for subfertility in Amhr2-Cre-derived insulin receptor mutants. Full article

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

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27 pages, 2477 KiB

Open AccessEditor’s ChoiceReview

Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses

by Tomas Ferreira and Santiago Rodriguez

Genes 2024, 15(5), 617; https://doi.org/10.3390/genes15050617 - 12 May 2024

Cited by 12 | Viewed by 7773

Abstract

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a [...] Read more.

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA’s high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease. Full article

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

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17 pages, 4282 KiB

Open AccessEditor’s ChoiceArticle

Soil Microbial Community Characteristics and Their Effect on Tea Quality under Different Fertilization Treatments in Two Tea Plantations

by Yu Lei, Ding Ding, Jihua Duan, Yi Luo, Feiyi Huang, Yankai Kang, Yingyu Chen and Saijun Li

Genes 2024, 15(5), 610; https://doi.org/10.3390/genes15050610 - 11 May 2024

Cited by 4 | Viewed by 2276

Abstract

Fertilization is an essential aspect of tea plantation management that supports a sustainable tea production and drastically influences soil microbial communities. However, few research studies have focused on the differences of microbial communities and the variation in tea quality in response to different [...] Read more.

Fertilization is an essential aspect of tea plantation management that supports a sustainable tea production and drastically influences soil microbial communities. However, few research studies have focused on the differences of microbial communities and the variation in tea quality in response to different fertilization treatments. In this work, the soil fertility, tea quality, and soil microbial communities were investigated in two domestic tea plantations following the application of chemical and organic fertilizers. We determined the content of mineral elements in the soil, including nitrogen, phosphorus, and potassium, and found that the supplementation of chemical fertilizer directly increased the content of mineral elements. However, the application of organic fertilizer significantly improved the accumulation of tea polyphenols and reduced the content of caffeine. Furthermore, amplicon sequencing results showed that the different ways of applying fertilizer have limited effect on the alpha diversity of the microbial community in the soil while the beta diversity was remarkably influenced. This work also suggests that the bacterial community structure and abundance were also relatively constant while the fungal community structure and abundance were dramatically influenced; for example, Chaetomiaceae at the family level, Hypocreaceae at the order level, Trichoderma at the genus level, and Fusarium oxysporum at the species level were predominantly enriched in the tea plantation applying organic fertilizer. Moreover, the bacterial and fungal biomarkers were also analyzed and it was found that Proteobacteria and Gammaproteobacteria (bacteria) and Tremellomycetes (fungi) were potentially characterized as biomarkers in the plantation under organic fertilization. These results provide a valuable basis for the application of organic fertilizer to improve the soil of tea plantations in the future. Full article

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

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13 pages, 2625 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Hormone Response Analysis of the COBL Gene Family in Barley

by Panrong Ren, Liang Ma, Wei Bao and Jie Wang

Genes 2024, 15(5), 612; https://doi.org/10.3390/genes15050612 - 11 May 2024

Cited by 1 | Viewed by 1577

Abstract

Barley (Hordeum vulgare L.), a diverse cereal crop, exhibits remarkable versatility in its applications, ranging from food and fodder to industrial uses. The content of cellulose in barley is significantly influenced by the COBRA genes, which encode the plant glycosylphosphatidylinositol (GPI)-anchored protein [...] Read more.

Barley (Hordeum vulgare L.), a diverse cereal crop, exhibits remarkable versatility in its applications, ranging from food and fodder to industrial uses. The content of cellulose in barley is significantly influenced by the COBRA genes, which encode the plant glycosylphosphatidylinositol (GPI)-anchored protein (GAP) that plays a pivotal role in the deposition of cellulose within the cell wall. The COBL (COBRA-Like) gene family has been discovered across numerous species, yet the specific members of this family in barley remain undetermined. In this study, we discovered 13 COBL genes within the barley genome using bioinformatics methods, subcellular localization, and protein structure analysis, finding that most of the barley COBL proteins have a signal peptide structure and are localized on the plasma membrane. Simultaneously, we constructed a phylogenetic tree and undertook a comprehensive analysis of the evolutionary relationships. Other characteristics of HvCOBL family members, including intraspecific collinearity, gene structure, conserved motifs, and cis-acting elements, were thoroughly characterized in detail. The assessment of HvCOBL gene expression in barley under various hormone treatments was conducted through qRT-PCR analysis, revealing jasmonic acid (JA) as the predominant hormonal regulator of HvCOBL gene expression. In summary, this study comprehensively identified and analyzed the barley COBL gene family, aiming to provide basic information for exploring the members of the HvCOBL gene family and to propose directions for further research. Full article

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

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20 pages, 7784 KiB

Open AccessEditor’s ChoiceArticle

Cloning and Function Analysis of the CsTAU1 in Response to Salt–Alkali Stress

by Fan Zhang, Dandan Li, Rina Sa, Ling Wang and Yunyan Sheng

Genes 2024, 15(5), 613; https://doi.org/10.3390/genes15050613 - 11 May 2024

Cited by 1 | Viewed by 1182

Abstract

To investigate the role of candidate genes for salt–alkali tolerance in cucumber (Cucumis sativus L.), this study screened CsTAU1 in the glutathione pathway from previous transcriptome data for cloning and functional analysis. Clone cucumber CsTAU1 contains one 675 bp open reading frame, [...] Read more.

To investigate the role of candidate genes for salt–alkali tolerance in cucumber (Cucumis sativus L.), this study screened CsTAU1 in the glutathione pathway from previous transcriptome data for cloning and functional analysis. Clone cucumber CsTAU1 contains one 675 bp open reading frame, containing one GST-N-Tau domain and one GST-C-Tau domain, and is expressed in cytoplasm. After successfully constructing overexpression vectors of CsTAU1 (+) and CsTAU1 (−), they were transferred into cucumber varieties ‘D1909’ (high salt alkali resistance) and ‘D1604’ (low salt alkali resistance) for salt–alkali resistance identification. It was found that under salt–alkali stress, CsTAU1 (+)-overexpressing plants showed strong resistance to salt–alkali stress, while CsTAU1 (−)-overexpressing plants showed the opposite situation. qRT-PCR analysis was performed on other glutathione pathway-related genes in CsTAU1-overexpressing plants. The expression patterns of LOC101219529 and LOC105434443 were the same as CsTAU1, and the introduction of CsTAU1 (+) increased the chlorophyll, α-Naphthylamine oxidation, glutathione S-transferase (GST), and catalase (CAT) content of cucumber. The research results provide a theoretical basis for cultivating salt–alkali-tolerant cucumber varieties. Full article

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

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14 pages, 991 KiB

Open AccessEditor’s ChoiceArticle

Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer’s Disease

by Iyappan Ramalakshmi Oviya, Divya Sankar, Sharanya Manoharan, Archana Prabahar and Kalpana Raja

Genes 2024, 15(5), 614; https://doi.org/10.3390/genes15050614 - 11 May 2024

Cited by 1 | Viewed by 1820

Abstract

Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains [...] Read more.

Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases—dementia, type 2 diabetes, hypertension, Parkinson’s disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes—PSEN1, PSEN2, MAPT, APP, APOE, NOTCH, and HFE—for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene–drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases. Full article

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

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17 pages, 2213 KiB

Open AccessEditor’s ChoiceArticle

Genetic Variants Underlying Plasticity in Natural Populations of Spadefoot Toads: Environmental Assessment versus Phenotypic Response

by Andrew J. Isdaner, Nicholas A. Levis, Ian M. Ehrenreich and David W. Pfennig

Genes 2024, 15(5), 611; https://doi.org/10.3390/genes15050611 - 11 May 2024

Cited by 1 | Viewed by 1546

Abstract

Many organisms facultatively produce different phenotypes depending on their environment, yet relatively little is known about the genetic bases of such plasticity in natural populations. In this study, we describe the genetic variation underlying an extreme form of plasticity––resource polyphenism––in Mexican spadefoot toad [...] Read more.

Many organisms facultatively produce different phenotypes depending on their environment, yet relatively little is known about the genetic bases of such plasticity in natural populations. In this study, we describe the genetic variation underlying an extreme form of plasticity––resource polyphenism––in Mexican spadefoot toad tadpoles, Spea multiplicata. Depending on their environment, these tadpoles develop into one of two drastically different forms: a carnivore morph or an omnivore morph. We collected both morphs from two ponds that differed in which morph had an adaptive advantage and performed genome-wide association studies of phenotype (carnivore vs. omnivore) and adaptive plasticity (adaptive vs. maladaptive environmental assessment). We identified four quantitative trait loci associated with phenotype and nine with adaptive plasticity, two of which exhibited signatures of minor allele dominance and two of which (one phenotype locus and one adaptive plasticity locus) did not occur as minor allele homozygotes. Investigations into the genetics of plastic traits in natural populations promise to provide novel insights into how such complex, adaptive traits arise and evolve. Full article

(This article belongs to the Special Issue Genomics of Evolution and Adaptation in Animals)

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15 pages, 6160 KiB

Open AccessEditor’s ChoiceArticle

miR-423-5p Regulates Skeletal Muscle Growth and Development by Negatively Inhibiting Target Gene SRF

by Yanqin Pang, Jing Liang, Jianfang Huang, Ganqiu Lan, Fumei Chen, Hui Ji and Yunxiang Zhao

Genes 2024, 15(5), 606; https://doi.org/10.3390/genes15050606 - 10 May 2024

Cited by 4 | Viewed by 1724

Abstract

The process of muscle growth directly affects the yield and quality of pork food products. Muscle fibers are created during the embryonic stage, grow following birth, and regenerate during adulthood; these are all considered to be phases of muscle development. A multilevel network [...] Read more.

The process of muscle growth directly affects the yield and quality of pork food products. Muscle fibers are created during the embryonic stage, grow following birth, and regenerate during adulthood; these are all considered to be phases of muscle development. A multilevel network of transcriptional, post-transcriptional, and pathway levels controls this process. An integrated toolbox of genetics and genomics as well as the use of genomics techniques has been used in the past to attempt to understand the molecular processes behind skeletal muscle growth and development in pigs under divergent selection processes. A class of endogenous noncoding RNAs have a major regulatory function in myogenesis. But the precise function of miRNA-423-5p in muscle development and the related molecular pathways remain largely unknown. Using target prediction software, initially, the potential target genes of miR-423-5p in the Guangxi Bama miniature pig line were identified using various selection criteria for skeletal muscle growth and development. The serum response factor (SRF) was found to be one of the potential target genes, and the two are negatively correlated, suggesting that there may be targeted interactions. In addition to being strongly expressed in swine skeletal muscle, miR-423-5p was also up-regulated during C2C12 cell development. Furthermore, real-time PCR analysis showed that the overexpression of miR-423-5p significantly reduced the expression of myogenin and the myogenic differentiation antigen (p < 0.05). Moreover, the results of the enzyme-linked immunosorbent assay (ELISA) demonstrated that the overexpression of miR-423-5p led to a significant reduction in SRF expression (p < 0.05). Furthermore, miR-423-5p down-regulated the luciferase activities of report vectors carrying the 3′ UTR of porcine SRF, confirming that SRF is a target gene of miR-423-5p. Taken together, miR-423-5p’s involvement in skeletal muscle differentiation may be through the regulation of SRF. Full article

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

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13 pages, 7740 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Analysis of Green Leaf Plants and White–Green Leaf Mutants in Haworthia cooperi var. pilifera

by Peiling Li, Maofei Ren, Juanjuan Chen, Jianhua Yue, Songhu Liu, Qingsong Zhu and Zhiyong Wang

Genes 2024, 15(5), 608; https://doi.org/10.3390/genes15050608 - 10 May 2024

Cited by 2 | Viewed by 1340

Abstract

Haworthia cooperi var. pilifera is a succulent plant with ornamental value. The white–green leaf mutant (wl) showed a significant difference in leaf color from the wild-type plant (WT). In this study, we integrated the transcriptomes of wl and WT plants to [...] Read more.

Haworthia cooperi var. pilifera is a succulent plant with ornamental value. The white–green leaf mutant (wl) showed a significant difference in leaf color from the wild-type plant (WT). In this study, we integrated the transcriptomes of wl and WT plants to screen differentially expressed genes related to leaf color variation. The results of transcriptome analysis showed that 84,163 unigenes were obtained after de novo assembly and the NR database annotated the largest number of unigenes, which accounted for 57.13%, followed by NT (43.02%), GO (39.84%), Swiss-Prot (39.25%), KEGG (36.06%), and COG (24.88%). Our finding showed that 2586 genes were differentially expressed in the two samples, including 1996 down-regulated genes and 590 up-regulated genes. GO analysis predicted that these differentially expressed genes (DEGs) participate in 12 cellular components, 20 biological processes, and 13 molecular function terms and KEGG analysis showed that metabolic pathways, plant–pathogen interaction, glycerophospholipid metabolism, endocytosis, plant hormone signal transduction, and ether lipid metabolism were enriched among all identified pathways. Through functional enrichment analysis of DEGs, we found that they were involved in chloroplast division and the biosynthesis of plant pigments, including chlorophyll, carotenoids, anthocyanin, and transcription factor families, which might be related to the formation mechanism of leaf color. Taken together, these results present insights into the difference in gene expression characteristics in leaves between WT and wl mutants and provide a new insight for breeding colorful leaf phenotypes in succulent plants. Full article

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

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15 pages, 890 KiB

Open AccessEditor’s ChoiceArticle

Is CYP2C Haplotype Relevant for Efficacy and Bleeding Risk in Clopidogrel-Treated Patients?

by Lana Ganoci, Jozefina Palić, Vladimir Trkulja, Katarina Starčević, Livija Šimičević, Nada Božina, Martina Lovrić-Benčić, Zdravka Poljaković and Tamara Božina

Genes 2024, 15(5), 607; https://doi.org/10.3390/genes15050607 - 10 May 2024

Cited by 1 | Viewed by 1461

Abstract

A recently discovered haplotype—CYP2C:TG—determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, [...] Read more.

A recently discovered haplotype—CYP2C:TG—determines the ultrarapid metabolism of several CYP2C19 substrates. The platelet inhibitor clopidogrel requires CYP2C19-mediated activation: the risk of ischemic events is increased in patients with a poor (PM) or intermediate (IM) CYP2C19 metabolizer phenotype (vs. normal, NM; rapid, RM; or ultrarapid, UM). We investigated whether the CYP2C:TG haplotype affected efficacy/bleeding risk in clopidogrel-treated patients. Adults (n = 283) treated with clopidogrel over 3–6 months were classified by CYP2C19 phenotype based on the CYP2C19*2*17 genotype, and based on the CYP2C19/CYP2C cluster genotype, and regarding carriage of the CYP2:TG haplotype, and were balanced on a number of covariates across the levels of phenotypes/haplotype carriage. Overall, 45 (15.9%) patients experienced ischemic events, and 49 (17.3%) experienced bleedings. By either classification, the incidence of ischemic events was similarly numerically higher in PM/IM patients (21.6%, 21.8%, respectively) than in mutually similar NM, RM, and UM patients (13.2–14.8%), whereas the incidence of bleeding events was numerically lower (13.1% vs. 16.6–20.5%). The incidence of ischemic events was similar in CYP2C:TG carries and non-carries (14.1% vs. 16.1%), whereas the incidence of bleedings appeared mildly lower in the former (14.9% vs. 20.1%). We observed no signal to suggest a major effect of the CYP2C19/CYP2C cluster genotype or CYP2C:TG haplotype on the clinical efficacy/safety of clopidogrel. Full article

(This article belongs to the Section Pharmacogenetics)

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20 pages, 2244 KiB

Open AccessEditor’s ChoiceArticle

Altered Expression of PDE4 Genes in Schizophrenia: Insights from a Brain and Blood Sample Meta-Analysis and iPSC-Derived Neurons

by Nitzan Burrack, Assif Yitzhaky, Liron Mizrahi, Meiyan Wang, Shani Stern and Libi Hertzberg

Genes 2024, 15(5), 609; https://doi.org/10.3390/genes15050609 - 10 May 2024

Cited by 3 | Viewed by 2881

Abstract

Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their genetic association and function in cognitive processes such as long-term potentiation. We conducted a systematic gene expression meta-analysis of four PDE4 [...] Read more.

Schizophrenia symptomatology includes negative symptoms and cognitive impairment. Several studies have linked schizophrenia with the PDE4 family of enzymes due to their genetic association and function in cognitive processes such as long-term potentiation. We conducted a systematic gene expression meta-analysis of four PDE4 genes (PDE4A-D) in 10 brain sample datasets (437 samples) and three blood sample datasets (300 samples). Subsequently, we measured mRNA levels in iPSC-derived hippocampal dentate gyrus neurons generated from fibroblasts of three groups: healthy controls, healthy monozygotic twins (MZ), and their MZ siblings with schizophrenia. We found downregulation of PDE4B in brain tissues, further validated by independent data of the CommonMind consortium (515 samples). Interestingly, the downregulation signal was present in a subgroup of the patients, while the others showed no differential expression or even upregulation. Notably, PDE4A, PDE4B, and PDE4D exhibited upregulation in iPSC-derived neurons compared to healthy controls, whereas in blood samples, PDE4B was found to be upregulated while PDE4A was downregulated. While the precise mechanism and direction of altered PDE4 expression necessitate further investigation, the observed multilevel differential expression across the brain, blood, and iPSC-derived neurons compellingly suggests the involvement of PDE4 genes in the pathophysiology of schizophrenia. Full article

(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders 2.0)

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12 pages, 3333 KiB

Open AccessEditor’s ChoiceArticle

PlantMine: A Machine-Learning Framework to Detect Core SNPs in Rice Genomics

by Kai Tong, Xiaojing Chen, Shen Yan, Liangli Dai, Yuxue Liao, Zhaoling Li and Ting Wang

Genes 2024, 15(5), 603; https://doi.org/10.3390/genes15050603 - 9 May 2024

Cited by 4 | Viewed by 1717

Abstract

As a fundamental global staple crop, rice plays a pivotal role in human nutrition and agricultural production systems. However, its complex genetic architecture and extensive trait variability pose challenges for breeders and researchers in optimizing yield and quality. Particularly to expedite breeding methods [...] Read more.

As a fundamental global staple crop, rice plays a pivotal role in human nutrition and agricultural production systems. However, its complex genetic architecture and extensive trait variability pose challenges for breeders and researchers in optimizing yield and quality. Particularly to expedite breeding methods like genomic selection, isolating core SNPs related to target traits from genome-wide data reduces irrelevant mutation noise, enhancing computational precision and efficiency. Thus, exploring efficient computational approaches to mine core SNPs is of great importance. This study introduces PlantMine, an innovative computational framework that integrates feature selection and machine learning techniques to effectively identify core SNPs critical for the improvement of rice traits. Utilizing the dataset from the 3000 Rice Genomes Project, we applied different algorithms for analysis. The findings underscore the effectiveness of combining feature selection with machine learning in accurately identifying core SNPs, offering a promising avenue to expedite rice breeding efforts and improve crop productivity and resilience to stress. Full article

(This article belongs to the Special Issue Genomic Studies of Plant Breeding)

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18 pages, 5673 KiB

Open AccessEditor’s ChoiceArticle

Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

by Maliha Islam and Susanta K. Behura

Genes 2024, 15(5), 604; https://doi.org/10.3390/genes15050604 - 9 May 2024

Cited by 1 | Viewed by 1904

Abstract

The objective of this study was to investigate gene regulation of the developing fetal brain from congenic or inbred mice strains that differed in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J [...] Read more.

The objective of this study was to investigate gene regulation of the developing fetal brain from congenic or inbred mice strains that differed in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J mice (long-lived) in comparison to B6.Cg-Cav1^tm1Mls/J (congenic, short-lived) and AKR/J (inbred, short-lived) mice on day(d) 12, 15, and 17 of gestation. The analysis showed a contrasting gene expression pattern during fetal brain development in these mice. Genes related to brain development, aging, and the regulation of alternative splicing were significantly differentially regulated in the fetal brain of the short-lived compared to long-lived mice during development from d15 and d17. A significantly reduced number of splice variants was observed on d15 compared to d12 or d17 in a strain-dependent manner. An epigenetic clock analysis of d15 fetal brain identified DNA methylations that were significantly associated with single-nucleotide polymorphic sites between AKR/J and C57BL/6J strains. These methylations were associated with genes that show epigenetic changes in an age-correlated manner in mice. Together, the finding of this study suggest that fetal brain development and longevity are epigenetically linked, supporting the emerging concept of the early-life origin of longevity. Full article

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

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15 pages, 4288 KiB

Open AccessEditor’s ChoiceArticle

Molecular and Physiological Effects of 17α-methyltestosterone on Sex Differentiation of Black Rockfish, Sebastes schlegelii

by Haijun Huang, Yuyan Liu, Qian Wang, Caichao Dong, Le Dong, Jingjing Zhang, Yu Yang, Xiancai Hao, Weijing Li, Ivana F. Rosa, Lucas B. Doretto, Xuebin Cao and Changwei Shao

Genes 2024, 15(5), 605; https://doi.org/10.3390/genes15050605 - 9 May 2024

Cited by 2 | Viewed by 1642

Abstract

It is widely known that all-female fish production holds economic value for aquaculture. Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. [...] Read more.

It is widely known that all-female fish production holds economic value for aquaculture. Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales of S. schlegelii for subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth of S. schlegelii, while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes (cyp19a1a and foxl2) while up-regulating male-related genes (amh) in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role in S. schlegelii sex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT in S. schlegelii and offers an initial insight into the underlying mechanism of sexual reversal in this species. Full article

(This article belongs to the Special Issue Omic Study and Genes in Fish Sex Determination and Differentiation)

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14 pages, 3678 KiB

Open AccessEditor’s ChoiceArticle

Normalized Clinical Severity Scores Reveal a Correlation between X Chromosome Inactivation and Disease Severity in Rett Syndrome

by Jonathan K. Merritt, Xiaolan Fang, Raymond C. Caylor, Steven A. Skinner, Michael J. Friez, Alan K. Percy and Jeffrey L. Neul

Genes 2024, 15(5), 594; https://doi.org/10.3390/genes15050594 - 8 May 2024

Cited by 1 | Viewed by 1929

Abstract

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome [...] Read more.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI), resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age-dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity, allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects. Full article

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

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15 pages, 2245 KiB

Open AccessEditor’s ChoiceArticle

Interleukin-1β Polymorphisms Are Genetic Markers of Susceptibility to Periprosthetic Joint Infection in Total Hip and Knee Arthroplasty

by Valentina Granata, Dario Strina, Valentina Possetti, Roberto Leone, Sonia Valentino, Katia Chiappetta, Mattia Loppini, Alberto Mantovani, Barbara Bottazzi, Rosanna Asselta, Cristina Sobacchi and Antonio Inforzato

Genes 2024, 15(5), 596; https://doi.org/10.3390/genes15050596 - 8 May 2024

Cited by 3 | Viewed by 1779

Abstract

Periprosthetic joint infections (PJIs) are serious complications of prosthetic surgery. The criteria for the diagnosis of PJI integrate clinical and laboratory findings in a complex and sometimes inconclusive workflow. Host immune factors hold potential as diagnostic biomarkers in bone and joint infections. We [...] Read more.

Periprosthetic joint infections (PJIs) are serious complications of prosthetic surgery. The criteria for the diagnosis of PJI integrate clinical and laboratory findings in a complex and sometimes inconclusive workflow. Host immune factors hold potential as diagnostic biomarkers in bone and joint infections. We reported that the humoral pattern-recognition molecule long pentraxin 3 (PTX3) predicts PJI in total hip and knee arthroplasty (THA and TKA, respectively). If and how genetic variation in PTX3 and inflammatory genes that affect its expression (IL-1β, IL-6, IL-10, and IL-17A) contributes to the risk of PJI is unknown. We conducted a case–control study on a Caucasian historic cohort of THA and TKA patients who had prosthesis explant due to PJI (cases) or aseptic complications (controls). Saliva was collected from 93 subjects and used to extract DNA and genotype PTX3, IL-1β, IL-6, IL-10, and IL-17A single-nucleotide polymorphisms (SNPs). Moreover, the concentration of IL-1β, IL-10, and IL-6 was measured in synovial fluid and plasma. No association was found between PTX3 polymorphisms and PJI; however, the AGG haplotype, encompassing rs2853550, rs1143634, and rs1143627 in IL-1β, was linked to the infection (p = 0.017). Also, synovial levels of all inflammatory markers were higher in cases than in controls, and a correlation emerged between synovial concentration of PTX3 and that of IL-1β in cases only (Spearman r = 0.67, p = 0.004). We identified a relationship between rs2853550 and the synovial concentration of IL-1β and PTX3. Our findings suggest that IL-1β SNPs could be used for the early identification of THA and TKA patients with a high risk of infection. Full article

(This article belongs to the Special Issue Updates of DNA Variations in Evolution and Human Diseases)

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19 pages, 3795 KiB

Open AccessEditor’s ChoiceArticle

Study on the Characteristics of Coarse Feeding Tolerance of Ding’an Pigs: Phenotypic and Candidate Genes Identification

by Yanxia Song, Mingming Xue, Feng Wang, Qiguo Tang, Yabiao Luo, Meili Zheng, Yubei Wang, Pengxiang Xue, Ningqi Dong, Ruiping Sun and Meiying Fang

Genes 2024, 15(5), 599; https://doi.org/10.3390/genes15050599 - 8 May 2024

Viewed by 1557

Abstract

Ding’an (DA) pig, a prominent local breed in Hainan Province, exhibits notable advantages in coarse feeding tolerance and high-quality meat. To explore the potential genetic mechanism of coarse feeding tolerance in DA pigs, 60-day-old full sibling pairs of DA and DLY (Duroc-Landrace-Yorkshire) pigs [...] Read more.

Ding’an (DA) pig, a prominent local breed in Hainan Province, exhibits notable advantages in coarse feeding tolerance and high-quality meat. To explore the potential genetic mechanism of coarse feeding tolerance in DA pigs, 60-day-old full sibling pairs of DA and DLY (Duroc-Landrace-Yorkshire) pigs were subjected to fed normal (5%) and high (10%) crude fiber diets for 56 days, respectively. The findings showed that increasing the crude fiber level had no impact on the apparent digestibility of crude fiber, intramuscular fat, and marbling scores in DA pigs, whereas these factors were significantly reduced in DLY pigs (p < 0.05). Through differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) of the colonic mucosal transcriptome data, 65 and 482 candidate genes with coarse feeding tolerance in DA pigs were identified, respectively. Joint analysis screened four key candidate genes, including LDHB, MLC1, LSG1, and ESM1, potentially serving as key regulated genes for coarse feeding tolerance. Functional analysis revealed that the most significant pathway enriched in differential genes associated with coarse feeding tolerance in Ding’an pigs was the signaling receptor binding. The results hold substantial significance for advancing our understanding of the genetic mechanisms governing coarse feeding tolerance in Ding’an pigs. Full article

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

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18 pages, 7369 KiB

Open AccessEditor’s ChoiceArticle

Expression and Characterization of an Efficient Alginate Lyase from Psychromonas sp. SP041 through Metagenomics Analysis of Rotten Kelp

by Ping Wang, Yi Cai, Hua Zhong, Ruiting Chen, Yuetao Yi, Yanrui Ye and Lili Li

Genes 2024, 15(5), 598; https://doi.org/10.3390/genes15050598 - 8 May 2024

Cited by 2 | Viewed by 1666

Abstract

Alginate is derived from brown algae, which can be cultivated in large quantities. It can be broken down by alginate lyase into alginate oligosaccharides (AOSs), which exhibit a higher added value and better bioactivity than alginate. In this study, metagenomic technology was used [...] Read more.

Alginate is derived from brown algae, which can be cultivated in large quantities. It can be broken down by alginate lyase into alginate oligosaccharides (AOSs), which exhibit a higher added value and better bioactivity than alginate. In this study, metagenomic technology was used to screen for genes that code for high-efficiency alginate lyases. The candidate alginate lyase gene alg169 was detected from Psychromonas sp. SP041, the most abundant species among alginate lyase bacteria on selected rotten kelps. The alginate lyase Alg169 was heterologously expressed in Escherichia coli BL21 (DE3), Ni-IDA-purified, and characterized. The optimum temperature and pH of Alg169 were 25 °C and 7.0, respectively. Metal ions including Mn²⁺, Co²⁺, Ca²⁺, Mg²⁺, Ni²⁺, and Ba²⁺ led to significantly increased enzyme activity. Alg169 exhibited a pronounced dependence on Na⁺, and upon treatment with Mn²⁺, its activity surged by 687.57%, resulting in the highest observed enzyme activity of 117,081 U/mg. Bioinformatic analysis predicted that Alg169 would be a double-domain lyase with a molecular weight of 65.58 kDa. It is a bifunctional enzyme with substrate specificity to polyguluronic acid (polyG) and polymannuronic acid (polyM). These results suggest that Alg169 is a promising candidate for the efficient manufacturing of AOSs from brown seaweed. Full article

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

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21 pages, 1321 KiB

Open AccessEditor’s ChoiceReview

Genetic Causes of Qualitative Sperm Defects: A Narrative Review of Clinical Evidence

by Andrea Graziani, Maria Santa Rocca, Cinzia Vinanzi, Giulia Masi, Giuseppe Grande, Luca De Toni and Alberto Ferlin

Genes 2024, 15(5), 600; https://doi.org/10.3390/genes15050600 - 8 May 2024

Cited by 9 | Viewed by 3893

Abstract

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical [...] Read more.

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed. Full article

(This article belongs to the Special Issue Beyond the Basics: Genetic Insights into Male Infertility)

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12 pages, 2644 KiB

Open AccessEditor’s ChoiceArticle

Genetic Screening Revealed the Negative Regulation of miR-310~313 Cluster Members on Imd Pathway during Gram-Negative Bacterial Infection in Drosophila

by Yao Li, Yixuan Sun, Ruimin Li, Hongjian Zhou, Shengjie Li and Ping Jin

Genes 2024, 15(5), 601; https://doi.org/10.3390/genes15050601 - 8 May 2024

Cited by 1 | Viewed by 1754

Abstract

Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the [...] Read more.

Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the synergistical regulation of miRNAs located within a cluster on the Imd-immune pathway remains obscured. In our study, a genetic screening with 52 transgenic UAS-miRNAs was performed to identify ten miRNAs or miRNA clusters, including the miR310~313 cluster, which may function on Imd-dependent immune responses. The miRNA RT-qPCR analysis showed that the expression of miR-310~313 cluster members exhibited an increase at 6–12 h post E. coli infection. Furthermore, the overexpression of the miR-310~313 cluster impaired the Drosophila survival. And the overexpression of miR-310/311/312 reduced Dpt expression, an indication of Imd pathway induced by Gram-negative bacteria. Conversely, the knockdown of miR-310/311/312 led to increases in Dpt expression. The Luciferase reporter expression assays and RT-qPCR analysis confirmed that miR-310~313 cluster members directly co-targeted and inhibited Imd transcription. These findings reveal that the members of the miR-310~313 cluster synergistically inhibit Imd-dependent immune responses by co-targeting the Imd gene in Drosophila. Full article

(This article belongs to the Topic MicroRNA: Mechanisms of Action, Physio-Pathological Implications, and Disease Biomarkers, 2nd Volume)

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14 pages, 3937 KiB

Open AccessEditor’s ChoiceArticle

Genetic Analysis of the ts-Lethal Mutant Δpa0665/pTS-pa0665 Reveals Its Role in Cell Morphology and Oxidative Phosphorylation in Pseudomonas aeruginosa

by Jiayin Zhu, Hulin Zhao and Zhili Yang

Genes 2024, 15(5), 590; https://doi.org/10.3390/genes15050590 - 7 May 2024

Cited by 2 | Viewed by 1294

Abstract

Pa0665 in Pseudomonas aeruginosa shares homologous sequences with that of the essential A-type iron–sulfur (Fe-S) cluster insertion protein ErpA in Escherichia coli. However, its essentiality in P. aeruginosa and its complementation with E. coli erpA has not been experimentally examined. To fulfill this [...] Read more.

Pa0665 in Pseudomonas aeruginosa shares homologous sequences with that of the essential A-type iron–sulfur (Fe-S) cluster insertion protein ErpA in Escherichia coli. However, its essentiality in P. aeruginosa and its complementation with E. coli erpA has not been experimentally examined. To fulfill this task, we constructed plasmid-based ts-mutant Δpa0665/pTS-pa0665 using a three-step protocol. The mutant displayed growth defects at 42 °C, which were complemented by expressing ec.erpA. Microscopic observations indicated a petite cell phenotype for Δpa0665/pTS-pa0665 at 42 °C, correlated with the downregulation of the oprG gene. RNA sequencing revealed significant transcriptional changes in genes associated with the oxidative phosphorylation (OXPHOS) system, aligning with reduced ATP levels in Δpa0665/pTS-pa0665 under 42 °C. Additionally, the ts-mutant showed heightened sensitivity to H₂O₂ at 42 °C. Overall, our study demonstrates the essential role of pa0665 for OXPHOS function and is complemented by ec.erpA. We propose that the plasmid-based ts-allele is useful for genetic analysis of essential genes of interest in P. aeruginosa. Full article

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

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23 pages, 2630 KiB

Open AccessEditor’s ChoiceArticle

The Association between Mutational Signatures and Clinical Outcomes among Patients with Early-Onset Breast Cancer

by Robert B. Basmadjian, Dylan E. O’Sullivan, May Lynn Quan, Sasha Lupichuk, Yuan Xu, Winson Y. Cheung and Darren R. Brenner

Genes 2024, 15(5), 592; https://doi.org/10.3390/genes15050592 - 7 May 2024

Cited by 1 | Viewed by 2138

Abstract

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package [...] Read more.

Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion–deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08–1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC. Full article

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

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16 pages, 1858 KiB

Open AccessEditor’s ChoiceArticle

Genotype–Phenotype Correlations in Alport Syndrome—A Single-Center Experience

by Ștefan Nicolaie Lujinschi, Bogdan Marian Sorohan, Bogdan Obrișcă, Alexandra Vrabie, Gabriela Lupușoru, Camelia Achim, Andreea Gabriella Andronesi, Andreea Covic and Gener Ismail

Genes 2024, 15(5), 593; https://doi.org/10.3390/genes15050593 - 7 May 2024

Cited by 3 | Viewed by 1771

Abstract

Background: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). Methods: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe [...] Read more.

Background: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). Methods: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival. Results: A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98–54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p < 0.001). Conclusions: Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses. Full article

(This article belongs to the Special Issue Genetic and Phenotypic Correlation: Gene–Disease Validation Series II)

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14 pages, 2916 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Characterization of the PHT1 Gene Family and Its Response to Mycorrhizal Symbiosis in Salvia miltiorrhiza under Phosphate Stress

by Xue Chen, Yanhong Bai, Yanan Lin, Hongyan Liu, Fengxia Han, Hui Chang, Menglin Li and Qian Liu

Genes 2024, 15(5), 589; https://doi.org/10.3390/genes15050589 - 6 May 2024

Cited by 3 | Viewed by 2002

Abstract

Phosphorus (P) is a vital nutrient element that is essential for plant growth and development, and arbuscular mycorrhizal fungi (AMF) can significantly enhance P absorption. The phosphate transporter protein 1 (PHT1) family mediates the uptake of P in plants. However, the PHT1 gene [...] Read more.

Phosphorus (P) is a vital nutrient element that is essential for plant growth and development, and arbuscular mycorrhizal fungi (AMF) can significantly enhance P absorption. The phosphate transporter protein 1 (PHT1) family mediates the uptake of P in plants. However, the PHT1 gene has not yet been characterized in Salvia miltiorrhiza. In this study, to gain insight into the functional divergence of PHT1 genes, nine SmPHT1 genes were identified in the S. miltiorrhiza genome database via bioinformatics tools. Phylogenetic analysis revealed that the PHT1 proteins of S. miltiorrhiza, Arabidopsis thaliana, and Oryza sativa could be divided into three groups. PHT1 in the same clade has a similar gene structure and motif, suggesting that the features of each clade are relatively conserved. Further tissue expression analysis revealed that SmPHT1 was expressed mainly in the roots and stems. In addition, phenotypic changes, P content, and PHT1 gene expression were analyzed in S. miltiorrhiza plants inoculated with AMF under different P conditions (0 mM, 0.1 mM, and 10 mM). P stress and AMF significantly affected the growth and P accumulation of S. miltiorrhiza. SmPHT1;6 was strongly expressed in the roots colonized by AMF, implying that SmPHT1;6 was a specific AMF-inducible PHT1. Taken together, these results provide new insights into the functional divergence and genetic redundancy of the PHT1 genes in response to P stress and AMF symbiosis in S. miltiorrhiza. Full article

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

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18 pages, 872 KiB

Open AccessEditor’s ChoiceReview

Immunogenetics of Systemic Sclerosis

by Olga Gumkowska-Sroka, Kacper Kotyla and Przemysław Kotyla

Genes 2024, 15(5), 586; https://doi.org/10.3390/genes15050586 - 5 May 2024

Cited by 2 | Viewed by 3155

Abstract

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as [...] Read more.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a “hyperfibrotic” state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease. Full article

(This article belongs to the Special Issue New Advances in Immunogenetics of Disease)

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21 pages, 9294 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Analysis of Transcription Factor R2R3-MYB Gene Family and Gene Expression Profiles during Anthocyanin Synthesis in Common Walnut (Juglans regia L.)

by Dongjun Zuo, Yujie Yan, Jiayu Ma and Peng Zhao

Genes 2024, 15(5), 587; https://doi.org/10.3390/genes15050587 - 5 May 2024

Cited by 2 | Viewed by 2040

Abstract

The R2R3-MYB gene family, encoding plant transcriptional regulators, participates in many metabolic pathways of plant physiology and development, including flavonoid metabolism and anthocyanin synthesis. This study proceeded as follows: the JrR2R3-MYB gene family was analyzed genome-wide, and the family members were identified and [...] Read more.

The R2R3-MYB gene family, encoding plant transcriptional regulators, participates in many metabolic pathways of plant physiology and development, including flavonoid metabolism and anthocyanin synthesis. This study proceeded as follows: the JrR2R3-MYB gene family was analyzed genome-wide, and the family members were identified and characterized using the high-quality walnut reference genome “Chandler 2.0”. All 204 JrR2R3-MYBs were established and categorized into 30 subgroups via phylogenetic analysis. JrR2R3-MYBs were unevenly distributed over 16 chromosomes. Most JrR2R3-MYBs had similar structures and conservative motifs. The cis-acting elements exhibit multiple functions of JrR2R3-MYBs such as light response, metabolite response, and stress response. We found that the expansion of JrR2R3-MYBs was mainly caused by WGD or segmental duplication events. Ka/Ks analysis indicated that these genes were in a state of negative purifying selection. Transcriptome results suggested that JrR2R3-MYBs were widely entangled in the process of walnut organ development and differentially expressed in different colored varieties of walnuts. Subsequently, we identified 17 differentially expressed JrR2R3-MYBs, 9 of which may regulate anthocyanin biosynthesis based on the results of a phylogenetic analysis. These genes were present in greater expression levels in ‘Zijing’ leaves than in ‘Lvling’ leaves, as revealed by the results of qRT-PCR experiments. These results contributed to the elucidation of the functions of JrR2R3-MYBs in walnut coloration. Collectively, this work provides a foundation for exploring the functional characteristics of the JrR2R3-MYBs in walnuts and improving the nutritional value and appearance quality of walnuts. Full article

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

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11 pages, 1597 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study

by Roxana Andra Coman, Vlad Horia Schitcu, Liviuta Budisan, Lajos Raduly, Cornelia Braicu, Bogdan Petrut, Ioan Coman, Ioana Berindan-Neagoe and Nadim Al Hajjar

Genes 2024, 15(5), 584; https://doi.org/10.3390/genes15050584 - 4 May 2024

Cited by 4 | Viewed by 2414

Abstract

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative [...] Read more.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis. Full article

(This article belongs to the Special Issue Non-coding RNAs in Human Health and Disease)

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12 pages, 1513 KiB

Open AccessEditor’s ChoiceBrief Report

Characterization of the Common Genetic Variation in the Spanish Population of Navarre

by Alberto Maillo, Estefania Huergo, María Apellániz-Ruiz, Edurne Urrutia-Lafuente, María Miranda, Josefa Salgado, Sara Pasalodos-Sanchez, Luna Delgado-Mora, Óscar Teijido, Ibai Goicoechea, Rosario Carmona, Javier Perez-Florido, Virginia Aquino, Daniel Lopez-Lopez, María Peña-Chilet, Sergi Beltran, Joaquín Dopazo, Iñigo Lasa, Juan José Beloqui, NAGEN-Scheme, Ángel Alonso and David Gomez-Cabrero Show full author list Hide full author list

Genes 2024, 15(5), 585; https://doi.org/10.3390/genes15050585 - 4 May 2024

Cited by 1 | Viewed by 2048

Abstract

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), [...] Read more.

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants. Full article

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

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14 pages, 962 KiB

Open AccessEditor’s ChoiceReview

Genetic Screening—Emerging Issues

by Martina C. Cornel, Karuna R. M. van der Meij, Carla G. van El, Tessel Rigter and Lidewij Henneman

Genes 2024, 15(5), 581; https://doi.org/10.3390/genes15050581 - 3 May 2024

Cited by 2 | Viewed by 4450

Abstract

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, [...] Read more.

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples’ reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit–harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems. Full article

(This article belongs to the Special Issue Human Genetics: Diseases, Community, and Counseling)

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13 pages, 1530 KiB

Open AccessEditor’s ChoiceArticle

MD3F: Multivariate Distance Drift Diffusion Framework for High-Dimensional Datasets

by Jessica Zielinski, Patricia Corby and Alexander V. Alekseyenko

Genes 2024, 15(5), 582; https://doi.org/10.3390/genes15050582 - 3 May 2024

Viewed by 1264

Abstract

High-dimensional biomedical datasets have become easier to collect in the last two decades with the advent of multi-omic and single-cell experiments. These can generate over 1000 measurements per sample or per cell. More recently, focus has been drawn toward the need for longitudinal [...] Read more.

High-dimensional biomedical datasets have become easier to collect in the last two decades with the advent of multi-omic and single-cell experiments. These can generate over 1000 measurements per sample or per cell. More recently, focus has been drawn toward the need for longitudinal datasets, with the appreciation that important dynamic changes occur along transitions between health and disease. Analysis of longitudinal omics data comes with many challenges, including type I error inflation and corresponding loss in power when thousands of hypothesis tests are needed. Multivariate analysis can yield approaches with higher statistical power; however, multivariate methods for longitudinal data are currently limited. We propose a multivariate distance-based drift-diffusion framework (MD3F) to tackle the need for a multivariate approach to longitudinal, high-throughput datasets. We show that MD3F can result in surprisingly simple yet valid and powerful hypothesis testing and estimation approaches using generalized linear models. Through simulation and application studies, we show that MD3F is robust and can offer a broadly applicable method for assessing multivariate dynamics in omics data. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Microbiome)

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12 pages, 1375 KiB

Open AccessEditor’s ChoiceArticle

Mapping of Leaf Rust Resistance Loci in Two Kenyan Wheats and Development of Linked Markers

by Davinder Singh, Peace Kankwatsa, Karanjeet S. Sandhu, Urmil K. Bansal, Kerrie L. Forrest and Robert F. Park

Genes 2024, 15(5), 583; https://doi.org/10.3390/genes15050583 - 3 May 2024

Cited by 1 | Viewed by 1705

Abstract

Leaf rust caused by the pathogen Puccinia triticina (Pt) is a destructive fungal disease of wheat that occurs in almost all wheat-growing areas across the globe. Genetic resistance has proven to be the best solution to mitigate the disease. Wheat breeders [...] Read more.

Leaf rust caused by the pathogen Puccinia triticina (Pt) is a destructive fungal disease of wheat that occurs in almost all wheat-growing areas across the globe. Genetic resistance has proven to be the best solution to mitigate the disease. Wheat breeders are continuously seeking new diversified and durable sources of resistance to use in developing new varieties. We developed recombinant inbred line (RIL) populations from two leaf rust-resistant genotypes (Kenya Kudu and AUS12568) introduced from Kenya to identify and characterize resistance to Pt and to develop markers linked closely to the resistance that was found. Our studies detected four QTL conferring adult plant resistance (APR) to leaf rust. Two of these loci are associated with known genes, Lr46 and Lr68, residing on chromosomes 1B and 7B, respectively. The remaining two, QLrKK_2B and QLrAus12568_5A, contributed by Kenya Kudu and AUS12568 respectively, are putatively new loci for Pt resistance. Both QLrKK_2B and QLrAus12568_5A were found to interact additively with Lr46 in significantly reducing the disease severity at adult plant growth stages in the field. We further developed a suite of six closely linked markers within the QLrAus12568_5A locus and four within the QLrKK_2B region. Among these, markers sunKASP_522 and sunKASP_524, flanking QLrAus12568_5A, and sunKASP_536, distal to QLrKK_2B, were identified as the most closely linked and reliable for marker-assisted selection. The markers were validated on a selection of 64 Australian wheat varieties and found to be polymorphic and robust, allowing for clear allelic discrimination. The identified new loci and linked molecular markers will enable rapid adoption by breeders in developing wheat varieties carrying diversified and durable resistance to leaf rust. Full article

(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)

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9 pages, 2690 KiB

Open AccessEditor’s ChoiceBrief Report

A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred

by Muhammad A. Usmani, Amama Ghaffar, Mohsin Shahzad, Javed Akram, Aisha I. Majeed, Kausar Malik, Khushbakht Fatima, Asma A. Khan, Zubair M. Ahmed, Sheikh Riazuddin and Saima Riazuddin

Genes 2024, 15(5), 580; https://doi.org/10.3390/genes15050580 - 2 May 2024

Viewed by 1993

Abstract

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person’s intellectual and adaptive functioning, and is caused by pathogenic variants in more [...] Read more.

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person’s intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD. Full article

(This article belongs to the Special Issue Next Generation Sequencing in Human Disease)

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12 pages, 4659 KiB

Open AccessEditor’s ChoiceArticle

Systematic Analysis of Zinc Finger-Homeodomain Transcription Factors (ZF-HDs) in Barley (Hordeum vulgare L.)

by Meng-Di Liu, Hao Liu, Wen-Yan Liu, Shou-Fei Ni, Zi-Yi Wang, Zi-Han Geng, Kong-Yao Zhu, Yan-Fang Wang and Yan-Hong Zhao

Genes 2024, 15(5), 578; https://doi.org/10.3390/genes15050578 - 1 May 2024

Cited by 2 | Viewed by 2126

Abstract

Zinc finger-homeodomain transcription factors (ZF-HDs) are pivotal in regulating plant growth, development, and diverse stress responses. In this study, we found 8 ZF-HD genes in barley genome. Theses eight HvZF-HD genes were located on five chromosomes, and classified into ZHD and MIF subfamily. [...] Read more.

Zinc finger-homeodomain transcription factors (ZF-HDs) are pivotal in regulating plant growth, development, and diverse stress responses. In this study, we found 8 ZF-HD genes in barley genome. Theses eight HvZF-HD genes were located on five chromosomes, and classified into ZHD and MIF subfamily. The collinearity, gene structure, conserved motif, and cis-elements of HvZF-HD genes were also analyzed. Real-time PCR results suggested that the expression of HvZF-HD4, HvZF-HD6, HvZF-HD7 and HvZF-HD8 were up-regulated after hormones (ABA, GA3 and MeJA) or PEG treatments, especially HvZF-HD6 was significantly induced. These results provide useful information of ZF-HD genes to future study aimed at barley breeding. Full article

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

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19 pages, 5558 KiB

Open AccessEditor’s ChoiceArticle

Mechanism of Apoptosis in Porcine Ovarian Granulosa Cells Triggered by T-2 Toxin

by Yige Chen, Xianrui Zheng, Ren Zhou, Huibin Zhang, Yangguang Liu, Xiaojing Hu and Zongjun Yin

Genes 2024, 15(5), 579; https://doi.org/10.3390/genes15050579 - 1 May 2024

Cited by 1 | Viewed by 4266

Abstract

T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its [...] Read more.

T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its toxicity remain unclear. With the goal of learning how T-2 affects reproduction in animals, we utilized primary porcine ovarian granulosa cells (pGCs) as a carrier in vitro and constructed concentration models for analyzing cell morphology and RNA-sequencing (RNA-seq). Our findings showed that T-2 could influence pGCs morphology, induce cell cycle arrest, and promote apoptosis in a dose-dependent manner. The results of RNA-seq analyses indicated that a total of 8216 genes exhibited significant differential expression (DEG) following T-2 treatment, of which 4812 were observed to be down-regulated and 3404 were up-regulated. The DEGs following T-2 toxin treatment of pGCs had a notable impact on many metabolic pathways such as PI3K-Akt, Ras, MAPK, and apoptosis, which in turn altered important physiological processes. Gene set enrichment analysis (GSEA) indicated that the differences in the harmful effects of T-2 might be caused by the varying control of cellular processes and the pathway responsible for steroid metabolism. These results present further insights regarding the mechanism of T-2 action on sow reproductive toxicity, enhance our understanding of T-2 reproductive toxicological effects, and lay a theoretical foundation for the judicious prevention of T-2-induced reproductive toxicity. Full article

(This article belongs to the Special Issue Advances in Pig Genetic and Genomic Breeding)

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17 pages, 3158 KiB

Open AccessEditor’s ChoiceArticle

A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors

by Anna Hartley, Luisa Burger, Cornelia L. Wincek, Lieke Dons, Tracy Li, Annabel Grewenig, Toros Taşgın, Manuela Urban, Alicia Roig-Merino, Mehrnaz Ghazvini and Richard P. Harbottle

Genes 2024, 15(5), 575; https://doi.org/10.3390/genes15050575 - 30 Apr 2024

Cited by 2 | Viewed by 2584

Abstract

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for [...] Read more.

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis. The application of less harmful nonviral vectors is limited as conventional plasmids cannot deliver the levels or duration of the factors necessary from a single transfection. Hence, plasmids that are most often used for reprogramming employ the potentially oncogenic Epstein–Barr nuclear antigen 1 (EBNA-1) system to ensure adequate levels and persistence of expression. In this study, we explored the use of nonviral SMAR DNA vectors to reprogram human fibroblasts into iPSCs. We show for the first time that iPSCs can be generated using nonviral plasmids without the use of EBNA-1 and that these DNA vectors can provide sufficient expression to induce pluripotency. We describe an optimised reprogramming protocol using these vectors that can produce high-quality iPSCs with comparable pluripotency and cellular function to those generated with viruses or EBNA-1 vectors. Full article

(This article belongs to the Special Issue Advances in Non-viral Gene Transfer for Gene Therapy Applications)

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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 5 | Viewed by 5677

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)

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15 pages, 610 KiB

Open AccessEditor’s ChoiceArticle

Defining a Haplotype Encompassing the LCORL-NCAPG Locus Associated with Increased Lean Growth in Beef Cattle

by Leif E. Majeres, Anna C. Dilger, Daniel W. Shike, Joshua C. McCann and Jonathan E. Beever

Genes 2024, 15(5), 576; https://doi.org/10.3390/genes15050576 - 30 Apr 2024

Cited by 3 | Viewed by 1833

Abstract

Numerous studies have shown genetic variation at the LCORL-NCAPG locus is strongly associated with growth traits in beef cattle. However, a causative molecular variant has yet to be identified. To define all possible candidate variants, 34 Charolais-sired calves were whole-genome sequenced, including 17 [...] Read more.

Numerous studies have shown genetic variation at the LCORL-NCAPG locus is strongly associated with growth traits in beef cattle. However, a causative molecular variant has yet to be identified. To define all possible candidate variants, 34 Charolais-sired calves were whole-genome sequenced, including 17 homozygous for a long-range haplotype associated with increased growth (QQ) and 17 homozygous for potential ancestral haplotypes for this region (qq). The Q haplotype was refined to an 814 kb region between chr6:37,199,897–38,014,080 and contained 218 variants not found in qq individuals. These variants include an insertion in an intron of NCAPG, a previously documented mutation in NCAPG (rs109570900), two coding sequence mutations in LCORL (rs109696064 and rs384548488), and 15 variants located within ATAC peaks that were predicted to affect transcription factor binding. Notably, rs384548488 is a frameshift variant likely resulting in loss of function for long isoforms of LCORL. To test the association of the coding sequence variants of LCORL with phenotype, 405 cattle from five populations were genotyped. The two variants were in complete linkage disequilibrium. Statistical analysis of the three populations that contained QQ animals revealed significant (p < 0.05) associations with genotype and birth weight, live weight, carcass weight, hip height, and average daily gain. These findings affirm the link between this locus and growth in beef cattle and describe DNA variants that define the haplotype. However, further studies will be required to define the true causative mutation. Full article

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

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12 pages, 784 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Genetic Evaluation in Patients with Special Reference to Late-Onset Sensorineural Hearing Loss

by Ikuyo Miyanohara, Junichiro Ohori, Minako Tabuchi, Shin-ya Nishio, Masaru Yamashita and Shin-ichi Usami

Genes 2024, 15(5), 571; https://doi.org/10.3390/genes15050571 - 29 Apr 2024

Viewed by 1603

Abstract

Hearing loss (HL) is a common and multi-complex etiological deficit that can occur at any age and can be caused by genetic variants, aging, toxic drugs, noise, injury, viral infection, and other factors. Recently, a high incidence of genetic etiologies in congenital HL [...] Read more.

Hearing loss (HL) is a common and multi-complex etiological deficit that can occur at any age and can be caused by genetic variants, aging, toxic drugs, noise, injury, viral infection, and other factors. Recently, a high incidence of genetic etiologies in congenital HL has been reported, and the usefulness of genetic testing has been widely accepted in congenital-onset or early-onset HL. In contrast, there have been few comprehensive reports on the relationship between late-onset HL and genetic causes. In this study, we performed next-generation sequencing analysis for 91 HL patients mainly consisting of late-onset HL patients. As a result, we identified 23 possibly disease-causing variants from 29 probands, affording a diagnostic rate for this study of 31.9%. The highest diagnostic rate was observed in the congenital/early-onset group (42.9%), followed by the juvenile/young adult-onset group (31.7%), and the middle-aged/aged-onset group (21.4%). The diagnostic ratio decreased with age; however, genetic etiologies were involved to a considerable degree even in late-onset HL. In particular, the responsible gene variants were found in 19 (55.9%) of 34 patients with a familial history and progressive HL. Therefore, this phenotype is considered to be a good candidate for genetic evaluation based on this diagnostic panel. Full article

(This article belongs to the Section Genetic Diagnosis)

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15 pages, 11756 KiB

Open AccessEditor’s ChoiceArticle

Identification of a Rye Spring Mutant Derived from a Winter Rye Variety by High-Altitude Environment Screening Using RNA Sequencing Technology

by Yanying Wang, Yixuan Liu, Chengqun Yu, Shizhan Chen, Yankun Li, Lina Wei, Junxi Wu and Jianping Yang

Genes 2024, 15(5), 572; https://doi.org/10.3390/genes15050572 - 29 Apr 2024

Viewed by 1536

Abstract

Wintergrazer-70 and Ganyin No1 are high-yield forage varieties suitable for cultivation in high-altitude areas of Tibet (4300 m above sea level). Ganyin No1 was developed from Wintergrazer-70, with the latter serving as its parent variety. Ganyin No1 was identified as a spring [...] Read more.

Wintergrazer-70 and Ganyin No1 are high-yield forage varieties suitable for cultivation in high-altitude areas of Tibet (4300 m above sea level). Ganyin No1 was developed from Wintergrazer-70, with the latter serving as its parent variety. Ganyin No1 was identified as a spring variety, and subsequent RNA sequencing was conducted. RNA sequencing analysis identified 4 differentially expressed genes related to vernalization and 28 genes related to photoperiod regulation. The Sc7296g5-i1G3 gene is related to the flowering inhibition of rye, which may be related to the phenotypic difference in the Ganyin No1 variety in winter and spring. This finding provides valuable insights for future research on Ganyin No1, especially in addressing feed shortages in Tibet during winter and spring. Full article

(This article belongs to the Special Issue Advances in Genetics and Genomics of Plants)

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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 14 | Viewed by 4122

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)

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23 pages, 1826 KiB

Open AccessEditor’s ChoiceReview

The Role of MicroRNAs in HIV Infection

by Nicolas Morando, Mara Cecilia Rosenzvit, Maria A. Pando and Jens Allmer

Genes 2024, 15(5), 574; https://doi.org/10.3390/genes15050574 - 29 Apr 2024

Cited by 10 | Viewed by 2915

Abstract

MicroRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in regulating gene expression at the post-transcriptional level. These regulatory molecules are integral to many biological processes and have been implicated in the pathogenesis of various diseases, including Human Immunodeficiency Virus [...] Read more.

MicroRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in regulating gene expression at the post-transcriptional level. These regulatory molecules are integral to many biological processes and have been implicated in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV) infection. This review aims to cover the current understanding of the multifaceted roles miRNAs assume in the context of HIV infection and pathogenesis. The discourse is structured around three primary focal points: (i) elucidation of the mechanisms through which miRNAs regulate HIV replication, encompassing both direct targeting of viral transcripts and indirect modulation of host factors critical for viral replication; (ii) examination of the modulation of miRNA expression by HIV, mediated through either viral proteins or the activation of cellular pathways consequent to viral infection; and (iii) assessment of the impact of miRNAs on the immune response and the progression of disease in HIV-infected individuals. Further, this review delves into the potential utility of miRNAs as biomarkers and therapeutic agents in HIV infection, underscoring the challenges and prospects inherent to this line of inquiry. The synthesis of current evidence positions miRNAs as significant modulators of the host-virus interplay, offering promising avenues for enhancing the diagnosis, treatment, and prevention of HIV infection. Full article

(This article belongs to the Special Issue Non-coding RNAs in Human Health and Disease)

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