Genes

18 pages, 1325 KB

Open AccessEditor’s ChoiceReview

Signaling Pathways Governing Cardiomyocyte Differentiation

by Isaiah K. Mensah and Humaira Gowher

Genes 2024, 15(6), 798; https://doi.org/10.3390/genes15060798 - 18 Jun 2024

Cited by 7 | Viewed by 6443

Cardiomyocytes are the largest cell type that make up the heart and confer beating activity to the heart. The proper differentiation of cardiomyocytes relies on the efficient transmission and perception of differentiation cues from several signaling pathways that influence cardiomyocyte-specific gene expression programs. [...] Read more.

Cardiomyocytes are the largest cell type that make up the heart and confer beating activity to the heart. The proper differentiation of cardiomyocytes relies on the efficient transmission and perception of differentiation cues from several signaling pathways that influence cardiomyocyte-specific gene expression programs. Signaling pathways also mediate intercellular communications to promote proper cardiomyocyte differentiation. We have reviewed the major signaling pathways involved in cardiomyocyte differentiation, including the BMP, Notch, sonic hedgehog, Hippo, and Wnt signaling pathways. Additionally, we highlight the differences between different cardiomyocyte cell lines and the use of these signaling pathways in the differentiation of cardiomyocytes from stem cells. Finally, we conclude by discussing open questions and current gaps in knowledge about the in vitro differentiation of cardiomyocytes and propose new avenues of research to fill those gaps. Full article

(This article belongs to the Section Epigenomics)

► Show Figures

Figure 1

19 pages, 8925 KB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of WRKY Transcription Factor Family in Chinese Rose and Response to Drought, Heat, and Salt Stress

by Xinyu Yan, Jiahui Zhao, Wei Huang, Cheng Liu, Xuan Hao, Chengye Gao, Minghua Deng and Jinfen Wen

Genes 2024, 15(6), 800; https://doi.org/10.3390/genes15060800 - 18 Jun 2024

Cited by 12 | Viewed by 2462

Abstract

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the [...] Read more.

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the Chinese rose genome and classified into three primary groups and five subgroups based on the structural and phylogenetic characteristics. The analysis of the conserved domains, motifs, and gene structure revealed that the RcWRKY genes within the same group had the same exon–intron organization and composition. Chromosome mapping and gene duplication revealed that the RcWRKY genes were randomly dispersed across seven chromosomes. Fragment duplication and refined selection may have influenced the evolution of the WRKY gene family in Chinese rose. The cis-acting elements in the WRKY promoter region revealed that the RcWRKY genes contained numerous abiotic stress response elements. The results of qRT-PCR revealed that the expression of RcWRKY was tissue-specific, with high expression being observed under drought, heat, and salt stress. Notably, RcWRKY49′s expression increased more than fivefold following salt stress, indicating that it is a crucial gene mediating the salt stress response of Chinese rose. These findings shed light on the regulatory role of RcWRKY in the growth and development of Chinese rose, and they serve as a foundation for future molecular breeding programs and gene discovery. Full article

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

► Show Figures

Figure 1

14 pages, 1052 KB

Open AccessEditor’s ChoiceArticle

Associations between Radiomics and Genomics in Non-Small Cell Lung Cancer Utilizing Computed Tomography and Next-Generation Sequencing: An Exploratory Study

by Alessandro Ottaiano, Francesca Grassi, Roberto Sirica, Emanuela Genito, Giovanni Ciani, Vittorio Patanè, Riccardo Monti, Maria Paola Belfiore, Fabrizio Urraro, Mariachiara Santorsola, Alfonso Maria Ponsiglione, Marco Montella, Salvatore Cappabianca, Alfonso Reginelli, Mario Sansone, Giovanni Savarese and Roberta Grassi

Genes 2024, 15(6), 803; https://doi.org/10.3390/genes15060803 - 18 Jun 2024

Cited by 11 | Viewed by 3099

Abstract

Background: Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC). [...] Read more.

Background: Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC). Methods: This exploratory, observational study integrated radiomic perspectives using computed tomography (CT) and genomic perspectives through next-generation sequencing (NGS) applied to liquid biopsies. Associations between radiomic features and genetic mutations were established using the Area Under the Receiver Operating Characteristic curve (AUC-ROC). Machine learning techniques, including Support Vector Machine (SVM) classification, aim to predict genetic mutations based on radiomic features. The prognostic impact of selected gene variants was assessed using Kaplan–Meier curves and Log-rank tests. Results: Sixty-six patients underwent screening, with fifty-seven being comprehensively characterized radiomically and genomically. Predominantly males (68.4%), adenocarcinoma was the prevalent histological type (73.7%). Disease staging is distributed across I/II (38.6%), III (31.6%), and IV (29.8%). Significant correlations were identified with mutations of ROS1 p.Thr145Pro (shape_Sphericity), ROS1 p.Arg167Gln (glszm_ZoneEntropy, firstorder_TotalEnergy), ROS1 p.Asp2213Asn (glszm_GrayLevelVariance, firstorder_RootMeanSquared), and ALK p.Asp1529Glu (glcm_Imc1). Patients with the ROS1 p.Thr145Pro variant demonstrated markedly shorter median survival compared to the wild-type group (9.7 months vs. not reached, p = 0.0143; HR: 5.35; 95% CI: 1.39–20.48). Conclusions: The exploration of the intersection between radiomics and cancer genetics in NSCLC is not only feasible but also holds the potential to improve genetic predictions and enhance prognostic accuracy. Full article

(This article belongs to the Special Issue Molecular Diagnostic and Prognostic Markers of Human Cancers)

► Show Figures

Figure 1

12 pages, 1078 KB

Open AccessEditor’s ChoiceArticle

Genomic Characterization of Quality Wool Traits in Spanish Merino Sheep

by Gabriel Anaya, Nora Laseca, Antonio Granero, Chiraz Ziadi, Francisco Arrebola, Andrés Domingo and Antonio Molina

Genes 2024, 15(6), 795; https://doi.org/10.3390/genes15060795 - 17 Jun 2024

Cited by 8 | Viewed by 2401

Abstract

The native Spanish Merino breed was the founder of all the other Merino and Merino-derived breeds worldwide. Despite the fact that this breed was created and improved to produce the highest quality fine wool, the global wool market crisis led to the wholescale [...] Read more.

The native Spanish Merino breed was the founder of all the other Merino and Merino-derived breeds worldwide. Despite the fact that this breed was created and improved to produce the highest quality fine wool, the global wool market crisis led to the wholescale crossing of most of the herds with breeds for meat purposes. Nevertheless, there are still some purebred animals with a high potential for producing quality wool. The objective of this study was to characterize the current wool quality of the breed and identify genes associated with these parameters. To achieve this, over 12,800 records from the most representative animals of the breed (registered in the herd book) were analyzed using the Australian OFDA 2000 system, for parameters such as fiber diameter (FD), standard deviation (SD), coefficient of variation (CV), fibers over 15 microns (>15%), staple length (SL), and comfort factor (CRV). Additionally, animals with the most extreme FD values were whole-genome sequenced using NGS. Genome-wide association studies (GWAS) determined the association of 74 variants with the different traits studied, which were located in 70 different genes. Of these genes, EDN2, COL18A1, and LRP1B, associated with fibers over 15%, and FGF12 and ADAM17, associated with SL, play a key role in hair follicle growth and development. Our study reveals the great potential for recovering this breed for fine wool production, and identifies five candidate genes whose understanding may aid in that selection process. Full article

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

► Show Figures

Figure 1

12 pages, 2948 KB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Profiling of the α-Amylase (AMY) Gene Family in Potato

by Yudan Duan and Liping Jin

Genes 2024, 15(6), 793; https://doi.org/10.3390/genes15060793 - 17 Jun 2024

Cited by 5 | Viewed by 2632

Abstract

Starch degradation provides energy and signaling molecules for plant growth, development, defense, and stress response. α-amylase (AMY) is one of the most important enzymes in this process. Potato tubers are rich in starch, and the hydrolysis of starch into sugar negatively [...] Read more.

Starch degradation provides energy and signaling molecules for plant growth, development, defense, and stress response. α-amylase (AMY) is one of the most important enzymes in this process. Potato tubers are rich in starch, and the hydrolysis of starch into sugar negatively impacts the frying quality of potato. Despite its importance, the AMY gene family has not been fully explored in potatoes. Here, we performed a detailed analysis of the StAMY gene family to determine its role in potato. Twenty StAMY genes were identified across the potato genome and were divided into three subgroups. The promoters of StAMY genes contained an array of cis-acting elements involved in growth and development, phytohormone signaling, and stress and defense responses. StAMY8, StAMY9, StAMY12, and StAMY20 were specifically expressed in mature tubers. Different StAMY gene family members tended to be upregulated in response to β-aminobutyric acid (BABA), Phytophthora infestans (P. infestans), benzothiadiazole (BTH), heat, salt, and drought stress. In addition, different StAMY gene family members tended to be responsive to abscisic acid (ABA), indole-3-acetic acid (IAA), gibberellic acid (GA3), and 6-benzylaminopurine (BAP) treatment. These results suggest that StAMY gene family members may be involved in starch and sugar metabolism, defense, stress response, and phytohormone signaling. The results of this study may be applicable to other starchy crops and lay a foundation for further research on the functions and regulatory mechanisms of AMY genes. Full article

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

► Show Figures

Figure 1

14 pages, 8402 KB

Open AccessEditor’s ChoiceArticle

Genetic Analysis of Egg Production Traits in Luhua Chickens: Insights from a Multi-Trait Animal Model and a Genome-Wide Association Study

by Qianwen Yang, Xubin Lu, Guohui Li, Huiyong Zhang, Chenghao Zhou, Jianmei Yin, Wei Han and Haiming Yang

Genes 2024, 15(6), 796; https://doi.org/10.3390/genes15060796 - 17 Jun 2024

Cited by 5 | Viewed by 3245

Abstract

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 [...] Read more.

Egg production plays a pivotal role in the economic viability of hens. To analyze the genetic rules of egg production, a total of 3151 Luhua chickens were selected, the egg production traits including egg weight at first laying (Start-EW), egg weight at 43 weeks (EW-43), egg number at 43 weeks (EN-43), and total egg number (EN-All) were recorded. Then, the effects of related factors on egg production traits were explored, using a multi-trait animal model for genetic parameter estimation and a genome-wide association study (GWAS). The results showed that body weight at first egg (BWFE), body weight at 43 weeks (BW-43), age at first egg (AFE), and seasons had significant effects on the egg production traits. Start-EW and EW-43 had moderate heritability of 0.30 and 0.21, while EN-43 and EN-All had low heritability of 0.13 and 0.16, respectively. Start-EW exhibited a robust positive correlation with EW-43, while Start-EW was negatively correlated with EN-43 and EN-All. Furthermore, gene ontology (GO) results indicated that Annexin A2 (ANXA2) and Frizzled family receptor 7 (FZD7) related to EW-43, Cyclin D1 (CCND1) and A2B adenosine receptor (ADORA2B) related to EN-All, and have been found to be mainly involved in metabolism and growth processes, and deserve more attention and further study. This study contributes to accelerating genetic progress in improving low heritability egg production traits in layers, especially in Luhua chickens. Full article

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

► Show Figures

Figure 1

29 pages, 1055 KB

Open AccessEditor’s ChoiceReview

Through the Cat-Map Gateway: A Brief History of Cataract Genetics

by Alan Shiels

Genes 2024, 15(6), 785; https://doi.org/10.3390/genes15060785 - 14 Jun 2024

Cited by 11 | Viewed by 6180

Abstract

Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract is acquired with aging as a multifactorial or complex trait. Cataract [...] Read more.

Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract is acquired with aging as a multifactorial or complex trait. Cataract may also be inherited as a classic Mendelian trait—often with an early or pediatric onset—with or without other ocular and/or systemic features. Since the early 1990s, over 85 genes and loci have been genetically associated with inherited and/or age-related forms of cataract. While many of these underlying genes—including those for lens crystallins, connexins, and transcription factors—recapitulate signature features of lens development and differentiation, an increasing cohort of unpredicted genes, including those involved in cell-signaling, membrane remodeling, and autophagy, has emerged—providing new insights regarding lens homeostasis and aging. This review provides a brief history of gene discovery for inherited and age-related forms of cataract compiled in the Cat-Map database and highlights potential gene-based therapeutic approaches to delay, reverse, or even prevent cataract formation that may help to reduce the increasing demand for cataract surgery. Full article

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

► Show Figures

Figure 1

22 pages, 3141 KB

Open AccessEditor’s ChoiceReview

Clinical Correlation of Transcription Factor SOX3 in Cancer: Unveiling Its Role in Tumorigenesis

by Helen Lima Del Puerto, Ana Paula G. S. Miranda, Dinah Qutob, Enio Ferreira, Felipe H. S. Silva, Bruna M. Lima, Barbara A. Carvalho, Bruna Roque-Souza, Eduardo Gutseit, Diego C. Castro, Emanuele T. Pozzolini, Nayara O. Duarte, Thacyana B. G. Lopes, Daiana Y. O. Taborda, Stella M. Quirino, Ahmed Elgerbi, John S. Choy and Adam Underwood

Genes 2024, 15(6), 777; https://doi.org/10.3390/genes15060777 - 13 Jun 2024

Cited by 7 | Viewed by 2952

Abstract

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, [...] Read more.

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics. Full article

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

► Show Figures

Figure 1

19 pages, 319 KB

Open AccessEditor’s ChoiceReview

Extracellular Vesicles in Multiple Sclerosis: Their Significance in the Development and Possible Applications as Therapeutic Agents and Biomarkers

by Ida Manna, Selene De Benedittis and Danilo Porro

Genes 2024, 15(6), 772; https://doi.org/10.3390/genes15060772 - 12 Jun 2024

Cited by 5 | Viewed by 2650

Abstract

Extracellular vesicles (EVs) are “micro-shuttles” that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic [...] Read more.

Extracellular vesicles (EVs) are “micro-shuttles” that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic acids, and in the modulation of the immune system and neuroinflammation. Because EVs can penetrate the blood–brain barrier and move from the central nervous system to the peripheral circulation, and vice versa, recent studies have shown a substantial role for EVs in several neurological diseases, including multiple sclerosis (MS). MS is a demyelinating disease where the main event is caused by T and B cells triggering an autoimmune reaction against myelin constituents. Recent research has elucidate the potential involvement of extracellular vesicles (EVs) in the pathophysiology of MS, although, to date, their potential role both as agents and therapeutic targets in MS is not fully defined. We present in this review a summary and comprehensive examination of EVs’ involvement in the pathophysiology of multiple sclerosis, exploring their potential applications as biomarkers and indicators of therapy response. Full article

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

16 pages, 1526 KB

Open AccessEditor’s ChoiceArticle

Identifying Regions of the Genome Associated with Conception Rate to the First Service in Holstein Heifers Bred by Artificial Insemination and as Embryo Transfer Recipients

by Victoria C. Kelson, Jennifer N. Kiser, Kimberly M. Davenport, Emaly M. Suarez, Brenda M. Murdoch and Holly L. Neibergs

Genes 2024, 15(6), 765; https://doi.org/10.3390/genes15060765 - 11 Jun 2024

Cited by 4 | Viewed by 2268

Abstract

Heifer conception rate to the first service (HCR1) is defined as the number of heifers that become pregnant to the first breeding service compared to the heifers bred. This study aimed to identify loci associated and gene sets enriched for HCR1 for heifers [...] Read more.

Heifer conception rate to the first service (HCR1) is defined as the number of heifers that become pregnant to the first breeding service compared to the heifers bred. This study aimed to identify loci associated and gene sets enriched for HCR1 for heifers that were bred by artificial insemination (AI, n = 2829) or were embryo transfer (ET, n = 2086) recipients, by completing a genome-wide association analysis and gene set enrichment analysis using SNP data (GSEA-SNP). Three unique loci, containing four positional candidate genes, were associated (p < 1 × 10⁻⁵) with HCR1 for ET recipients, while the GSEA-SNP identified four gene sets (NES ≥ 3) and sixty-two leading edge genes (LEGs) enriched for HCR1. While no loci were associated with HCR1 bred by AI, one gene set and twelve LEGs were enriched (NES ≥ 3) for HCR1 with the GSEA-SNP. This included one gene (PKD2) shared between HCR1 AI and ET services. Identifying loci associated or enriched for HCR1 provides an opportunity to use them as genomic selection tools to facilitate the selection of cattle with higher reproductive efficiency, and to better understand embryonic loss. Full article

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

► Show Figures

Figure 1

13 pages, 2561 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 9 | Viewed by 2610

Abstract

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

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

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

► Show Figures

Figure 1

15 pages, 12702 KB

Open AccessEditor’s ChoiceArticle

Chloroplast Genomes of Vitis flexuosa and Vitis amurensis: Molecular Structure, Phylogenetic, and Comparative Analyses for Wild Plant Conservation

by Ji Eun Kim, Keyong Min Kim, Yang Su Kim, Gyu Young Chung, Sang Hoon Che and Chae Sun Na

Genes 2024, 15(6), 761; https://doi.org/10.3390/genes15060761 - 10 Jun 2024

Cited by 8 | Viewed by 1983

Abstract

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis [...] Read more.

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges. Full article

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

► Show Figures

Figure 1

15 pages, 8294 KB

Open AccessEditor’s ChoiceArticle

Long Noncoding RNA 6302 Regulates Chicken Preadipocyte Differentiation by Targeting SLC22A16

by Xiangfei Ma, Yuehua He, Cong Liu, Tingqi Zhu, Donghua Li, Wenting Li, Guirong Sun and Xiangtao Kang

Genes 2024, 15(6), 758; https://doi.org/10.3390/genes15060758 - 9 Jun 2024

Cited by 4 | Viewed by 1700

Abstract

The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. SLC22A16 is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role [...] Read more.

The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. SLC22A16 is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role in regulating chicken adipogenesis has not been reported. In this study, the function of SLC22A16 in chicken abdominal preadipocytes was investigated. SLC22A16 is significantly upregulated during abdominal adipocyte differentiation. The overexpression of SLC2A16 upregulated the expression of adipogenic marker genes and proliferation-related genes, and promoted the proliferation of adipocytes and the accumulation of triglycerides. The knockdown of SLC22A16 downregulated the expression of adipogenic marker genes and proliferation-related genes, inhibited the proliferation of adipocytes, and impaired the accumulation of triglycerides in adipocytes. In addition, LNC6302 was differentially expressed in abdominal preadipocytes and mature adipocytes, and was significantly positively correlated with the expression of SLC22A16. Interference with LNC6302 inhibits the expression of adipogenic marker genes and proliferation-related genes. The data supported the notion that LNC6302 promotes the differentiation of chicken abdominal adipocytes by cis-regulating the expression of SLC22A16. This study identified the role of SLC22A16 in the differentiation and proliferation of chicken adipocytes, providing a potential target for improving abdominal adipogenesis in chickens. Full article

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

► Show Figures

Figure 1

13 pages, 4458 KB

Open AccessEditor’s ChoiceArticle

Fine Mapping of QTLs for Alkaline Tolerance in Crucian Carp (Carassius auratus) Using Genome-Wide SNP Markers

by Liang Zhang, Baofeng Su, Jing Huang, Limin Zhang, Yumei Chang and Guo Hu

Genes 2024, 15(6), 751; https://doi.org/10.3390/genes15060751 - 7 Jun 2024

Cited by 4 | Viewed by 1628

Abstract

Crucian carp (Carassius auratus) is widely distributed in the world and has become an economically freshwater fish. The population in Lake Dali Nur can tolerate the extreme alkaline environment with alkalinity over 50 mmol/L (pH 9.6), thus providing a special model for [...] Read more.

Crucian carp (Carassius auratus) is widely distributed in the world and has become an economically freshwater fish. The population in Lake Dali Nur can tolerate the extreme alkaline environment with alkalinity over 50 mmol/L (pH 9.6), thus providing a special model for exploring alkali-tolerant molecular markers in an extremely alkaline environment. In this study, we constructed a high-density and high-resolution linkage map with 16,224 SNP markers based on genotyping-by-sequencing (GBS) consisting of 152 progenies and conducted QTL studies for alkali-tolerant traits. The total length of the linkage map was 3918.893 cM, with an average distance of 0.241 cM. Two QTLs for the ammonia-N-tolerant trait were detected on LG27 and LG45. A QTL for the urea-N-tolerant trait was detected on LG27. Interestingly, mapping the two QTLs on LG27 revealed that the mapped genes were both located in the intron of CDC42. GO functional annotation and KEGG enrichment analysis results indicated that the biological functions might be involved in the cell cycle, cellular senescence, MAPK, and Ras signaling pathways. These findings suggest that CDC42 may play an important role in the process of dealing with extremely alkaline environments. Full article

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

► Show Figures

Figure 1

22 pages, 13502 KB

Open AccessEditor’s ChoiceArticle

The Analysis, Description, and Examination of the Maize LAC Gene Family’s Reaction to Abiotic and Biotic Stress

by Tonghan Wang, Yang Liu, Kunliang Zou, Minhui Guan, Yutong Wu, Ying Hu, Haibing Yu, Junli Du and Degong Wu

Genes 2024, 15(6), 749; https://doi.org/10.3390/genes15060749 - 6 Jun 2024

Cited by 5 | Viewed by 2221

Abstract

Laccase (LAC) is a diverse group of genes found throughout the plant genome essential for plant growth and the response to stress by converting monolignin into intricate lignin formations. However, a comprehensive investigation of maize laccase has not yet been documented. A bioinformatics [...] Read more.

Laccase (LAC) is a diverse group of genes found throughout the plant genome essential for plant growth and the response to stress by converting monolignin into intricate lignin formations. However, a comprehensive investigation of maize laccase has not yet been documented. A bioinformatics approach was utilized in this research to conduct a thorough examination of maize (Zea mays L.), resulting in the identification and categorization of 22 laccase genes (ZmLAC) into six subfamilies. The gene structure and motifs of each subgroup were largely consistent. The distribution of the 22 LAC genes was uneven among the maize chromosomes, with the exception of chromosome 9. The differentiation of the genes was based on fragment replication, and the differentiation time was about 33.37 million years ago. ZmLAC proteins are primarily acidic proteins. There are 18 cis-acting elements in the promoter sequences of the maize LAC gene family associated with growth and development, stress, hormones, light response, and stress response. The analysis of tissue-specific expression revealed a high expression of the maize LAC gene family prior to the V9 stage, with minimal expression at post-V9. Upon reviewing the RNA-seq information from the publicly available transcriptome, it was discovered that ZmLAC5, ZmLAC10, and ZmLAC17 exhibited significant expression levels when exposed to various biotic and abiotic stress factors, suggesting their crucial involvement in stress responses and potential value for further research. This study offers an understanding of the functions of the LAC genes in maize’s response to biotic and abiotic stress, along with a theoretical basis for comprehending the molecular processes at play. Full article

(This article belongs to the Special Issue Maize Molecular Genetics and Functional Genomics in 2024)

► Show Figures

Figure 1

11 pages, 250 KB

Open AccessEditor’s ChoiceReview

Unraveling the Genetic Foundations of Broiler Meat Quality: Advancements in Research and Their Impact

by Tian Lu, Bahareldin Ali Abdalla Gibril, Jiguo Xu and Xinwei Xiong

Genes 2024, 15(6), 746; https://doi.org/10.3390/genes15060746 - 6 Jun 2024

Cited by 6 | Viewed by 5957

Abstract

As societal progress elevates living standards, the focus on meat consumption has shifted from quantity to quality. In broiler production, optimizing meat quality has become paramount, prompting efforts to refine various meat attributes. Recent advancements in sequencing technologies have revealed the genome’s complexity, [...] Read more.

As societal progress elevates living standards, the focus on meat consumption has shifted from quantity to quality. In broiler production, optimizing meat quality has become paramount, prompting efforts to refine various meat attributes. Recent advancements in sequencing technologies have revealed the genome’s complexity, surpassing previous conceptions. Through experimentation, numerous genetic elements have been linked to crucial meat quality traits in broiler chickens. This review synthesizes the current understanding of genetic determinants associated with meat quality attributes in broilers. Researchers have unveiled the pivotal insights detailed herein by employing diverse genomic methodologies such as QTL-based investigations, candidate gene studies, single-nucleotide polymorphism screening, genome-wide association studies, and RNA sequencing. These studies have identified numerous genes involved in broiler meat quality traits, including meat lightness (COL1A2 and ACAA2), meat yellowness (BCMO1 and GDPD5), fiber diameter (myostatin and LncIRS1), meat pH (PRDX4), tenderness (CAPN1), and intramuscular fat content (miR-24-3p and ANXA6). Consequently, a comprehensive exploration of these genetic elements is imperative to devise novel molecular markers and potential targets, promising to revolutionize strategies for enhancing broiler meat quality. Full article

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

15 pages, 1865 KB

Open AccessEditor’s ChoiceArticle

Effects of Environmental Hypoxia on Serum Hematological and Biochemical Parameters, Hypoxia-Inducible Factor (hif) Gene Expression and HIF Pathway in Hybrid Sturgeon (Acipenser schrenckii ♂ × Acipenser baerii ♀)

by Yuanyuan Ren, Yuan Tian, Bo Cheng, Yang Liu and Huanhuan Yu

Genes 2024, 15(6), 743; https://doi.org/10.3390/genes15060743 - 5 Jun 2024

Cited by 6 | Viewed by 1754

Abstract

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons (Acipenser [...] Read more.

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons (Acipenser schrenckii ♂ × Acipenser baerii ♀). A total of 180 hybrid sturgeon adults were exposed to dissolved oxygen (DO) levels of 7.00 ± 0.2 mg/L (control, N), 3.5 ± 0.2 mg/L (moderate hypoxia, MH) or 1.00 ± 0.1 mg/L (severe hypoxia, SH) and were sampled at 1 h, 6 h and 24 h after hypoxia. The results showed that the red blood cell (RBC) counts and the hemoglobin (HGB) concentration were significantly increased 6 h and 24 h after hypoxia in the SH group. The serum cortisol concentrations gradually increased with the decrease in the DO levels. Moreover, several serum biochemical parameters (AST, AKP, HBDB, LDH, GLU, TP and T-Bil) were significantly altered at 24 h in the SH group. The HIFs are transcription activators that function as master regulators in hypoxia. In this study, a complete set of six hif genes were identified and characterized in hybrid sturgeon for the first time. After hypoxia, five out of six sturgeon hif genes were significantly differentially expressed in gills, especially hif-1α and hif-3α, with more than 20-fold changes, suggesting their important roles in adaptation to hypoxia in hybrid sturgeon. A meta-analysis indicated that the HIF pathway, a major pathway for adaptation to hypoxic environments, was activated in the liver of the hybrid sturgeon 24 h after the hypoxia challenge. Our study demonstrated that hypoxia, particularly severe hypoxia (1.00 ± 0.1 mg/L), could cause considerable stress for the hybrid sturgeon. These results shed light on their adaptive mechanisms and potential biomarkers for hypoxia tolerance, aiding in aquaculture and conservation efforts. Full article

(This article belongs to the Special Issue Genetic Studies of Fish)

► Show Figures

Figure 1

14 pages, 902 KB

Open AccessEditor’s ChoiceReview

Human Endogenous Retroviruses in Neurodegenerative Diseases

by Gabrielle L. Adler, Kelvin Le, YuHong Fu and Woojin Scott Kim

Genes 2024, 15(6), 745; https://doi.org/10.3390/genes15060745 - 5 Jun 2024

Cited by 14 | Viewed by 6414

Abstract

Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated [...] Read more.

Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated in the pathogenesis of neurodegenerative diseases, a group of CNS diseases characterized by a progressive loss of structure and function of neurons, resulting in cell death and multiple physiological dysfunctions. Much evidence indicates that HERVs are initiators or drivers of neurodegenerative processes in multiple sclerosis and amyotrophic lateral sclerosis, and clinical trials have been designed to target HERVs. In recent years, the role of HERVs has been explored in other major neurodegenerative diseases, including frontotemporal dementia, Alzheimer’s disease and Parkinson’s disease, with some interesting discoveries. This review summarizes and evaluates the past and current research on HERVs in neurodegenerative diseases. It discusses the potential role of HERVs in disease manifestation and neurodegeneration. It critically reviews antiretroviral strategies used in the therapeutic intervention of neurodegenerative diseases. Full article

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

► Show Figures

Figure 1

13 pages, 4555 KB

Open AccessEditor’s ChoiceArticle

A Divergent Platelet Transcriptome in Patients with Lipedema and Lymphedema

by Alliefair Scalise, Anu Aggarwal, Naseer Sangwan, Annelise Hamer, Suman Guntupalli, Huijun Edelyn Park, Jose O. Aleman and Scott J. Cameron

Genes 2024, 15(6), 737; https://doi.org/10.3390/genes15060737 - 4 Jun 2024

Cited by 4 | Viewed by 3258

Abstract

Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, [...] Read more.

Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema. Full article

(This article belongs to the Special Issue Genetics of Obesity)

► Show Figures

Figure 1

16 pages, 1987 KB

Open AccessEditor’s ChoiceArticle

Dual-Model GWAS Analysis and Genomic Selection of Maize Flowering Time-Related Traits

by Zehui Fan, Shaohang Lin, Jiale Jiang, Yukang Zeng, Yao Meng, Jiaojiao Ren and Penghao Wu

Genes 2024, 15(6), 740; https://doi.org/10.3390/genes15060740 - 4 Jun 2024

Cited by 8 | Viewed by 2590

Abstract

An appropriate flowering period is an important selection criterion in maize breeding. It plays a crucial role in the ecological adaptability of maize varieties. To explore the genetic basis of flowering time, GWAS and GS analyses were conducted using an associating panel consisting [...] Read more.

An appropriate flowering period is an important selection criterion in maize breeding. It plays a crucial role in the ecological adaptability of maize varieties. To explore the genetic basis of flowering time, GWAS and GS analyses were conducted using an associating panel consisting of 379 multi-parent DH lines. The DH population was phenotyped for days to tasseling (DTT), days to pollen-shedding (DTP), and days to silking (DTS) in different environments. The heritability was 82.75%, 86.09%, and 85.26% for DTT, DTP, and DTS, respectively. The GWAS analysis with the FarmCPU model identified 10 single-nucleotide polymorphisms (SNPs) distributed on chromosomes 3, 8, 9, and 10 that were significantly associated with flowering time-related traits. The GWAS analysis with the BLINK model identified seven SNPs distributed on chromosomes 1, 3, 8, 9, and 10 that were significantly associated with flowering time-related traits. Three SNPs 3_198946071, 9_146646966, and 9_152140631 showed a pleiotropic effect, indicating a significant genetic correlation between DTT, DTP, and DTS. A total of 24 candidate genes were detected. A relatively high prediction accuracy was achieved with 100 significantly associated SNPs detected from GWAS, and the optimal training population size was 70%. This study provides a better understanding of the genetic architecture of flowering time-related traits and provides an optimal strategy for GS. Full article

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

► Show Figures

Figure 1

17 pages, 6409 KB

Open AccessEditor’s ChoiceArticle

Knockout of the Chlorophyll a Oxygenase Gene OsCAO1 Reduces Chilling Tolerance in Rice Seedlings

by Jiayi Xiong, Genping Wen, Jin Song, Xiaoyi Liu, Qiuhong Chen, Guilian Zhang, Yunhua Xiao, Xiong Liu, Huabing Deng, Wenbang Tang, Feng Wang and Xuedan Lu

Genes 2024, 15(6), 721; https://doi.org/10.3390/genes15060721 - 2 Jun 2024

Cited by 5 | Viewed by 2418

Abstract

Chilling stress is one of the main abiotic factors affecting rice growth and yield. In rice, chlorophyllide a oxygenase encoded by OsCAO1 is responsible for converting chlorophyllide a to chlorophyllide b, playing a crucial role in photosynthesis and thus rice growth. However, [...] Read more.

Chilling stress is one of the main abiotic factors affecting rice growth and yield. In rice, chlorophyllide a oxygenase encoded by OsCAO1 is responsible for converting chlorophyllide a to chlorophyllide b, playing a crucial role in photosynthesis and thus rice growth. However, little is known about the function of OsCAO1 in chilling stress responses. The presence of the cis-acting element involved in low-temperature responsiveness (LTR) in the OsCAO1 promoter implied that OsCAO1 probably is a cold-responsive gene. The gene expression level of OsCAO1 was usually inhibited by low temperatures during the day and promoted by low temperatures at night. The OsCAO1 knockout mutants generated by the CRISPR-Cas9 technology in rice (Oryza sativa L.) exhibited significantly weakened chilling tolerance at the seedling stage. OsCAO1 dysfunction led to the accumulation of reactive oxygen species and malondialdehyde, an increase in relative electrolyte leakage, and a reduction in antioxidant gene expression under chilling stress. In addition, the functional deficiency of OsCAO1 resulted in more severe damage to chloroplast morphology, such as abnormal grana thylakoid stacking, caused by low temperatures. Moreover, the rice yield was reduced in OsCAO1 knockout mutants. Therefore, the elevated expression of OsCAO1 probably has the potential to increase both rice yield and chilling tolerance simultaneously, providing a strategy to cultivate chilling-tolerant rice varieties with high yields. Full article

(This article belongs to the Special Issue Genetic Research and Plant Breeding 2.0)

► Show Figures

Figure 1

17 pages, 2724 KB

Open AccessEditor’s ChoiceArticle

Phylogeny, Genetic Diversity and Population Structure of Fritillaria cirrhosa and Its Relatives Based on Chloroplast Genome Data

by Jiao Huang, Xia Hu, Yong Zhou, Yan-Jie Peng and Zhong Liu

Genes 2024, 15(6), 730; https://doi.org/10.3390/genes15060730 - 2 Jun 2024

Cited by 4 | Viewed by 2069

Abstract

Fritillaria cirrhosa and its relatives have been utilized in traditional Chinese medicine for many years and are under priority protection in China. Despite their medicinal and protective value, research on their phylogeny, genetic diversity, and divergence remains limited. Here, we investigate the chloroplast [...] Read more.

Fritillaria cirrhosa and its relatives have been utilized in traditional Chinese medicine for many years and are under priority protection in China. Despite their medicinal and protective value, research on their phylogeny, genetic diversity, and divergence remains limited. Here, we investigate the chloroplast genome variation architecture of 46 samples of F. cirrhosa and its relatives collected from various regions, encompassing the majority of wild populations across diverse geographical areas. The results indicate abundant variations in 46 accessions including 1659 single-nucleotide polymorphisms and 440 indels. Six variable markers (psbJ, ndhD, ycf1, ndhG, trnT-trnL, and rpl32-trnL) were identified. Phylogenetic and network analysis, population structure analysis, and principal component analysis showed that the 46 accessions formed five clades with significant divergence, which were related to their geographical distribution. The regions spanning from the southern Hengduan Mountains to the Qinghai–Tibet Plateau exhibited the highest levels of genetic diversity. F. cirrhosa and its relatives may have suffered a genetic bottleneck and have a relatively low genetic diversity level. Moreover, geographical barriers and discrete patches may have accelerated population divergence. The study offers novel perspectives on the phylogeny, genetic diversity, and population structure of F. cirrhosa and its relatives, information that can inform conservation and utilization strategies in the future. Full article

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

► Show Figures

Figure 1

11 pages, 6285 KB

Open AccessEditor’s ChoiceArticle

Genetic Identification of Medicinal Citrus Cultivar ‘Local Juhong’ Using Molecular Markers and Genomics

by Peng Chen, Jingbo Liu, Qi Tang, Tie Zhou, Lingxia Guo, Yuanyuan Xu, Lijun Chai, Qiang Xu, Ziniu Deng and Xianxin Li

Genes 2024, 15(6), 719; https://doi.org/10.3390/genes15060719 - 1 Jun 2024

Cited by 4 | Viewed by 1896

Abstract

The citrus cultivar ‘Local Juhong’, which has historically been used as a traditional Chinese medicinal material, originated in Yuanjiang County, Hunan Province.Its parental type and genetic background are indistinct as of yet. Morphological observation shows that ‘Local Juhong’ has a slight oblateness in [...] Read more.

The citrus cultivar ‘Local Juhong’, which has historically been used as a traditional Chinese medicinal material, originated in Yuanjiang County, Hunan Province.Its parental type and genetic background are indistinct as of yet. Morphological observation shows that ‘Local Juhong’ has a slight oblateness in fruit shape, a relatively smooth pericarp, a fine and slightly raised oil vacuole, and an inward concave at the blossom end. The tree form and fruit and leaf morphology of ‘Local Juhong’ are similar to those of ‘Huangpi’ sour orange. To reveal the genetic background of ‘Local Juhong’, 21 citrus accessions were evaluated using nuclear and chloroplast SSR markers and whole-genome SNP information. ‘Local Juhong’ was grouped with mandarins and sub-grouped with ‘Miyagawa Wase’ and ‘Yanxi Wanlu’ in a nuclear SSR analysis, which indicated that its pollen parent might be mandarins. It was closely clustered with orange and pummelo in the chloroplast SSR analysis. The genomic sequence similarity rate of ‘Local Juhong’ with mandarin and pummelo heterozygosity was 70.88%; the main part was the heterozygosity, except for the unknown (19.66%), mandarin (8.73%), and pummelo (3.9%) parts. Thus, ‘Local Juhong’ may be an F₁ hybrid with pummelo as the female parent and mandarin as the male parent, sharing sisterhood with ‘Huangpi’ sour orange. Full article

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

► Show Figures

Figure 1

11 pages, 1230 KB

Open AccessEditor’s ChoiceReview

RNF213 Polymorphisms in Intracranial Artery Dissection

by Marialuisa Zedde, Ilaria Grisendi, Federica Assenza, Manuela Napoli, Claudio Moratti, Claudio Pavone, Lara Bonacini, Giovanna Di Cecco, Serena D’Aniello, Maria Simona Stoenoiu, Alexandre Persu, Franco Valzania and Rosario Pascarella

Genes 2024, 15(6), 725; https://doi.org/10.3390/genes15060725 - 1 Jun 2024

Cited by 4 | Viewed by 2581

Abstract

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial [...] Read more.

The ring finger protein 213 gene (RNF213) is involved in several vascular diseases, both intracranial and systemic ones. Some variants are common in the Asian population and are reported as a risk factor for moyamoya disease, intracranial stenosis and intracranial aneurysms. Among intracranial vascular diseases, both moyamoya disease and intracranial artery dissection are more prevalent in the Asian population. We performed a systematic review of the literature, aiming to assess the rate of RNF213 variants in patients with spontaneous intracranial dissections. Four papers were identified, providing data on 53 patients with intracranial artery dissection. The rate of RNF213 variants is 10/53 (18.9%) and it increases to 10/29 (34.5%), excluding patients with vertebral artery dissection. All patients had the RNF213 p.Arg4810Lys variant. RNF213 variants seems to be involved in intracranial dissections in Asian cohorts. The small number of patients, the inclusion of only patients of Asian descent and the small but non-negligible coexistence with moyamoya disease familiarity might be limiting factors, requiring further studies to confirm these preliminary findings and the embryological interpretation. Full article

(This article belongs to the Section Neurogenomics)

► Show Figures

Figure 1

18 pages, 1617 KB

Open AccessEditor’s ChoiceReview

Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond

by Lucas W. Rowe and Thomas A. Ciulla

Genes 2024, 15(6), 720; https://doi.org/10.3390/genes15060720 - 1 Jun 2024

Cited by 23 | Viewed by 10802

Abstract

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing [...] Read more.

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases. Full article

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

► Show Figures

Figure 1

16 pages, 6292 KB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Complete Chloroplast Genomes of Rubus in China: Hypervariable Regions and Phylogenetic Relationships

by Yufen Xu, Yongquan Li, Yanzhao Chen, Longyuan Wang, Bine Xue, Xianzhi Zhang, Wenpei Song, Wei Guo and Wei Wu

Genes 2024, 15(6), 716; https://doi.org/10.3390/genes15060716 - 31 May 2024

Cited by 8 | Viewed by 1868

Abstract

With more than 200 species of native Rubus, China is considered a center of diversity for this genus. Due to a paucity of molecular markers, the phylogenetic relationships for this genus are poorly understood. In this study, we sequenced and assembled the [...] Read more.

With more than 200 species of native Rubus, China is considered a center of diversity for this genus. Due to a paucity of molecular markers, the phylogenetic relationships for this genus are poorly understood. In this study, we sequenced and assembled the plastomes of 22 out of 204 Chinese Rubus species (including varieties) from three of the eight sections reported in China, i.e., the sections Chamaebatus, Idaeobatus, and Malachobatus. Plastomes were annotated and comparatively analyzed with the inclusion of two published plastomes. The plastomes of all 24 Rubus species were composed of a large single-copy region (LSC), a small single-copy region (SSC), and a pair of inverted repeat regions (IRs), and ranged in length from 155,464 to 156,506 bp. We identified 112 unique genes, including 79 protein-coding genes, 29 transfer RNAs, and four ribosomal RNAs. With highly consistent gene order, these Rubus plastomes showed strong collinearity, and no significant changes in IR boundaries were noted. Nine divergent hotspots were identified based on nucleotide polymorphism analysis: trnH-psbA, trnK-rps16, rps16-trnQ-psbK, petN-psbM, trnT-trnL, petA-psbJ, rpl16 intron, ndhF-trnL, and ycf1. Based on whole plastome sequences, we obtained a clearer phylogenetic understanding of these Rubus species. All sampled Rubus species formed a monophyletic group; however, sections Idaeobatus and Malachobatus were polyphyletic. These data and analyses demonstrate the phylogenetic utility of plastomes for systematic research within Rubus. Full article

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

► Show Figures

Figure 1

17 pages, 1228 KB

Open AccessEditor’s ChoiceReview

Inherited Retinal Diseases and Retinal Organoids as Preclinical Cell Models for Inherited Retinal Disease Research

by Kristen E. Ashworth, Jessica Weisbrod and Brian G. Ballios

Genes 2024, 15(6), 705; https://doi.org/10.3390/genes15060705 - 28 May 2024

Cited by 10 | Viewed by 6121

Abstract

Inherited retinal diseases (IRDs) are a large group of genetically and clinically diverse blinding eye conditions that result in progressive and irreversible photoreceptor degeneration and vision loss. To date, no cures have been found, although strides toward treatments for specific IRDs have been [...] Read more.

Inherited retinal diseases (IRDs) are a large group of genetically and clinically diverse blinding eye conditions that result in progressive and irreversible photoreceptor degeneration and vision loss. To date, no cures have been found, although strides toward treatments for specific IRDs have been made in recent years. To accelerate treatment discovery, retinal organoids provide an ideal human IRD model. This review aims to give background on the development and importance of retinal organoids for the human-based in vitro study of the retina and human retinogenesis and retinal pathologies. From there, we explore retinal pathologies in the context of IRDs and the current landscape of IRD treatment discovery. We discuss the usefulness of retinal organoids in this context (as a patient-derived cell model for IRDs) to precisely understand the pathogenesis and potential mechanisms behind a specific IRD-causing variant of interest. Finally, we discuss the importance and promise of retinal organoids in treatment discovery for IRDs, now and in the future. Full article

(This article belongs to the Special Issue Genetics in Retinal Diseases)

► Show Figures

Figure 1

20 pages, 23634 KB

Open AccessEditor’s ChoiceArticle

Expression of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Candidate Genes EDA2R, PCDH9, and TRAF7 in Normal Human Kidney Development and CAKUT

by Jelena Kelam, Nela Kelam, Natalija Filipović, Luka Komić, Anita Racetin, Dora Komić, Sandra Kostić, Ivana Kuzmić Prusac and Katarina Vukojević

Genes 2024, 15(6), 702; https://doi.org/10.3390/genes15060702 - 28 May 2024

Cited by 9 | Viewed by 2656

Abstract

Approximately half of the cases of chronic kidney disease (CKD) in childhood are caused by congenital anomalies of the kidney and urinary tract (CAKUT). Specific genes were identified as having significant importance in regard to the underlying genetic factors responsible for the CAKUT [...] Read more.

Approximately half of the cases of chronic kidney disease (CKD) in childhood are caused by congenital anomalies of the kidney and urinary tract (CAKUT). Specific genes were identified as having significant importance in regard to the underlying genetic factors responsible for the CAKUT phenotype, and in our research, we focused on analyzing and comparing the expression levels of ectodysplasin A2 receptor (EDA2R), protocadherin9 (PCDH9), and TNF receptor-associated factor 7 (TRAF7) proteins in the cortex and medulla of healthy control kidneys during developmental phases 2, 3, and 4. We also performed an analysis of the area percentages of the mentioned proteins in the cortical and medullary sections of healthy embryonic and fetal kidneys compared to those affected by CAKUT, including duplex kidneys (DK), horseshoe kidneys (HK), hypoplastic kidneys (HYP), and dysplastic kidneys (DYS). We found that the CAKUT candidate gene proteins EDA2R, PCDH9, and TRAF7 are all expressed during normal human kidney development stages. In DYS, the expression of EDA2R was higher than in normal kidneys, likely due to EDA2R’s role in apoptosis, which was upregulated in specific cases and could possibly contribute to the formation of DYS. The expression of PCDH9 was lower in HK, which can be attributed to the possible role of PCDH9 in cell migration suppression. Decreased PCDH9 expression is linked to increased cell migration, potentially contributing to the development of HK. The level of TRAF7 expression was reduced in all examined kidney disorders compared to normal kidneys, suggesting that this reduction might be attributed to the crucial role of TRAF7 in the formation of endothelium and ciliogenesis, both of which are essential for normal kidney development. Further research is required to ascertain the function of these proteins in both the typical development of the kidney and in CAKUT. Full article

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

► Show Figures

Figure 1

11 pages, 7875 KB

Open AccessEditor’s ChoiceArticle

Overexpression of GhGSTF9 Enhances Salt Stress Tolerance in Transgenic Arabidopsis

by Huimin Li, Yihui Liu, Jie Wu, Kexin Chang, Guangqiang Zhang, Hang Zhao, Nianwei Qiu and Ying Bao

Genes 2024, 15(6), 695; https://doi.org/10.3390/genes15060695 - 27 May 2024

Cited by 4 | Viewed by 2348

Abstract

Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to [...] Read more.

Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to its relatively strong tolerance to salt. This characteristic renders it a valuable subject for investigating the molecular mechanisms underlying plant salt tolerance and for identifying genes that confer salt tolerance. In this study, focus was placed on examining a salt-tolerant variety, E991, and a salt-sensitive variety, ZM24. A combined analysis of transcriptomic data from these cotton varieties led to the identification of potential salt stress-responsive genes within the glutathione S-transferase (GST) family. These versatile enzyme proteins, prevalent in animals, plants, and microorganisms, were demonstrated to be involved in various abiotic stress responses. Our findings indicate that suppressing GhGSTF9 in cotton led to a notably salt-sensitive phenotype, whereas heterologous overexpression in Arabidopsis plants decreases the accumulation of reactive oxygen species under salt stress, thereby enhancing salt stress tolerance. This suggests that GhGSTF9 serves as a positive regulator in cotton’s response to salt stress. These results offer new target genes for developing salt-tolerant cotton varieties. Full article

(This article belongs to the Special Issue Cotton Genes, Genetics, and Genomics)

► Show Figures

Figure 1

34 pages, 2981 KB

Open AccessEditor’s ChoiceReview

The Evolving Scenario of ES-SCLC Management: From Biology to New Cancer Therapeutics

by Pamela Trillo Aliaga, Ester Del Signore, Valeria Fuorivia, Gianluca Spitaleri, Riccardo Asnaghi, Ilaria Attili, Carla Corvaja, Ambra Carnevale Schianca, Antonio Passaro and Filippo de Marinis

Genes 2024, 15(6), 701; https://doi.org/10.3390/genes15060701 - 27 May 2024

Cited by 6 | Viewed by 6238

Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease [...] Read more.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge. Full article

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

► Show Figures

Figure 1

13 pages, 2370 KB

Open AccessEditor’s ChoiceArticle

Unlocking the Genetic Identity of Endangered Paphiopedilum Orchids: A DNA Barcoding Approach

by Małgorzata Karbarz, Dominika Szlachcikowska, Angelika Zapał and Agnieszka Leśko

Genes 2024, 15(6), 689; https://doi.org/10.3390/genes15060689 - 26 May 2024

Cited by 6 | Viewed by 2638

Abstract

Orchids of the genus Paphiopedilum, also called slippers, are among the most valued representatives of the Orchidaceae family due to their aesthetic qualities. Due to overexploitation, deforestation, and illegal trade in these plants, especially in the vegetative phase, Paphiopedilum requires special protection. This [...] Read more.

Orchids of the genus Paphiopedilum, also called slippers, are among the most valued representatives of the Orchidaceae family due to their aesthetic qualities. Due to overexploitation, deforestation, and illegal trade in these plants, especially in the vegetative phase, Paphiopedilum requires special protection. This genus is listed in Appendix I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Their precise identification is of great importance for the preservation of genetic resources and biodiversity of the orchid family (Orchidaceae). Therefore, the main objective of the study was to investigate the usefulness of the DNA barcoding technique for the identification of endangered orchids of the genus Paphiopedilum and to determine the effectiveness of five loci: matK, rbcL, ITS2, atpF-atpH and trnH-psbA as potential molecular markers for species of this genus. Among single locus barcodes, matK was the most effective at identifying species (64%). Furthermore, matK, ITS2, matK + rbcL, and matK + trnH-psbA barcodes can be successfully used as a complementary tool to identify Paphiopedilum orchids while supporting morphological data provided by taxonomists. Full article

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

► Show Figures

Figure 1

16 pages, 694 KB

Open AccessEditor’s ChoiceReview

Cardiac Remodeling and Ventricular Pacing: From Genes to Mechanics

by Onoufrios Malikides, Emmanouel Simantirakis, Evangelos Zacharis, Konstantinos Fragkiadakis, George Kochiadakis and Maria Marketou

Genes 2024, 15(6), 671; https://doi.org/10.3390/genes15060671 - 23 May 2024

Cited by 5 | Viewed by 3011

Abstract

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic [...] Read more.

Cardiac remodeling and ventricular pacing represent intertwined phenomena with profound implications for cardiovascular health and therapeutic interventions. This review explores the intricate relationship between cardiac remodeling and ventricular pacing, spanning from the molecular underpinnings to biomechanical alterations. Beginning with an examination of genetic predispositions and cellular signaling pathways, we delve into the mechanisms driving myocardial structural changes and electrical remodeling in response to pacing stimuli. Insights into the dynamic interplay between pacing strategies and adaptive or maladaptive remodeling processes are synthesized, shedding light on the clinical implications for patients with various cardiovascular pathologies. By bridging the gap between basic science discoveries and clinical translation, this review aims to provide a comprehensive understanding of cardiac remodeling in the context of ventricular pacing, paving the way for future advancements in cardiovascular care. Full article

(This article belongs to the Special Issue Cardiovascular Disease: Precision Medicine, Pharmacogenomics and Genetics)

► Show Figures

Figure 1

15 pages, 816 KB

Open AccessEditor’s ChoiceReview

Advances in and Perspectives on Transgenic Technology and CRISPR-Cas9 Gene Editing in Broccoli

by Li Zhang, Sufang Meng, Yumei Liu, Fengqing Han, Tiemin Xu, Zhiwei Zhao and Zhansheng Li

Genes 2024, 15(6), 668; https://doi.org/10.3390/genes15060668 - 23 May 2024

Cited by 7 | Viewed by 4034

Abstract

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in [...] Read more.

Broccoli, a popular international Brassica oleracea crop, is an important export vegetable in China. Broccoli is not only rich in protein, vitamins, and minerals but also has anticancer and antiviral activities. Recently, an Agrobacterium-mediated transformation system has been established and optimized in broccoli, and transgenic transformation and CRISPR-Cas9 gene editing techniques have been applied to improve broccoli quality, postharvest shelf life, glucoraphanin accumulation, and disease and stress resistance, among other factors. The construction and application of genetic transformation technology systems have led to rapid development in broccoli worldwide, which is also good for functional gene identification of some potential traits in broccoli. This review comprehensively summarizes the progress in transgenic technology and CRISPR-Cas9 gene editing for broccoli over the past four decades. Moreover, it explores the potential for future integration of digital and smart technologies into genetic transformation processes, thus demonstrating the promise of even more sophisticated and targeted crop improvements. As the field continues to evolve, these innovations are expected to play a pivotal role in the sustainable production of broccoli and the enhancement of its nutritional and health benefits. Full article

(This article belongs to the Special Issue Molecular Genetics of Important Traits in Cruciferous Vegetables)

► Show Figures

Figure 1

32 pages, 6274 KB

Open AccessEditor’s ChoiceArticle

Hypoxia in the Blue Mussel Mytilus chilensis Induces a Transcriptome Shift Associated with Endoplasmic Reticulum Stress, Metabolism, and Immune Response

by Milton Montúfar-Romero, Valentina Valenzuela-Muñoz, Diego Valenzuela-Miranda and Cristian Gallardo-Escárate

Genes 2024, 15(6), 658; https://doi.org/10.3390/genes15060658 - 22 May 2024

Cited by 9 | Viewed by 2776

Abstract

The increase in hypoxia events, a result of climate change in coastal and fjord ecosystems, impacts the health and survival of mussels. These organisms deploy physiological and molecular responses as an adaptive mechanism to maintain cellular homeostasis under environmental stress. However, the specific [...] Read more.

The increase in hypoxia events, a result of climate change in coastal and fjord ecosystems, impacts the health and survival of mussels. These organisms deploy physiological and molecular responses as an adaptive mechanism to maintain cellular homeostasis under environmental stress. However, the specific effects of hypoxia on mussels of socioeconomic interest, such as Mytilus chilensis, are unknown. Using RNA-seq, we investigated the transcriptomic profiles of the gills, digestive gland, and adductor muscle of M. chilensis under hypoxia (10 days at 2 mg L⁻¹) and reoxygenation (10 days at 6 mg L⁻¹). There were 15,056 differentially expressed transcripts identified in gills, 11,864 in the digestive gland, and 9862 in the adductor muscle. The response varied among tissues, showing chromosomal changes in Chr1, Chr9, and Chr10 during hypoxia. Hypoxia regulated signaling genes in the Toll-like, mTOR, citrate cycle, and apoptosis pathways in gills, indicating metabolic and immunological alterations. These changes suggest that hypoxia induced a metabolic shift in mussels, reducing reliance on aerobic respiration and increasing reliance on anaerobic metabolism. Furthermore, hypoxia appeared to suppress the immune response, potentially increasing disease susceptibility, with negative implications for the mussel culture industry and natural bed populations. This study provides pivotal insights into metabolic and immunological adaptations to hypoxia in M. chilensis, offering candidate genes for adaptive traits. Full article

(This article belongs to the Section Genes & Environments)

► Show Figures

Figure 1

19 pages, 1198 KB

Open AccessEditor’s ChoiceReview

PIWI-Interacting RNAs: A Pivotal Regulator in Neurological Development and Disease

by Xian Pan, Wang Dai, Zhenzhen Wang, Siqi Li, Tao Sun and Nan Miao

Genes 2024, 15(6), 653; https://doi.org/10.3390/genes15060653 - 21 May 2024

Cited by 7 | Viewed by 3409

Abstract

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon [...] Read more.

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon transcripts without the seed pairing. Numerous studies have shown that piRNAs are abundantly expressed in the brain, and many of them are aberrantly regulated in central neural system (CNS) disorders. However, the role of piRNAs in the related developmental and pathological processes is unclear. The elucidation of piRNAs/PIWI would greatly improve the understanding of CNS development and ultimately lead to novel strategies to treat neural diseases. In this review, we summarized the relevant structure, properties, and databases of piRNAs and their functional roles in neural development and degenerative disorders. We hope that future studies of these piRNAs will facilitate the development of RNA-based therapeutics for CNS disorders. Full article

(This article belongs to the Special Issue Advances in Nervous System Disorders)

► Show Figures

Figure 1

15 pages, 18790 KB

Open AccessEditor’s ChoiceArticle

Whole-Transcriptome Analysis Sheds Light on the Biological Contexts of Intramuscular Fat Deposition in Ningxiang Pigs

by Zhao Jin, Hu Gao, Yawei Fu, Ruimin Ren, Xiaoxiao Deng, Yue Chen, Xiaohong Hou, Qian Wang, Gang Song, Ningyu Fan, Haiming Ma, Yulong Yin and Kang Xu

Genes 2024, 15(5), 642; https://doi.org/10.3390/genes15050642 - 19 May 2024

Cited by 5 | Viewed by 2596

Abstract

The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups [...] Read more.

The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups (%) to elucidate potential mechanisms. In summary, 285 differentially expressed genes (DEGs), 14 differentially expressed miRNAs (DEMIs), 83 differentially expressed lncRNAs (DELs), and 79 differentially expressed circRNAs (DECs) were identified. DEGs were widely associated with IMF deposition and liposome differentiation. Furthermore, competing endogenous RNA (ceRNA) regulatory networks were constructed through co-differential expression analyses, which included circRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 47 DECs) and lncRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 36 DELs) regulatory networks. The circRNAs sus-TRPM7_0005, sus-MTUS1_0004, the lncRNAs SMSTRG.4269.1, and MSTRG.7983.2 regulate the expression of six lipid metabolism-related target genes, including PLCB1, BAD, and GADD45G, through the binding sites of 2-4068, miR-7134-3p, and miR-190a. For instance, MSTRG.4269.1 regulates its targets PLCB1 and BAD via miRNA 2_4068. Meanwhile, sus-TRPM7_0005 controls its target LRP5 through ssc-miR-7134-3P. These findings indicate molecular regulatory networks that could potentially be applied for the marker-assisted selection of IMF to enhance pork quality. Full article

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

► Show Figures

Figure 1

21 pages, 4847 KB

Open AccessEditor’s ChoiceArticle

Inverse and Proportional Trans Modulation of Gene Expression in Human Aneuploidies

by Shuai Zhang, Ruixue Wang, Ludan Zhang, James A. Birchler and Lin Sun

Genes 2024, 15(5), 637; https://doi.org/10.3390/genes15050637 - 17 May 2024

Cited by 5 | Viewed by 1983

Abstract

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried [...] Read more.

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionally trans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes in components of gene regulatory complexes.In summary, this study demonstrates the existence of trans-acting effects and compensation mechanisms in human aneuploidies and contributes to our understanding of gene expression regulation in unbalanced genomes and disease states. Full article

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

► Show Figures

Figure 1

15 pages, 4078 KB

Open AccessEditor’s ChoiceArticle

Establishment of Parentage Identification Method for Sea Urchin Strongylocentrotus intermedius Based on SSR-seq Technology

by Xuechun Jiang, Lei Liu, Hao Guo, Peng Liu, Wenzhuo Tian, Fanjiang Ou, Jun Ding, Weijie Zhang and Yaqing Chang

Genes 2024, 15(5), 630; https://doi.org/10.3390/genes15050630 - 16 May 2024

Cited by 5 | Viewed by 1897

Abstract

To establish a parentage identification method for Strongylocentrotus intermedius, 15 microsatellite loci and simple sequence repeat sequencing (SSR-seq) technology were used to perform SSR sequencing and typing of the validation population with known pedigree information and the simulation population. Cervus v3.0 was [...] Read more.

To establish a parentage identification method for Strongylocentrotus intermedius, 15 microsatellite loci and simple sequence repeat sequencing (SSR-seq) technology were used to perform SSR sequencing and typing of the validation population with known pedigree information and the simulation population. Cervus v3.0 was used for gene frequency statistics, simulated analysis, and parentage identification analysis. The results showed that, in validation population, using 15 microsatellite loci, the highest success rate of parent pairs identification was 86%, the highest success rate of female parent identification was 93%, and the highest success rate of male parent identification was 90%. The simulated population was analyzed using 12–15 loci, and the identification rate was up to 90%. In cases where accurate parentage was not achieved, individuals could exhibit genetic similarities with 1–3 male or female parents. Individuals identified as lacking a genetic relationship can be selected as parents to prevent inbreeding. This study shows that parent pairs or single parents of most offspring can be identified successfully using these 15 selected loci. The results lay a foundation for the establishment of a parentage identification method for S. intermedius. Full article

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

► Show Figures

Figure 1

17 pages, 4692 KB

Open AccessEditor’s ChoiceArticle

Genomic and Transcriptome Analysis Reveals the Biosynthesis Network of Cordycepin in Cordyceps militaris

by Linshan Chai, Jianmei Li, Lingling Guo, Shuyu Zhang, Fei Chen, Wanqin Zhu and Yu Li

Genes 2024, 15(5), 626; https://doi.org/10.3390/genes15050626 - 15 May 2024

Cited by 7 | Viewed by 3247

Abstract

Cordycepin is the primary active compound of Cordyceps militaris. However, the definitive genetic mechanism governing cordycepin synthesis in fruiting body growth and development remains elusive, necessitating further investigation. This study consists of 64 C. militaris strains collected from northeast China. The high-yielding [...] Read more.

Cordycepin is the primary active compound of Cordyceps militaris. However, the definitive genetic mechanism governing cordycepin synthesis in fruiting body growth and development remains elusive, necessitating further investigation. This study consists of 64 C. militaris strains collected from northeast China. The high-yielding cordycepin strain CMS19 was selected for the analysis of cordycepin production and the genetic basis of cordycepin anabolism. First, the whole-genome sequencing of CMS19 yielded a final size of 30.96 Mb with 8 contigs and 9781 protein-coding genes. The genome component revealed the presence of four additional secondary metabolite gene clusters compared with other published genomes, suggesting the potential for the production of new natural products. The analyses of evolutionary and genetic differentiation revealed a close relationship between C. militaris and Beauveria bassiana. The population of strains distributed in northeast China exhibited the significant genetic variation. Finally, functional genes associated with cordycepin synthesis were identified using a combination of genomic and transcriptomic analyses. A large number of functional genes associated with energy and purine metabolism were significantly enriched, facilitating the reconstruction of a hypothetical cordycepin metabolic pathway. Therefore, our speculation of the cordycepin metabolism pathway involved 24 genes initiating from the glycolysis and pentose phosphate pathways, progressing through purine metabolism, and culminating in the core region of cordycepin synthesis. These findings could offer fundamental support for scientific utilizations of C. militaris germplasm resources and standardized cultivation for cordycepin production. Full article

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

► Show Figures

Figure 1

13 pages, 1377 KB

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 7 | Viewed by 2625

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)

► Show Figures

Figure 1

13 pages, 3567 KB

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 10 | Viewed by 2702

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)

► Show Figures

Figure 1

27 pages, 2477 KB

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 29 | Viewed by 17287

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)

► Show Figures

Figure 1

17 pages, 4282 KB

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 9 | Viewed by 2958

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)

► Show Figures

Figure 1

15 pages, 6160 KB

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 5 | Viewed by 2223

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)

► Show Figures

Figure 1

12 pages, 3333 KB

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 9 | Viewed by 2359

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)

► Show Figures

Figure 1

21 pages, 1321 KB

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 11 | Viewed by 9840

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)

► Show Figures

Figure 1

18 pages, 872 KB

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 5 | Viewed by 5079

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)

► Show Figures

Figure 1

11 pages, 1597 KB

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 8 | Viewed by 3193

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)

► Show Figures

Figure 1

30 pages, 6195 KB

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 12 | Viewed by 7659

Abstract

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

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

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

► Show Figures

Figure 1

15 pages, 610 KB

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 10 | Viewed by 2642

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)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI