Genes

15 pages, 12702 KiB

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 4 | Viewed by 1543

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)

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15 pages, 8294 KiB

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 2 | Viewed by 1322

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)

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17 pages, 4507 KiB

Open AccessEditor’s ChoiceArticle

Looking into the Quantification of Forensic Samples with Real-Time PCR

by Ugo Ricci, Dario Ciappi, Ilaria Carboni, Claudia Centrone, Irene Giotti, Martina Petti, Brogi Alice and Elisabetta Pelo

Genes 2024, 15(6), 759; https://doi.org/10.3390/genes15060759 - 9 Jun 2024

Viewed by 2329

Abstract

The quantification of human DNA extracts from forensic samples plays a key role in the forensic genetics process, ensuring maximum efficiency and avoiding repeated analyses, over-amplified samples, or unnecessary examinations. In our laboratory, we use the Quantifiler^® Trio system to quantify DNA [...] Read more.

The quantification of human DNA extracts from forensic samples plays a key role in the forensic genetics process, ensuring maximum efficiency and avoiding repeated analyses, over-amplified samples, or unnecessary examinations. In our laboratory, we use the Quantifiler^® Trio system to quantify DNA extracts from a wide range of samples extracted from traces (bloodstains, saliva, semen, tissues, etc.), including swabs from touched objects, which are very numerous in the forensic context. This method has been extensively used continuously for nine years, following an initial validation process, and is part of the ISO/IEC 17025 accredited method. In routine practice, based on the quantitative values determined from the extracts of each trace, we use a standard method or a low-copy-number method that involves repeating the amplification with the generation of a consensus genetic profile. Nowadays, when the quantification results are less than 0.003 ng/μL in the minimum extraction volume (40 μL), we do not proceed with the DNA extract analysis. By verifying the limits of the method, we make a conscious cost-benefit choice, in particular by using the least amount of DNA needed to obtain sufficiently robust genetic profiles appropriate for submission to the Italian DNA Forensic Database. In this work, we present a critical re-evaluation of this phase of the method, which is based on the use of standard curves obtained from the average values of the control DNA analysed in duplicate. Considering the various contributions to uncertainty that are difficult to measure, such as manual pipetting or analytical phases carried out by different operators, we have decided to thoroughly investigate the contribution of variability in the preparation of calibration curves to the final results. Thus, 757 samples from 20 independent experiments were re-evaluated using two different standards for the construction of curves, determining the quantitative differences between the two methods. The experiments also determined the parameters of the slope, Y-intercept, R², and the values of the synthetic control probe to verify how these parameters can provide information on the final outcome of each analysis. The outcome of this revalidation demonstrated that it is preferable to use quantification ranges rather than exact quantitative limits before deciding how to analyse the extracts via PCR or forgoing the determination of profiles. Additionally, we present some preliminary data related to the analysis of samples that would not have been analysed based on the initial validation, from which genetic profiles were obtained after applying a concentration method to the extracts. Our goal is to improve the accredited analytical method, with a careful risk assessment as indicated by accreditation standards, ensuring that no source of evidence is lost in the reconstruction of a criminal event. Full article

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

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20 pages, 6837 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Analysis of Anthocyanidin Reductase Gene Family in Lychee (Litchi chinensis Sonn.)

by Bin Liang, Xiuxu Ye, Huanling Li, Fang Li, Shujun Wang, Chengdong Jiang, Jiabao Wang and Peng Wang

Genes 2024, 15(6), 757; https://doi.org/10.3390/genes15060757 - 8 Jun 2024

Cited by 1 | Viewed by 1627

Abstract

Anthocyanidin reductase (ANR) is a key enzyme regulating anthocyanin synthesis and accumulation in plants. Here, lychee ANR genes were globally identified, their sequence and phylogenetic characteristics were analyzed, and their spatiotemporal expression patterns were characterized. A total of 51 ANR family [...] Read more.

Anthocyanidin reductase (ANR) is a key enzyme regulating anthocyanin synthesis and accumulation in plants. Here, lychee ANR genes were globally identified, their sequence and phylogenetic characteristics were analyzed, and their spatiotemporal expression patterns were characterized. A total of 51 ANR family members were identified in the lychee genome. The length of the encoded amino acid residues ranged from 87 aa to 289 aa, the molecular weight ranged from 9.49 KD to 32.40 KD, and the isoelectric point (pI) ranged from 4.83 to 9.33. Most of the members were acidic proteins. Most members of the LcANR family were located in the cytoplasm. The 51 LcANR family members were unevenly distributed in 11 chromosomes, and their exons and motif conserved structures were significantly different from each other. Promoters in over 90% of LcANR members contained anaerobically induced response elements, and 88% contained photoresponsive elements. Most LcANR family members had low expression in nine lychee tissues and organs (root, young leaf, bud, female flower, male flower, pericarp, pulp, seed, and calli), and some members showed tissue-specific expression patterns. The expression of one gene, LITCHI029356.m1, decreased with the increase of anthocyanin accumulation in ‘Feizixiao’ and ‘Ziniangxi’ pericarp, which was negatively correlated with pericarp coloring. The identified LcANR gene was heterologously expressed in tobacco K326, and the function of the LcANR gene was verified. This study provides a basis for the further study of LcANR function, particularly the role in lychee pericarp coloration. Full article

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

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20 pages, 2095 KiB

Open AccessEditor’s ChoiceArticle

Association between Variants of the TRPV1 Gene and Body Composition in Sub-Saharan Africans

by Maddalena Giannì, Marco Antinucci, Stefania Bertoncini, Luca Taglioli, Cristina Giuliani, Donata Luiselli, Davide Risso, Elisabetta Marini, Gabriella Morini and Sergio Tofanelli

Genes 2024, 15(6), 752; https://doi.org/10.3390/genes15060752 - 7 Jun 2024

Cited by 1 | Viewed by 1538

Abstract

In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved [...] Read more.

In humans, the transient receptor potential vanilloid 1 (TRPV1) gene is activated by exogenous (e.g., high temperatures, irritating compounds such as capsaicin) and endogenous (e.g., endocannabinoids, inflammatory factors, fatty acid metabolites, low pH) stimuli. It has been shown to be involved in several processes including nociception, thermosensation, and energy homeostasis. In this study, we investigated the association between TRPV1 gene variants, sensory perception (to capsaicin and PROP), and body composition (BMI and bioimpedance variables) in human populations. By comparing sequences deposited in worldwide databases, we identified two haplotype blocks (herein referred to as H1 and H2) that show strong stabilizing selection signals (MAF approaching 0.50, Tajima’s D > +4.5) only in individuals with sub-Saharan African ancestry. We therefore studied the genetic variants of these two regions in 46 volunteers of sub-Saharan descent and 45 Italian volunteers (both sexes). Linear regression analyses showed significant associations between TRPV1 diplotypes and body composition, but not with capsaicin perception. Specifically, in African women carrying the H1-b and H2-b haplotypes, a higher percentage of fat mass and lower extracellular fluid retention was observed, whereas no significant association was found in men. Our results suggest the possible action of sex-driven balancing selection at the non-coding sequences of the TRPV1 gene, with adaptive effects on water balance and lipid deposition. Full article

(This article belongs to the Special Issue Genetic Variation and Human Population Evolution)

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13 pages, 4458 KiB

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 2 | Viewed by 1176

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)

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11 pages, 250 KiB

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 2 | Viewed by 4206

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)

13 pages, 1480 KiB

Open AccessEditor’s ChoiceReview

Y Chromosome Story—Ancient Genetic Data as a Supplementary Tool for the Analysis of Modern Croatian Genetic Pool

by Dragan Primorac, Jelena Šarac, Dubravka Havaš Auguštin, Natalija Novokmet, Tamer Bego, Ron Pinhasi, Mario Šlaus, Mario Novak and Damir Marjanović

Genes 2024, 15(6), 748; https://doi.org/10.3390/genes15060748 - 6 Jun 2024

Cited by 1 | Viewed by 4437

Abstract

Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe’s population. SEE, [...] Read more.

Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe’s population. SEE, including modern Croatian territory, was a crucial passage from the Near East and even more distant regions and human populations in this region, as almost any other European population represents a remarkable genetic mixture. Modern humans have continuously occupied this region since the Upper Paleolithic era, and different (pre)historical events have left a distinctive genetic signature on the historical narrative of this region. Our views of its history have been mostly renewed in the last few decades by extraordinary data obtained from Y-chromosome studies. In recent times, the international research community, bringing together geneticists and archaeologists, has steadily released a growing number of ancient genomes from this region, shedding more light on its complex past population dynamics and shaping the genetic pool in Croatia and this part of Europe. Full article

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

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17 pages, 3709 KiB

Open AccessEditor’s ChoiceArticle

Cytogenetic and Molecular Effects of Kaolin’s Foliar Application in Grapevine (Vitis vinifera L.) under Summer’s Stressful Growing Conditions

by Ana Carvalho, Lia-Tânia Dinis, Ana Luzio, Sara Bernardo, José Moutinho-Pereira and José Lima-Brito

Genes 2024, 15(6), 747; https://doi.org/10.3390/genes15060747 - 6 Jun 2024

Cited by 2 | Viewed by 1286

Abstract

Grapevine varieties from “Douro Superior” (NE Portugal) experience high temperatures, solar radiation, and water deficit during the summer. This summer’s stressful growing conditions induce nucleic acids, lipids, and protein oxidation, which cause cellular, physiological, molecular, and biochemical changes. Cell cycle anomalies, mitosis delay, [...] Read more.

Grapevine varieties from “Douro Superior” (NE Portugal) experience high temperatures, solar radiation, and water deficit during the summer. This summer’s stressful growing conditions induce nucleic acids, lipids, and protein oxidation, which cause cellular, physiological, molecular, and biochemical changes. Cell cycle anomalies, mitosis delay, or cell death may occur at the cellular level, leading to reduced plant productivity. However, the foliar application of kaolin (KL) can mitigate the impact of abiotic stress by decreasing leaf temperature and enhancing antioxidant defence. Hence, this study hypothesised that KL-treated grapevine plants growing in NE Portugal would reveal, under summer stressful growing conditions, higher progression and stability of the leaf mitotic cell cycle than the untreated (control) plants. KL was applied after veraison for two years. Leaves, sampled 3 and 5 weeks later, were cytogenetically, molecularly, and biochemically analysed. Globally, integrating these multidisciplinary data confirmed the decreased leaf temperature and enhanced antioxidant defence of the KL-treated plants, accompanied by an improved regularity and completion of the leaf cell cycle relative to the control plants. Nevertheless, the KL efficacy was significantly influenced by the sampling date and/or variety. In sum, the achieved results confirmed the hypothesis initially proposed. Full article

(This article belongs to the Special Issue DNA Damage Repair and Plant Stress Response)

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22 pages, 13502 KiB

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 3 | Viewed by 1557

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)

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13 pages, 1165 KiB

Open AccessEditor’s ChoiceBrief Report

Utilization of qPCR to Determine Duration and Environmental Drivers Contributing to the Persistence of Human DNA in Soil

by Hannah L. Noel, Rebecca L. George, Brittania Bintz, Maureen Peters Hickman and Frankie West

Genes 2024, 15(6), 741; https://doi.org/10.3390/genes15060741 - 5 Jun 2024

Viewed by 1799

Abstract

Little is known about the underlying mechanisms that contribute to the persistence and degradation of DNA within soil. The goals of this study are to determine the duration of mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA) persistence in soils enriched by surface-level human [...] Read more.

Little is known about the underlying mechanisms that contribute to the persistence and degradation of DNA within soil. The goals of this study are to determine the duration of mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA) persistence in soils enriched by surface-level human decomposition and to better understand the contribution of environmental factors. The surface-level decomposition of three human cadavers was documented over 11 weeks. Based on quantitative PCR results, we found nuDNA to persist in soils six weeks post-placement, while mtDNA was recoverable for the entire 11-week decomposition period. Principle components analyses and Spearman’s rank correlations revealed that (1) time, (2) total body score, and (3) weekly average air temperature were significantly correlated with concentrations of nuDNA and mtDNA in soil, suggesting these factors play a role in the degradation of DNA in soils. Full article

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

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15 pages, 1865 KiB

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 2 | Viewed by 1344

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)

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14 pages, 1366 KiB

Open AccessEditor’s ChoiceArticle

The Usefulness of qPCR Data for Sample Pre-Assessment and Interpretation of Genetic Typing Results

by Martina Onofri, Simona Severini, Federica Tommolini, Massimo Lancia, Cristiana Gambelunghe, Luigi Carlini and Eugenia Carnevali

Genes 2024, 15(6), 744; https://doi.org/10.3390/genes15060744 - 5 Jun 2024

Viewed by 1207

Abstract

DNA quantification is a crucial step in the STR typing workflow for human identification purposes. Given the reaction’s nature, qPCR assays may be subjected to the same stochastic effects of traditional PCR for low-input concentrations. The study aims to evaluate the precision of [...] Read more.

DNA quantification is a crucial step in the STR typing workflow for human identification purposes. Given the reaction’s nature, qPCR assays may be subjected to the same stochastic effects of traditional PCR for low-input concentrations. The study aims to evaluate the precision of the PowerQuant^® (Promega) kit assay measurements and the degree of variability for DNA templates falling below the optimal threshold of the PowerPlex^® ESX-17 Fast STR typing kit (Promega). Five three-fold dilutions of the 2800 M control DNA (Promega) were set up. Each dilution (concentrations: 0.05, 0.0167, 0.0055, 0.00185, and 0.000617 ng/µL) was quantified and amplified in four replicates. Variability for qPCR results, STR profile completeness, and EPGs’ peak height were evaluated. The qPCR-estimated concentration of casework samples was correlated with profile completeness and peak intensity, to assess the predictive value of qPCR results for the successful STR typing of scarce samples. qPCR was subjected to stochastic effects, of which the degree was inversely proportional to the initial input template. Quantitation results and the STR profile’s characteristics were strongly correlated. Due to the intrinsic nature of real casework samples, a qPCR-derived DNA concentration threshold for correctly identifying probative STR profiles may be difficult to establish. Quantitation data may be useful in interpreting and corroborating STR typing results and for clearly illustrating them to the stakeholders. Full article

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

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14 pages, 902 KiB

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 7 | Viewed by 3150

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)

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22 pages, 4103 KiB

Open AccessEditor’s ChoiceReview

Effects of Pathogenic Mutants of the Neuroprotective RNase 5-Angiogenin in Amyotrophic Lateral Sclerosis (ALS)

by Giovanni Gotte

Genes 2024, 15(6), 738; https://doi.org/10.3390/genes15060738 - 4 Jun 2024

Viewed by 1654

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic [...] Read more.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic aggregates. However, efficacious therapeutic approaches are still lacking. Notably, heterozygous missense mutations affecting the gene coding for RNase 5, an enzyme also called angiogenin (ANG), were found to favor ALS onset. This is also true for the less-studied but angiogenic RNase 4. This review reports the substrate targets and illustrates the neuroprotective role of native ANG in the neo-vascularization of motoneurons. Then, it discusses the molecular determinants of many pathogenic ANG mutants, which almost always cause loss of function related to ALS, resulting in failures in angiogenesis and motoneuron protection. In addition, ANG mutations are sometimes combined with variants of other factors, thereby potentiating ALS effects. However, the activity of the native ANG enzyme should be finely balanced, and not excessive, to avoid possible harmful effects. Considering the interplay of these angiogenic RNases in many cellular processes, this review aims to stimulate further investigations to better elucidate the consequences of mutations in ANG and/or RNase 4 genes, in order to achieve early diagnosis and, possibly, successful therapies against ALS. Full article

(This article belongs to the Special Issue Research Strategies to Unveil the Genetic and Molecular Basis of ALS)

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13 pages, 4555 KiB

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 2 | Viewed by 2396

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)

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16 pages, 1987 KiB

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 4 | Viewed by 1816

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)

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8 pages, 1703 KiB

Open AccessEditor’s ChoicePerspective

Hope on the Horizon? Aptamers in Diagnosis of Invasive Fungal Infections

by Sadegh Khodavaisy and Jianping Xu

Genes 2024, 15(6), 733; https://doi.org/10.3390/genes15060733 - 3 Jun 2024

Viewed by 1312

Abstract

Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due to their stability, ease of production, and specificity to signature molecules of fungal pathogens, short single-stranded sequences of DNA, RNA, and XNA, [...] Read more.

Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due to their stability, ease of production, and specificity to signature molecules of fungal pathogens, short single-stranded sequences of DNA, RNA, and XNA, collectively called aptamers, have emerged as promising diagnostic markers. In this perspective, we summarize recent progress in aptamer-based diagnostic tools for IFIs and discuss how these tools could potentially meet the needs and provide economical and simple solutions for point-of-care for better management of IFIs. Full article

(This article belongs to the Special Issue Feature Papers in Microbial Genetics in 2024)

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24 pages, 3745 KiB

Open AccessEditor’s ChoiceArticle

Genetic Differentiation of Reed Canarygrass (Phalaris arundinacea L.) within Eastern Europe and Eurasia

by Neil O. Anderson, Edvina Krokaitė-Kudakienė, Lina Jocienė, Tomas Rekašius, Olga A. Chernyagina, Algimantas Paulauskas and Eugenija Kupčinskienė

Genes 2024, 15(6), 734; https://doi.org/10.3390/genes15060734 - 3 Jun 2024

Cited by 1 | Viewed by 1115

Abstract

Worldwide molecular research of economically important Phalaris arundinacea (Poaceae) is mainly focused on the invasions of this species from Europe to North America. Until the present study, the genetic diversity of the P. arundinacea had not been studied across the Baltic countries. The [...] Read more.

Worldwide molecular research of economically important Phalaris arundinacea (Poaceae) is mainly focused on the invasions of this species from Europe to North America. Until the present study, the genetic diversity of the P. arundinacea had not been studied across the Baltic countries. The objective of this research is to evaluate the diversity of Lithuanian populations of P. arundinacea at simple sequence repeat (SSR) loci comparatively among populations of the Baltic countries, Luxembourg, and the Russian Far East (Eurasian), evaluating differentiation between Lithuanian populations and ornamental accessions, and relating these with environmental features. For six selected Lithuanian river basin populations, GBS low density SNPs were used to determine genetic diversity. Bayesian analysis showed that Eurasian populations of Phalaris arundinacea consist of two gene clusters. Statistically significant genetic differentiation among European and Eurasian populations was documented. Lithuanian genotypes growing naturally along rivers are genetically distinct from cultivated ornamentals. GBS-SNPs divided the six selected Nemunas river basins into three distinct groups with one, two, or three rivers in separate groupings for genetic diversity. Genetic diversity is primarily within, rather than among, Lithuanian, eastern European, and Eurasian populations of P. arundinacea across the continent. Thus, restoration efforts would benefit from local population seed origination. Full article

(This article belongs to the Section Genes & Environments)

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18 pages, 4737 KiB

Open AccessEditor’s ChoiceArticle

Extracellular Vesicles from NSC-34 MN-like Cells Transfected with Mutant SOD1 Modulate Inflammatory Status of Raw 264.7 Macrophages

by Elisabetta Carata, Marco Muci, Stefania Mariano, Simona Di Giulio, Annamaria Nigro, Alessandro Romano and Elisa Panzarini

Genes 2024, 15(6), 735; https://doi.org/10.3390/genes15060735 - 3 Jun 2024

Cited by 3 | Viewed by 1711

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs–macrophage [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting the brain and spinal cord. Non-neuronal cells, including macrophages, may contribute to the disruption of motor neurons (MNs), neuromuscular junction dismantling and clinical signs of ALS. Understanding the modality and the effect of MNs–macrophage communication is pivotal. Here, we focus on extracellular vesicle (EVS)-mediated communication and, in particular, we analyze the response of macrophages. NSC-34 cells transfected with mutant SOD1 (G93A, A4V, G85R, G37R) and differentiated towards MN-like cells, and Raw 264.7 macrophages are the cellular models of the study. mSOD1 NSC-34 cells release a high number of vesicles, both large-lEVs (300 nm diameter) and small-sEVs (90 nm diameter), containing inflammation-modulating molecules, and are efficiently taken up by macrophages. RT-PCR analysis of inflammation mediators demonstrated that the conditioned medium of mSOD1 NSC-34 cells polarizes Raw 264.7 macrophages towards both pro-inflammatory and anti-inflammatory phenotypes. sEVs act on macrophages in a time-dependent manner: an anti-inflammatory response mediated by TGFβ firstly starts (12 h); successively, the response shifts towards a pro-inflammation IL-1β-mediated (48 h). The response of macrophages is strictly dependent on the SOD1 mutation type. The results suggest that EVs impact physiological and behavioral macrophage processes and are of potential relevance to MN degeneration. Full article

(This article belongs to the Special Issue Research Strategies to Unveil the Genetic and Molecular Basis of ALS)

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8 pages, 460 KiB

Open AccessEditor’s ChoiceArticle

Polymorphisms in the Dopaminergic Receptor D3 Gene Correlate with Disease Progression Rate in Relapsing–Remitting Multiple Sclerosis Patients

by Marco Ferrari, Domizia Vecchio, Sandra D’Alfonso, Alessandra Gemma, Franca Marino, Cristoforo Comi and Marco Cosentino

Genes 2024, 15(6), 736; https://doi.org/10.3390/genes15060736 - 3 Jun 2024

Cited by 2 | Viewed by 1243

Abstract

Background: Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single [...] Read more.

Background: Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single nucleotide polymorphisms (SNPs) in dopaminergic receptor (DR) genes have been extensively studied, their role in MS progression remains unexplored. Therefore, the aim of this explorative study is to investigate the potential association between functional SNPs in DR genes and MS progression. Methods: Caucasian patients with relapsing–remitting (RR) MS were enrolled, and disease progression assessed by the Multiple Sclerosis Severity Score (MSSS). Results: Out of the 59 RRMS patients enrolled, those with the G/G genotype for rs6280 and rs1800828 SNPs in DRD3 showed significantly higher MSSSs compared to those with ancestral and heterozygous genotypes. Conclusions: If confirmed in a larger prospective study, the reported findings could contribute to a better understanding of MS pathophysiological mechanisms, opening the way for the identification of marker(s) for assessing MS progression as well as novel therapeutic strategies. A personalized approach to MS management has the potential to improve the overall well-being of MS patients and alleviate the burden on their caregivers. Full article

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

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17 pages, 6409 KiB

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 1 | Viewed by 1795

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)

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14 pages, 2702 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiota, Human Blood Metabolites, and Esophageal Cancer: A Mendelian Randomization Study

by Xiuzhi Li, Bingchen Xu, Han Yang and Zhihua Zhu

Genes 2024, 15(6), 729; https://doi.org/10.3390/genes15060729 - 2 Jun 2024

Viewed by 2778

Abstract

Background: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear. Purpose: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis. Methods: [...] Read more.

Background: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear. Purpose: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis. Methods: Genome-wide association studies (GWASs) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWAS of esophageal cancer specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and ESCA, mediation MR analyses were performed for 1091 blood metabolites and 309 metabolite ratios. Results: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with ESCA but all the 12 gut microbiota metabolic pathways with ESCA indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to ESCA. Conclusion: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and ESCA. Full article

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

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17 pages, 2724 KiB

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 1 | Viewed by 1538

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)

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21 pages, 4499 KiB

Open AccessEditor’s ChoiceArticle

Transcriptional Comparison Reveals Differential Resistance Mechanisms between CMV-Resistant PBC688 and CMV-Susceptible G29

by Guangjun Guo, Baogui Pan, Chengsheng Gong, Shubin Wang, Jinbing Liu, Changzhou Gao and Weiping Diao

Genes 2024, 15(6), 731; https://doi.org/10.3390/genes15060731 - 2 Jun 2024

Viewed by 1413

Abstract

The Cucumber mosaic virus (CMV) presents a significant threat to pepper cultivation worldwide, leading to substantial yield losses. We conducted a transcriptional comparative study between CMV-resistant (PBC688) and -susceptible (G29) pepper accessions to understand the mechanisms of CMV resistance. PBC688 effectively suppressed CMV [...] Read more.

The Cucumber mosaic virus (CMV) presents a significant threat to pepper cultivation worldwide, leading to substantial yield losses. We conducted a transcriptional comparative study between CMV-resistant (PBC688) and -susceptible (G29) pepper accessions to understand the mechanisms of CMV resistance. PBC688 effectively suppressed CMV proliferation and spread, while G29 exhibited higher viral accumulation. A transcriptome analysis revealed substantial differences in gene expressions between the two genotypes, particularly in pathways related to plant–pathogen interactions, MAP kinase, ribosomes, and photosynthesis. In G29, the resistance to CMV involved key genes associated with calcium-binding proteins, pathogenesis-related proteins, and disease resistance. However, in PBC688, the crucial genes contributing to CMV resistance were ribosomal and chlorophyll a–b binding proteins. Hormone signal transduction pathways, such as ethylene (ET) and abscisic acid (ABA), displayed distinct expression patterns, suggesting that CMV resistance in peppers is associated with ET and ABA. These findings deepen our understanding of CMV resistance in peppers, facilitating future research and variety improvement. Full article

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

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18 pages, 2694 KiB

Open AccessEditor’s ChoiceArticle

Radiogenomics-Based Risk Prediction of Glioblastoma Multiforme with Clinical Relevance

by Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D. Chan, Pora Kim and Xiaobo Zhou

Genes 2024, 15(6), 718; https://doi.org/10.3390/genes15060718 - 1 Jun 2024

Cited by 2 | Viewed by 2419

Abstract

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients’ survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction [...] Read more.

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients’ survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed to develop a prognostic model to evaluate the tumor progression potential of GBM patients following standard therapies. We applied a dictionary learning scheme to obtain imaging features of GBM patients with PsP or true tumor progression (TTP) from the Wake dataset. Based on these radiographic features, we conducted a radiogenomics analysis to identify the significantly associated genes. These significantly associated genes were used as features to construct a 2YS (2-year survival rate) logistic regression model. GBM patients were classified into low- and high-survival risk groups based on the individual 2YS scores derived from this model. We tested our model using an independent The Cancer Genome Atlas Program (TCGA) dataset and found that 2YS scores were significantly associated with the patient’s overall survival. We used two cohorts of the TCGA data to train and test our model. Our results show that the 2YS scores-based classification results from the training and testing TCGA datasets were significantly associated with the overall survival of patients. We also analyzed the survival prediction ability of other clinical factors (gender, age, KPS (Karnofsky performance status), normal cell ratio) and found that these factors were unrelated or weakly correlated with patients’ survival. Overall, our studies have demonstrated the effectiveness and robustness of the 2YS model in predicting the clinical outcomes of GBM patients after standard therapies. Full article

(This article belongs to the Section Neurogenomics)

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11 pages, 6285 KiB

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 3 | Viewed by 1375

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)

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18 pages, 1617 KiB

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 11 | Viewed by 6166

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)

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14 pages, 5622 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Robertsonian Translocation between Human Chromosomes 21 and 22, Inherited across Three Generations, without Any Phenotypic Effect

by Concetta Federico, Desiree Brancato, Francesca Bruno, Daiana Galvano, Mariella Caruso and Salvatore Saccone

Genes 2024, 15(6), 722; https://doi.org/10.3390/genes15060722 - 1 Jun 2024

Cited by 1 | Viewed by 3209

Abstract

Chromosomal translocations can result in phenotypic effects of varying severity, depending on the position of the breakpoints and the rearrangement of genes within the interphase nucleus of the translocated chromosome regions. Balanced translocations are often asymptomatic phenotypically and are typically detected due to [...] Read more.

Chromosomal translocations can result in phenotypic effects of varying severity, depending on the position of the breakpoints and the rearrangement of genes within the interphase nucleus of the translocated chromosome regions. Balanced translocations are often asymptomatic phenotypically and are typically detected due to a decrease in fertility resulting from issues during meiosis. Robertsonian translocations are among the most common chromosomal abnormalities, often asymptomatic, and can persist in the population as a normal polymorphism. We serendipitously discovered a Robertsonian translocation between chromosome 21 and chromosome 22, which is inherited across three generations without any phenotypic effect, notably only in females. In situ hybridization with alpha-satellite DNAs revealed the presence of both centromeric sequences in the translocated chromosome. The reciprocal translocation resulted in a partial deletion of the short arm of both chromosomes 21, and 22, with the ribosomal RNA genes remaining present in the middle part of the new metacentric chromosome. The rearrangement did not cause alterations to the long arm. The spread of an asymptomatic heterozygous chromosomal polymorphism in a population can lead to mating between heterozygous individuals, potentially resulting in offspring with a homozygous chromosomal configuration for the anomaly they carry. This new karyotype may not produce phenotypic effects in the individual who presents it. The frequency of karyotypes with chromosomal rearrangements in asymptomatic heterozygous form in human populations is likely underestimated, and molecular karyotype by array Comparative Genomic Hybridization (array-CGH) analysis does not allow for the identification of this type of chromosomal anomaly, making classical cytogenetic analysis the preferred method for obtaining clear results on a karyotype carrying a balanced rearrangement. Full article

(This article belongs to the Special Issue Chromosomal Rearrangements in the Light of Evolutionary Genomics)

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15 pages, 1065 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Shapley Values Enhances Transcriptomics Insights across Some Common Uterine Pathologies

by José A. Castro-Martínez, Eva Vargas, Leticia Díaz-Beltrán and Francisco J. Esteban

Genes 2024, 15(6), 723; https://doi.org/10.3390/genes15060723 - 1 Jun 2024

Cited by 3 | Viewed by 1773

Abstract

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing [...] Read more.

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Genetic Causes of Human Infertility)

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11 pages, 1230 KiB

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

Viewed by 1756

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)

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20 pages, 2274 KiB

Open AccessEditor’s ChoiceReview

Molecular Mechanisms Governing Sight Loss in Inherited Cone Disorders

by Chloe Brotherton and Roly Megaw

Genes 2024, 15(6), 727; https://doi.org/10.3390/genes15060727 - 1 Jun 2024

Cited by 1 | Viewed by 2440

Abstract

Inherited cone disorders (ICDs) are a heterogeneous sub-group of inherited retinal disorders (IRDs), the leading cause of sight loss in children and working-age adults. ICDs result from the dysfunction of the cone photoreceptors in the macula and manifest as the loss of colour [...] Read more.

Inherited cone disorders (ICDs) are a heterogeneous sub-group of inherited retinal disorders (IRDs), the leading cause of sight loss in children and working-age adults. ICDs result from the dysfunction of the cone photoreceptors in the macula and manifest as the loss of colour vision and reduced visual acuity. Currently, 37 genes are associated with varying forms of ICD; however, almost half of all patients receive no molecular diagnosis. This review will discuss the known ICD genes, their molecular function, and the diseases they cause, with a focus on the most common forms of ICDs, including achromatopsia, progressive cone dystrophies (CODs), and cone–rod dystrophies (CORDs). It will discuss the gene-specific therapies that have emerged in recent years in order to treat patients with some of the more common ICDs. Full article

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

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17 pages, 4566 KiB

Open AccessEditor’s ChoiceArticle

Construction of a Full-Length Transcriptome of Western Honeybee Midgut Tissue and Improved Genome Annotation

by He Zang, Sijia Guo, Shunan Dong, Yuxuan Song, Kunze Li, Xiaoxue Fan, Jianfeng Qiu, Yidi Zheng, Haibin Jiang, Ying Wu, Yang Lü, Dafu Chen and Rui Guo

Genes 2024, 15(6), 728; https://doi.org/10.3390/genes15060728 - 1 Jun 2024

Cited by 1 | Viewed by 1675

Abstract

Honeybees are an indispensable pollinator in nature with pivotal ecological, economic, and scientific value. However, a full-length transcriptome for Apis mellifera, assembled with the advanced third-generation nanopore sequencing technology, has yet to be reported. Here, nanopore sequencing of the midgut tissues of [...] Read more.

Honeybees are an indispensable pollinator in nature with pivotal ecological, economic, and scientific value. However, a full-length transcriptome for Apis mellifera, assembled with the advanced third-generation nanopore sequencing technology, has yet to be reported. Here, nanopore sequencing of the midgut tissues of uninoculated and Nosema ceranae-inoculated A. mellifera workers was conducted, and the full-length transcriptome was then constructed and annotated based on high-quality long reads. Next followed improvement of sequences and annotations of the current reference genome of A. mellifera. A total of 5,942,745 and 6,664,923 raw reads were produced from midguts of workers at 7 days post-inoculation (dpi) with N. ceranae and 10 dpi, while 7,100,161 and 6,506,665 raw reads were generated from the midguts of corresponding uninoculated workers. After strict quality control, 6,928,170, 6,353,066, 5,745,048, and 6,416,987 clean reads were obtained, with a length distribution ranging from 1 kb to 10 kb. Additionally, 16,824, 17,708, 15,744, and 18,246 full-length transcripts were respectively detected, including 28,019 nonredundant ones. Among these, 43,666, 30,945, 41,771, 26,442, and 24,532 full-length transcripts could be annotated to the Nr, KOG, eggNOG, GO, and KEGG databases, respectively. Additionally, 501 novel genes (20,326 novel transcripts) were identified for the first time, among which 401 (20,255), 193 (13,365), 414 (19,186), 228 (12,093), and 202 (11,703) were respectively annotated to each of the aforementioned five databases. The expression and sequences of three randomly selected novel transcripts were confirmed by RT-PCR and Sanger sequencing. The 5′ UTR of 2082 genes, the 3′ UTR of 2029 genes, and both the 5′ and 3′ UTRs of 730 genes were extended. Moreover, 17,345 SSRs, 14,789 complete ORFs, 1224 long non-coding RNAs (lncRNAs), and 650 transcription factors (TFs) from 37 families were detected. Findings from this work not only refine the annotation of the A. mellifera reference genome, but also provide a valuable resource and basis for relevant molecular and -omics studies. Full article

(This article belongs to the Special Issue Genomics, Transcriptomics, and Proteomics of Insects)

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16 pages, 6292 KiB

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 2 | Viewed by 1251

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)

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16 pages, 498 KiB

Open AccessEditor’s ChoiceArticle

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study

by Antonios Ragkousis, Dimitrios Kazantzis, Ilias Georgalas, Panagiotis Theodossiadis, Christos Kroupis and Irini Chatziralli

Genes 2024, 15(6), 712; https://doi.org/10.3390/genes15060712 - 30 May 2024

Viewed by 1234

Abstract

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation [...] Read more.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3′G(801)A] for SDF-1 gene was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02–6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01–7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion. Full article

(This article belongs to the Special Issue Genetic Research of Retinal Diseases)

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22 pages, 3101 KiB

Open AccessEditor’s ChoiceArticle

Characterization of the Hepatic Transcriptome for Divergent Immune-Responding Sheep Following Natural Exposure to Gastrointestinal Nematodes

by Olivia Willoughby, Niel A. Karrow, Samla Marques Freire Cunha, Victoria Asselstine, Bonnie A. Mallard and Ángela Cánovas

Genes 2024, 15(6), 713; https://doi.org/10.3390/genes15060713 - 30 May 2024

Viewed by 1338

Abstract

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host’s response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the [...] Read more.

Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host’s response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high (n = 5) or medium (n = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls (n = 4), and with biased antibody-mediated (AbMR, n = 5) or cell-mediated (CMR, n = 5) adaptive immune responsiveness compared to uninfected controls (n = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection. Full article

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

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4 pages, 154 KiB

Open AccessEditor’s ChoiceEditorial

Pharmacogenomics: Challenges and Future

by Mariamena Arbitrio

Genes 2024, 15(6), 714; https://doi.org/10.3390/genes15060714 - 30 May 2024

Viewed by 3078

Abstract

Over the last few decades, the implementation of pharmacogenomics (PGx) in clinical practice has improved tailored drug prescriptions [...] Full article

(This article belongs to the Special Issue Pharmacogenomics: Challenges and Future)

15 pages, 4848 KiB

Open AccessEditor’s ChoiceArticle

Detection Method for Gene Doping in a Mouse Model Expressing Human Erythropoietin from Adeno-Associated Virus Vector-9

by Takehito Sugasawa, Atsushi Hirokawa, Norihiro Otani, Yasuharu Kanki, Kieu DM Nguyen, Tohru Takemasa, Koichi Watanabe, Yoshinori Takeuchi, Naoya Yahagi and Yoichiro Takahashi

Genes 2024, 15(6), 709; https://doi.org/10.3390/genes15060709 - 29 May 2024

Cited by 2 | Viewed by 2318

Abstract

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to [...] Read more.

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9, including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future. Full article

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

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25 pages, 3165 KiB

Open AccessEditor’s ChoiceReview

Determinants of Chromatin Organization in Aging and Cancer—Emerging Opportunities for Epigenetic Therapies and AI Technology

by Rogerio M. Castilho, Leonard S. Castilho, Bruna H. Palomares and Cristiane H. Squarize

Genes 2024, 15(6), 710; https://doi.org/10.3390/genes15060710 - 29 May 2024

Cited by 1 | Viewed by 2893

Abstract

This review article critically examines the pivotal role of chromatin organization in gene regulation, cellular differentiation, disease progression and aging. It explores the dynamic between the euchromatin and heterochromatin, coded by a complex array of histone modifications that orchestrate essential cellular processes. We [...] Read more.

This review article critically examines the pivotal role of chromatin organization in gene regulation, cellular differentiation, disease progression and aging. It explores the dynamic between the euchromatin and heterochromatin, coded by a complex array of histone modifications that orchestrate essential cellular processes. We discuss the pathological impacts of chromatin state misregulation, particularly in cancer and accelerated aging conditions such as progeroid syndromes, and highlight the innovative role of epigenetic therapies and artificial intelligence (AI) in comprehending and harnessing the histone code toward personalized medicine. In the context of aging, this review explores the use of AI and advanced machine learning (ML) algorithms to parse vast biological datasets, leading to the development of predictive models for epigenetic modifications and providing a framework for understanding complex regulatory mechanisms, such as those governing cell identity genes. It supports innovative platforms like CEFCIG for high-accuracy predictions and tools like GridGO for tailored ChIP-Seq analysis, which are vital for deciphering the epigenetic landscape. The review also casts a vision on the prospects of AI and ML in oncology, particularly in the personalization of cancer therapy, including early diagnostics and treatment optimization for diseases like head and neck and colorectal cancers by harnessing computational methods, AI advancements and integrated clinical data for a transformative impact on healthcare outcomes. Full article

(This article belongs to the Section Epigenomics)

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14 pages, 1691 KiB

Open AccessEditor’s ChoiceArticle

Genome Size Variation in Sesamum indicum L. Germplasm from Niger

by Najat Takvorian, Hamissou Zangui, Abdel Kader Naino Jika, Aïda Alouane and Sonja Siljak-Yakovlev

Genes 2024, 15(6), 711; https://doi.org/10.3390/genes15060711 - 29 May 2024

Viewed by 1302

Abstract

Sesamum indicum L. (Pedaliaceae) is one of the most economically important oil crops in the world, thanks to the high oil content of its seeds and its nutritional value. It is cultivated all over the world, mainly in Asia and Africa. Well adapted [...] Read more.

Sesamum indicum L. (Pedaliaceae) is one of the most economically important oil crops in the world, thanks to the high oil content of its seeds and its nutritional value. It is cultivated all over the world, mainly in Asia and Africa. Well adapted to arid environments, sesame offers a good opportunity as an alternative subsistence crop for farmers in Africa, particularly Niger, to cope with climate change. For the first time, the variation in genome size among 75 accessions of the Nigerien germplasm was studied. The sample was collected throughout Niger, revealing various morphological, biochemical and phenological traits. For comparison, an additional accession from Thailand was evaluated as an available Asian representative. In the Niger sample, the 2C DNA value ranged from 0.77 to 1 pg (753 to 978 Mbp), with an average of 0.85 ± 0.037 pg (831 Mbp). Statistical analysis showed a significant difference in 2C DNA values among 58 pairs of Niger accessions (p-value < 0.05). This significant variation indicates the likely genetic diversity of sesame germplasm, offering valuable insights into its possible potential for climate-resilient agriculture. Our results therefore raise a fundamental question: is intraspecific variability in the genome size of Nigerien sesame correlated with specific morphological and physiological traits? Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Cytogenomics")

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20 pages, 23634 KiB

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 4 | Viewed by 1801

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)

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12 pages, 3745 KiB

Open AccessEditor’s ChoiceArticle

Placental Transcriptome Analysis in Connection with Low Litter Birth Weight Phenotype (LBWP) Sows

by Julia Linck Moroni, Stephen Tsoi, Irene I. Wenger, Graham S. Plastow and Michael K. Dyck

Genes 2024, 15(6), 703; https://doi.org/10.3390/genes15060703 - 28 May 2024

Viewed by 1388

Abstract

It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the [...] Read more.

It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the litter birth weight phenotype (LBWP) in sows, thereby impacting the BW of entire litters, but the biological and molecular pathways behind this phenomenon are largely unknown. The aim of this study was to investigate the differential gene expression in placental tissues at day 30 of gestation between low LBWP (LLBWP) vs. high LBWP (HLBWP) sows from a purebred Large White maternal line. Using mRNA sequencing, we found 45 differentially expressed genes (DEGs) in placental tissues of LLBWP and HLBWP sows. Furthermore, (GO) enrichment of upregulated DEGs predicted that there were two biological processes significantly related to cornification and regulation of cell population proliferation. To better understand the molecular interaction between cell proliferation and cornification, we conducted transcriptional factor binding site (TFBS) prediction analysis. The results indicated that a highly significant TFBS was located at the 5′ upstream of all four upregulated genes (CDSN, DSG3, KLK14, KRT17), recognized by transcription factors EGR4 and FOSL1. Our findings provide novel insight into how transcriptional regulation of two different biological processes interact in placental tissues of LLBWP sows. Full article

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

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18 pages, 7311 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Analysis of Newborn Hanwoo Calves: Effects of Maternal Overnutrition during Mid- to Late Pregnancy on Subcutaneous Adipose Tissue and Liver

by Borhan Shokrollahi, Hyun-Jeong Lee, Youl Chang Baek, Shil Jin, Gi-Suk Jang, Sung Jin Moon, Kyung-Hwan Um, Sun Sik Jang and Myung Sun Park

Genes 2024, 15(6), 704; https://doi.org/10.3390/genes15060704 - 28 May 2024

Cited by 2 | Viewed by 1380

Abstract

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet [...] Read more.

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP—higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, HSPA6 emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj-p value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein–protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition’s substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study’s limitations (sample size) underscore the necessity for further research. Full article

(This article belongs to the Special Issue Breeding and Functional Genomics in Animals)

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17 pages, 1228 KiB

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 4 | Viewed by 3953

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)

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17 pages, 5121 KiB

Open AccessEditor’s ChoiceArticle

A Mouse Model of X-Linked Chronic Granulomatous Disease for the Development of CRISPR/Cas9 Gene Therapy

by Seren Sevim-Wunderlich, Tu Dang, Jana Rossius, Frank Schnütgen and Ralf Kühn

Genes 2024, 15(6), 706; https://doi.org/10.3390/genes15060706 - 28 May 2024

Cited by 1 | Viewed by 1889

Abstract

Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked CYBB gene that abrogate reactive oxygen species (ROS) production in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoietic stem and progenitor cells (HSPCs) [...] Read more.

Chronic granulomatous disease (CGD) is an inherited immunodeficiency disease mainly caused by mutations in the X-linked CYBB gene that abrogate reactive oxygen species (ROS) production in phagocytes and microbial defense. Gene repair using the CRISPR/Cas9 system in hematopoietic stem and progenitor cells (HSPCs) is a promising technology for therapy for CGD. To support the establishment of efficient and safe gene therapies for CGD, we generated a mouse model harboring a patient-derived mutation in the CYBB gene. Our CybbC517del mouse line shows the hallmarks of CGD and provides a source for Cybb-deficient HSPCs that can be used to evaluate gene-therapy approaches in vitro and in vivo. In a setup using Cas9 RNPs and an AAV repair vector in HSPCs, we show that the mutation can be repaired in 19% of treated cells and that treatment restores ROS production by macrophages. In conclusion, our CybbC517del mouse line provides a new platform for refining and evaluating novel gene therapies and studying X-CGD pathophysiology. Full article

(This article belongs to the Special Issue Rodent Genetic Models for Human Diseases)

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11 pages, 7875 KiB

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

Viewed by 1807

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)

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23 pages, 1460 KiB

Open AccessEditor’s ChoiceReview

Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production

by Jana Key, Suzana Gispert and Georg Auburger

Genes 2024, 15(6), 694; https://doi.org/10.3390/genes15060694 - 27 May 2024

Cited by 1 | Viewed by 3581

Abstract

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, especially during stress periods, but their substrates are poorly defined. Mammalian [...] Read more.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, especially during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING-activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to humans, despite their secondary role in proteolysis. Based on recent proteomic–metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules and CLPX on multi-enzyme condensates as first-aid systems near the inner mitochondrial membrane. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, mitochondrial RNA granules and nucleoids, and the D-foci-mediated degradation of toxic double-stranded mtRNA/mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, as other mitochondrial peptidases: MPPs at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space. Full article

(This article belongs to the Special Issue Animal Models for Human Diseases: Advances in Genome Editing)

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11 pages, 1536 KiB

Open AccessEditor’s ChoiceArticle

Identification of Barley yellow mosaic virus Isolates Breaking rym3 Resistance in Japan

by Hongjing Zhu, Takeshi Okiyama, Kohei Mishina, Shinji Kikuchi, Hidenori Sassa, Takao Komatsuda, Tsuneo Kato and Youko Oono

Genes 2024, 15(6), 697; https://doi.org/10.3390/genes15060697 - 27 May 2024

Cited by 1 | Viewed by 1709

Abstract

In early spring 2018, significant mosaic disease symptoms were observed for the first time on barley leaves (Hordeum vulgare L., cv. New Sachiho Golden) in Takanezawa, Tochigi Prefecture, Japan. This cultivar carries the resistance gene rym3 (rym; resistance to yellow mosaic). Through [...] Read more.

In early spring 2018, significant mosaic disease symptoms were observed for the first time on barley leaves (Hordeum vulgare L., cv. New Sachiho Golden) in Takanezawa, Tochigi Prefecture, Japan. This cultivar carries the resistance gene rym3 (rym; resistance to yellow mosaic). Through RNA-seq analysis, Barley yellow mosaic virus (BaYMV-Takanezawa) was identified in the roots of all five plants (T01–T05) in the field. Phylogenetic analysis of RNA1, encompassing known BaYMV pathotypes I through V, revealed that it shares the same origin as isolate pathotype IV (BaYMV-Ohtawara pathotype). However, RNA2 analysis of isolates revealed the simultaneous presence of two distinct BaYMV isolates, BaYMV-Takanezawa-T01 (DRR552862, closely related to pathotype IV) and BaYMV-Takanezawa-T02 (DRR552863, closely related to pathotype III). The amino acid sequences of the BaYMV-Takanezawa isolates displayed variations, particularly in the VPg and N-terminal region of CP, containing mutations not found in other domains of the virus genome. Changes in the CI (RNA1 amino acid residue 459) and CP (RNA1 amino acid residue 2138) proteins correlated with pathogenicity. These findings underscore the importance of monitoring and understanding the genetic diversity of BaYMV for effective disease management strategies in crop breeding. Full article

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

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15 pages, 1837 KiB

Open AccessEditor’s ChoiceArticle

Trans-Activation of the Coactivator-Associated Arginine Methyltransferase 1 (Carm1) Gene by the Oncogene Product Tax of Human T-Cell Leukemia Virus Type 1

by Rahma F. Hayati, Rinka Nakajima, Yaxuan Zhou, Mashiro Shirasawa, Lin Zhao, Mariana Fikriyanti, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki and Kiyoshi Ohtani

Genes 2024, 15(6), 698; https://doi.org/10.3390/genes15060698 - 27 May 2024

Cited by 1 | Viewed by 1885

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes [...] Read more.

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the Carm1 gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene IL-2Rα, concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of IL-2Rα and Cyclin D2 gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the Carm1 gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the Carm1 gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion. Full article

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

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34 pages, 2981 KiB

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 1 | Viewed by 3349

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)

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