Genes

21 pages, 373 KB

Open AccessEditor’s ChoiceReview

The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions

by Alice Man, Matteo Di Scipio, Shan Grewal, Yujin Suk, Elisabetta Trinari, Resham Ejaz and Robyn Whitney

Genes 2024, 15(3), 332; https://doi.org/10.3390/genes15030332 - 4 Mar 2024

Cited by 28 | Viewed by 9113

Abstract

The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival. Upregulation of the mTOR pathway has been shown to cause malformations of cortical development, medically refractory epilepsies, and neurodevelopmental disorders, collectively described as mTORopathies. Tuberous [...] Read more.

The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival. Upregulation of the mTOR pathway has been shown to cause malformations of cortical development, medically refractory epilepsies, and neurodevelopmental disorders, collectively described as mTORopathies. Tuberous sclerosis complex (TSC) serves as the prototypical mTORopathy. Characterized by the development of benign tumors in multiple organs, pathogenic variants in TSC1 or TSC2 disrupt the TSC protein complex, a negative regulator of the mTOR pathway. Variants in critical domains of the TSC complex, especially in the catalytic TSC2 subunit, correlate with increased disease severity. Variants in less crucial exons and non-coding regions, as well as those undetectable with conventional testing, may lead to milder phenotypes. Despite the assumption of complete penetrance, expressivity varies within families, and certain variants delay disease onset with milder neurological effects. Understanding these genotype–phenotype correlations is crucial for effective clinical management. Notably, 15% of patients have no mutation identified by conventional genetic testing, with the majority of cases postulated to be caused by somatic TSC1/TSC2 variants which present complex diagnostic challenges. Advancements in genetic testing, prenatal screening, and precision medicine hold promise for changing the diagnostic and treatment paradigm for TSC and related mTORopathies. Herein, we explore the genetic and molecular mechanisms of TSC and other mTORopathies, emphasizing contemporary genetic methods in understanding and diagnosing the condition. Full article

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

11 pages, 588 KB

Open AccessEditor’s ChoiceReview

Lignin Biosynthesis and Its Diversified Roles in Disease Resistance

by Qing-Hu Ma

Genes 2024, 15(3), 295; https://doi.org/10.3390/genes15030295 - 25 Feb 2024

Cited by 34 | Viewed by 9991

Abstract

Lignin is complex, three-dimensional biopolymer existing in plant cell wall. Lignin biosynthesis is increasingly highlighted because it is closely related to the wide applications in agriculture and industry productions, including in pulping process, forage digestibility, bio-fuel, and carbon sequestration. The functions of lignin [...] Read more.

Lignin is complex, three-dimensional biopolymer existing in plant cell wall. Lignin biosynthesis is increasingly highlighted because it is closely related to the wide applications in agriculture and industry productions, including in pulping process, forage digestibility, bio-fuel, and carbon sequestration. The functions of lignin in planta have also attracted more attentions recently, particularly in plant defense response against different pathogens. In this brief review, the progress in lignin biosynthesis is discussed, and the lignin’s roles in disease resistance are thoroughly elucidated. This issue will help in developing broad-spectrum resistant crops in agriculture. Full article

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

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17 pages, 2274 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 7 | Viewed by 2209

Abstract

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

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

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

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21 pages, 355 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 16 | Viewed by 8406

Abstract

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

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

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

9 pages, 593 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 4 | Viewed by 2015

Abstract

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

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

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

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15 pages, 2734 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 12 | Viewed by 3105

Abstract

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

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

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

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31 pages, 2026 KB

Open AccessEditor’s ChoiceReview

Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing

by Valeria Barili, Enrico Ambrosini, Beatrice Bortesi, Roberta Minari, Erika De Sensi, Ilenia Rita Cannizzaro, Antonietta Taiani, Maria Michiara, Angelica Sikokis, Daniela Boggiani, Chiara Tommasi, Olga Serra, Francesco Bonatti, Alessia Adorni, Anita Luberto, Patrizia Caggiati, Davide Martorana, Vera Uliana, Antonio Percesepe, Antonino Musolino and Benedetta Pellegrino Show full author list Hide full author list

Genes 2024, 15(2), 219; https://doi.org/10.3390/genes15020219 - 8 Feb 2024

Cited by 20 | Viewed by 10858

Abstract

Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian, fallopian tube, and peritoneal cancers marked by elevated incidences of genomic aberrations that correspond to poor prognoses. These genes are in fact [...] Read more.

Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian, fallopian tube, and peritoneal cancers marked by elevated incidences of genomic aberrations that correspond to poor prognoses. These genes are in fact involved in genetic integrity, particularly in the process of homologous recombination (HR) DNA repair, a high-fidelity repair system for mending DNA double-strand breaks. In addition to its implication in HBOC pathogenesis, the impairment of HR has become a prime target for therapeutic intervention utilizing poly (ADP-ribose) polymerase (PARP) inhibitors. In the present review, we introduce the molecular roles of HR orchestrated by BRCA1 and BRCA2 within the framework of sensitivity to PARP inhibitors. We examine the genetic architecture underneath breast and ovarian cancer ranging from high- and mid- to low-penetrant predisposing genes and taking into account both germline and somatic variations. Finally, we consider higher levels of complexity of the genomic landscape such as polygenic risk scores and other approaches aiming to optimize therapeutic and preventive strategies for breast and ovarian cancer. Full article

(This article belongs to the Section Genetic Diagnosis)

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13 pages, 1899 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 12 | Viewed by 4578

Abstract

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

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

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

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29 pages, 676 KB

Open AccessEditor’s ChoiceReview

NF-κB: Governing Macrophages in Cancer

by Jessica Cornice, Daniela Verzella, Paola Arboretto, Davide Vecchiotti, Daria Capece, Francesca Zazzeroni and Guido Franzoso

Genes 2024, 15(2), 197; https://doi.org/10.3390/genes15020197 - 31 Jan 2024

Cited by 46 | Viewed by 12779

Abstract

Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumor progression and or-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophage phenotypes: [...] Read more.

Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumor progression and or-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophage phenotypes: M1-like or pro-inflammatory and M2-like or anti-inflammatory. NF-κB transcription factors are central regulators of TAMs in cancers, where they often drive macrophage polarization toward an M2-like phenotype. Therefore, the NF-κB pathway is an attractive therapeutic target for cancer immunotherapy in a wide range of human tumors. Hence, targeting NF-κB pathway in the myeloid compartment is a potential clinical strategy to overcome microenvironment-induced immunosuppression and increase anti-tumor immunity. In this review, we discuss the role of NF-κB as a key driver of macrophage functions in tumors as well as the principal strategies to overcome tumor immunosuppression by targeting the NF-κB pathway. Full article

(This article belongs to the Special Issue Cell Signalling and Inflammation in Cancer)

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24 pages, 752 KB

Open AccessFeature PaperEditor’s ChoiceReview

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

by Vincent Zimmern and Berge Minassian

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

Cited by 13 | Viewed by 6855

Abstract

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

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

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

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15 pages, 2737 KB

Open AccessEditor’s ChoiceArticle

Population Genomics Reveals the Underlying Structure of the Small Pelagic European Sardine and Suggests Low Connectivity within Macaronesia

by Rute R. da Fonseca, Paula F. Campos, Alba Rey-Iglesia, Gustavo V. Barroso, Lucie A. Bergeron, Manuel Nande, Fernando Tuya, Sami Abidli, Montse Pérez, Isabel Riveiro, Pablo Carrera, Alba Jurado-Ruzafa, M. Teresa G. Santamaría, Rui Faria, André M. Machado, Miguel M. Fonseca, Elsa Froufe and L. Filipe C. Castro

Genes 2024, 15(2), 170; https://doi.org/10.3390/genes15020170 - 27 Jan 2024

Cited by 14 | Viewed by 4984

Abstract

The European sardine (Sardina pilchardus, Walbaum 1792) is indisputably a commercially important species. Previous studies using uneven sampling or a limited number of makers have presented sometimes conflicting evidence of the genetic structure of S. pilchardus populations. Here, we show that [...] Read more.

The European sardine (Sardina pilchardus, Walbaum 1792) is indisputably a commercially important species. Previous studies using uneven sampling or a limited number of makers have presented sometimes conflicting evidence of the genetic structure of S. pilchardus populations. Here, we show that whole genome data from 108 individuals from 16 sampling areas across 5000 km of the species’ distribution range (from the Eastern Mediterranean to the archipelago of Azores) support at least three genetic clusters. One includes individuals from Azores and Madeira, with evidence of substructure separating these two archipelagos in the Atlantic. Another cluster broadly corresponds to the center of the distribution, including the sampling sites around Iberia, separated by the Almeria–Oran front from the third cluster that includes all of the Mediterranean samples, except those from the Alboran Sea. Individuals from the Canary Islands appear to belong to the Mediterranean cluster. This suggests at least two important geographical barriers to gene flow, even though these do not seem complete, with many individuals from around Iberia and the Mediterranean showing some patterns compatible with admixture with other genetic clusters. Genomic regions corresponding to the top outliers of genetic differentiation are located in areas of low recombination indicative that genetic architecture also has a role in shaping population structure. These regions include genes related to otolith formation, a calcium carbonate structure in the inner ear previously used to distinguish S. pilchardus populations. Our results provide a baseline for further characterization of physical and genetic barriers that divide European sardine populations, and information for transnational stock management of this highly exploited species towards sustainable fisheries. Full article

(This article belongs to the Special Issue Feature Papers in Population and Evolutionary Genetics and Genomics 2023)

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12 pages, 4372 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 5 | Viewed by 1995

Abstract

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

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

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

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22 pages, 6400 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 15 | Viewed by 10136

Abstract

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

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

(This article belongs to the Section Viral Genomics)

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12 pages, 4186 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 12 | Viewed by 5626

Abstract

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

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

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

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13 pages, 1488 KB

Open AccessEditor’s ChoiceReview

Pericytes as the Orchestrators of Vasculature and Adipogenesis

by Caroline de Carvalho Picoli, Alexander Birbrair and Ziru Li

Genes 2024, 15(1), 126; https://doi.org/10.3390/genes15010126 - 19 Jan 2024

Cited by 17 | Viewed by 6985

Abstract

Pericytes (PCs) are located surrounding the walls of small blood vessels, particularly capillaries and microvessels. In addition to their functions in maintaining vascular integrity, participating in angiogenesis, and regulating blood flow, PCs also serve as a reservoir for multi-potent stem/progenitor cells in white, [...] Read more.

Pericytes (PCs) are located surrounding the walls of small blood vessels, particularly capillaries and microvessels. In addition to their functions in maintaining vascular integrity, participating in angiogenesis, and regulating blood flow, PCs also serve as a reservoir for multi-potent stem/progenitor cells in white, brown, beige, and bone marrow adipose tissues. Due to the complex nature of this cell population, the identification and characterization of PCs has been challenging. A comprehensive understanding of the heterogeneity of PCs may enhance their potential as therapeutic targets for metabolic syndromes or bone-related diseases. This mini-review summarizes multiple PC markers commonly employed in lineage-tracing studies, with an emphasis on their contribution to adipogenesis and functions in different adipose depots under diverse metabolic conditions. Full article

(This article belongs to the Special Issue Cellular and Developmental Biology of Lipid Metabolism)

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25 pages, 2939 KB

Open AccessEditor’s ChoiceReview

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases

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

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

Cited by 13 | Viewed by 4515

Abstract

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

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

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

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15 pages, 5093 KB

Open AccessEditor’s ChoiceArticle

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

by Parastoo Karimian, Yuri Trusov and Jose Ramon Botella

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

Cited by 5 | Viewed by 2367

Abstract

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

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

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

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24 pages, 1417 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 10 | Viewed by 4909

Abstract

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

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

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

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18 pages, 3455 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 6 | Viewed by 4147

Abstract

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

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

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

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12 pages, 2104 KB

Open AccessEditor’s ChoiceArticle

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

by Zulvikar Syambani Ulhaq and William Ka Fai Tse

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

Cited by 12 | Viewed by 3415

Abstract

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

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

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

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13 pages, 457 KB

Open AccessEditor’s ChoiceStudy Protocol

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

by Roberto Canitano and Yuri Bozzi

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

Cited by 3 | Viewed by 4940

Abstract

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

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

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

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23 pages, 629 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 13 | Viewed by 7259

Abstract

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

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

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

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18 pages, 3505 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 2561

Abstract

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

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

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

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24 pages, 1542 KB

Open AccessEditor’s ChoiceReview

Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations

by Raafiah Izhar, Margherita Borriello, Antonella La Russa, Rossella Di Paola, Ananya De, Giovambattista Capasso, Diego Ingrosso, Alessandra F. Perna and Mariadelina Simeoni

Genes 2024, 15(1), 37; https://doi.org/10.3390/genes15010037 - 26 Dec 2023

Cited by 42 | Viewed by 9845

Abstract

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs [...] Read more.

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life. Full article

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

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15 pages, 3680 KB

Open AccessEditor’s ChoiceArticle

Dynamic Expression Profile of Follicles at Different Stages in High- and Low-Production Laying Hens

by Lan Yang, Xuewei Fan, Kaiyuan Tian, Sensen Yan, Chunhong Xu, Yixiang Tian, Chengpeng Xiao, Xintao Jia, Junlai Shi, Ying Bai and Wenting Li

Genes 2024, 15(1), 40; https://doi.org/10.3390/genes15010040 - 26 Dec 2023

Cited by 12 | Viewed by 2873

Abstract

Improving the efficiency of hens and extending the egg-laying cycle require maintaining high egg production in the later stages. The ovarian follicles, as the primary functional units for ovarian development and oocyte maturation, play a crucial role in regulating the continuous ovulation of [...] Read more.

Improving the efficiency of hens and extending the egg-laying cycle require maintaining high egg production in the later stages. The ovarian follicles, as the primary functional units for ovarian development and oocyte maturation, play a crucial role in regulating the continuous ovulation of hens. The egg production rate of laying hens is mostly affected by proper follicle growth and ovulation in the ovaries. The objective of this study was to identify the key genes and signaling pathways involved in the development of ovarian follicles in Taihang hens through transcriptome screening. In this study, RNA sequencing was used to compare and analyze the transcriptomes of ovarian follicles at four developmental stages: small white follicles (SWF), small yellow follicles (SYF), F5 follicles, and F2 follicles, from two groups: the high continual production group (H-Group) and the low continual production group (L-Group). A total of 24 cDNA libraries were constructed, and significant differential expression of 96, 199, 591, and 314 mRNAs was detected in the SWF, SYF, F5, and F2 follicles of the H and L groups, respectively. Based on the results of GO and KEGG enrichment analyses, each stage of follicle growth possesses distinct molecular genetic features, which have important effects on follicle development and significantly promote the formation of continuous production traits through the biosynthesis of steroid hormones, cytokine–cytokine receptor interaction, and neuroactive ligand–receptor interaction. Additionally, through STEM analysis, we identified 59 DEGs, including ZP4, KCNH1, IGFs, HMGA2, and CDH1, potentially associated with follicular development within four significant modules. This study represents the first transcriptome investigation of follicles in hens with high and low egg-producing characteristics at four crucial developmental stages. These findings provide important molecular evidence for understanding the regulation of follicular development and its variations. Full article

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

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18 pages, 14236 KB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 2419

Abstract

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

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

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

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16 pages, 4389 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 12 | Viewed by 3183

Abstract

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

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

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

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12 pages, 2629 KB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 3 | Viewed by 5221

Abstract

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

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

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

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14 pages, 2305 KB

Open AccessEditor’s ChoiceArticle

Rare Deletions or Large Duplications Contribute to Genetic Variation in Patients with Severe Tinnitus and Meniere Disease

by Alba Escalera-Balsera, Alberto M. Parra-Perez, Alvaro Gallego-Martinez, Lidia Frejo, Juan Martin-Lagos, Victoria Rivero de Jesus, Paz Pérez-Vázquez, Patricia Perez-Carpena and Jose A. Lopez-Escamez

Genes 2024, 15(1), 22; https://doi.org/10.3390/genes15010022 - 22 Dec 2023

Cited by 2 | Viewed by 2493

Abstract

Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare [...] Read more.

Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare missense single nucleotide variants in synaptic genes. Rare structural variants (SVs) may also contribute to MD and severe tinnitus. In this study, we analyzed exome sequencing data from 310 MD Spanish patients and selected 75 patients with severe tinnitus based on a Tinnitus Handicap Inventory (THI) score > 68. Three rare deletions were identified in two unrelated individuals overlapping the ERBB3 gene in the positions: NC_000012.12:g.56100028_56100172del, NC_000012.12:g.56100243_56101058del, and NC_000012.12:g.56101359_56101526del. Moreover, an ultra-rare large duplication was found covering the AP4M1, COPS6, MCM7, TAF6, MIR106B, MIR25, and MIR93 genes in another two patients in the NC_000007.14:g.100089053_100112257dup region. All the coding genes exhibited expression in brain and inner ear tissues. These results confirm the contribution of large SVs to severe tinnitus in MD and pinpoint new candidate genes to get a better molecular understanding of the disease. Full article

(This article belongs to the Special Issue Molecular and Genetic Diagnosis of Rare Diseases)

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21 pages, 2772 KB

Open AccessEditor’s ChoiceReview

Hotspot Regions of Quantitative Trait Loci and Candidate Genes for Ear-Related Traits in Maize: A Literature Review

by Xingjie Zhang, Jiachen Sun, Yudong Zhang, Jinfeng Li, Meichen Liu, Linzhuo Li, Shaoxiong Li, Tingzhao Wang, Ranjan Kumar Shaw, Fuyan Jiang and Xingming Fan

Genes 2024, 15(1), 15; https://doi.org/10.3390/genes15010015 - 21 Dec 2023

Cited by 12 | Viewed by 3148

Abstract

In this study, hotspot regions, QTL clusters, and candidate genes for eight ear-related traits of maize (ear length, ear diameter, kernel row number, kernel number per row, kernel length, kernel width, kernel thickness, and 100-kernel weight) were summarized and analyzed over the past [...] Read more.

In this study, hotspot regions, QTL clusters, and candidate genes for eight ear-related traits of maize (ear length, ear diameter, kernel row number, kernel number per row, kernel length, kernel width, kernel thickness, and 100-kernel weight) were summarized and analyzed over the past three decades. This review aims to (1) comprehensively summarize and analyze previous studies on QTLs associated with these eight ear-related traits and identify hotspot bin regions located on maize chromosomes and key candidate genes associated with the ear-related traits and (2) compile major and stable QTLs and QTL clusters from various mapping populations and mapping methods and techniques providing valuable insights for fine mapping, gene cloning, and breeding for high-yield and high-quality maize. Previous research has demonstrated that QTLs for ear-related traits are distributed across all ten chromosomes in maize, and the phenotypic variation explained by a single QTL ranged from 0.40% to 36.76%. In total, 23 QTL hotspot bins for ear-related traits were identified across all ten chromosomes. The most prominent hotspot region is bin 4.08 on chromosome 4 with 15 QTLs related to eight ear-related traits. Additionally, this study identified 48 candidate genes associated with ear-related traits. Out of these, five have been cloned and validated, while twenty-eight candidate genes located in the QTL hotspots were defined by this study. This review offers a deeper understanding of the advancements in QTL mapping and the identification of key candidates associated with eight ear-related traits. These insights will undoubtedly assist maize breeders in formulating strategies to develop higher-yield maize varieties, contributing to global food security. Full article

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

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26 pages, 1490 KB

Open AccessEditor’s ChoiceReview

Biological Aging Acceleration Due to Environmental Exposures: An Exciting New Direction in Toxicogenomics Research

by Sudipta Dutta, Jaclyn M. Goodrich, Dana C. Dolinoy and Douglas M. Ruden

Genes 2024, 15(1), 16; https://doi.org/10.3390/genes15010016 - 21 Dec 2023

Cited by 10 | Viewed by 6810

Abstract

Biological clock technologies are designed to assess the acceleration of biological age (B-age) in diverse cell types, offering a distinctive opportunity in toxicogenomic research to explore the impact of environmental stressors, social challenges, and unhealthy lifestyles on health impairment. These clocks also play [...] Read more.

Biological clock technologies are designed to assess the acceleration of biological age (B-age) in diverse cell types, offering a distinctive opportunity in toxicogenomic research to explore the impact of environmental stressors, social challenges, and unhealthy lifestyles on health impairment. These clocks also play a role in identifying factors that can hinder aging and promote a healthy lifestyle. Over the past decade, researchers in epigenetics have developed testing methods that predict the chronological and biological age of organisms. These methods rely on assessing DNA methylation (DNAm) levels at specific CpG sites, RNA levels, and various biomolecules across multiple cell types, tissues, and entire organisms. Commonly known as ‘biological clocks’ (B-clocks), these estimators hold promise for gaining deeper insights into the pathways contributing to the development of age-related disorders. They also provide a foundation for devising biomedical or social interventions to prevent, reverse, or mitigate these disorders. This review article provides a concise overview of various epigenetic clocks and explores their susceptibility to environmental stressors. Full article

(This article belongs to the Section Genes & Environments)

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15 pages, 578 KB

Open AccessEditor’s ChoiceReview

Healthy Live Births after the Transfer of Mosaic Embryos: Self-Correction or PGT-A Overestimation?

by Gerard Campos, Romualdo Sciorio and Steven Fleming

Genes 2024, 15(1), 18; https://doi.org/10.3390/genes15010018 - 21 Dec 2023

Cited by 8 | Viewed by 8623

Abstract

The implementation of next generation sequencing (NGS) in preimplantation genetic testing for aneuploidy (PGT-A) has led to a higher prevalence of mosaic diagnosis within the trophectoderm (TE) sample. Regardless, mosaicism could potentially increase the rate of live-born children with chromosomic syndromes, though available [...] Read more.

The implementation of next generation sequencing (NGS) in preimplantation genetic testing for aneuploidy (PGT-A) has led to a higher prevalence of mosaic diagnosis within the trophectoderm (TE) sample. Regardless, mosaicism could potentially increase the rate of live-born children with chromosomic syndromes, though available data from the transfer of embryos with putative PGT-A mosaicism are scarce but reassuring. Even with lower implantation and higher miscarriage rates, mosaic embryos can develop into healthy live births. Therefore, this urges an explanation for the disappearance of aneuploid cells throughout development, to provide guidance in the management of mosaicism in clinical practice. Technical overestimation of mosaicism, together with some sort of “self-correction” mechanisms during the early post-implantation stages, emerged as potential explanations. Unlike the animal model, in which the elimination of genetically abnormal cells from the future fetal lineage has been demonstrated, in human embryos this capability remains unverified even though the germ layer displays an aneuploidy-induced cell death lineage preference with higher rates of apoptosis in the inner cell mass (ICM) than in the TE cells. Moreover, the reported differential dynamics of cell proliferation and apoptosis between euploid, mosaic, and aneuploid embryos, together with pro-apoptosis gene products (cfDNA and mRNA) and extracellular vesicles identified in the blastocoel fluid, may support the hypothesis of apoptosis as a mechanism to purge the preimplantation embryo of aneuploid cells. Alternative hypotheses, like correction of aneuploidy by extrusion of a trisomy chromosome or by monosomic chromosome duplication, are even, though they represent an extremely rare phenomenon. On the other hand, the technical limitations of PGT-A analysis may lead to inaccuracy in embryo diagnoses, identifying as “mosaic” those embryos that are uniformly euploid or aneuploid. NGS assumption of “intermediate copy number profiles” as evidence of a mixture of euploid and aneuploid cells in a single biopsy has been reported to be poorly predictive in cases of mosaicism diagnosis. Additionally, the concordance found between the TE and the ICM in cases of TE biopsies displaying mosaicism is lower than expected, and it correlates differently depending on the type (whole chromosome versus segmental) and the level of mosaicism reported. Thus, in cases of low-/medium-level mosaicism (<50%), aneuploid cells would rarely involve the ICM and other regions. However, in high-level mosaics (≥50%), abnormal cells in the ICM should display higher prevalence, revealing more uniform aneuploidy in most embryos, representing a technical variation in the uniform aneuploidy range, and therefore might impair the live birth rate. Full article

(This article belongs to the Special Issue Epigenetic Regulatory Network during Embryonic Development Revealed by Single-Cell Sequencing)

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19 pages, 3241 KB

Open AccessEditor’s ChoiceArticle

A Missense Mutation in the Collagen Triple Helix of EDA Is Associated with X-Linked Recessive Hypohidrotic Ectodermal Dysplasia in Fleckvieh Cattle

by Sina Reinartz, Christine Weiß, Maike Heppelmann, Marion Hewicker-Trautwein, Maren Hellige, Laure Willen, Karsten Feige, Pascal Schneider and Ottmar Distl

Genes 2024, 15(1), 8; https://doi.org/10.3390/genes15010008 - 20 Dec 2023

Cited by 2 | Viewed by 1997

Abstract

Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive [...] Read more.

Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive HAD (XHED). Whole genome and Sanger sequencing of cDNA showed a perfect association of the missense mutation g.85716041G>A (ss2019497443, rs1114816375) within the EDA gene with all three cases following an X-linked recessive inheritance, but normal EDAR and EDARADD. This mutation causes an exchange of glycine (G) with arginine (R) at amino acid position 227 (p.227G>R) in the second collagen triple helix repeat domain of EDA. The EDA variant was associated with a significant reduction and underdevelopment of hair follicles along with a reduced outgrowth of hairs, a complete loss of seromucous nasolabial and mucous tracheal and bronchial glands and a malformation of and reduction in number of teeth. Thermostability of EDA G227R was reduced, consistent with a relatively mild hair and tooth phenotype. However, incisors and canines were more severely affected in one of the calves, which correlated with the presence of a homozygous missense mutation of RNF111 (g.51306765T>G), a putative candidate gene possibly associated with tooth number in EDA-deficient Fleckvieh calves. Full article

(This article belongs to the Special Issue Genomic View of Cattle Breeding and Domestication)

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16 pages, 5345 KB

Open AccessEditor’s ChoiceArticle

Whole-Transcriptome Sequencing of Ovary Reveals the ceRNA Regulation Network in Egg Production of Gaoyou Duck

by Lei Zhang, Rui Zhu, Guobo Sun, Jian Wang, Qisheng Zuo and Shanyuan Zhu

Genes 2024, 15(1), 9; https://doi.org/10.3390/genes15010009 - 20 Dec 2023

Cited by 5 | Viewed by 2148

Abstract

To investigate the regulatory mechanism of the competing endogenous RNAs (ceRNAs) on the egg performance of Gaoyou ducks, full transcriptome sequencing was performed to analyze the ovarian tissues in Gaoyou ducks. The ducks were categorized into high- and low-yield groups based on the [...] Read more.

To investigate the regulatory mechanism of the competing endogenous RNAs (ceRNAs) on the egg performance of Gaoyou ducks, full transcriptome sequencing was performed to analyze the ovarian tissues in Gaoyou ducks. The ducks were categorized into high- and low-yield groups based on the individual in-cage egg production records and the hematoxylin–eosin (HE) staining results. The differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) were further processed by GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. In total, 72 DEmRNAs; 23 DElncRNAs; 4 DEcircRNAs; and 5 signaling pathways, including the ovarian steroidogenesis, PI3K-Akt, hedgehog, tryptophan metabolism, and oocyte meiosis signaling pathways, were significantly enriched. These results suggest that they could be associated with the Gaoyou duck’s ovarian function and affect the total egg production or double-yolked egg production. Furthermore, a coregulation network based on the related candidate ceRNAs across the high- and low-yield egg production groups was constructed. Our findings provide new insights into the mechanisms underlying the molecular regulation of related circRNA/lncRNA–miRNA–mRNA in the egg production and double-yolked egg traits of Gaoyou ducks. Full article

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

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19 pages, 1325 KB

Open AccessEditor’s ChoiceArticle

The Phylogenetic Relationship of Lamiinae (Coleoptera: Cerambycidae) Using Mitochondrial Genomes

by Ke Li, Sheng-Wu Yu, Hao Hu, Yu-Feng Feng, Kenneth B. Storey, Yue Ma, Jia-Yong Zhang and Dan-Na Yu

Genes 2024, 15(1), 13; https://doi.org/10.3390/genes15010013 - 20 Dec 2023

Cited by 9 | Viewed by 3034

Abstract

Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological [...] Read more.

Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological characteristics are not sufficient to resolve species phylogenetic studies perfectly. At the same time, the full mitochondrial genome contains more comprehensive genetic data. Benefiting from the development of next-generation sequencing (NGS), mitochondrial genomes can be easily acquired and used as reliable molecular markers to investigate phylogenetic relationships within Cerambycidae. Using NGS technology, we obtained 11 mitochondrial genome sequences of Lamiinae species. Based on this newly generated mitochondrial genome dataset matrix, we reconstructed the phylogeny of Lamiinae. The Bayesian Inference and Maximum Likelihood analyses strongly support the monophyly of four tribes (Lamiini, Batocerini, Mesosini, and Saperdini), whereas the tribe Acanthocinini was identified as paraphyletic. Other mitochondrial structural features were also observed: the start codon in the nad1 gene of all 11 mitochondrial genomes is TTG; 17–22 bp intergenic spacers (IGS) with a ‘TACTA’ motif were found between trnS2 and nad1. Moreover, two long IGS were found in Mesosa myops and Batocera sp. Tandem repeats were found in the IGS of Batocera sp. Full article

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

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10 pages, 2639 KB

Open AccessEditor’s ChoiceCase Report

Novel Homozygous FA2H Variant Causing the Full Spectrum of Fatty Acid Hydroxylase-Associated Neurodegeneration (SPG35)

by Alexander German, Jelena Jukic, Andreas Laner, Philipp Arnold, Eileen Socher, Angelika Mennecke, Manuel A. Schmidt, Jürgen Winkler, Angela Abicht and Martin Regensburger

Genes 2024, 15(1), 14; https://doi.org/10.3390/genes15010014 - 20 Dec 2023

Cited by 8 | Viewed by 2613

Abstract

Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, [...] Read more.

Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity. Full article

(This article belongs to the Special Issue Human Developmental Disability, Neurogenetics and Rare Diseases: From Basic Science to Genetic Counseling)

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23 pages, 2949 KB

Open AccessEditor’s ChoiceReview

The Role of the AT-Rich Interaction Domain 1A Gene (ARID1A) in Human Carcinogenesis

by Jing Jing Li and Cheok Soon Lee

Genes 2024, 15(1), 5; https://doi.org/10.3390/genes15010005 - 19 Dec 2023

Cited by 7 | Viewed by 4208

Abstract

The switch/sucrose non-fermentable (SWI/SNF) (SWI/SNF) complex uses energy from ATP hydrolysis to mobilise nucleosomes on chromatin. Components of SWI/SNF are mutated in 20% of all human cancers, of which mutations in AT-rich binding domain protein 1A (ARID1A) are the most common. [...] Read more.

The switch/sucrose non-fermentable (SWI/SNF) (SWI/SNF) complex uses energy from ATP hydrolysis to mobilise nucleosomes on chromatin. Components of SWI/SNF are mutated in 20% of all human cancers, of which mutations in AT-rich binding domain protein 1A (ARID1A) are the most common. ARID1A is mutated in nearly half of ovarian clear cell carcinoma and around one-third of endometrial and ovarian carcinomas of the endometrioid type. This review will examine in detail the molecular functions of ARID1A, including its role in cell cycle control, enhancer regulation, and the prevention of telomerase activity. ARID1A has key roles in the maintenance of genomic integrity, including DNA double-stranded break repair, DNA decatenation, integrity of the cohesin complex, and reduction in replication stress, and is also involved in mismatch repair. The role of ARID1A loss in the pathogenesis of some of the most common human cancers is discussed, with a particular emphasis on gynaecological cancers. Finally, several promising synthetic lethal strategies, which exploit the specific vulnerabilities of ARID1A-deficient cancer cells, are briefly mentioned. Full article

(This article belongs to the Special Issue Cancer Systems Biology and Genomics)

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23 pages, 1791 KB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study to Identify Possible Candidate Genes of Snap Bean Leaf and Pod Color

by Burcu Celebioglu, John P. Hart, Timothy Porch, Phillip Griffiths and James R. Myers

Genes 2023, 14(12), 2234; https://doi.org/10.3390/genes14122234 - 18 Dec 2023

Cited by 5 | Viewed by 2444

Abstract

Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral [...] Read more.

Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral nutrition because every nutrient deficiency and many diseases produce symptoms that affect color. In order to identify significant loci related to both leaf and pod color in a snap bean (Phaseolus vulgaris L.) diversity panel, a genome-wide association study (GWAS) was carried out. Leaf color in one and pod traits in multiple environments were characterized using a colorimeter. L*a*b* color data were recorded and used to calculate chroma (C*) and hue angle (H°). Leaves were evaluated at three positions (lower, middle, and upper) in the canopy and both pod exterior and interior colors were obtained. GWAS was conducted using two reference genomes that represent the Andean (G19833) and Middle American (5-593) domestication centers. Narrow sense heritabilities were calculated using the mixed linear model (MLM) method in genome association and prediction integrated tool (GAPIT), and significant single nucleotide polymorphisms (SNPs) for each color parameter were obtained using the Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) GWAS model with two principal components (PCAs). In comparison to pod color traits, narrow sense heritabilities of leaf traits were low and similar for both reference genomes. Generally, narrow sense heritability for all traits was highest in the lower, followed by middle, and then upper leaf positions. Heritability for both pod interior and exterior color traits was higher using the G19833 reference genome compared to 5-593 when evaluated by year and means across years. Forty-five significant SNPs associated with leaf traits and 872 associated with pods, totaling 917 significant SNPs were identified. Only one SNP was found in common for both leaf and pod traits on Pv03 in the 5-593 reference genome. One-hundred thirteen significant SNPs, 30 in leaves and 83 in pods had phenotypic variation explained (PVE) of 10% or greater. Fourteen SNPs (four from G19833 and ten from 5-593) with ≥10 PVE%, large SNP effect, and largest p-value for L* and H° pod exterior was identified on Pv01, Pv02, Pv03, and Pv08. More SNPs were associated with pod traits than with leaf traits. The pod interior did not exhibit colors produced by anthocyanins or flavonols which allowed the differentiation of potential candidate genes associated with chloroplast and photosynthetic activity compared to the pod exterior where candidate genes related to both flavonoids and photosynthesis affected color. Several SNPs were associated with known qualitative genes including the wax pod locus (y), persistent color (pc), purple pods (V), and two genes expressed in seeds but not previously reported to affect other plant tissues (B and J). An evaluation of significant SNPs within annotated genes found a number, within a 200 kb window, involved in both flavonoid and photosynthetic biosynthetic pathways. Full article

(This article belongs to the Topic Vegetable Breeding, Genetics and Genomics)

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10 pages, 636 KB

Open AccessEditor’s ChoiceBrief Report

Effects of Platelet Count on Blood Pressure: Evidence from Observational and Genetic Investigations

by Zhen He, Zekai Chen, Martin H. de Borst, Qingying Zhang, Harold Snieder, Chris H. L. Thio and on behalf of the International Consortium of Blood Pressure

Genes 2023, 14(12), 2233; https://doi.org/10.3390/genes14122233 - 18 Dec 2023

Cited by 5 | Viewed by 3121

Abstract

Platelet count has been associated with blood pressure, but whether this association reflects causality remains unclear. To strengthen the evidence, we conducted a traditional observational analysis in the Lifelines Cohort Study (n = 167,785), and performed bi-directional Mendelian randomization (MR) with summary [...] Read more.

Platelet count has been associated with blood pressure, but whether this association reflects causality remains unclear. To strengthen the evidence, we conducted a traditional observational analysis in the Lifelines Cohort Study (n = 167,785), and performed bi-directional Mendelian randomization (MR) with summary GWAS data from the UK Biobank (n = 350,475) and the International Consortium of Blood Pressure (ICBP) (n = 299,024). Observational analyses showed positive associations between platelet count and blood pressure (OR = 1.12 per SD, 95% CI: 1.10 to 1.14 for hypertension; B = 0.07, 95% CI: 0.07 to 0.08 for SBP; B = 0.07 per SD, 95% CI: 0.06 to 0.07 for DBP). In MR, a genetically predicted higher platelet count was associated with higher SBP (B = 0.02 per SD, 95% CI = 0.00 to 0.04) and DBP (B = 0.03 per SD, 95% CI = 0.01 to 0.05). IVW models and sensitivity analyses of the association between platelet count and DBP were consistent, but not all sensitivity analyses were statistically significant for the platelet count-SBP relation. Our findings indicate that platelet count has modest but significant effects on SBP and DBP, suggesting causality and providing further insight into the pathophysiology of hypertension. Full article

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

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16 pages, 4334 KB

Open AccessEditor’s ChoiceArticle

Integrated Metabolomic and Transcriptomic Analysis of Puerarin Biosynthesis in Pueraria montana var. thomsonii at Different Growth Stages

by Xinyi Hu, Ting Zhu, Xinyi Min, Jianing He, Cong Hou and Xia Liu

Genes 2023, 14(12), 2230; https://doi.org/10.3390/genes14122230 - 18 Dec 2023

Cited by 4 | Viewed by 2476

Abstract

Puerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the [...] Read more.

Puerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the accumulation of metabolites in the puerarin pathway are not detailed, and it is still controversial at the last step of the 8-C-glycosylation reaction. In this study, we conducted a comprehensive analysis of the metabolomic and transcriptomic changes in Pueraria montana var. thomsonii during two growing years, focusing on the vigorous growth and dormant stages, to elucidate the underlying mechanisms governing the changes in metabolite and gene expression within the puerarin biosynthesis pathway. In a comparison of the two growth stages in the two groups, puerarin and daidzin, the main downstream metabolites in the puerarin biosynthesis pathway, were found to accumulate mainly during the vigorous growth stage. We also identified 67 common differentially expressed genes in this pathway based on gene expression differences at different growth stages. Furthermore, we identified four candidate 8-C-GT genes that potentially contribute to the conversion of daidzein into puerarin and eight candidate 7-O-GT genes that may be involved in the conversion of daidzein into daidzin. A co-expression network analysis of important UGTs and HIDs along with daidzein and puerarin was conducted. Overall, our study contributes to the knowledge of puerarin biosynthesis and offers information about the stage at which the 8-C-glycosylation reaction occurs in biosynthesis. These findings provide valuable insights into the cultivation and quality enhancement of Pueraria montana var. thomsonii. Full article

(This article belongs to the Special Issue Medicinal Plant Research from an Omics Perspective)

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10 pages, 1216 KB

Open AccessEditor’s ChoiceArticle

Influence of Model Structures on Predictors of Protein Stability Changes from Single-Point Mutations

by Cesare Rollo, Corrado Pancotti, Giovanni Birolo, Ivan Rossi, Tiziana Sanavia and Piero Fariselli

Genes 2023, 14(12), 2228; https://doi.org/10.3390/genes14122228 - 17 Dec 2023

Cited by 3 | Viewed by 2626

Abstract

Missense variation in genomes can affect protein structure stability and, in turn, the cell physiology behavior. Predicting the impact of those variations is relevant, and the best-performing computational tools exploit the protein structure information. However, most of the current protein sequence variants are [...] Read more.

Missense variation in genomes can affect protein structure stability and, in turn, the cell physiology behavior. Predicting the impact of those variations is relevant, and the best-performing computational tools exploit the protein structure information. However, most of the current protein sequence variants are unresolved, and comparative or ab initio tools can provide a structure. Here, we evaluate the impact of model structures, compared to experimental structures, on the predictors of protein stability changes upon single-point mutations, where no significant changes are expected between the original and the mutated structures. We show that there are substantial differences among the computational tools. Methods that rely on coarse-grained representation are less sensitive to the underlying protein structures. In contrast, tools that exploit more detailed molecular representations are sensible to structures generated from comparative modeling, even on single-residue substitutions. Full article

(This article belongs to the Special Issue Feature Papers in Technologies and Resources for Genetics 2023)

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20 pages, 21419 KB

Open AccessEditor’s ChoiceArticle

Comparison of Single Cell Transcriptome Sequencing Methods: Of Mice and Men

by Bastian V. H. Hornung, Zakia Azmani, Alexander T. den Dekker, Edwin Oole, Zeliha Ozgur, Rutger W. W. Brouwer, Mirjam C. G. N. van den Hout and Wilfred F. J. van IJcken

Genes 2023, 14(12), 2226; https://doi.org/10.3390/genes14122226 - 16 Dec 2023

Cited by 5 | Viewed by 4055

Abstract

Single cell RNAseq has been a big leap in many areas of biology. Rather than investigating gene expression on a whole organism level, this technology enables scientists to get a detailed look at rare single cells or within their cell population of interest. [...] Read more.

Single cell RNAseq has been a big leap in many areas of biology. Rather than investigating gene expression on a whole organism level, this technology enables scientists to get a detailed look at rare single cells or within their cell population of interest. The field is growing, and many new methods appear each year. We compared methods utilized in our core facility: Smart-seq3, PlexWell, FLASH-seq, VASA-seq, SORT-seq, 10X, Evercode, and HIVE. We characterized the equipment requirements for each method. We evaluated the performances of these methods based on detected features, transcriptome diversity, mitochondrial RNA abundance and multiplets, among others and benchmarked them against bulk RNA sequencing. Here, we show that bulk transcriptome detects more unique transcripts than any single cell method. While most methods are comparable in many regards, FLASH-seq and VASA-seq yielded the best metrics, e.g., in number of features. If no equipment for automation is available or many cells are desired, then HIVE or 10X yield good results. In general, more recently developed methods perform better. This also leads to the conclusion that older methods should be phased out, and that the development of single cell RNAseq methods is still progressing considerably. Full article

(This article belongs to the Special Issue Computational Analysis of Single-Cell Transcriptome Data)

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26 pages, 3106 KB

Open AccessEditor’s ChoiceReview

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

by Brian J. Harvey and Harry M. Harvey

Genes 2023, 14(12), 2225; https://doi.org/10.3390/genes14122225 - 16 Dec 2023

Cited by 13 | Viewed by 4097

Abstract

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive [...] Read more.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear oestrogen signalling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of oestrogen in CRC through various genomic and nongenomic signalling pathways involving membrane and nuclear oestrogen receptors. Furthermore, we examine the interplay between oestrogen receptors and other signalling pathways, in particular the Wnt/β-catenin proliferative pathway and hypoxia in shaping biological sex differences and oestrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting oestrogen signalling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon. Full article

(This article belongs to the Special Issue Signaling Pathway of Cancer)

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12 pages, 2481 KB

Open AccessEditor’s ChoiceArticle

Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds

by Jacklin Sedhom and Lee A. Solomon

Genes 2023, 14(12), 2221; https://doi.org/10.3390/genes14122221 - 15 Dec 2023

Cited by 2 | Viewed by 2726

Abstract

Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for [...] Read more.

Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites. We further revealed direct readout information shared among three evolutionarily related lambdoid phages: λ-phage, Enterobacteria phage VT2-Sakai, and Stx2 converting phage I, suggesting that the λ-CI protein could bind to the operator sites of these other phages. In this study, we show that λ-CI can indeed bind the other two phages’ cognate binding sites as predicted using our algorithm, validating the hypotheses from that paper. We go on to demonstrate the importance of specific hydrogen bond donors and acceptors that are maintained despite changes to the nucleobase itself, and another that has an important role in recognition and binding. This in vitro validation of our algorithm supports its use as a tool to predict alternative binding sites for DNA-binding proteins. Full article

(This article belongs to the Topic Bioinformatics and Intelligent Information Processing)

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10 pages, 1205 KB

Open AccessEditor’s ChoiceArticle

Glycogen Storage Disease: Expert Opinion on Clinical Diagnosis Revisited after Molecular Testing

by Rafael de Marchi, Tatiele Nalin, Fernanda Sperb-Ludwig, Franciele Cabral Pinheiro, Ida Vanessa Doederlein Schwartz and Carlos Eduardo Steiner

Genes 2023, 14(12), 2219; https://doi.org/10.3390/genes14122219 - 15 Dec 2023

Cited by 2 | Viewed by 2345

Abstract

This study sought to analyze whether an accurate diagnosis of the type and subtype of hepatic Glycogen Storage Diseases (GSDs) could be performed based on general clinical and biochemical aspects via comparing the proposed diagnostic hypotheses with the molecular results. Twelve physicians with [...] Read more.

This study sought to analyze whether an accurate diagnosis of the type and subtype of hepatic Glycogen Storage Diseases (GSDs) could be performed based on general clinical and biochemical aspects via comparing the proposed diagnostic hypotheses with the molecular results. Twelve physicians with experience in hepatic GSDs reviewed 45 real cases comprising a standardized summary of clinical and laboratory data. There was no relation between the hit rate and the time since graduation, the time of experience in GSD, and the number of patients treated during their careers. The average assertiveness was 47%, with GSD Ia and Ib being the best-identified types, while no expert correctly identified GSD IXc. Underage investigation for later manifestations, incomplete clinical description, and complementary analysis, the overvaluation of a specific clinical finding (“false positive”) or the discarding of the diagnosis in the absence of it (“false negative”), as well as the lack of knowledge of the rarest GSD types, may have impacted the accuracy of the assessment. This study emphasized that characteristics considered as determinants in identifying the specific types or subtypes of GSD are not exclusive, thus becoming factors that may have induced the evaluators to misdiagnose. Full article

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

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20 pages, 9118 KB

Open AccessEditor’s ChoiceArticle

The Genome of the Yellow Mealworm, Tenebrio molitor: It’s Bigger Than You Think

by Brenda Oppert, Aaron T. Dossey, Fu-Chyun Chu, Eva Šatović-Vukšić, Miroslav Plohl, Timothy P. L. Smith, Sergey Koren, Morgan L. Olmstead, Dewey Leierer, Gail Ragan and J. Spencer Johnston

Genes 2023, 14(12), 2209; https://doi.org/10.3390/genes14122209 - 14 Dec 2023

Cited by 15 | Viewed by 11537

Abstract

Background: Insects are a sustainable source of protein for human food and animal feed. We present a genome assembly, CRISPR gene editing, and life stage-specific transcriptomes for the yellow mealworm, Tenebrio molitor, one of the most intensively farmed insects worldwide. Methods: Long [...] Read more.

Background: Insects are a sustainable source of protein for human food and animal feed. We present a genome assembly, CRISPR gene editing, and life stage-specific transcriptomes for the yellow mealworm, Tenebrio molitor, one of the most intensively farmed insects worldwide. Methods: Long and short reads and long-range data were obtained from a T. molitor male pupa. Sequencing transcripts from 12 T. molitor life stages resulted in 279 million reads for gene prediction and genetic engineering. A unique plasmid delivery system containing guide RNAs targeting the eye color gene vermilion flanking the muscle actin gene promoter and EGFP marker was used in CRISPR/Cas9 transformation. Results: The assembly is approximately 53% of the genome size of 756.8 ± 9.6 Mb, measured using flow cytometry. Assembly was complicated by a satellitome of at least 11 highly conserved satDNAs occupying 28% of the genome. The injection of the plasmid into embryos resulted in knock-out of Tm vermilion and knock-in of EGFP. Conclusions: The genome of T. molitor is longer than current assemblies (including ours) due to a substantial amount (26.5%) of only one highly abundant satellite DNA sequence. Genetic sequences and transformation tools for an insect important to the food and feed industries will promote the sustainable utilization of mealworms and other farmed insects. Full article

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

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24 pages, 1003 KB

Open AccessEditor’s ChoiceReview

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies

by Shabnam Nohesara, Hamid Mostafavi Abdolmaleky, Jin-Rong Zhou and Sam Thiagalingam

Genes 2023, 14(12), 2217; https://doi.org/10.3390/genes14122217 - 14 Dec 2023

Cited by 16 | Viewed by 5668

Abstract

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are [...] Read more.

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems. Full article

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

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14 pages, 5013 KB

Open AccessEditor’s ChoiceArticle

RNA-Sequencing Analysis Revealed Genes Associated with Sweet Potato (Ipomoea batatas (L.) Lam.) Responses to Stem Rot during Different Infection Stages

by Chen Li, Liang Zhang, Honghu Ji, Weihan Song, Ziyu Zhong, Meiqiao Jiang, Yungang Zhang, Qiang Li, Linrun Cheng and Meng Kou

Genes 2023, 14(12), 2215; https://doi.org/10.3390/genes14122215 - 14 Dec 2023

Cited by 3 | Viewed by 2135

Abstract

The sweet potato, which is an important tuber crop in China, is susceptible to a variety of pathogens and insect pests during cultivation and production. Stem rot is a common sweet potato disease that seriously affects tuber yield and quality. Unfortunately, there have [...] Read more.

The sweet potato, which is an important tuber crop in China, is susceptible to a variety of pathogens and insect pests during cultivation and production. Stem rot is a common sweet potato disease that seriously affects tuber yield and quality. Unfortunately, there have been relatively few studies on the mechanism mediating the stem rot resistance of sweet potatoes. In this study, a transcriptome sequencing analysis was completed using Xushu 48 samples at different stages (T1, T2, and T3) of the stem rot infection. The T1 vs. T2, T1 vs. T3, and T2 vs. T3 comparisons detected 44,839, 81,436, and 61,932 differentially expressed genes (DEGs), respectively. The DEGs encoded proteins primarily involved in alanine, aspartate, and glutamate metabolism (ko00250), carbon fixation in photosynthetic organisms (ko00710), and amino sugar and nucleotide sugar metabolism (ko00520). Furthermore, some candidate genes induced by phytopathogen infections were identified, including gene-encoding receptor-like protein kinases (RLK5 and RLK7), an LRR receptor-like serine/threonine protein kinase (SERK1), and transcription factors (bHLH137, ERF9, MYB73, and NAC053). The results of this study provide genetic insights that are relevant to future explorations of sweet potato stem rot resistance, while also providing the theoretical basis for breeding sweet potato varieties that are resistant to stem rot and other diseases. Full article

(This article belongs to the Special Issue Sweet Potato Genetics and Genomics)

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17 pages, 3250 KB

Open AccessEditor’s ChoiceArticle

Role of bZIP Transcription Factors in Response to NaCl Stress in Tamarix ramosissima under Exogenous Potassium (K⁺)

by Yahui Chen, Min Zhang, Dezong Sui, Jiang Jiang and Lei Wang

Genes 2023, 14(12), 2203; https://doi.org/10.3390/genes14122203 - 13 Dec 2023

Cited by 1 | Viewed by 1681

Abstract

Salt stress is a significant environmental factor affecting plant growth and development, with NaCl stress being one of the most common types of salt stress. The halophyte, Tamarix ramosissima Ledeb (T. ramosissima), is frequently utilized for the afforestation of saline-alkali [...] Read more.

Salt stress is a significant environmental factor affecting plant growth and development, with NaCl stress being one of the most common types of salt stress. The halophyte, Tamarix ramosissima Ledeb (T. ramosissima), is frequently utilized for the afforestation of saline-alkali soils. Indeed, there has been limited research and reports by experts and scholars on the regulatory mechanisms of basic leucine zipper (bZIP) genes in T. ramosissima when treated with exogenous potassium (K⁺) to alleviate the effects of NaCl stress. This study focused on the bZIP genes in T. ramosissima roots under NaCl stress with additional KCl applied. We identified key candidate genes and metabolic pathways related to bZIP and validated them through quantitative real-time PCR (qRT-PCR). The results revealed that under NaCl stress with additional KCl applied treatments at 0 h, 48 h, and 168 h, based on Pfam protein domain prediction and physicochemical property analysis, we identified 20 related bZIP genes. Notably, four bZIP genes (bZIP_2, bZIP_6, bZIP_16, and bZIP_18) were labeled with the plant hormone signal transduction pathway, showing a predominant up-regulation in expression levels. The results suggest that these genes may mediate multiple physiological pathways under NaCl stress with additional KCl applied at 48 h and 168 h, enhancing signal transduction, reducing the accumulation of ROS, and decreasing oxidative damage, thereby enhancing the tolerance of T. ramosissima to NaCl stress. This study provides gene resources and a theoretical basis for further breeding of salt-tolerant Tamarix species and the involvement of bZIP transcription factors in mitigating NaCl toxicity. Full article

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

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16 pages, 4084 KB

Open AccessEditor’s ChoiceArticle

The Supersymmetry Genetic Code Table and Quadruplet Symmetries of DNA Molecules Are Unchangeable and Synchronized with Codon-Free Energy Mapping during Evolution

by Marija Rosandić and Vladimir Paar

Genes 2023, 14(12), 2200; https://doi.org/10.3390/genes14122200 - 12 Dec 2023

Cited by 4 | Viewed by 2351

Abstract

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: (1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)] and (2) of bases in the [...] Read more.

The Supersymmetry Genetic code (SSyGC) table is based on five physicochemical symmetries: (1) double mirror symmetry on the principle of the horizontal and vertical mirror symmetry axis between all bases (purines [A, G) and pyrimidines (U, C)] and (2) of bases in the form of codons; (3) direct–complement like codon/anticodon symmetry in the sixteen alternating boxes of the genetic code columns; (4) A + T-rich and C + G-rich alternate codons in the same row between both columns of the genetic code; (5) the same position between divided and undivided codon boxes in relation to horizontal mirror symmetry axis. The SSyGC table has a unique physicochemical purine–pyrimidine symmetry net which is as the core symmetry common for all, with more than thirty different nuclear and mitochondrial genetic codes. This net is present in the SSyGC table of all RNA and DNA living species. None of these symmetries are present in the Standard Genetic Code (SGC) table which is constructed on the alphabetic horizontal and vertical U-C-A-G order of bases. Here, we show that the free energy value of each codon incorporated as fundamentally mapping the “energy code” in the SSyGC table is compatible with mirror symmetry. On the other hand, in the SGC table, the same free energy values of codons are dispersed and a mirror symmetry between them is not recognizable. At the same time, the mirror symmetry of the SSyGC table and the DNA quadruplets together with our classification of codons/trinucleotides are perfectly imbedded in the mirror symmetry energy mapping of codons/trinucleotides and point out in favor of maintaining the integrity of the genetic code and DNA genome. We also argue that physicochemical symmetries of the SSyGC table in the manner of the purine–pyrimidine symmetry net, the quadruplet symmetry of DNA molecule, and the free energy of codons have remined unchanged during all of evolution. The unchangeable and universal symmetry properties of the genetic code, DNA molecules, and the energy code are decreasing disorder between codons/trinucleotides and shed a new light on evolution. Diversity in all living species on Earth is broad, but the symmetries of the Supersymmetry Genetic Code as the code of life and the DNA quadruplets related to the “energy code” are unique, unchangeable, and have the power of natural laws. Full article

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

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