Genes

11 pages, 774 KiB

Open AccessReview

Application of CRISPR/Cas9 Technology in Rice Germplasm Innovation and Genetic Improvement

by Jijin Chen, Zhening Miao, Deyan Kong, Anning Zhang, Feiming Wang, Guolan Liu, Xinqiao Yu, Lijun Luo and Yi Liu

Genes 2024, 15(11), 1492; https://doi.org/10.3390/genes15111492 - 20 Nov 2024

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Abstract

Improving the efficiency of germplasm innovation has always been the aim of rice breeders. Traditional hybrid breeding methods for variety selection rarely meet the practical needs of rice production. The emergence of genome-editing technologies, such as CRISPR/Cas9, provides a new approach to the [...] Read more.

Improving the efficiency of germplasm innovation has always been the aim of rice breeders. Traditional hybrid breeding methods for variety selection rarely meet the practical needs of rice production. The emergence of genome-editing technologies, such as CRISPR/Cas9, provides a new approach to the genetic improvement of crops such as rice. The number of published scientific papers related to “gene editing” and “CRISPR/Cas9” retrievable on websites both from China and other countries exhibited an increasing trend, year by year, from 2014 to 2023. Research related to gene editing in rice accounts for 33.4% and 12.3% of all the literature on gene editing published in China and other countries, respectively, much higher than that on maize and wheat. This article reviews recent research on CRISPR/Cas9 gene-editing technology in rice, especially germplasm innovation and genetic improvement of commercially promoted varieties with improved traits such as disease, insect, and herbicide resistance, salt tolerance, quality, nutrition, and safety. The aim is to provide a reference for the precise and efficient development of new rice cultivars that meet market demand. Full article

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

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10 pages, 893 KiB

Open AccessArticle

MIR27A rs895819 CC Genotype Severely Reduces miR-27a Plasma Expression Levels

by Georgia Ragia, Myria Pallikarou, Chrysoula Michou and Vangelis G. Manolopoulos

Genes 2024, 15(11), 1491; https://doi.org/10.3390/genes15111491 - 20 Nov 2024

Viewed by 274

Abstract

Background/Objectives: MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We [...] Read more.

Background/Objectives: MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of MIR27A rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression. Methods: A total of 59 individuals with no medical history of cancer were included in this study. MIR27A rs895819 genotyping and miR-27a-3p expression were analyzed by using predesigned TaqMan assays. Results: The frequency of TT, TC, and CC genotypes was present at a prevalence of 50.8%, 44.1%, and 5.1%, respectively. Individuals carrying the CC genotype presented with decreased miR-27a-3p expression (0.422 fold-change versus TT, p = 0.041; 0.461 fold-change versus TC, p = 0.064), whereas no differences were present between TT and TC individuals (1.092 fold-change, p = 0.718). miR-27a-3p expression was decreased in CC individuals under a recessive model of inheritance (0.440 fold-change, p = 0.047). No differences were found in dominant (TT vs. TC+CC, 0.845 fold-change, p = 0.471) or over dominant (TT+CC vs. TC, 0.990 fold-change, p = 0.996) models of inheritance. Conclusions: MIR27A rs895819CC genotype leads to severely reduced miR-27a-3p expression in plasma. Further study of this association is warranted in cancer patients to apply MIR27A genotyping in therapeutics to identify fluoropyrimidine-treated patients who are at a decreased risk of experiencing fluoropyrimidine-induced severe toxicity. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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10 pages, 3169 KiB

Open AccessCase Report

Multiple Osteochondritis Dissecans as Main Manifestation of Multiple Epiphyseal Dysplasia Caused by a Novel Cartilage Oligomeric Matrix Protein Pathogenic Variant: A Clinical Report

by Antonio Mazzotti, Elena Artioli, Evelise Brizola, Alice Moroni, Morena Tremosini, Alessia Di Cecco, Salvatore Gallone, Cesare Faldini, Luca Sangiorgi and Maria Gnoli

Genes 2024, 15(11), 1490; https://doi.org/10.3390/genes15111490 - 20 Nov 2024

Viewed by 288

Abstract

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness [...] Read more.

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness that evolve into degenerative joint disease. MED, caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene, is the most common form of the disease. COMP-MED usually shows significant involvement of the capital femoral epiphyses and irregular acetabulum; instead, COL9A1-, COL9A2-, and COL9A3-MED appear to have more severe knee involvement than hips, resulting in a milder presentation than COMP-MED cases. Other complications have been reported, in particular osteochondritis dissecans (OCD), which has been described in two large COL9A2-related MED families associated with myopathy. Methods: Here, we report the case of a 24-year-old man affected by COMP-MED with a positive family history for the disease and a clinical presentation that interestingly is characterized by the presence of multiple OCD. Results: To our knowledge, this is the first case of COMP mutations related to multiple OCD as the main clinical feature. Conclusions: This report can expand the clinical phenotype related to the pathogenic variants of the COMP gene, as it shows that multiple OCD can also be present in COMP-related MED as well as in COL9A2-related MED. Full article

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

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18 pages, 1651 KiB

Open AccessReview

An Updated Analysis of Exon-Skipping Applicability for Duchenne Muscular Dystrophy Using the UMD-DMD Database

by Jamie Leckie, Abdullah Zia and Toshifumi Yokota

Genes 2024, 15(11), 1489; https://doi.org/10.3390/genes15111489 - 20 Nov 2024

Viewed by 658

Abstract

Background/Objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only [...] Read more.

Background/Objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only benefit a subset of patients. Understanding the broad applicability of exon-skipping approaches is essential for prioritizing the development of additional therapies with the greatest potential impact on the DMD population. This review offers an updated analysis of all theoretical exon-skipping strategies and their applicability across the patient population, with a specific focus on DMD-associated mutations documented in the UMD-DMD database. Unlike previous studies, this approach leverages the inclusion of phenotypic data for each mutation, providing a more comprehensive and clinically relevant perspective. Methods: The theoretical applicability of all single and double exon-skipping strategies, along with multi exon-skipping strategies targeting exons 3–9 and 45–55, was evaluated for all DMD mutations reported in the UMD-DMD database. Results: Single and double exon-skipping approaches were applicable for 92.8% of large deletions, 93.7% of small lesions, 72.4% of duplications, and 90.3% of all mutations analyzed. Exon 51 was the most relevant target and was applicable for 10.6% of all mutations and 17.2% of large deletions. Additionally, two multi-exon-skipping approaches, targeting exons 45–55 and 3–9, were relevant for 70.6% of large deletions and 19.2% of small lesions. Conclusions: Current FDA-approved ASOs were applicable to 27% of the UMD-DMD population analyzed, leaving a significant portion of patients without access to exon-skipping therapies. The clinical translation of alternative approaches is critical to expanding the accessibility of these therapies for the DMD population. Full article

(This article belongs to the Section Bioinformatics)

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20 pages, 7102 KiB

Open AccessArticle

Characterization and Phylogenetic Analysis of the First Complete Chloroplast Genome of Shizhenia pinguicula (Orchidaceae: Orchideae)

by Yuan Chen, Yanlin Zhao, Quan Yan, Wei Wu, Qingqing Lin, Guoqiang Chen, Yanfang Zheng, Mingqing Huang, Shiming Fan and Yanxiang Lin

Genes 2024, 15(11), 1488; https://doi.org/10.3390/genes15111488 - 20 Nov 2024

Viewed by 377

Abstract

Background: Genomic analysis is crucial for better understanding the evolutionary history of species and for their conservation. Shizhenia pinguicula is a rare medicinal plant endemic to China. However, the complete chloroplast genome of this species has not been reported to date. Insufficient genomic [...] Read more.

Background: Genomic analysis is crucial for better understanding the evolutionary history of species and for their conservation. Shizhenia pinguicula is a rare medicinal plant endemic to China. However, the complete chloroplast genome of this species has not been reported to date. Insufficient genomic research on S. pinguicula has hindered effective conservation efforts for this valuable plant. Methods: In this study, we sequenced and assembled the first complete chloroplast genome of S. pinguicula using Illumina sequencing technology. We conducted a comparative analysis of its chloroplast genome with related species and reconstructed phylogenetic relationships. Results: The chloroplast genome of S. pinguicula exhibited a typical quadripartite structure with a length of 158,658 bp. A total of 123 genes, 118 simple sequence repeats, and 51 dispersed repetitive sequences were identified. The inverted repeat boundaries were significantly expanded, along with the pseudogenization and loss of multiple NDH genes. Codon usage bias is primarily influenced by natural selection and other factors, with the ycf3 gene under positive selection. Additionally, 10 hypervariable regions were detected for species identification and evolutionary studies. Phylogenetic analysis indicated that Ponerorchis gracilis and Hemipilia yajiangensis form a clade, with S. pinguicula as their sister species, located at the basal position of the Ponerorchis-Hemipilia alliance. Conclusions: The chloroplast genome structure and gene content of S. pinguicula exhibit certain degrees of variation compared to other species within the Orchidinae subtribe. This genome should be useful for further investigations into the biology of Shizhenia and the development of biodiversity conservation strategies. Full article

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

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14 pages, 2404 KiB

Open AccessArticle

Prognostic Relevance of Copy Number Losses in Ovarian Cancer

by Andrea Jemma, Alessandra Ardizzoia, Serena Redaelli, Angela Bentivegna, Marialuisa Lavitrano and Donatella Conconi

Genes 2024, 15(11), 1487; https://doi.org/10.3390/genes15111487 - 19 Nov 2024

Viewed by 481

Abstract

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as [...] Read more.

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients’ prognosis. Methods: Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Results: Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Conclusions: Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients’ prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers. Full article

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

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14 pages, 2487 KiB

Open AccessArticle

S100A9 Affects Milk Protein Content by Regulating Amino Acid Transporters and the PI3K-Akt, WNT, and mTOR Signaling Pathways

by Xinyi Zhang, Jun Teng, Zhujun Chen, Changheng Zhao, Li Jiang and Qin Zhang

Genes 2024, 15(11), 1486; https://doi.org/10.3390/genes15111486 - 19 Nov 2024

Viewed by 284

Abstract

Background: Calgranulin B (S100A9) was found to be strongly associated with milk protein percentage in dairy cattle in our previous genome-wide association study. Methods: SNPs in S100A9 were identified via pooled sequencing, and genotyping of 1054 cows was performed individually using [...] Read more.

Background: Calgranulin B (S100A9) was found to be strongly associated with milk protein percentage in dairy cattle in our previous genome-wide association study. Methods: SNPs in S100A9 were identified via pooled sequencing, and genotyping of 1054 cows was performed individually using MassArray with MALDI-TOFMS technology. Association analyses between the S100A9 SNPs and five milk production traits were conducted using SAS 9.2 software. Functional studies of S100A9 were conducted using quantitative PCR, Western blot, CCK-8, and immunofluorescence assays. Results: In the present study, we further verified that two SNPs in S100A9, g.17115387 C>A and g.17115176 C>A, were significantly associated with milk protein percentage. We found that S100A9 could affect the expressions of caseins CSN1S1, CSN2, and CSN3 in MAC-T cells by regulating the expressions of amino acid transporter genes. We investigated the effects of S100A9 on the PI3K-Akt, WNT, and mTOR pathways, which are well known to play important roles in mammary gland development and milk protein synthesis. Our results suggest that S100A9 regulates the expressions of the relevant genes in these pathways, and thus potentially influences the protein synthesis in the mammary gland. Conclusions: This study demonstrates the important role of the S100A9 gene in the milk protein trait of dairy cattle and provides new insights into the molecular mechanism of milk protein content. Full article

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

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24 pages, 6742 KiB

Open AccessArticle

SNP Polymorphisms Are Associated with Environmental Factors in Sockeye Salmon Populations Across the Northwest Pacific: Insights from Redundancy Analysis

by Anastasia M. Khrustaleva

Genes 2024, 15(11), 1485; https://doi.org/10.3390/genes15111485 - 19 Nov 2024

Viewed by 423

Abstract

The SNP variation in sockeye salmon across the Asian part of its range was studied in 23 samples from 16 lake–river systems of the West Pacific Coast to improve understanding of genetic adaptation in response to spawning watersheds conditions. Identification of candidate SNPs [...] Read more.

The SNP variation in sockeye salmon across the Asian part of its range was studied in 23 samples from 16 lake–river systems of the West Pacific Coast to improve understanding of genetic adaptation in response to spawning watersheds conditions. Identification of candidate SNPs and environmental factors that can contribute to local adaptations in sockeye salmon populations was carried out using redundancy analysis (RDA), a powerful tool for landscape genetics proven to be effective in genotype–environment association studies. Climatic and hydrographic indices (7 indices in total), reflecting abiotic conditions in freshwater habitats of sockeye salmon and characterizing the temperature regime in the river basin, its variability during the year, the amount of precipitation, as well as the height of the maximum tide in the estuary, were used as predictor factors. Among the 45 analyzed SNPs, several loci (ALDOB-135, HGFA, and RAG3-93) correlated with predictors gradients along the northwest Pacific coast were identified. The putative candidate loci localized in genes involved in the immune and inflammatory responses, as well as genes encoding temperature-sensitive enzymes and some hormones regulating ion homeostasis in fish during the anadromous migration and smoltification, were potentially associated with environmental conditions in natal rivers. The findings could have implications for aquaculture, conservation, and resource management in the context of global climate change. Full article

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

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17 pages, 9643 KiB

Open AccessArticle

Comparative Chloroplast Genome Study of Zingiber in China Sheds Light on Plastome Characterization and Phylogenetic Relationships

by Maoqin Xia, Dongzhu Jiang, Wuqin Xu, Xia Liu, Shanshan Zhu, Haitao Xing, Wenlin Zhang, Yong Zou and Hong-Lei Li

Genes 2024, 15(11), 1484; https://doi.org/10.3390/genes15111484 - 19 Nov 2024

Viewed by 343

Abstract

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear. Methods: To address this issue, the [...] Read more.

Background: Zingiber Mill., a morphologically diverse herbaceous perennial genus of Zingiberaceae, is distributed mainly in tropical to warm-temperate Asia. In China, species of Zingiber have crucial medicinal, edible, and horticultural values; however, their phylogenetic relationships remain unclear. Methods: To address this issue, the complete plastomes of the 29 Zingiber accessions were assembled and characterized. Comparative plastome analysis and phylogenetic analysis were conducted to develop genomic resources and elucidate the intraspecific phylogeny of Zingiber. Results: The newly reported plastomes ranged from 161,495 to 163,880 bp in length with highly conserved structure. Results of comparative analysis suggested that IR expansions/contractions and changes of repeats were the main reasons that influenced the genome size of the Zingiber plastome. A large number of SSRs and six highly variable regions (rpl20, clpP, ycf1, petA-psbJ, rbcL-accD, and rpl32-trnL) have been identified, which could serve as potential DNA markers for future population genetics or phylogeographic studies on this genus. The well-resolved plastome phylogeny suggested that Zingiber could be divided into three clades, corresponding to sect. Pleuranthesis (sect. Zingiber + sect. Dymczewiczia) and sect. Cryptanthium. Conclusions: Overall, this study provided a robust phylogeny of Zingiber plants in China, and the newly reported plastome data and plastome-derived markers will be of great significance for the accurate identification, protection, and agricultural management of Zingiber resources in the future. Full article

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

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12 pages, 4363 KiB

Open AccessCase Report

Small Complex Rearrangement in HINT1-Related Axonal Neuropathy

by Alessandra Tessa, Mariapaola Schifino, Eliana Salvo, Rosanna Trovato, Luca Cesana, Silvia Frosini, Rosa Pasquariello, Giada Sgherri, Roberta Battini, Maria Clara Bonaglia, Filippo Maria Santorelli and Guja Astrea

Genes 2024, 15(11), 1483; https://doi.org/10.3390/genes15111483 - 19 Nov 2024

Viewed by 482

Abstract

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent [...] Read more.

Background: Autosomal recessive inherited pathogenetic variants in the histidine triad nucleotide-binding protein 1 (HINT1) gene are responsible for an axonal Charcot-Marie-Tooth neuropathy associated with neuromyotonia, a phenomenon resulting from peripheral nerve hyperexcitability that causes a spontaneous muscle activity such as persistent muscle contraction, impaired relaxation and myokymias. Methods: Herein, we describe two brothers in whom biallelic HINT1 variants were identified following a multidisciplinary approach. Results: The younger brother came to our attention for clinical evaluation of moderate intellectual disability, language developmental delay, and some behavioral issues. His elder brother presented mild intellectual disability, hyperactivity, tiptoe walking, and gait ataxia. At first evaluation, motor impairment with frequent falls, pes cavus, and distal hyposthenia with reduced osteotendinous reflexes were found in both. Grip myotonic phenomenon was also noted. Blood tests revealed mildly elevated creatine kinase, and neurophysiology investigations revealed predominantly axonal polyneuropathy. Muscle MRI highlighted fibro-adipose infiltration, prevalent in the lower limbs. Gene panel testing detected a heterozygous HINT1 variant (c.355C>T/p.(Arg119Trp)) on the paternal allele. A further in-depth analysis using Integrative Genomics Viewer and Optical Genome Mapping led us to identify an additional variant in HINT1 represented by a complex rearrangement located in the region 5′UTR-exon 1-intron 1, not previously described. Conclusions: This complex rearrangement could have been overlooked if the clinical picture had not been evaluated as a whole (from a clinical, neurophysiological, and neuroimaging point of view). Neuropsychiatric manifestations (intellectual disability, hyperactivity, etc.) are part of the picture of HINT1-related neuromyotonia. Full article

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

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18 pages, 3968 KiB

Open AccessArticle

Comparative and Spatial Transcriptome Analysis of Rhododendron decorum Franch. During the Flowering Period and Revelation of the Plant Defense Mechanism

by Weiwei Liu, Chenghua Yu, Kaiye Yang, Ling Wang, Zhongyu Fan and Xinchun Mo

Genes 2024, 15(11), 1482; https://doi.org/10.3390/genes15111482 - 18 Nov 2024

Viewed by 441

Abstract

Background: Rhododendron is a globally distributed and extensive genus, comprising over 1000 species. In the southwestern mountains of China, there exists a remarkable diversity of Rhododendron, with Yunnan Province alone harboring more than 600 species. R. decorum Franch. has long been utilized [...] Read more.

Background: Rhododendron is a globally distributed and extensive genus, comprising over 1000 species. In the southwestern mountains of China, there exists a remarkable diversity of Rhododendron, with Yunnan Province alone harboring more than 600 species. R. decorum Franch. has long been utilized by local communities for its medicinal and edible properties. However, the transcriptional regulation function, medicinal properties, and edibility characteristics of R. decorum Franch. currently lack a solid theoretical basis. Methods: Total RNA was extracted from leaves, corollas and androecium/gynoecium of R. decorum Franch. in Heqing county, followed by the construction of cDNA libraries and the de novo assembly of transcriptomes. Results: A total of 63,050 unigenes were extracted from the flowers and leaf organs of R. decorum Franch. Among these unigenes, 43,517 were predicted to be coding sequences, with 32,690 being effectively annotated. Differential gene expression enrichment was observed among different organs within their respective transcriptomes; notably floral organs exhibited significant defense against plant diseases along with signal transduction functions. Furthermore, during the flower harvesting period, all floral organs exhibited gene enrichment pathways associated with carbohydrate metabolism. Additionally, the stamen and pistil displayed flavonoid metabolism pathways, suggesting their potential applications as functional food or medicine. Conclusions: Our results shed light on plant–pathogen defense mechanisms and the molecular bias of flavonoids biosynthesis on flower organs during the flowering period, which might help to understand the consumption of R. decorum Franch. corollas by the Bai nationality of Heqing county. Full article

(This article belongs to the Special Issue Molecular Genetics and Multi-omics in Medicinal Plants)

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10 pages, 1507 KiB

Open AccessArticle

L-Histidine Modulates the Catalytic Activity and Conformational Changes of the HD3 Deoxyribozyme

by Nae Sakimoto, Hirofumi Imanaka, Elisa Tomita-Sudo, Tomoka Akita and Junji Kawakami

Genes 2024, 15(11), 1481; https://doi.org/10.3390/genes15111481 - 17 Nov 2024

Viewed by 464

Abstract

Background/Objectives: Riboswitches are functional nucleic acids that regulate biological processes by interacting with small molecules, such as metabolites, influencing gene expression. Artificial functional nucleic acids, including deoxyribozymes, have been developed through in vitro selection for various catalytic functions. In a previous study, [...] Read more.

Background/Objectives: Riboswitches are functional nucleic acids that regulate biological processes by interacting with small molecules, such as metabolites, influencing gene expression. Artificial functional nucleic acids, including deoxyribozymes, have been developed through in vitro selection for various catalytic functions. In a previous study, an l-histidine-dependent deoxyribozyme was identified, exhibiting RNA cleavage activity in the presence of l-histidine resembling ribonuclease catalytic mechanisms. This study aims to clarify the role of l-histidine in the activity and structural formation of the l-histidine-dependent deoxyribozyme (HD), focusing on the binding properties and conformational changes of its derivative HD3. Methods: Conformational changes in HD3 were analyzed using circular dichroism (CD) under varying concentrations of l-histidine. Direct binding analysis was conducted using carbon-14 (¹⁴C)-labeled l-histidine and a liquid scintillation counter. The catalytic activity of HD3 in the presence of different l-histidine concentrations was measured. Results: The binding constant for l-histidine-induced conformational changes (K_a(CD)) was found to be 2.0 × 10³ (M⁻¹), whereas for catalytic activity (K_a(Rxn)) and scintillation counting (K_a(RI)), it was approximately 1.0 × 10³ (M⁻¹). Conclusions: l-Histidine plays an essential role in both the catalytic activity and structural formation of the HD3 deoxyribozyme. The consistent binding constants across different experimental methods highlight the significant contribution of l-histidine to the active folding of deoxyribozymes. Full article

(This article belongs to the Special Issue Molecular Oncology: Deciphering the Molecular Landscape of Cancer Treatment)

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22 pages, 6489 KiB

Open AccessArticle

Nucleotide and Amino Acid Analyses of Unique Infectious Bronchitis Virus (IBV) Variants from Canadian Poultry Flocks with Drop in Egg Production

by Muhammad Farooq, Ahmed Ali, Mohamed S. H. Hassan and Mohamed Faizal Abdul-Careem

Genes 2024, 15(11), 1480; https://doi.org/10.3390/genes15111480 - 17 Nov 2024

Viewed by 533

Abstract

Background/Objectives: Infectious bronchitis (IB) is a highly infectious avian disease caused by the infectious bronchitis virus (IBV). The disease causes lesions mainly in the respiratory, reproductive, and renal systems and has a significant economic impact on the poultry industry worldwide. Methods: We discovered [...] Read more.

Background/Objectives: Infectious bronchitis (IB) is a highly infectious avian disease caused by the infectious bronchitis virus (IBV). The disease causes lesions mainly in the respiratory, reproductive, and renal systems and has a significant economic impact on the poultry industry worldwide. Methods: We discovered two unique IBV isolates (T-62: PP737794.1 and CL-61: PP783617.1) circulating in Canada and molecularly characterized them. Results: The phylogenetic analysis revealed that the IBV isolates belong to genotype I and fall between lineages 25 and 7. Further analysis of the T-62 IBV isolate indicated that it is a potential recombinant of the Iowa state isolate (IA1162/2020-MW) and that the CL-61 strain of the IBV is also a recombinant IBV with the Connecticut (Conn) vaccine strain as its major parent. The S1 glycoprotein of the CL-61 and T-62 strains of the IBV had 85.7% and 73.2% amino acid (aa) identities respectively compared to the Conn vaccine strain. There were 67 and 129 aa substitutions among the S1 glycoprotein of the CL-61 and T-62 strains of the IBV compared to the Conn vaccine, respectively. Importantly, two and nineteen of these aa variations were in hypervariable regions 1 (HVR1) and HVR3. Finally, the two IBV isolates possessed a higher affinity for the sialic acid ligand compared to the DMV/1639 and Mass/SES IBV strains. Conclusions: Genetic recombination in the IBV results in the continual emergence of new variants, posing challenges for the poultry industry. As indicated by our analyses, live attenuated vaccine strains play a role in the genetic recombination of the IBV, resulting in the emergence of variants. Full article

(This article belongs to the Section Viral Genomics)

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14 pages, 1645 KiB

Open AccessArticle

Effects of Density Stress During Transportation on the Antioxidant Activity and Immuno-Related Gene Expression in Yellowfin Seabream (Acanthopagrus latus Houttuyn, 1782)

by Xiulin Nong, Kecheng Zhu, Huayang Guo, Baosuo Liu, Nan Zhang, Qin Zhang and Dianchang Zhang

Genes 2024, 15(11), 1479; https://doi.org/10.3390/genes15111479 - 17 Nov 2024

Viewed by 420

Abstract

Background/Objectives: Maintaining an optimum transport density is essential for protecting water quality, lowering stress levels, and increasing fish survival rates. Transporting marine fish fry involves major dangers. The purpose of this study was to evaluate the impact of transport stress at varying densities [...] Read more.

Background/Objectives: Maintaining an optimum transport density is essential for protecting water quality, lowering stress levels, and increasing fish survival rates. Transporting marine fish fry involves major dangers. The purpose of this study was to evaluate the impact of transport stress at varying densities on the immune-related gene expression, antioxidant capacity, and survival rate of yellowfin seabream (Acanthopagrus latus) fry. Methods: A 12 h simulated transport experiment was conducted with A. latus fry divided into six density groups. For 1–2 cm fry, densities of 900, 1200, and 1500 fry per pouch were used to assess antioxidant enzyme activity; and for 4–5 cm fry, densities of 100, 125, and 150 fry per pouch were used for gene expression analysis. The key parameters measured included survival rates, antioxidant enzyme activities in liver and intestinal tissues, and expression levels of HSP90α and caspase-3 genes. Results: The findings showed that recovery time and density both affected the observed responses and that transport density had a substantial effect on antioxidant enzyme activity in all tissues. The intestinal and liver tissues showed a considerable decrease in antioxidant enzyme activity, suggesting that these tissues may be able to respond to oxidative stress. Moreover, under high-density transport conditions, there were notable increases in the expression of caspase-3 and HSP90α, suggesting the activation of immune response systems. This research offers valuable new understandings into the relationship between transport density and immunological and antioxidant modulation in A. latus fry. Conclusions: The results provide a scientific foundation for enhancing aquaculture transport conditions, which will ultimately lead to decreased fish mortality and improved general health during transit, resulting in more sustainable and effective aquaculture methods. Full article

(This article belongs to the Special Issue Genetic Breeding of Aquaculture 2nd Edition)

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12 pages, 1593 KiB

Open AccessArticle

D299T Mutation in CYP76F14 Led to a Decrease in Wine Bouquet Precursor Production in Wine Grape

by Wanhao Liu, Huilin Xiao, Matthew Shi, Meiling Tang and Zhizhong Song

Genes 2024, 15(11), 1478; https://doi.org/10.3390/genes15111478 - 16 Nov 2024

Viewed by 538

Abstract

Background: Bouquet is a crucial characteristic indicative of wine quality that develops during the aging stage. The cytochrome P450 VvCYP76F14 multi-functionally catalyzes linalool into (E)-8-hydroxylinalool, (E)-8-oxolinalool, and (E)-8-carboxylinalool, which are direct precursors for wine bouquet. Wine bouquet [...] Read more.

Background: Bouquet is a crucial characteristic indicative of wine quality that develops during the aging stage. The cytochrome P450 VvCYP76F14 multi-functionally catalyzes linalool into (E)-8-hydroxylinalool, (E)-8-oxolinalool, and (E)-8-carboxylinalool, which are direct precursors for wine bouquet. Wine bouquet was closely related to VvCYP76F14 activities. Method: The VvCYP76F14 genes were cloned from five wine grape varieties using a homologous cloning method. The variation in residues of VvCYP76F14s were assessed by multiple alignment of amino acid sequences. Functional studies were implemented by in vitro enzyme activity and transient over-expression systems. Results: D299T variation was observed in VvCYP76F14s of ‘Yantai 2-2-08’, ‘Yantai 2-2-19’, and ‘Yantai 2-3-37’ offspring lines, which was correlated with the decreased content of wine bouquet precursors of (E)-8-hydroxylinalool, (E)-8-oxolinalool, and (E)-8-carboxylinalool, respectively. Notably, the key amino acid residue D299 was located at the phase 0 intron positions of VvCYP76F14 genes isolated from distinct wine grape varieties or offspring lines, respectively. Notably, VvCYP76F14s of the ‘Yantai2-2-08’, ‘Yantai 2-2-19’, and ‘Yantai 2-3-37’ mutant lines exhibited lower in vitro enzymatic activities than those of ‘L35’ and ‘Merlot’. In addition, the transient expression of VvCYP76F14 cloned from ‘L35’ and ‘Merlot’ restored the levels of wine bouquet precursors in berries of three D299T mutant lines, respectively, whereas VvCYP76F14 cloned from D299T mutant lines failed. Conclusions: D299T variation was observed in three offspring lines and D299T mutation in VvCYP76F14 led to the decrease in wine bouquet precursor contents. VvCYP76F14 was implicated in the regulation of wine bouquet precursors in wine grapes. Full article

(This article belongs to the Special Issue Advances in Genetics and Breeding of Fruit Trees)

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12 pages, 775 KiB

Open AccessArticle

Runs of Homozygosity Islands in Autochthonous Spanish Cattle Breeds

by C. Hervás-Rivero, N. Mejuto-Vázquez, D. López-Carbonell, J. Altarriba, C. Diaz, A. Molina, R. Rodríguez-Bermúdez, J. Piedrafita, J. A. Baro and L. Varona

Genes 2024, 15(11), 1477; https://doi.org/10.3390/genes15111477 - 15 Nov 2024

Viewed by 381

Abstract

Background/Objectives: Understanding the genetic architecture of autochthonous European cattle breeds is important for developing effective conservation strategies and sustainable breeding programs. Spanish beef cattle, which trace their origins to ancient migrations from the Near East with later admixture from African populations, exhibit a [...] Read more.

Background/Objectives: Understanding the genetic architecture of autochthonous European cattle breeds is important for developing effective conservation strategies and sustainable breeding programs. Spanish beef cattle, which trace their origins to ancient migrations from the Near East with later admixture from African populations, exhibit a rich genetic diversity shaped by environmental adaptation and selective breeding. Runs of Homozygosity (ROH) are extended stretches of identical genetic material inherited from both parents. They serve as indicators of inbreeding and selection signatures within populations. ROH islands, or regions of the genome where ROH segments are highly concentrated across individuals within a breed, indicate genomic regions under selective pressure. Methods: This study explores the distribution of ROH islands across seven Spanish beef cattle breeds (Asturiana de los Valles, Avileña-Negra Ibérica, Bruna dels Pirineus, Morucha, Retinta, Pirenaica, and Rubia Gallega). By analyzing high-density SNP data, we characterized ROH patterns and identified genomic regions with high levels of homozygosity, which may indicate selection pressures or common ancestry. Results: Our findings revealed breed-specific ROH patterns as well as shared ROH islands, underscoring genetic relationships and differentiation among the breeds. Notably, Morucha displayed the highest number of ROH, while Asturiana de los Valles had the fewest. F_ROH values, which indicate genomic inbreeding, varied among the breeds, with Morucha and Retinta being associated with higher values. We identified 57 ROH islands, with shared regions among populations that suggest common ancestral selection pressures. Key genes within these regions, like MSTN, are associated with muscle growth, body weight, and fertility. Conclusions: This study offers valuable insights for breeding strategies and conservation efforts, highlighting the genetic diversity and historical background of Spanish cattle breeds. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

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14 pages, 8290 KiB

Open AccessReview

Mechanistic Role of TRIM26 in Viral Infection and Host Defense

by Mona Sharma, Ke Liu, Jianchao Wei, Zhiyong Ma and Yafeng Qiu

Genes 2024, 15(11), 1476; https://doi.org/10.3390/genes15111476 - 15 Nov 2024

Viewed by 484

Abstract

Tripartite motif protein 26 (TRIM26) is an E3 ubiquitin ligase and a member of the TRIM family. Similar to other TRIM proteins, TRIM26 consists of three domains, collectively termed RBCC: a Really Interesting New Gene (RING) domain, one B-Box domain, and a C [...] Read more.

Tripartite motif protein 26 (TRIM26) is an E3 ubiquitin ligase and a member of the TRIM family. Similar to other TRIM proteins, TRIM26 consists of three domains, collectively termed RBCC: a Really Interesting New Gene (RING) domain, one B-Box domain, and a C terminal domain consisting of a PRY/SPRY domain. The PRY/SPRY domain exhibits relatively higher conservation compared with the RING and B-Box domains, suggesting potentially similar roles across TRIM26 proteins from various species. TRIM26 either directly interacts with viral proteins or modulates immune responses to engage with a viral infection, serving as either a protective or detrimental host factor depending on the circumvent of the viral infection. The present review focuses on understanding the mechanisms of TRIM26 during viral infection and its potential future applications. Full article

(This article belongs to the Special Issue Advances in Genes and Genomics of Aquatic Animals and Pathogens)

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7 pages, 779 KiB

Open AccessCommunication

The Recurrent E-Cadherin (CDH1) Mutation c.760G>A Causes Orofacial Clefts but Does Not Predispose to Hereditary Cancer

by Lea Gossner, Dietmar Rieder, Thomas Müller and Andreas R. Janecke

Genes 2024, 15(11), 1475; https://doi.org/10.3390/genes15111475 - 15 Nov 2024

Viewed by 389

Abstract

Objective: Congenital, non-syndromic orofacial clefts (CL/P) are infrequently monogenic in etiology. However, heterozygous pathogenic CDH1 germline variants were reported in a few non-syndromic CL/P families, as well as in one syndromic form of CL/P: the blepharocheilodontic syndrome. CDH1 encodes epithelial cadherin (E-cadherin), [...] Read more.

Objective: Congenital, non-syndromic orofacial clefts (CL/P) are infrequently monogenic in etiology. However, heterozygous pathogenic CDH1 germline variants were reported in a few non-syndromic CL/P families, as well as in one syndromic form of CL/P: the blepharocheilodontic syndrome. CDH1 encodes epithelial cadherin (E-cadherin), and close to 300 different pathogenic CDH1 variants are listed in the ClinVar mutation database. The majority of CDH1 germline variants are implicated in hereditary diffuse gastric cancer (HDGC) susceptibility. The purpose of this study was to classify the CDH1 c.760G>A (p.Asp254Asn) mutation with respect to its resulting phenotype. Methods: Exome sequencing and targeted Sanger sequencing were performed in a family segregating CL/P. A review of pathogenic CDH1 variants in ClinVar and those identified in a PubMed/MEDLINE search was performed. Results: We identified a family with six individuals, who were 35–77 years old (mean 56 years) at their last examination, uniformly affected with bilateral CL/P. The CDH1 c.760G>A variant segregated with CL/P. This variant had been reported in 21 individuals, most often children and young adults, from six families. We determined a significant sex preponderance for this variant regarding CL/P: all 16 male and 5 of 11 female heterozygotes presented with CL/P. Furthermore, none of the heterozygous individuals in seven families reported any gastrointestinal tumors. Conclusions: The recurrent CDH1 c.760G>A mutation confers a high risk for CL/P, with strong male preponderance. This review of 27 mutation carriers, including 3 who were 68, 70, and 77 years of age, indicates that c.760G>A does not confer an increased risk for HDGC. The relevance of differentiating craniofacial from cancer phenotypes in mutation carriers is substantial for precision medicine and for counseling families. Full article

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

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15 pages, 1107 KiB

Open AccessArticle

Differential Gene Expression Associated with Idiopathic Epilepsy in Belgian Shepherd Dogs

by Nathan Kinsey, Janelle M. Belanger and Anita M. Oberbauer

Genes 2024, 15(11), 1474; https://doi.org/10.3390/genes15111474 - 15 Nov 2024

Viewed by 796

Abstract

Background: Idiopathic epilepsy (IE) disproportionately affects Belgian shepherd dogs and although genomic risk markers have been identified previously in the breed, causative variants have not been described. Methods: The current study analyzed differences in whole blood RNA expression associated with IE and with [...] Read more.

Background: Idiopathic epilepsy (IE) disproportionately affects Belgian shepherd dogs and although genomic risk markers have been identified previously in the breed, causative variants have not been described. Methods: The current study analyzed differences in whole blood RNA expression associated with IE and with a previously identified IE risk haplotype on canine chromosome (CFA) 14 using a transcriptomics RNA-seq approach. Results: MFSD2A and a likely pseudogene of RPL19, both of which are genes implicated in seizure activity, were upregulated in dogs with IE. Genes in the interferon signaling pathway were downregulated in Belgian shepherds with IE. The CFA14 risk haplotype was associated with upregulation of CLIC1, ACE2, and PIGN and downregulation of EPDR1, all known to be involved with epilepsy or the Wnt/β-catenin signaling pathway. Conclusions: These results highlight the value of assessing gene expression in canine IE research to uncover genomic contributory factors. Full article

(This article belongs to the Special Issue The Role of RNA Regulation in Development and Disease)

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12 pages, 4410 KiB

Open AccessArticle

Whole-Genome Sequence and Characterization of Ralstonia solanacearum MLY102 Isolated from Infected Tobacco Stalks

by Guan Lin, Juntao Gao, Junxian Zou, Denghui Li, Yu Cui, Yong Liu, Lingxue Kong and Shiwang Liu

Genes 2024, 15(11), 1473; https://doi.org/10.3390/genes15111473 - 15 Nov 2024

Viewed by 554

Abstract

Background/Objectives: Bacterial wilt disease is a soil-borne disease caused by Ralstonia solanacearum that causes huge losses to crop economies worldwide. Methods: In this work, strain MLY102 was isolated and further identified as R. solanacearum from a diseased tobacco stalk. The genomic properties of [...] Read more.

Background/Objectives: Bacterial wilt disease is a soil-borne disease caused by Ralstonia solanacearum that causes huge losses to crop economies worldwide. Methods: In this work, strain MLY102 was isolated and further identified as R. solanacearum from a diseased tobacco stalk. The genomic properties of MLY102 were explored by performing biochemical characterization, genome sequencing, compositional analysis, functional annotation and comparative genomic analysis. Results: MLY102 had a pinkish-red color in the center of the colony surrounded by a milky-white liquid with fluidity on TTC medium. The biochemical results revealed that MLY102 can utilize carbon sources, including D-glucose (dGLU), cane sugar (SAC) and D-trehalose dihydrate (dTRE). Genome sequencing through the DNBSEQ and PacBio platforms revealed a genome size of 5.72 Mb with a G+C content of 67.59%. The genome consists of a circular chromosome and a circular giant plasmid with 5283 protein-coding genes. A comparison of the genomes revealed that MLY102 is closely related to GMI1000 and CMR15 but has 498 special genes and 13 homologous genes in the species-specific gene family, indicating a high degree of genomic uniqueness. Conclusions: The unique characteristics and genomic data of MLY102 can provide important reference values for the prevention and control of bacterial wilt disease. Full article

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

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18 pages, 1786 KiB

Open AccessArticle

The Evolution of Complex Multicellularity in Land Plants

by Hossein Madhani and Arsham Nejad Kourki

Genes 2024, 15(11), 1472; https://doi.org/10.3390/genes15111472 - 14 Nov 2024

Viewed by 390

Abstract

The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary [...] Read more.

The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary Transitions in Individuality (ETIs), which focuses on formerly independent entities forming higher-level units that lose their reproductive autonomy. While much of the ETI literature has concentrated on the early stages of multicellularity, such as the formation and maintenance stages, this paper seeks to address the less explored transformation stage. To do so, we apply an approach that we call Transitions in Structural Complexity (TSCs), which focuses on the emergence of new units of organization via the three key evolutionary processes of modularization, subfunctionalization, and integration to the evolution of land plants. To lay the groundwork, we first explore the relationships between sex, individuality, and units of selection to highlight a sexual life cycle-based perspective on ETIs by examining the early stages of the transition to multicellularity (formation) in the sexual life cycle of the unicellular common ancestor of land plants, emphasizing the differences between the transition to multicellularity in eumetazoans and land plants. We then directly apply the TSC approach in this group, identifying key evolutionary events such as the distinct evolutionary innovations like shoot, root, vascular systems, and specialized reproductive structures, arguing that bringing these under the broader rubric of TSCs affords a degree of explanatory unification. By examining these evolutionary processes, this paper provides a new perspective on the evolution of multicellularity in land plants, highlighting both parallels and distinctions with the animal kingdom. Full article

(This article belongs to the Special Issue The Genetics and Evolution of Multicellularity)

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14 pages, 4866 KiB

Open AccessArticle

Retinal Patterns and the Role of Autofluorescence in Choroideremia

by Federica E. Poli, Robert E. MacLaren and Jasmina Cehajic-Kapetanovic

Genes 2024, 15(11), 1471; https://doi.org/10.3390/genes15111471 - 14 Nov 2024

Viewed by 395

Abstract

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the CHM gene, which result in a [...] Read more.

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the CHM gene, which result in a deficiency in Rab-escort protein-1, a key element for intracellular trafficking of vesicles, including those carrying melanin. As choroideremia primarily affects the retinal pigment epithelium, fundus autofluorescence, which focuses on the fluorescent properties of pigments within the retina, is an established imaging modality used for the assessment and monitoring of affected patients. Methods and Results: In this manuscript, we demonstrate the use of both short-wavelength blue and near-infrared autofluorescence and how these imaging modalities reveal distinct disease patterns in choroideremia. In addition, we show how these structural measurements relate to retinal functional measures, namely microperimetry, and discuss the potential role of these retinal imaging modalities in clinical practice and research studies. Moreover, we discuss the mechanisms underlying retinal autofluorescence patterns by imaging with a particular focus on melanin pigment. Conclusions: This could be of particular significance given the current progress in therapeutic options, including gene replacement therapy. Full article

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

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12 pages, 612 KiB

Open AccessArticle

Characteristics and Yield of Modern Approaches for the Diagnosis of Genetic Causes of Kidney Stone Disease

by Andrea Spasiano, Mirko Treccani, Elisa De Tomi, Giovanni Malerba, Giovanni Gambaro and Pietro Manuel Ferraro

Genes 2024, 15(11), 1470; https://doi.org/10.3390/genes15111470 (registering DOI) - 14 Nov 2024

Viewed by 454

Abstract

Background: Kidney stone disease (KSD) is characterized by an increasing prevalence worldwide, representing an important clinical issue and a financial burden for healthcare systems. A KSD-causing monogenic variant is traditionally expected in up to 30% of children and 1–5% of adults forming stones, [...] Read more.

Background: Kidney stone disease (KSD) is characterized by an increasing prevalence worldwide, representing an important clinical issue and a financial burden for healthcare systems. A KSD-causing monogenic variant is traditionally expected in up to 30% of children and 1–5% of adults forming stones, confirmed by a strong connection between a positive family history and KSD. The insufficient use of genetic testing in these patients is associated with a lack of perceived benefit and a scarce awareness of inherited kidney diseases. Genetic testing has important practical implications, such as the possibility of earlier diagnoses, familial counseling, and tailored therapy, based on the evaluation of fine-mapped pathogenic variants. Our aim is to analyze the current evidence on genetic testing in KSD patients to whom genetic tests were applied without strict a priori selection criteria, to provide an overview of its diagnostic yield and factors potentially affecting it (such as the age of KSD onset, a familial history of KSD, consanguinity, and extrarenal features). Methods: A literature review was performed, selecting original articles published in the last 10 years concerning genetic investigations in patients affected by nephrolithiasis or nephrocalcinosis. Available data were subsequently extracted and analyzed. Results: In total, 13 studies on 1675 patients (77% pediatric populations) were included; 333 patients were determined to be affected by a monogenic disorder, with an overall yield of about 20%. The likelihood of a positive genetic finding was much higher in pediatric (26%) than adult populations (8%). Cystinuria was the most common diagnosis in both populations. After the removal of conditions that could be identified with a stone composition analysis or urinary chemistry investigation, the diagnostic yield dropped to 19% among pediatric patients and below 5% for adults. Conclusions: Genetic testing should be considered in KSD pediatric patients and in selected subgroups of adults with suggestive features when a diagnosis is not established after stone examination and blood as well as urine metabolic profiling. Full article

(This article belongs to the Special Issue From Genetic to Molecular Basis of Kidney Damage)

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13 pages, 3150 KiB

Open AccessArticle

FAN1 Deletion Variant in Basenji Dogs with Fanconi Syndrome

by Fabiana H. G. Farias, Tendai Mhlanga-Mutangadura, Juyuan Guo, Liz Hansen, Gary S. Johnson and Martin L. Katz

Genes 2024, 15(11), 1469; https://doi.org/10.3390/genes15111469 - 14 Nov 2024

Viewed by 461

Abstract

Background: Fanconi syndrome is a disorder of renal proximal tubule transport characterized by metabolic acidosis, amino aciduria, glucosuria, and phosphaturia. There are acquired and hereditary forms of this disorder. A late-onset form of Fanconi syndrome in Basenjis was first described in 1976 and [...] Read more.

Background: Fanconi syndrome is a disorder of renal proximal tubule transport characterized by metabolic acidosis, amino aciduria, glucosuria, and phosphaturia. There are acquired and hereditary forms of this disorder. A late-onset form of Fanconi syndrome in Basenjis was first described in 1976 and is now recognized as an inherited disease in these dogs. In part because of the late onset of disease signs, the disorder has not been eradicated from the breed by selective mating. A study was therefore undertaken to identify the molecular genetic basis of the disease so that dogs could be screened prior to breeding in order to avoid generating affected offspring. Methods: Linkage analysis within a large family of Basenjis that included both affected and unaffected individuals was performed to localize the causative variant within the genome. Significant linkage was identified between chromosome 3 (CFA3) makers and the disease phenotype. Fine mapping restricted the region to a 2.7 Mb section of CFA3. A whole genome sequence of a Basenji affected with Fanconi syndrome was generated, and the sequence data were examined for the presence of potentially deleterious homozygous variants within the mapped region. Results: A homozygous 317 bp deletion was identified in the last exon of FAN1 of the proband. 78 Basenjis of known disease status were genotyped for the deletion variant. Among these dogs, there was almost complete concordance between genotype and phenotype. The only exception was one dog that was homozygous for the deletion variant but did not exhibit signs of Fanconi syndrome. Conclusions: These data indicate that the disorder is very likely the result of FAN1 deficiency. The mechanism by which this deficiency causes the disease signs remains to be elucidated. FAN1 has endonuclease and exonuclease activity that catalyzes incisions in regions of double-stranded DNA containing interstrand crosslinks. FAN1 inactivation may cause Fanconi syndrome in Basenjis by sensitization of kidney proximal tubule cells to toxin-mediated DNA crosslinking, resulting in the accumulation of genomic and mitochondrial DNA damage in the kidney. Differential exposure to environmental toxins that promote DNA crosslink formation may explain the wide age-at-onset variability for the disorder in Basenjis. Full article

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

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14 pages, 2082 KiB

Open AccessArticle

Dynamics of SARS-CoV-2 Spike RBD Protein Mutation and Pathogenicity Consequences in Indonesian Circulating Variants in 2020–2022

by Nabiel Muhammad Haykal, Fadilah Fadilah, Beti Ernawati Dewi, Linda Erlina, Aisyah Fitriannisa Prawiningrum and Badriul Hegar

Genes 2024, 15(11), 1468; https://doi.org/10.3390/genes15111468 - 14 Nov 2024

Viewed by 579

Abstract

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This [...] Read more.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This research analyzes the mutation trend in various RBD samples from Indonesia published in the Global Initiative on Sharing All Influenza Data (GISAID) database using genomic profiling. Method: Patients in Indonesia infected with SARS-CoV-2, whose samples have been published in genomic databases, were selected for this research. The collected data were processed for analysis following several bioinformatics protocols: visualization into phylogenetic trees, 3D rendering, and the assessment of mutational impact. Results: In Indonesia, there are 25 unique SARS-CoV-2 clades and 318 unique SARS-CoV-2 RBD mutations from the earliest COVID-19 sample to samples collected in 2022, with T478K being the most prevalent RBD mutation and 22B being the most abundant clade. The Omicron variant has a lower docking score, higher protein destabilization, and higher K_D than the Delta variant and the original virus. Conclusions: The study findings reveal a decreasing trend in virus pathogenicity as a potential trade-off to increase transmissibility via mutations in RBD over the years. Full article

(This article belongs to the Special Issue Bioinformatics of Human Diseases)

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12 pages, 471 KiB

Open AccessArticle

A Modular Genetic Approach to Newborn Screening from Spinal Muscular Atrophy to Sickle Cell Disease—Results from Six Years of Genetic Newborn Screening

by Jessica Bzdok, Ludwig Czibere, Siegfried Burggraf, Natalie Pauly, Esther M. Maier, Wulf Röschinger, Marc Becker and Jürgen Durner

Genes 2024, 15(11), 1467; https://doi.org/10.3390/genes15111467 - 13 Nov 2024

Viewed by 517

Abstract

Background/Objectives: Genetic newborn screening (NBS) has already entered the phase of common practice in many countries. In Germany, spinal muscular atrophy (SMA), severe combined immunodeficiency (SCID) and sickle cell disease (SCD) are currently a mandatory part of NBS. Here, we describe the experience [...] Read more.

Background/Objectives: Genetic newborn screening (NBS) has already entered the phase of common practice in many countries. In Germany, spinal muscular atrophy (SMA), severe combined immunodeficiency (SCID) and sickle cell disease (SCD) are currently a mandatory part of NBS. Here, we describe the experience of six years of genetic NBS including the prevalence of those three diseases in Germany. Methods: Samples and nucleic acids were extracted from dried blood spot cards, commonly used for NBS. A qPCR assay was used to detect disease-causing variants for SMA and SCD, and the detection of T-cell receptor excision circles (TRECs) was performed for SCID screening. Results: The results of the NBS of over 1 million newborns for SMA, approximately 770,000 for SCID and over 410,000 for SCD are discussed in detail. In these newborns, we have identified 121 cases of SMA, 15 cases of SCID and syndrome-based immunodeficiencies and 77 cases of SCD or β-thalassemia. Conclusions: The flexibility of multiplex qPCR is assessed as an effective tool for incorporating different molecular genetic markers for screening. The processing of dried blood spot (DBS) filter cards for molecular genetic assays and the assays are described in detail; turn-around times and cost estimations are included to give an insight into the processes and discuss further options for optimization. The identified cases are in the range expected for the total number of screened newborns, but present a more exact view on the actual prevalences for Germany. Full article

(This article belongs to the Special Issue Genetic Newborn Screening)

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17 pages, 2889 KiB

Open AccessArticle

Genome-Wide Characterization of Solanum tuberosum CCoAOMT Gene Family and Identification of StCCoAOMT Genes Involved in Anthocyanin Biosynthesis

by Yaxuan Peng, Suao Sheng, Tongtong Wang, Jiafeng Song, Daijuan Wang, Yixuan Zhang, Jielan Cheng, Tingting Zheng, Zhaoyan Lv, Xiaobiao Zhu and Hualan Hou

Genes 2024, 15(11), 1466; https://doi.org/10.3390/genes15111466 - 13 Nov 2024

Viewed by 440

Abstract

Background: The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays essential roles in the methylation of various secondary metabolites, including anthocyanins. Despite the wide identification of the CCoAOMT family in plants, the characterization and function of CCoAOMT protein members in Solanum tuberosum remain poorly understood. Methods [...] Read more.

Background: The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays essential roles in the methylation of various secondary metabolites, including anthocyanins. Despite the wide identification of the CCoAOMT family in plants, the characterization and function of CCoAOMT protein members in Solanum tuberosum remain poorly understood. Methods and Results: In this study, a total of 12 StCCoAOMT members were identified in the genome of S. tuberosum using the Blastp and HMM search and were unevenly located on eight chromosomes. Collinearity analysis revealed that four tandem duplicated gene pairs and two segmental duplicated gene pairs existed in the S. tuberosum genome, demonstrating that duplication events play a key role in the expansion of the CCoAOMT family. All StCCoAOMTs were clustered into group I and group II based on phylogenetic analysis, which was further verified by the conserved motifs and gene structures analysis. The cis-acting elements analysis illustrated that StCCoAOMTs might be important for photosynthesis, hormone responses, and abiotic stress. Expression analysis demonstrated that StCCoAOMT genes have diverse transcript levels in various tissues and that StCCoAOMT10 was significantly expressed in purple potatoes with abundant anthocyanin content according to RNA-seq data and qRT-PCR assays. In addition, the subcellular localization assay validated that the StCCoAOMT10 protein was mainly localized in the cytoplasm and nucleus. Conclusions: These results will be of great importance for a better understanding of the features of CCoAOMT family members, especially of the candidate genes involved in the methylation of anthocyanins in S. tuberosum, and also for improving the nutritional quality of S. tuberosum. Full article

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

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25 pages, 6587 KiB

Open AccessArticle

Transcriptome Analysis Reveals the Crucial Role of Phenylalanine Ammonia-Lyase in Low Temperature Response in Ammopiptanthus mongolicus

by Ning Wang, Yilin Zhu, Yijun Zhou, Fei Gao and Suxia Cui

Genes 2024, 15(11), 1465; https://doi.org/10.3390/genes15111465 - 13 Nov 2024

Viewed by 449

Abstract

Background: Ammopiptanthus mongolicus is a rare temperate evergreen shrub with high tolerance to low temperature, and understanding the related gene expression regulatory network can help advance research on the mechanisms of plant tolerance to abiotic stress. Methods: Here, time-course transcriptome analysis was [...] Read more.

Background: Ammopiptanthus mongolicus is a rare temperate evergreen shrub with high tolerance to low temperature, and understanding the related gene expression regulatory network can help advance research on the mechanisms of plant tolerance to abiotic stress. Methods: Here, time-course transcriptome analysis was applied to investigate the gene expression network in A. mongolicus under low temperature stress. Results: A total of 12,606 differentially expressed genes (DEGs) were identified at four time-points during low temperature stress treatment, and multiple pathways, such as plant hormones, secondary metabolism, and cell membranes, were significantly enriched in the DEGs. Trend analysis found that the expression level of genes in cluster 19 continued to upregulate under low temperatures, and the genes in cluster 19 were significantly enriched in plant hormone signaling and secondary metabolic pathways. Based on the transcriptome data, the expression profiles of the genes in abscisic acid, salicylic acid, and flavonoid metabolic pathways were analyzed. It was found that biosynthesis of abscisic acid and flavonoids may play crucial roles in the response to low temperature stress. Furthermore, members of the phenylalanine ammonia-lyase (PAL) family in A. mongolicus were systematically identified and their structures and evolution were characterized. Analysis of cis-acting elements showed that the PAL genes in A. mongolicus were closely related to abiotic stress response. Expression pattern analysis showed that PAL genes responded to various environmental stresses, such as low temperature, supporting their involvement in the low temperature response in A. mongolicus. Conclusions: Our study provides important data for understanding the mechanisms of tolerance to low temperatures in A. mongolicus. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Molecular Genetics and Genomics—2nd Edition)

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9 pages, 1312 KiB

Open AccessCase Report

Inherited Unbalanced Reciprocal Translocation with 18p11.32p11.21 Tetrasomy and 9q34.3 Trisomy in a Fetus Revealed by Cell-Free Fetal DNA (cffDNA) Testing: Cytogenetic and Cytogenomic Characterization in Prenatal Diagnosis

by Carmela Ardisia, Luigia De Falco, Giovanni Savarese, Raffaella Ruggiero, Teresa Suero, Nadia Petrillo, Monica Ianniello, Roberto Sirica, Alessio Mori, Davide Cino, Maria Barbato, Giuseppina Vitiello and Antonio Fico

Genes 2024, 15(11), 1464; https://doi.org/10.3390/genes15111464 - 13 Nov 2024

Viewed by 407

Abstract

Background/Objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50–80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of [...] Read more.

Background/Objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50–80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of gestation, who is a balanced reciprocal translocation 46,XX,t(9;18)(q34;q11.2) carrier, with a high-risk non-invasive prenatal screening test, NIPT, for chromosome 18 aneuploidy. Methods: The highlighted aneuploidy was characterized with cytogenetic, FISH and SNP-array techniques. Results: Cytogenetic analysis, performed on flask-cultured amniocytes, indicated a 48,XX,+2mar karyotype on 50 metaphases. SNP array analysis showed a 15.3 Mb duplication of chromosome 18p (arr[hg19]18p11.32-p11.21(12,842-15,303,932)x4), consistent with a partial tetrasomy 18p, and a 926 kbp duplication of chromosome 9q (arr[GRCh37]9q34.3(140,118,286-141,044,489)x3), consistent with partial trisomy 9q. FISH analysis with a 9q34.3 probe was performed on flask-cultured amniocytes’ metaphases, highlighting the presence of a third signal on one of the two marker chromosomes (18p11.32-p11.21). Conclusions: The evidence of such partial aneuploidies suggests that different mutational events may be possible at meiotic segregation or probably post-meiotic segregation. The results obtained highlight the high sensitivity of the screening test, NIPT, with massive parallel sequencing, and the usefulness of cytogenetics, cytogenomics and molecular biology techniques, in synergy, to characterize and confirm positive NIPT results. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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Open AccessArticle

Noonan Syndrome: Relation of Genotype to Cardiovascular Phenotype—A Multi-Center Retrospective Study

by Nikola Ilic, Stasa Krasic, Nina Maric, Vladimir Gasic, Jovana Krstic, Dimitrije Cvetkovic, Vesna Miljkovic, Boris Zec, Ales Maver, Vladislav Vukomanovic and Adrijan Sarajlija

Genes 2024, 15(11), 1463; https://doi.org/10.3390/genes15111463 - 13 Nov 2024

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Abstract

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of [...] Read more.

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. Methods: We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. Results: The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in PTPN11 were most commonly associated with pulmonary valve stenosis (PVS), while RAF1 mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development (p = 0.755), even though the likelihood ratio showed significance in that regard (p = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. Conclusions: The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype–phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies. Full article

(This article belongs to the Special Issue Application of Next-Generation Sequencing in Genetic Diseases Diagnosis)

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Genes, Volume 15, Issue 11 (November 2024) – 141 articles

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