Genes

14 pages, 2733 KiB

Open AccessEditor’s ChoiceArticle

Quantitative Trait Loci Mapping and Comparative Transcriptome Analysis of Fruit Weight (FW) in Watermelon (Citrullus lanatus L.)

by Song Guo, Mei Tian, Huiying Du, Shengfeng Liu, Rong Yu and Huolin Shen

Genes 2024, 15(7), 933; https://doi.org/10.3390/genes15070933 - 17 Jul 2024

Cited by 1 | Viewed by 1417

Abstract

The watermelon (Citrullus lanatus L.) holds substantial economic value as a globally cultivated horticultural crop. However, the genetic architecture of watermelon fruit weight (FW) remains poorly understood. In this study, we used sh14-11 with small fruit and N14 with big fruit to [...] Read more.

The watermelon (Citrullus lanatus L.) holds substantial economic value as a globally cultivated horticultural crop. However, the genetic architecture of watermelon fruit weight (FW) remains poorly understood. In this study, we used sh14-11 with small fruit and N14 with big fruit to construct 100 recombinant inbred lines (RILs). Based on whole-genome resequencing (WGR), 218,127 single nucleotide polymorphisms (SNPs) were detected to construct a high-quality genetic map. After quantitative trait loci (QTL) mapping, a candidate interval of 31–38 Mb on chromosome 2 was identified for FW. Simultaneously, the bulked segregant analysis (BSA) in the F2 population corroborated the identification of the same interval, encompassing the homologous gene linked to the known FW-related gene fas. Additionally, RNA-seq was carried out across 11 tissues from sh14-11 and N14, revealing expression profiles that identified 1695 new genes and corrected the annotation of 2941 genes. Subsequent differential expression analysis unveiled 8969 differentially expressed genes (DEGs), with 354 of these genes exhibiting significant differences across four key developmental stages. The integration of QTL mapping and differential expression analysis facilitated the identification of 14 FW-related genes, including annotated TGA and NAC transcription factors implicated in fruit development. This combined approach offers valuable insights into the genetic basis of FW, providing crucial resources for enhancing watermelon cultivation. Full article

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

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21 pages, 1382 KiB

Open AccessEditor’s ChoiceArticle

Differential Gene Expression in Contrasting Common Bean Cultivars for Drought Tolerance during an Extended Dry Period

by Talita Pijus Ponce, Michely da Silva Bugança, Victória Stern da Silva, Rogério Fernandes de Souza, Vânia Moda-Cirino and Juarez Pires Tomaz

Genes 2024, 15(7), 935; https://doi.org/10.3390/genes15070935 - 17 Jul 2024

Cited by 1 | Viewed by 1599

Abstract

Common beans (Phaseolus vulgaris L.), besides being an important source of nutrients such as iron, magnesium, and protein, are crucial for food security, especially in developing countries. Common bean cultivation areas commonly face production challenges due to drought occurrences, mainly during the [...] Read more.

Common beans (Phaseolus vulgaris L.), besides being an important source of nutrients such as iron, magnesium, and protein, are crucial for food security, especially in developing countries. Common bean cultivation areas commonly face production challenges due to drought occurrences, mainly during the reproductive period. Dry spells last approximately 20 days, enough time to compromise production. Hence, it is crucial to understand the genetic and molecular mechanisms that confer drought tolerance to improve common bean cultivars’ adaptation to drought. Sixty six RNASeq libraries, generated from tolerant and sensitive cultivars in drought time sourced from the R5 phenological stage at 0 to 20 days of water deficit were sequenced, generated over 1.5 billion reads, that aligned to 62,524 transcripts originating from a reference transcriptome, as well as 6673 transcripts obtained via de novo assembly. Differentially expressed transcripts were functionally annotated, revealing a variety of genes associated with molecular functions such as oxidoreductase and transferase activity, as well as biological processes related to stress response and signaling. The presence of regulatory genes involved in signaling cascades and transcriptional control was also highlighted, for example, LEA proteins and dehydrins associated with dehydration protection, and transcription factors such as WRKY, MYB, and NAC, which modulate plant response to water deficit. Additionally, genes related to membrane and protein protection, as well as water and ion uptake and transport, were identified, including aquaporins, RING-type E3 ubiquitin transferases, antioxidant enzymes such as GSTs and CYPs, and thioredoxins. This study highlights the complexity of plant response to water scarcity, focusing on the functional diversity of the genes involved and their participation in the biological processes essential for plant adaptation to water stress. The identification of regulatory and cell protection genes offers promising prospects for genetic improvement aiming at the production of common bean varieties more resistant to drought. These findings have the potential to drive sustainable agriculture, providing valuable insights to ensure food security in a context of climate change. Full article

(This article belongs to the Special Issue Molecular Biology of Crop Abiotic Stress Resistance)

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12 pages, 835 KiB

Open AccessEditor’s ChoiceReview

Interstitial Lung Diseases and Non-Small Cell Lung Cancer: Particularities in Pathogenesis and Expression of Driver Mutations

by Fotios Sampsonas, Pinelopi Bosgana, Vasiliki Bravou, Argyrios Tzouvelekis, Foteinos-Ioannis Dimitrakopoulos and Eleni Kokkotou

Genes 2024, 15(7), 934; https://doi.org/10.3390/genes15070934 - 17 Jul 2024

Viewed by 1803

Abstract

Introduction: Interstitial lung diseases are a varied group of diseases associated with chronic inflammation and fibrosis. With the emerging and current treatment options, survival rates have vastly improved. Having in mind that the most common type is idiopathic pulmonary fibrosis and that a [...] Read more.

Introduction: Interstitial lung diseases are a varied group of diseases associated with chronic inflammation and fibrosis. With the emerging and current treatment options, survival rates have vastly improved. Having in mind that the most common type is idiopathic pulmonary fibrosis and that a significant proportion of these patients will develop lung cancer as the disease progresses, prompt diagnosis and personalized treatment of these patients are fundamental. Scope and methods: The scope of this review is to identify and characterize molecular and pathogenetic pathways that can interconnect Interstitial Lung Diseases and lung cancer, especially driver mutations in patients with NSCLC, and to highlight new and emerging treatment options in that view. Results: Common pathogenetic pathways have been identified in sites of chronic inflammation in patients with interstitial lung diseases and lung cancer. Of note, the expression of driver mutations in EGFR, BRAF, and KRAS G12C in patients with NSCLC with concurrent interstitial lung disease is vastly different compared to those patients with NSCLC without Interstitial Lung Disease. Conclusions: NSCLC in patients with Interstitial Lung Disease is a challenging diagnostic and clinical entity, and a personalized medicine approach is fundamental to improving survival and quality of life. Newer anti-fibrotic medications have improved survival in IPF/ILD patients; thus, the incidence of lung cancer is going to vastly increase in the next 5–10 years. Full article

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

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13 pages, 4035 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of Nitrate Transporter (NRT) Gene Family in Eucalyptus grandis

by Guangyou Li, Deming Yang, Yang Hu, Jianmin Xu and Zhaohua Lu

Genes 2024, 15(7), 930; https://doi.org/10.3390/genes15070930 - 17 Jul 2024

Cited by 2 | Viewed by 1363

Abstract

Eucalyptus grandis is an important planted hardwood tree worldwide with fast growth and good wood performance. The nitrate transporter (NRT) gene family is a major core involved in nitrogen (N) absorption and utilization in plants, but the comprehensive characterization of NRT genes in E. grandis [...] Read more.

Eucalyptus grandis is an important planted hardwood tree worldwide with fast growth and good wood performance. The nitrate transporter (NRT) gene family is a major core involved in nitrogen (N) absorption and utilization in plants, but the comprehensive characterization of NRT genes in E. grandis remains mostly elusive. In this study, a total of 75 EgNRT genes were identified from the genome of E. grandis that were distributed unevenly across ten chromosomes, except Chr9. A phylogenetic analysis showed that the EgNRT proteins could be divided into three classes, namely NRT1, NRT2 and NRT3, which contained 69, 4 and 2 members, respectively. The cis-regulatory elements in the promoter regions of EgNRT genes were mainly involved in phytohormone and stress response. The transcriptome analysis indicated that the differentially expressed genes of leaf and root in E. grandis under different N supply conditions were mainly involved in the metabolic process and plant hormone signal transduction. In addition, the transcriptome-based and RT-qPCR analysis revealed that the expression of 13 EgNRT genes, especially EgNRT1.3, EgNRT1.38, EgNRT1.39 and EgNRT1.52, was significantly upregulated in the root under low-N-supply treatment, suggesting that those genes might play a critical role in root response to nitrate deficiency. Taken together, these results would provide valuable information for characterizing the roles of EgNRTs and facilitate the clarification of the molecular mechanism underlying EgNRT-mediated N absorption and distribution in E. grandis. Full article

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

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14 pages, 4869 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptome Analysis of the Hypothalamic–Pituitary–Gonadal Axis of Jinhu Grouper (Epinephelus fuscoguttatus ♀ × Epinephelus tukula ♂) and Tiger Grouper (Epinephelus fuscoguttatus)

by Yishu Qiu, Pengfei Duan, Xiaoyu Ding, Zhentong Li, Xinyi Wang, Linlin Li, Yang Liu, Linna Wang and Yongsheng Tian

Genes 2024, 15(7), 929; https://doi.org/10.3390/genes15070929 - 16 Jul 2024

Cited by 1 | Viewed by 1404

Abstract

Jinhu groupers, the hybrid offspring of tiger groupers (Epinephelus fuscoguttatus) and potato groupers (Epinephelus tukula), have excellent heterosis in fast growth and strong stress resistance. However, compared with the maternal tiger grouper, Jinhu groupers show delayed gonadal development. To [...] Read more.

Jinhu groupers, the hybrid offspring of tiger groupers (Epinephelus fuscoguttatus) and potato groupers (Epinephelus tukula), have excellent heterosis in fast growth and strong stress resistance. However, compared with the maternal tiger grouper, Jinhu groupers show delayed gonadal development. To explore the interspecific difference in gonadal development, we compared the transcriptomes of brain, pituitary, and gonadal tissues between Jinhu groupers and tiger groupers at 24-months old. In total, 3034 differentially expressed genes (DEGs) were obtained. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses showed that the osteoclast differentiation, oocyte meiosis, and ovarian steroidogenesis may be involved in the difference in gonadal development. Trend analysis showed that the DEGs were mainly related to signal transduction and cell growth and death. Additionally, differences in expression levels of nr4a1, pgr, dmrta2, tbx19, and cyp19a1 may be related to gonadal retardation in Jinhu groupers. A weighted gene co-expression network analysis revealed three modules (i.e., saddlebrown, paleturquoise, and greenyellow) that were significantly related to gonadal development in the brain, pituitary, and gonadal tissues, respectively, of Jinhu groupers and tiger groupers. Network diagrams of the target modules were constructed and the respective hub genes were determined (i.e., cdh6, col18a1, and hat1). This study provides additional insight into the molecular mechanism underlying ovarian stunting in grouper hybrids. Full article

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

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10 pages, 1076 KiB

Open AccessEditor’s ChoiceArticle

TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil

by Tatiana Strava Corrêa, Paula Fontes Asprino, Eduarda Sabá Cordeiro de Oliveira, Ana Carolina Rathsam Leite, Luiza Weis, Maria Isabel Achatz, Claudiner Pereira de Oliveira, Renata Lazari Sandoval and Romualdo Barroso-Sousa

Genes 2024, 15(7), 928; https://doi.org/10.3390/genes15070928 - 16 Jul 2024

Cited by 2 | Viewed by 1747

Abstract

Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is [...] Read more.

Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention. Full article

(This article belongs to the Special Issue Genomics of Breast Cancer)

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13 pages, 1742 KiB

Open AccessEditor’s ChoiceReview

How Important Are Genetic Diversity and Cultivar Uniformity in Wheat? The Case of Gliadins

by Eugene Metakovsky, Viktor A. Melnik, Laura Pascual and Colin W. Wrigley

Genes 2024, 15(7), 927; https://doi.org/10.3390/genes15070927 - 16 Jul 2024

Cited by 4 | Viewed by 1633

Abstract

Improvements in self-pollinated crops rely on crosses between different genotypes. It has been suggested that the repeated use of “the best” genotypes may lead to the restriction of the genetic diversity of the crop. In wheat, the analysis of gliadin (storage protein) polymorphism [...] Read more.

Improvements in self-pollinated crops rely on crosses between different genotypes. It has been suggested that the repeated use of “the best” genotypes may lead to the restriction of the genetic diversity of the crop. In wheat, the analysis of gliadin (storage protein) polymorphism has provided evidence that genetic diversity was high and stable throughout the 20th century. Moreover, a worldwide analysis of gliadin polymorphism shows that genetic diversity is structured spatially across countries and their regions. Therefore, the analysis of gliadin genotypes in a given grain sample can provide reliable information about the origin of grains in this sample. An unexpected finding is that many registered common wheat cultivars are genetically non-uniform and composed of authentic biotypes (genotypically related lines originated from the initial cross) in spite of current crop-registration rules that include a strict demand for each new cultivar to be genetically uniform (DUS rules). In summary, the results suggest that each cultivar is the fruit of joint effects of a breeder and of a region’s environmental factors. We believe this finding will not be restricted to wheat and suggest there may be a need to re-evaluate relevant rules of cultivar registration for crop species in general. Full article

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

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16 pages, 1382 KiB

Open AccessEditor’s ChoiceArticle

A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark

by Yang Pei, Melanie Tanguy, Adam Giess, Abhijit Dixit, Louise C. Wilson, Richard J. Gibbons, Stephen R. F. Twigg, Greg Elgar and Andrew O. M. Wilkie

Genes 2024, 15(7), 925; https://doi.org/10.3390/genes15070925 - 16 Jul 2024

Cited by 3 | Viewed by 3334

Abstract

The identification of structural variants (SVs) in genomic data represents an ongoing challenge because of difficulties in reliable SV calling leading to reduced sensitivity and specificity. We prepared high-quality DNA from 9 parent–child trios, who had previously undergone short-read whole-genome sequencing (Illumina platform) [...] Read more.

The identification of structural variants (SVs) in genomic data represents an ongoing challenge because of difficulties in reliable SV calling leading to reduced sensitivity and specificity. We prepared high-quality DNA from 9 parent–child trios, who had previously undergone short-read whole-genome sequencing (Illumina platform) as part of the Genomics England 100,000 Genomes Project. We reanalysed the genomes using both Bionano optical genome mapping (OGM; 8 probands and one trio) and Nanopore long-read sequencing (Oxford Nanopore Technologies [ONT] platform; all samples). To establish a “truth” dataset, we asked whether rare proband SV calls (n = 234) made by the Bionano Access (version 1.6.1)/Solve software (version 3.6.1_11162020) could be verified by individual visualisation using the Integrative Genomics Viewer with either or both of the Illumina and ONT raw sequence. Of these, 222 calls were verified, indicating that Bionano OGM calls have high precision (positive predictive value 95%). We then asked what proportion of the 222 true Bionano SVs had been identified by SV callers in the other two datasets. In the Illumina dataset, sensitivity varied according to variant type, being high for deletions (115/134; 86%) but poor for insertions (13/58; 22%). In the ONT dataset, sensitivity was generally poor using the original Sniffles variant caller (48% overall) but improved substantially with use of Sniffles2 (36/40; 90% and 17/23; 74% for deletions and insertions, respectively). In summary, we show that the precision of OGM is very high. In addition, when applying the Sniffles2 caller, the sensitivity of SV calling using ONT long-read sequence data outperforms Illumina sequencing for most SV types. Full article

(This article belongs to the Special Issue Advances of Optical Genome Mapping in Human Genetics)

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11 pages, 1776 KiB

Open AccessEditor’s ChoiceArticle

Genetic Analysis of 252 Index Cases with Inherited Retinal Diseases Using a Panel of 351 Retinal Genes

by Maria Abu Elasal, Samira Mousa, Manar Salameh, Anat Blumenfeld, Samer Khateb, Eyal Banin and Dror Sharon

Genes 2024, 15(7), 926; https://doi.org/10.3390/genes15070926 - 16 Jul 2024

Cited by 1 | Viewed by 1248

Abstract

Inherited retinal diseases (IRDs) are extremely heterogeneous with at least 350 causative genes, complicating the process of genetic diagnosis. We analyzed samples of 252 index cases with IRDs using the Blueprint Genetics panel for “Retinal Dystrophy” that includes 351 genes. The cause of [...] Read more.

Inherited retinal diseases (IRDs) are extremely heterogeneous with at least 350 causative genes, complicating the process of genetic diagnosis. We analyzed samples of 252 index cases with IRDs using the Blueprint Genetics panel for “Retinal Dystrophy” that includes 351 genes. The cause of disease could be identified in 55% of cases. A clear difference was obtained between newly recruited cases (74% solved) and cases that were previously analyzed by panels or whole exome sequencing (26% solved). As for the mode of inheritance, 75% of solved cases were autosomal recessive (AR), 10% were X-linked, 8% were autosomal dominant, and 7% were mitochondrial. Interestingly, in 12% of solved cases, structural variants (SVs) were identified as the cause of disease. The most commonly identified genes were ABCA4, EYS and USH2A, and the most common mutations were MAK-c.1297_1298ins353 and FAM161A-c.1355_1356del. In line with our previous IRD carrier analysis, we identified heterozygous AR mutations that were not the cause of disease in 36% of cases. The studied IRD panel was found to be efficient in gene identification. Some variants were misinterpreted by the pipeline, and therefore, multiple analysis tools are recommended to obtain a more accurate annotation of potential disease-causing variants. Full article

(This article belongs to the Section Genetic Diagnosis)

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10 pages, 2029 KiB

Open AccessEditor’s ChoiceArticle

Genetic Variations of MSTN and Callipyge in Tibetan Sheep: Implications for Early Growth Traits

by Kai Zhao, Xue Li, Dehui Liu, Lei Wang, Quanbang Pei, Buying Han, Zian Zhang, Dehong Tian, Song Wang, Jincai Zhao, Bin Huang and Fuqiang Zhang

Genes 2024, 15(7), 921; https://doi.org/10.3390/genes15070921 - 15 Jul 2024

Cited by 1 | Viewed by 1294

Abstract

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin ( [...] Read more.

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study’s results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep. Full article

(This article belongs to the Special Issue Genetics and Breeding in Sheep and Goats)

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11 pages, 1117 KiB

Open AccessEditor’s ChoiceArticle

Intellectual Disabilities and Neurocognitive Impairment in Adult Patients with Inherited Metabolic Diseases: A UK Single Centre Experience

by John Warner-Levy, Adrian H. Heald, Daniel Hand, Reena Sharma, Rachel Thomasson and Karolina M. Stepien

Genes 2024, 15(7), 923; https://doi.org/10.3390/genes15070923 - 15 Jul 2024

Viewed by 2073

Abstract

Inherited metabolic diseases (IMDs) are a group of heterogeneous genetic disorders resulting in substrate accumulation, energy deficiency, or complex molecular defects due to the failure of specific molecules to act as enzymes, cofactors, transporters, or receptors in specific metabolic pathways. The pathophysiological changes [...] Read more.

Inherited metabolic diseases (IMDs) are a group of heterogeneous genetic disorders resulting in substrate accumulation, energy deficiency, or complex molecular defects due to the failure of specific molecules to act as enzymes, cofactors, transporters, or receptors in specific metabolic pathways. The pathophysiological changes seen in IMDs are sometimes associated with intellectual disability (ID) or neurocognitive decline, necessitating multidisciplinary input. We here describe our experience at one tertiary metabolic centre in the UK. We reviewed the case prevalence and existing service provision in one adult IMD service covering a multi-ethnic population of 10 million in North England. In our cohort of 2268 IMD patients, 1598 patients had general metabolic conditions (70.5%), and 670 had lysosomal storage disease/disorders (LSD)s (29.5%). The overall prevalence of ID and neurocognitive decline was found to be 15.7% (n = 357), with patients with LSDs accounting for 23.5% (n = 84) of affected patients. Given the prevalence of ID in adults with IMDs, access to multidisciplinary input from neuropsychology and neuropsychiatry services is important. Education of healthcare professionals to diagnose IMDs in patients with ID, in addition to neurocognitive and neuropsychiatric presentations, will avoid missed diagnoses of IMD and will have a positive effect on patient outcomes. Full article

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

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9 pages, 998 KiB

Open AccessEditor’s ChoiceArticle

A Unique Comprehensive Model to Screen Newborns for Severe Combined Immunodeficiency—An Ontario Single-Centre Experience Spanning 2013–2023

by Abdulrahman Al Ghamdi, Jessica Willett Pachul, Azhar Al Shaqaq, Meghan Fraser, Abby Watts-Dickens, Nicole Yang, Linda Vong, Vy H. D. Kim, Victoria Mok Siu, Anne Pham-Huy, Rae Brager, Brenda Reid and Chaim M. Roifman

Genes 2024, 15(7), 920; https://doi.org/10.3390/genes15070920 - 15 Jul 2024

Cited by 2 | Viewed by 1539

Abstract

Background: Severe combined immunodeficiency (SCID) is a life-threatening genetic disorder caused by critical defects of the immune system. Almost all cases are lethal if not treated within the first two years of life. Early diagnosis and intervention are thus essential for improving patient [...] Read more.

Background: Severe combined immunodeficiency (SCID) is a life-threatening genetic disorder caused by critical defects of the immune system. Almost all cases are lethal if not treated within the first two years of life. Early diagnosis and intervention are thus essential for improving patient outcomes. In 2013, Ontario became the first Canadian province to perform newborn screening (NBS) for SCID by T cell receptor excision circles (TRECs) analysis, a surrogate marker of thymic function and lymphocyte maturation. Methods: This retrospective study reports on nearly 10 years of NBS for SCID at a quaternary referral centre. Results: From August 2013 to April 2023, our centre’s densely populated catchment area flagged 162 newborns with low TRECs levels, including 10 cases with SCID. Follow-up revealed other causes of low TRECs, including non-SCID T cell lymphopenia (secondary/reversible or idiopathic causes, and syndromic conditions) and prematurity. A small number of cases with normal repeat TRECs levels and/or T cell subsets were also flagged. Province-wide data from around this period revealed at least 24 diagnosed cases of SCID or Leaky SCID. Conclusions: This is the first report of NBS outcomes in a Canadian province describing the causative genetic defects, and the non-SCID causes of a positive NBS for SCID. Full article

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

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12 pages, 2107 KiB

Open AccessEditor’s ChoiceArticle

Exploring Microorganisms Associated to Acute Febrile Illness and Severe Neurological Disorders of Unknown Origin: A Nanopore Metagenomics Approach

by Keldenn Melo Farias Moreno, Virgínia Antunes de Andrade, Felipe Campos de Melo Iani, Vagner Fonseca, Maurício Teixeira Lima, Emerson de Castro Barbosa, Luiz Marcelo Ribeiro Tomé, Natália Rocha Guimarães, Hegger Machado Fritsch, Talita Adelino, Tatiana Oliveira Fereguetti, Maíra Cardoso Aspahan, Tereza Gamarano Barros, Luiz Carlos Junior Alcantara and Marta Giovanetti

Genes 2024, 15(7), 922; https://doi.org/10.3390/genes15070922 - 15 Jul 2024

Cited by 1 | Viewed by 1816

Abstract

Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical [...] Read more.

Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Genome and Evolution of Viruses)

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18 pages, 2362 KiB

Open AccessEditor’s ChoiceArticle

T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise

by Benedikt Gasser, Alain Dössegger, Marie-Noëlle Giraud and Martin Flück

Genes 2024, 15(7), 918; https://doi.org/10.3390/genes15070918 - 14 Jul 2024

Cited by 5 | Viewed by 1575

Abstract

Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young [...] Read more.

Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers. Full article

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

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15 pages, 2534 KiB

Open AccessEditor’s ChoiceReview

Sulfotransferase 4A1 Coding Sequence and Protein Structure Are Highly Conserved in Vertebrates

by Robert C. A. M. van Waardenburg and Charles N. Falany

Genes 2024, 15(7), 914; https://doi.org/10.3390/genes15070914 - 13 Jul 2024

Cited by 1 | Viewed by 1639

Abstract

Cytosolic sulfotransferases (SULTs) are Phase 2 drug-metabolizing enzymes that catalyze the conjugation of sulfonate to endogenous and xenobiotic compounds, increasing their hydrophilicity and excretion from cells. To date, 13 human SULTs have been identified and classified into five families. SULT4A1 mRNA encodes two [...] Read more.

Cytosolic sulfotransferases (SULTs) are Phase 2 drug-metabolizing enzymes that catalyze the conjugation of sulfonate to endogenous and xenobiotic compounds, increasing their hydrophilicity and excretion from cells. To date, 13 human SULTs have been identified and classified into five families. SULT4A1 mRNA encodes two variants: (1) the wild type, encoding a 284 amino acid, ~33 kDa protein, and (2) an alternative spliced variant resulting from a 126 bp insert between exon 6 and 7, which introduces a premature stop codon that enhances nonsense-mediated decay. SULT4A1 is classified as an SULT based on sequence and structural similarities, including PAPS-domains, active-site His, and the dimerization domain; however, the catalytic pocket lid ‘Loop 3’ size is not conserved. SULT4A1 is uniquely expressed in the brain and localized in the cytosol and mitochondria. SULT4A1 is highly conserved, with rare intronic polymorphisms that have no outward manifestations. However, the SULT4A1 haplotype is correlated with Phelan–McDermid syndrome and schizophrenia. SULT4A1 knockdown revealed potential SULT4A1 functions in photoreceptor signaling and knockout mice display hampered neuronal development and behavior. Mouse and yeast models revealed that SULT4A1 protects the mitochondria from endogenously and exogenously induced oxidative stress and stimulates cell division, promoting dendritic spines’ formation and synaptic transmission. To date, no physiological enzymatic activity has been associated with SULT4A1. Full article

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

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21 pages, 3433 KiB

Open AccessEditor’s ChoiceArticle

Genetic Ancestry and Self-Reported “Skin Color/Race” in the Urban Admixed Population of São Paulo City, Brazil

by Jaqueline L. Pereira, Camila A. de Souza, Jennyfer E. M. Neyra, Jean M. R. S. Leite, Andressa Cerqueira, Regina C. Mingroni-Netto, Julia M. P. Soler, Marcelo M. Rogero, Flavia M. Sarti and Regina M. Fisberg

Genes 2024, 15(7), 917; https://doi.org/10.3390/genes15070917 - 13 Jul 2024

Cited by 1 | Viewed by 3458

Abstract

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess [...] Read more.

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual’s genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations. Full article

(This article belongs to the Special Issue Human Genome Diversity: History and Health)

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20 pages, 1804 KiB

Open AccessEditor’s ChoiceReview

Phenotypic Expansion of Autosomal Dominant LZTR1-Related Disorders with Special Emphasis on Adult-Onset Features

by Vera Uliana, Enrico Ambrosini, Antonietta Taiani, Sofia Cesarini, Ilenia Rita Cannizzaro, Anna Negrotti, Walter Serra, Gabriele Quintavalle, Lucia Micale, Carmela Fusco, Marco Castori, Davide Martorana, Beatrice Bortesi, Laura Belli, Antonio Percesepe, Francesco Pisani and Valeria Barili

Genes 2024, 15(7), 916; https://doi.org/10.3390/genes15070916 - 13 Jul 2024

Cited by 3 | Viewed by 3746

Abstract

Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, [...] Read more.

Leucine zipper-like transcription regulator 1 (LZTR1) acts as a negative factor that suppresses RAS function and MAPK signaling; mutations in this protein may dysregulate RAS ubiquitination and lead to impaired degradation of RAS superfamily proteins. Germline LZTR1 variants are reported in Noonan syndrome, either autosomal dominant or autosomal recessive, and in susceptibility to schwannomatosis. This article explores the genetic and phenotypic diversity of the autosomal dominant LZTR1-related disorders, compiling a cohort of previously published patients (51 with the Noonan phenotype and 123 with schwannomatosis) and presenting two additional adult-onset cases: a male with schwannomatosis and Parkinson’s disease and a female with Noonan syndrome, generalized joint hypermobility, and breast cancer. This review confirms that autosomal dominant LZTR1-related disorders exhibit an extreme phenotypic variability, ranging from relatively mild manifestations to severe and multi-systemic involvement, and offers updated frequences of each clinical feature. The aim is to precisely define the clinical spectrum of LZTR1-related diseases, using also two new emblematic clinical cases. Gaining insight into the mechanisms underneath this variability is crucial to achieve precision diagnostics and the development of therapeutic interventions. Full article

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

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21 pages, 6208 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of APX Gene Family in Citrus maxima and Expression Analysis at Different Postharvest Preservation Times

by Yu Zhang, Yujiao Peng, Huixin Zhang, Qiuyu Gao, Fangfei Song, Xueyu Cui and Fulei Mo

Genes 2024, 15(7), 911; https://doi.org/10.3390/genes15070911 - 12 Jul 2024

Cited by 2 | Viewed by 1582

Abstract

Ascorbate peroxidase (APX) is a crucial enzyme involved in cellular antioxidant defense and plays a pivotal role in modulating reactive oxygen species (ROS) levels under various environmental stresses in plants. This study utilized bioinformatics methods to identify and analyze the APX gene family [...] Read more.

Ascorbate peroxidase (APX) is a crucial enzyme involved in cellular antioxidant defense and plays a pivotal role in modulating reactive oxygen species (ROS) levels under various environmental stresses in plants. This study utilized bioinformatics methods to identify and analyze the APX gene family of pomelo, while quantitative real-time PCR (qRT-PCR) was employed to validate and analyze the expression of CmAPXs at different stages of fruit postharvest. This study identified 96 members of the CmAPX family in the entire pomelo genome, with uneven distribution across nine chromosomes and occurrences of gene fragment replication. The subcellular localization includes peroxisome, cytoplasm, chloroplasts, and mitochondria. The CmAPX family exhibits a similar gene structure, predominantly consisting of two exons. An analysis of the upstream promoter regions revealed a significant presence of cis-acting elements associated with light (Box 4, G-Box), hormones (ABRE, TCA-element), and stress-related (MBS, LTR, ARE) responses. Phylogenetic and collinearity analyses revealed that the CmAPX gene family can be classified into three subclasses, with seven collinear gene pairs. Furthermore, CmAPXs are closely related to citrus, pomelo, and lemon, followed by Arabidopsis, and exhibit low homology with rice. Additionally, the transcriptomic heat map and qPCR results revealed that the expression levels of CmAPX57, CmAPX34, CmAPX50, CmAPX4, CmAPX5, and CmAPX81 were positively correlated with granulation degree, indicating the activation of the endogenous stress resistance system in pomelo cells by these genes, thereby conferring resistance to ROS. This finding is consistent with the results of GO enrichment analysis. Furthermore, 38 miRNAs were identified as potential regulators targeting the CmAPX family for post-transcriptional regulation. Thus, this study has preliminarily characterized members of the APX gene family in pomelo and provided valuable insights for further research on their antioxidant function and molecular mechanism. Full article

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

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12 pages, 2224 KiB

Open AccessEditor’s ChoiceArticle

invdup(8)(8q24.13q24.3)—A Complex Alteration and Its Clinical Consequences

by Rafaella Mergener, Marcela Rodrigues Nunes, Ana Kalise Böttcher, Monique Banik Siqueira, Helena Froener Peruzzo, Milene Carvalho Merola, Mariluce Riegel and Paulo Ricardo Gazzola Zen

Genes 2024, 15(7), 910; https://doi.org/10.3390/genes15070910 - 12 Jul 2024

Cited by 1 | Viewed by 1597

Abstract

Structural variation is a source of genetic variation that, in some cases, may trigger pathogenicity. Here, we describe two cases, a mother and son, with the same partial inverted duplication of the long arm of chromosome 8 [invdup(8)(q24.21q24.21)] of 17.18 Mb, showing different [...] Read more.

Structural variation is a source of genetic variation that, in some cases, may trigger pathogenicity. Here, we describe two cases, a mother and son, with the same partial inverted duplication of the long arm of chromosome 8 [invdup(8)(q24.21q24.21)] of 17.18 Mb, showing different clinical manifestations: microcephaly, dorsal hypertrichosis, seizures and neuropsychomotor development delay in the child, and a cleft lip/palate, down-slanted palpebral fissures and learning disabilities in the mother. The deleterious outcome, in general, is reflected by the gain or loss of genetic material. However, discrepancies among the clinical manifestations raise some concerns about the genomic configuration within the chromosome and other genetic modifiers. With that in mind, we also performed a literature review of research published in the last 20 years about the duplication of the same, or close, chromosome region, seeking the elucidation of at least some relevant clinical features. Full article

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

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16 pages, 6478 KiB

Open AccessEditor’s ChoiceArticle

Comprehensive Identification and Expression Profiling of Epidermal Pattern Factor (EPF) Gene Family in Oilseed Rape (Brassica napus L.) under Salt Stress

by Shanshan Wang, Wei Wang, Jingdong Chen, Heping Wan, Huixia Zhao, Xiaoyun Liu, Xigang Dai, Changli Zeng and Danyun Xu

Genes 2024, 15(7), 912; https://doi.org/10.3390/genes15070912 - 12 Jul 2024

Viewed by 1402

Abstract

Rapeseed is a crucial oil crop globally, and in recent years, abiotic stress has increasingly affected its growth, development, yield, and quality. Salt stress is a significant abiotic factor that restricts crop production. The EPF gene family is vital in managing salt stress [...] Read more.

Rapeseed is a crucial oil crop globally, and in recent years, abiotic stress has increasingly affected its growth, development, yield, and quality. Salt stress is a significant abiotic factor that restricts crop production. The EPF gene family is vital in managing salt stress by controlling stomatal development and opening, which reduces water loss and increases plant salt tolerance. To explore the features of the EPF gene family in Brassica napus and their expression under salt stress, this study utilized Arabidopsis EPF protein sequences as seed sequences, including their PF17181 and PF16851 domains. A total of 27 members of the EPF gene family were detected within the rapeseed genome. The study examined the physicochemical properties, gene structure, phylogenetic relationships, and collinearity of BnEPFs. Through transcriptomes, we employed the qPCR method to determine the relative expression levels of BnEPF genes potentially associated with rapeseed stress resistance under both non-salt and salt stress conditions. Subsequently, we assessed their influence on rapeseed plants subjected to salt stress. During salt stress conditions, all BnEPF genes displayed a downregulation trend, indicating their potential impact on stomatal development and signal transduction pathways, consequently improving rapeseed’s resistance to salt stress. The study findings establish a basis for exploring the roles of BnEPFs and offer candidate genes for breeding stress-resistant varieties and enhancing the yield in rapeseed. Full article

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

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16 pages, 5650 KiB

Open AccessEditor’s ChoiceArticle

Illuminating Genetic Diversity and Selection Signatures in Matou Goats through Whole-Genome Sequencing Analysis

by Ruiyao HuangFu, Haobang Li, Yang Luo, Fang He, Cheng Huan, Zulfiqar Ahmed, Baizhong Zhang, Chuzhao Lei and Kangle Yi

Genes 2024, 15(7), 909; https://doi.org/10.3390/genes15070909 - 12 Jul 2024

Cited by 1 | Viewed by 1586

Abstract

(1) Background: Matou goats, native to Hunan and Hubei provinces in China, are renowned for their exceptional meat and skin quality. However, a comprehensive whole-genome-based exploration of the genetic architecture of this breed is scant in the literature. (2) Methods: To address this [...] Read more.

(1) Background: Matou goats, native to Hunan and Hubei provinces in China, are renowned for their exceptional meat and skin quality. However, a comprehensive whole-genome-based exploration of the genetic architecture of this breed is scant in the literature. (2) Methods: To address this substantial gap, we used whole-genome sequences of 20 Matou goats and compared them with published genomic data of 133 goats of different breeds across China. This comprehensive investigation sought to assess genetic diversity, population structure, and the presence of genomic selection signals. (3) Results: The whole genome of Matou goat populations yielded a substantial catalog of over 19 million single nucleotide polymorphisms (SNPs), primarily distributed within intergenic and intron regions. The phylogenetic tree analysis revealed distinct clades corresponding to each goat population within the dataset. Notably, this analysis positioned Matou goats in a closer genetic affinity with Guizhou White goats, compared to other recognized goat breeds. This observation was corroborated by principal component analysis (PCA) and admixture analysis. Remarkably, Matou goats exhibited diminished genetic diversity and a notable degree of inbreeding, signifying a reduced effective population size. Moreover, the study employed five selective sweep detection methods (including PI, CLR, PI-Ratio, Fst, and XP-EHH) to screen top signal genes associated with critical biological functions, encompassing cardiomyocytes, immunity, coat color, and meat quality. (4) Conclusions: In conclusion, this study significantly advances our understanding of the current genetic landscape and evolutionary dynamics of Matou goats. These findings underscore the importance of concerted efforts in resource conservation and genetic enhancement for this invaluable breed. Full article

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

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15 pages, 2306 KiB

Open AccessEditor’s ChoiceArticle

Exploring the Influence of Fok1/Apa1 Polymorphic Variants on Adolescent Mental Health and Response to Vitamin D Supplementation in Embryonic Hippocampal Cell Lines

by Giulia Gizzi, Federico Fiorani, Samuela Cataldi, Martina Mandarano, Elisa Delvecchio, Claudia Mazzeschi and Elisabetta Albi

Genes 2024, 15(7), 913; https://doi.org/10.3390/genes15070913 - 12 Jul 2024

Viewed by 1315

Abstract

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson’s and Alzheimer’s diseases. This study aimed to establish the association between [...] Read more.

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson’s and Alzheimer’s diseases. This study aimed to establish the association between Fok1/Apa1 polymorphic variants and anxious/depressive symptoms in nonclinical adolescents from central Italy, with the goal of identifying the risk of developing both symptoms. We found no significant difference in genotype distribution or dominant/recessive models of Fok1/Apa1 VDR polymorphic variants between subjects with anxious/depressive symptoms and controls. HN9.10e cell lines carrying the AA genotype for Fok1 and the CC genotype for Apa1 responded better to treatment with vitamin D3 than cell lines carrying the AG genotype for Fok1 and CA genotype for Apa1. Cell lines carrying the GG genotype for Fok1 and the AA genotype for Apa1 did not respond at all, suggesting avenues for future studies in both the general population and individuals with mental and/or neuropsychiatric disorders. These studies suggest that the level of response to vitamin D3 administered to prevent and/or treat mental or neurological disorders could depend on the polymorphic variants of the vitamin D receptor. Full article

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

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23 pages, 2299 KiB

Open AccessEditor’s ChoiceReview

Emerging Microorganisms and Infectious Diseases: One Health Approach for Health Shared Vision

by Maria Vittoria Ristori, Valerio Guarrasi, Paolo Soda, Nicola Petrosillo, Fiorella Gurrieri, Umile Giuseppe Longo, Massimo Ciccozzi, Elisabetta Riva and Silvia Angeletti

Genes 2024, 15(7), 908; https://doi.org/10.3390/genes15070908 - 11 Jul 2024

Cited by 5 | Viewed by 7582

Abstract

Emerging infectious diseases (EIDs) are newly emerging and reemerging infectious diseases. The National Institute of Allergy and Infectious Diseases identifies the following as emerging infectious diseases: SARS, MERS, COVID-19, influenza, fungal diseases, plague, schistosomiasis, smallpox, tick-borne diseases, and West Nile fever. The factors [...] Read more.

Emerging infectious diseases (EIDs) are newly emerging and reemerging infectious diseases. The National Institute of Allergy and Infectious Diseases identifies the following as emerging infectious diseases: SARS, MERS, COVID-19, influenza, fungal diseases, plague, schistosomiasis, smallpox, tick-borne diseases, and West Nile fever. The factors that should be taken into consideration are the genetic adaptation of microbial agents and the characteristics of the human host or environment. The new approach to identifying new possible pathogens will have to go through the One Health approach and omics integration data, which are capable of identifying high-priority microorganisms in a short period of time. New bioinformatics technologies enable global integration and sharing of surveillance data for rapid public health decision-making to detect and prevent epidemics and pandemics, ensuring timely response and effective prevention measures. Machine learning tools are being more frequently utilized in the realm of infectious diseases to predict sepsis in patients, diagnose infectious diseases early, and forecast the effectiveness of treatment or the appropriate choice of antibiotic regimen based on clinical data. We will discuss emerging microorganisms, omics techniques applied to infectious diseases, new computational solutions to evaluate biomarkers, and innovative tools that are useful for integrating omics data and electronic medical records data for the clinical management of emerging infectious diseases. Full article

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

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19 pages, 1973 KiB

Open AccessEditor’s ChoiceReview

The Potential Links between lncRNAs and Drug Tolerance in Lung Adenocarcinoma

by William J. H. Davis, Catherine J. Drummond, Sarah Diermeier and Glen Reid

Genes 2024, 15(7), 906; https://doi.org/10.3390/genes15070906 - 11 Jul 2024

Viewed by 2463

Abstract

Lung cancer patients treated with targeted therapies frequently respond well but invariably relapse due to the development of drug resistance. Drug resistance is in part mediated by a subset of cancer cells termed “drug-tolerant persisters” (DTPs), which enter a dormant, slow-cycling state that [...] Read more.

Lung cancer patients treated with targeted therapies frequently respond well but invariably relapse due to the development of drug resistance. Drug resistance is in part mediated by a subset of cancer cells termed “drug-tolerant persisters” (DTPs), which enter a dormant, slow-cycling state that enables them to survive drug exposure. DTPs also exhibit stem cell-like characteristics, broad epigenetic reprogramming, altered metabolism, and a mutagenic phenotype mediated by adaptive mutability. While several studies have characterised the transcriptional changes that lead to the altered phenotypes exhibited in DTPs, these studies have focused predominantly on protein coding changes. As long non-coding RNAs (lncRNAs) are also implicated in the phenotypes altered in DTPs, it is likely that they play a role in the biology of drug tolerance. In this review, we outline how lncRNAs may contribute to the key characteristics of DTPs, their potential roles in tolerance to targeted therapies, and the emergence of genetic resistance in lung adenocarcinoma. Full article

(This article belongs to the Section RNA)

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13 pages, 2719 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Urinary Exosome microRNA Profile of von Hippel Lindau Syndrome Patients with Clear Cell Renal Cell Carcinoma

by Beatriz Walter-Rodriguez, Christopher J. Ricketts, W. Marston Linehan and Maria J. Merino

Genes 2024, 15(7), 905; https://doi.org/10.3390/genes15070905 - 11 Jul 2024

Cited by 5 | Viewed by 1744

Abstract

Introduction: Renal cell carcinoma is one of the ten more common malignant tumors worldwide, with a high incidence and mortality rate. Kidney cancer frequently presents at an advanced stage, and it is almost invariably fatal. Much progress has been made in identifying molecular [...] Read more.

Introduction: Renal cell carcinoma is one of the ten more common malignant tumors worldwide, with a high incidence and mortality rate. Kidney cancer frequently presents at an advanced stage, and it is almost invariably fatal. Much progress has been made in identifying molecular targets for therapy in the hope of improving survival rates, but still, we have no good markers for early detection or progression of the disease. Von Hippel Lindau syndrome (VHL) is an autosomal dominant cancer hereditary syndrome in which affected individuals are at risk of developing bilateral and multifocal renal cell carcinomas (RCC) as well as other tumors. These patients provide an ideal platform to investigate the potential of urinary exosomal miRNA biomarkers in the early development of ccRCC, as these patients are regularly imaged and tumors are actively monitored until the tumor reaches 3 cm before surgical excision. This allows for pre- and post-surgical urine collection and comparison to excised tumor tissues. Studying different biomarkers in urine can provide comprehensive molecular profiling available to patients and physicians and can be a great source of additional tumor genetic information. Methods: Pre- and postoperative urine samples were obtained from a cohort of VHL patients undergoing surveillance and surgical excision of ccRCCs, and exosomes were extracted. MicroRNA-Seq analysis was performed on miRNA extracted from both urine-derived exosomes and FFPE material from excised ccRCCs. Results: MicroRNA-Seq analysis highlighted a significant difference in the urinary exosome-derived miRNA expression profiles between VHL patients and normal control individuals. This included decreased expression of the miR-320 family, such as miR-320a, known to be decreased in sporadic ccRCC and suppressed by the HIF1α transcription factor activated by the loss of the VHL gene. MiR-542-5p represented a potential marker of VHL-associated ccRCC that was lowly expressed in normal control urinary exosomes, significantly increased in the preoperative urinary exosomes of tumor-bearing VHL patients, and subsequently reduced to normal levels of expression after tumor excision. In concordance with this, the expression of miR-542-5p was increased in the VHL-associated ccRCC in comparison to the normal kidney. Conclusions: This study shows the potential for miRNA profiling of exosomes from readily available biofluids to both distinguish VHL patient urine from normal control urine microRNAs and to provide biomarkers for the presence of VHL syndrome-associated ccRCC. Further validation studies are necessary to demonstrate the utility of urinary exosome-derived miRNAs as biomarkers in kidney cancer. Full article

(This article belongs to the Special Issue Genetic Markers and Liquid Biopsy for Kidney Diseases)

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15 pages, 1824 KiB

Open AccessEditor’s ChoiceReview

A Comprehensive Review of HER2 in Cancer Biology and Therapeutics

by Xiaoqing Cheng

Genes 2024, 15(7), 903; https://doi.org/10.3390/genes15070903 - 11 Jul 2024

Cited by 32 | Viewed by 18028

Abstract

Human epidermal growth factor receptor 2 (HER2), a targetable transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family, plays a crucial role in cell proliferation, survival, and differentiation. Aberrant HER2 signaling is implicated in various cancers, particularly in breast and gastric [...] Read more.

Human epidermal growth factor receptor 2 (HER2), a targetable transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family, plays a crucial role in cell proliferation, survival, and differentiation. Aberrant HER2 signaling is implicated in various cancers, particularly in breast and gastric cancers, where HER2 overexpression or amplification correlates with aggressive tumor behavior and poor prognosis. HER2-activating mutations contribute to accelerated tumorigenesis and metastasis. This review provides an overview of HER2 biology, signaling pathways, mechanisms of dysregulation, and diagnostic approaches, as well as therapeutic strategies targeting HER2 in cancer. Understanding the intricate details of HER2 regulation is essential for developing effective targeted therapies and improving patient outcomes. Full article

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

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10 pages, 567 KiB

Open AccessEditor’s ChoiceArticle

Genetic Variants of the Receptor Activator Nuclear of κB Ligand Gene Increase the Risk of Rheumatoid Arthritis in a Mexican Mestizo Population: A Case–Control Study

by Nava-Valdivia Cesar Arturo, Gamez-Nava Jorge Ivan, Contreras-Haro Betsabe, Perez-Guerrero Edsaul Emilio, Esparza-Guerrero Yussef, Rodriguez-Jimenez Norma Alejandra, Gonzalez-Heredia Tonatiuh, Villagomez-Vega Alejandra, Nuño-Arana Ismael, Totsuka-Sutto Sylvia Elena, Ponce-Guarneros Juan Manuel, Jacobo-Cuevas Heriberto, Alvarez-Ayala Efren Gerardo, Gonzalez-Lopez Laura and Saldaña-Cruz Ana Miriam

Genes 2024, 15(7), 907; https://doi.org/10.3390/genes15070907 - 11 Jul 2024

Cited by 1 | Viewed by 1312

Abstract

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead [...] Read more.

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead to a higher risk of rheumatoid arthritis (RA). Objective: To assess the association of rs9533155 (-693C>G) and rs9533156 (-643T>C) genetic variants with RA risk. Methods: A case–control study was carried out. A total of 94 patients with RA (RA group) and 134 subjects without any rheumatologic disease (control group) were included. Genetic DNA was extracted from peripheral white blood cells (leukocytes). Genetic variant rs9533155 (-693C>G) was screened by an approach based on Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), while rs9533156 (-643T>C) was screened using quantitative polymerase chain reaction (qPCR) with TaqMan probes. RANKL serum levels were measured by ELISA. Results: For rs9533155 (-693C>G), the polymorphic homozygous genotype frequencies (CC) were higher in the RA group (p = 0.006). Individuals carrying the risk genotype presented higher levels of serum RANKL. Carriers of the polymorphic homozygous genotype in the dominant model (CC vs. CG + GG) had an increased risk of developing RA (OR: 1.8, 95% CI 1.04 to 3.1). No association between rs9533156 (-643T>C) and the haplotypes with RA risk was observed. Conclusion: The rs9533155 (-693C>G) genetic variant exhibits a potential role in RA risk. The studied population had no association with the rs9533156 (-643T>C) genetic variant. Full article

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

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12 pages, 5214 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Bioinformatics Analysis of the FK506 Binding Protein Family in Rice

by Fanhao Nie, Minghao Wang, Linlin Liu, Xuefei Ma and Juan Zhao

Genes 2024, 15(7), 902; https://doi.org/10.3390/genes15070902 - 10 Jul 2024

Cited by 2 | Viewed by 1455

Abstract

The FK506 Binding Protein (FKBP), ubiquitously present across diverse species, is characterized by its evolutionarily conserved FK506 binding domain (FKBd). In plants, evidence suggests that this gene family plays integral roles in regulating growth, development, and responses to environmental stresses. Notably, research on [...] Read more.

The FK506 Binding Protein (FKBP), ubiquitously present across diverse species, is characterized by its evolutionarily conserved FK506 binding domain (FKBd). In plants, evidence suggests that this gene family plays integral roles in regulating growth, development, and responses to environmental stresses. Notably, research on the identification and functionality of FKBP genes in rice remains limited. Therefore, this study utilized bioinformatic tools to identify 30 FKBP-encoding genes in rice. It provides a detailed analysis of their chromosomal locations, evolutionary relationships with the Arabidopsis thaliana FKBP family, and gene structures. Further analysis of the promoter elements of these rice FKBP genes revealed a high presence of stress-responsive elements. Quantitative PCR assays under drought and heat stress conditions demonstrated that genes OsFKBP15-2, OsFKBP15-3, OsFKBP16-3, OsFKBP18, and OsFKBP42b are inducible by these adverse conditions. These findings suggest a significant role for the rice FKBP gene family in stress adaptation. This research establishes a critical foundation for deeper explorations of the functional roles of the OsFKBP genes in rice. Full article

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

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18 pages, 2782 KiB

Open AccessEditor’s ChoiceArticle

Revealing Differential RNA Editing Specificity of Human ADAR1 and ADAR2 in Schizosaccharomyces pombe

by Niubing Zhang, Ping Chen, Zilin Cui, Xiaojuan Zhou, Chenhui Hao, Bingran Xie, Pei Hao, Bang-Ce Ye, Xuan Li and Xinyun Jing

Genes 2024, 15(7), 898; https://doi.org/10.3390/genes15070898 - 9 Jul 2024

Viewed by 2247

Abstract

Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional modification mediated by the adenosine deaminases acting on RNA (ADAR) family of enzymes, expanding the transcriptome by altering selected nucleotides A to I in RNA molecules. Recently, A-to-I editing has been explored for correcting disease-causing [...] Read more.

Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional modification mediated by the adenosine deaminases acting on RNA (ADAR) family of enzymes, expanding the transcriptome by altering selected nucleotides A to I in RNA molecules. Recently, A-to-I editing has been explored for correcting disease-causing mutations in RNA using therapeutic guide oligonucleotides to direct ADAR editing at specific sites. Humans have two active ADARs whose preferences and specificities are not well understood. To investigate their substrate specificity, we introduced hADAR1 and hADAR2, respectively, into Schizosaccharomyces pombe (S. pombe), which lacks endogenous ADARs, and evaluated their editing activities in vivo. Using transcriptome sequencing of S. pombe cultured at optimal growth temperature (30 °C), we identified 483 A-to-I high-confident editing sites for hADAR1 and 404 for hADAR2, compared with the non-editing wild-type control strain. However, these sites were mostly divergent between hADAR1 and hADAR2-expressing strains, sharing 33 common sites that are less than 9% for each strain. Their differential specificity for substrates was attributed to their differential preference for neighboring sequences of editing sites. We found that at the -3-position relative to the editing site, hADAR1 exhibits a tendency toward T, whereas hADAR2 leans toward A. Additionally, when varying the growth temperature for hADAR1- and hADAR2-expressing strains, we observed increased editing sites for them at both 20 and 35 °C, compared with them growing at 30 °C. However, we did not observe a significant shift in hADAR1 and hADAR2’s preference for neighboring sequences across three temperatures. The vast changes in RNA editing sites at lower and higher temperatures were also observed for hADAR2 previously in budding yeast, which was likely due to the influence of RNA folding at these different temperatures, among many other factors. We noticed examples of longer lengths of dsRNA around the editing sites that induced editing at 20 or 35 °C but were absent at the other two temperature conditions. We found genes’ functions can be greatly affected by editing of their transcripts, for which over 50% of RNA editing sites for both hADAR1 and hADAR2 in S. pombe were in coding sequences (CDS), with more than 60% of them resulting in amino acid changes in protein products. This study revealed the extensive differences in substrate selectivity between the two active human ADARS, i.e., ADAR1 and ADAR2, and provided novel insight when utilizing the two different enzymes for in vivo treatment of human genetic diseases using the RNA editing approach. Full article

(This article belongs to the Special Issue RNAs in Biology)

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14 pages, 4204 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Evolutionary and Mutational Analysis of the Bos taurus Pax Gene Family

by Jintao Zhong, Wenliang Wang, Yifei Li, Jia Wei, Shuangshuang Cui, Ning Song, Yunhai Zhang and Hongyu Liu

Genes 2024, 15(7), 897; https://doi.org/10.3390/genes15070897 - 9 Jul 2024

Viewed by 2434

Abstract

Bos taurus is known for its tolerance of coarse grains, adaptability, high temperature, humidity, and disease resistance. Primarily, cattle are raised for their meat and milk, and pinpointing genes associated with traits relevant to meat production can enhance their overall productivity. The aim [...] Read more.

Bos taurus is known for its tolerance of coarse grains, adaptability, high temperature, humidity, and disease resistance. Primarily, cattle are raised for their meat and milk, and pinpointing genes associated with traits relevant to meat production can enhance their overall productivity. The aim of this study was to identify the genome, analyze the evolution, and explore the function of the Pax gene family in B. taurus to provide a new molecular target for breeding in meat-quality-trait cattle. In this study, 44 Pax genes were identified from the genome database of five species using bioinformatics technology, indicating that the genetic relationships of bovids were similar. The Pax3 and Pax7 protein sequences of the five animals were highly consistent. In general, the Pax gene of the buffalo corresponds to the domestic cattle. In summary, there are differences in affinity between the Pax family genes of buffalo and domestic cattle in the Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6 subfamilies. We believe that Pax1/9 has an effect on the growth traits of buffalo and domestic cattle. The Pax3/7 gene is conserved in the evolution of buffalo and domestic animals and may be a key gene regulating the growth of B. taurus. The Pax2/5/8 subfamily affects coat color, reproductive performance, and milk production performance in cattle. The Pax4/6 subfamily had an effect on the milk fat percentage of B. taurus. The results provide a theoretical basis for understanding the evolutionary, structural, and functional characteristics of the Pax family members of B. taurus and for molecular genetics and the breeding of meat-production B. taurus species. Full article

(This article belongs to the Special Issue Genetics and Breeding of Cattle Volume II)

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11 pages, 1481 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Codon Usage Bias in Chloroplast Genomes of Dryas octopetala var. asiatica (Rosaceae)

by Lizhen Ling, Shudong Zhang and Tao Yang

Genes 2024, 15(7), 899; https://doi.org/10.3390/genes15070899 - 9 Jul 2024

Cited by 4 | Viewed by 1270

Abstract

Dryas octopetala var. asiatica, a dwarf shrub belonging to the Rosaceae family and native to Asia, exhibits notable plasticity in photosynthesis in response to temperature variations. However, the codon usage patterns and factors influencing them in the chloroplast genome of this species [...] Read more.

Dryas octopetala var. asiatica, a dwarf shrub belonging to the Rosaceae family and native to Asia, exhibits notable plasticity in photosynthesis in response to temperature variations. However, the codon usage patterns and factors influencing them in the chloroplast genome of this species have not yet been documented. This study sequenced and assembled the complete genome of D. octopetala var. asiatica. The annotated genes in the chloroplast genome were analyzed for codon composition through multivariate statistical methods including a neutrality plot, a parity rule 2 (PR2) bias plot, and an effective number of codons (ENC) plot using CodonW 1.4.2 software. The results indicated that the mean GC content of 53 CDSs was 38.08%, with the average GC content at the third codon base position being 27.80%, suggesting a preference for A/U(T) at the third codon position in chloroplast genes. Additionally, the chloroplast genes exhibited a weak overall codon usage bias (CUB) based on ENC values and other indicators. Correlation analysis showed a significant negative correlation between ENC value and GC2, an extremely positive correlation with GC3, but no correlation with GC1 content. These findings highlight the importance of the codon composition at the third position in influencing codon usage bias. Furthermore, our analysis indicated that the CUB of the chloroplast genome of D. octopetala var. asiatica was primarily influenced by natural selection and other factors. Finally, this study identified UCA, CCU, GCU, AAU, GAU, and GGU as the optimal codons. These results offer a foundational understanding for genetic modification and evolutionary dynamics of the chloroplast genome of D. octopetala var. asiatica. Full article

(This article belongs to the Special Issue Plant Plastid Genome and Phylogenetics)

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15 pages, 2057 KiB

Open AccessEditor’s ChoiceReview

Mechanisms and Future Research Perspectives on Mitochondrial Diseases Associated with Isoleucyl-tRNA Synthetase Gene Mutations

by Masaki Watanabe and Nobuya Sasaki

Genes 2024, 15(7), 894; https://doi.org/10.3390/genes15070894 - 8 Jul 2024

Cited by 1 | Viewed by 2271

Abstract

Aminoacyl-tRNA synthetases are essential enzymes for the accurate translation of genetic information. IARS1 and IARS2 are isoleucyl-tRNA synthetases functioning in the cytoplasm and mitochondria, respectively, with genetic mutations in these enzymes causing diverse clinical phenotypes in specific organs and tissues. Mutations in IARS1 [...] Read more.

Aminoacyl-tRNA synthetases are essential enzymes for the accurate translation of genetic information. IARS1 and IARS2 are isoleucyl-tRNA synthetases functioning in the cytoplasm and mitochondria, respectively, with genetic mutations in these enzymes causing diverse clinical phenotypes in specific organs and tissues. Mutations in IARS1 and IARS2 have recently been linked to mitochondrial diseases. This review aims to explore the relationship between IARS1 and IARS2 and these diseases, providing a comprehensive overview of their association with mitochondrial diseases. Mutations in IARS1 cause weak calf syndrome in cattle and mitochondrial diseases in humans, leading to growth retardation and liver dysfunction. Mutations in IARS2 are associated with Leigh syndrome, craniosynostosis and abnormal genitalia syndrome. Future research is expected to involve genetic analysis of a larger number of patients, identifying new mutations in IARS1 and IARS2, and elucidating their impact on mitochondrial function. Additionally, genetically modified mice and the corresponding phenotypic analysis will serve as powerful tools for understanding the functions of these gene products and unraveling disease mechanisms. This will likely promote the development of new therapies and preventive measures. Full article

(This article belongs to the Collection Study on Genotypes and Phenotypes of Pediatric Clinical Rare Diseases)

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31 pages, 3267 KiB

Open AccessEditor’s ChoiceArticle

Identification and Candidate Gene Evaluation of a Large Fast Neutron-Induced Deletion Associated with a High-Oil Phenotype in Soybean Seeds

by William R. Serson, Mohammad Fazel Soltani Gishini, Robert M. Stupar, Adrian O. Stec, Paul R. Armstrong and David Hildebrand

Genes 2024, 15(7), 892; https://doi.org/10.3390/genes15070892 - 8 Jul 2024

Viewed by 1999

Abstract

Since the dawn of agriculture, crops have been genetically altered for desirable characteristics. This has included the selection of natural and induced mutants. Increasing the production of plant oils such as soybean (Glycine max) oil as a renewable resource for food [...] Read more.

Since the dawn of agriculture, crops have been genetically altered for desirable characteristics. This has included the selection of natural and induced mutants. Increasing the production of plant oils such as soybean (Glycine max) oil as a renewable resource for food and fuel is valuable. Successful breeding for higher oil levels in soybeans, however, usually results in reduced seed protein. A soybean fast neutron population was screened for oil content, and three high oil mutants with minimal reductions in protein levels were found. Three backcross F2 populations derived from these mutants exhibited segregation for seed oil content. DNA was pooled from the high-oil and normal-oil plants within each population and assessed by comparative genomic hybridization. A deletion encompassing 20 gene models on chromosome 14 was found to co-segregate with the high-oil trait in two of the three populations. Eighteen genes in the deleted region have known functions that appear unrelated to oil biosynthesis and accumulation pathways, while one of the unknown genes (Glyma.14G101900) may contribute to the regulation of lipid droplet formation. This high-oil trait can facilitate the breeding of high-oil soybeans without protein reduction, resulting in higher meal protein levels. Full article

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

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7 pages, 213 KiB

Open AccessEditor’s ChoiceArticle

Early Non-Invasive Prenatal Testing at 6–9 Weeks of Gestation

by Alexandros Katrachouras, Harry Kontos, Kyriacos Konis, Chara Skentou and George Makrydimas

Genes 2024, 15(7), 895; https://doi.org/10.3390/genes15070895 - 8 Jul 2024

Cited by 1 | Viewed by 4225

Abstract

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a [...] Read more.

Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis^® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6–9 weeks of gestation (group 1) and at 11–14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The “Vanadis” prenatal NIPT assay can successfully be used early during the first trimester at 6–9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies. Full article

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

12 pages, 2589 KiB

Open AccessEditor’s ChoiceArticle

Mitochondrial Genome Characteristics Reveal Evolution of Acanthopsetta nadeshnyi (Jordan and Starks, 1904) and Phylogenetic Relationships

by Li-min Yang, Jing-feng Xue, Xiao-man Zhao, Ke Ding, Zhao-wen Liu, Zhou-si-yu Wang, Jian-bing Chen and You-kun Huang

Genes 2024, 15(7), 893; https://doi.org/10.3390/genes15070893 - 8 Jul 2024

Cited by 1 | Viewed by 1329

Abstract

In the present study, the mitochondrial genomic characteristics of Acanthopsetta nadeshnyi have been reported and have depicted the phylogenetic relationship among Pleuronectidae. Combined with a comparative analysis of 13 PCGs, the TN93 model was used to review the neutral evolution and habitat evolution [...] Read more.

In the present study, the mitochondrial genomic characteristics of Acanthopsetta nadeshnyi have been reported and have depicted the phylogenetic relationship among Pleuronectidae. Combined with a comparative analysis of 13 PCGs, the TN93 model was used to review the neutral evolution and habitat evolution catalysis of the mitogenome to verify the distancing and purification selectivity of the mitogenome in Pleuronectidae. At the same time, a species differentiation and classification model based on mitogenome analysis data was established. This study is expected to provide a new perspective on the phylogenetic relationship and taxonomic status of A. nadeshnyi and lay a foundation for further exploration of environmental and biological evolutionary mechanisms. 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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11 pages, 1470 KiB

Open AccessEditor’s ChoiceArticle

Influence of ACTN3 R577X Polymorphism on Blood Creatine Kinase Levels Relative to Number of Sprints in Brazilian Professional Soccer Players

by Kathleen Y. de Almeida, Hirofumi Zempo, Mika Saito, Tiago Cetolin, Rodrigo dos Santos Guimarães, Andrea Rita Marrero, Aderbal S. Aguiar, Jr. and Naoki Kikuchi

Genes 2024, 15(7), 896; https://doi.org/10.3390/genes15070896 - 8 Jul 2024

Viewed by 1645

Abstract

This study sought to assess how post-game creatine kinase (CK) levels correlate with the number of sprints and the impact of the ACTN3 polymorphism on this response. This research constituted a descriptive/observational, retrospective cross-sectional study. DNA was extracted from blood samples for ACTN3 [...] Read more.

This study sought to assess how post-game creatine kinase (CK) levels correlate with the number of sprints and the impact of the ACTN3 polymorphism on this response. This research constituted a descriptive/observational, retrospective cross-sectional study. DNA was extracted from blood samples for ACTN3 polymorphism genotyping. CK was measured 48 h after official matches, and the number of sprints (>19 km/h) was tracked using Global Positioning System (GPS) technology. The main cohort included 23 professional soccer players from the top tier of the Brazilian Championship. We analyzed 115 GPS + CK data sets. The replication cohort comprised 18 professional soccer players from the First Division of the Championship, had the same methodology applied, and featured a total of 90 GPS (sprints > 25.2 km/h) + CK data sets. For the main cohort, a significant positive correlation was seen between the number of sprints and the CK levels (p = 0.009). Athletes with the ACTN3 RR genotype had higher CK levels as more sprints were performed during the match (p = 0.017). However, the relationship was not found for X allele carriers (p > 0.05). For the replication cohort, there was a near-significant correlation between CK levels and the number of sprints (p = 0.05), and RR individuals showed a significant association (p = 0.01), whereas X allele carriers did not (p = 0.06). A greater number of sprints during matches is linked to higher CK levels, primarily among players with the ACTN3 RR genotype, which is potentially due to an increased presence of type II muscle fibers. These findings were replicated for both cohorts of elite Brazilian soccer players, emphasizing the importance of genetic factors in injury prevention. Full article

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

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12 pages, 1000 KiB

Open AccessEditor’s ChoiceArticle

New Virus Variant Detection Based on the Optimal Natural Metric

by Hongyu Yu and Stephen S.-T. Yau

Genes 2024, 15(7), 891; https://doi.org/10.3390/genes15070891 - 7 Jul 2024

Viewed by 4886

Abstract

The highly variable SARS-CoV-2 virus responsible for the COVID-19 pandemic frequently undergoes mutations, leading to the emergence of new variants that present novel threats to public health. The determination of these variants often relies on manual definition based on local sequence characteristics, resulting [...] Read more.

The highly variable SARS-CoV-2 virus responsible for the COVID-19 pandemic frequently undergoes mutations, leading to the emergence of new variants that present novel threats to public health. The determination of these variants often relies on manual definition based on local sequence characteristics, resulting in delays in their detection relative to their actual emergence. In this study, we propose an algorithm for the automatic identification of novel variants. By leveraging the optimal natural metric for viruses based on an alignment-free perspective to measure distances between sequences, we devise a hypothesis testing framework to determine whether a given viral sequence belongs to a novel variant. Our method demonstrates high accuracy, achieving nearly 100% precision in identifying new variants of SARS-CoV-2 and HIV-1 as well as in detecting novel genera in Orthocoronavirinae. This approach holds promise for timely surveillance and management of emerging viral threats in the field of public health. Full article

(This article belongs to the Special Issue Statistical Methods for Genetic Epidemiology)

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10 pages, 3506 KiB

Open AccessEditor’s ChoiceArticle

Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease

by Zoha Kamali, Nafiseh Esmaeil, Chris H. L. Thio, Ahmad Vaez and Harold Snieder

Genes 2024, 15(7), 889; https://doi.org/10.3390/genes15070889 - 6 Jul 2024

Viewed by 1784

Abstract

Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of [...] Read more.

Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. Methods: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Results: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). Conclusions: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases. Full article

(This article belongs to the Special Issue Genetic Insights into Population Adaptations Associated with Immunity and Host Defense)

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12 pages, 2947 KiB

Open AccessEditor’s ChoiceArticle

Does Sunlight Affect the Quality for Purposes of DNA Analysis of Blood Stain Evidence Collected from Different Surfaces?

by Livia Sliskovic, Ivana Milos, Antonia Zecic, Sendi Kuret and Davorka Sutlovic

Genes 2024, 15(7), 888; https://doi.org/10.3390/genes15070888 - 6 Jul 2024

Cited by 1 | Viewed by 2926

Abstract

The aim of this study was to investigate the effect of sunlight on the degradation of DNA samples taken from blood stains from different types of surfaces. A blood sample obtained from a single male donor was placed on seven different surfaces (galvanized [...] Read more.

The aim of this study was to investigate the effect of sunlight on the degradation of DNA samples taken from blood stains from different types of surfaces. A blood sample obtained from a single male donor was placed on seven different surfaces (galvanized sheet, iron rod, newspaper, white printer paper, glass, soil, and ceramic panel). Samples were kept, during a 4-week summer period, in a room, but next to an open window. Every 7 days, 1 mm² of blood sample was collected from each substrate and stored in labeled tube for later analysis. DNA was extracted with the Chelex method, amplified using AmpFISTR^TM Minifiler^TM Plus Amplification Kit, and quantified using a Quantifiler^TM Human DNA Quantification kit. After 7 days of sun exposure, the highest DNA concentration was determined to be from the sample from a galvanized sheet stain, followed by, in order of decreasing concentration, the ceramic panel, glass, newspaper, iron rod, and white printer paper surface. As expected, the DNA concentration from all samples decreased as the sunlight exposure time progressed. The results obtained after the amplification in the MiniFiler^TM system were in correlation with the DNA concentrations measured by the qPCR method for all samples, except for the glass, soil, and white printer paper samples. The obtained data show that DNA degradation is correlated to the length of sunlight exposure and to the type of surface the samples are collected from. A negative qPCR result does not mean negative PCR amplification in the STR system; therefore, both methods should be applied when analyzing forensic samples collected from trace evidence. Full article

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

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15 pages, 5797 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis and Phylogeny of the Complete Chloroplast Genomes of Nine Cynanchum (Apocynaceae) Species

by Erdong Zhang, Xueling Ma, Ting Guo, Yujie Wu and Lei Zhang

Genes 2024, 15(7), 884; https://doi.org/10.3390/genes15070884 - 5 Jul 2024

Cited by 4 | Viewed by 1513

Abstract

Cynanchum belongs to the Apocynaceae family and is a morphologically diverse genus that includes around 200 shrub or perennial herb species. Despite the utilization of CPGs, few molecular phylogenetic studies have endeavored to elucidate infrafamilial relationships within Cynanchum through extensive taxon sampling. In [...] Read more.

Cynanchum belongs to the Apocynaceae family and is a morphologically diverse genus that includes around 200 shrub or perennial herb species. Despite the utilization of CPGs, few molecular phylogenetic studies have endeavored to elucidate infrafamilial relationships within Cynanchum through extensive taxon sampling. In this research, we constructed a phylogeny and estimated divergence time based on the chloroplast genomes (CPGs) of nine Cynanchum species. We sequenced and annotated nine chloroplast (CP) genomes in this study. The comparative analysis of these genomes from these Cynanchum species revealed a typical quadripartite structure, with a total sequence length ranging from 158,283 to 161,241 base pairs (bp). The CP genome (CPG) was highly conserved and moderately differentiated. Through annotation, we identified a total of 129–132 genes. Analysis of the boundaries of inverted repeat (IR) regions showed consistent positioning: the rps19 gene was located in the IRb region, varying from 46 to 50 bp. IRb/SSC junctions were located between the trnN and ndhF genes. We did not detect major expansions or contractions in the IR region or rearrangements or insertions in the CPGs of the nine Cynanchum species. The results of SSR analysis revealed a variation in the number of SSRs, ranging from 112 to 150. In five types of SSRs, the largest number was mononucleotide repeats, and the smallest number was hexanucleotide repeats. The number of long repeats in the cp genomes of nine Cynanchum species was from 35 to 80. In nine species of Cynanchum, the GC3s values ranged from 26.80% to 27.00%, indicating a strong bias towards A/U-ending codons. Comparative analyses revealed four hotspot regions in the CPG, ndhA-ndhH, trnI-GAU-rrn16, psbI-trnS-GCU, and rps7-ndhB, which could potentially serve as molecular markers. In addition, phylogenetic tree construction based on the CPG indicated that the nine Cynanchum species formed a monophyletic group. Molecular dating suggested that Cynanchum diverged from its sister genus approximately 18.87 million years ago (Mya) and species diversification within the Cynanchum species primarily occurred during the recent Miocene epoch. The divergence time estimation presented in this study will facilitate future research on Cynanchum, aid in species differentiation, and facilitate diverse investigations into this economically and ecologically important genus. Full article

(This article belongs to the Section Genes & Environments)

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12 pages, 669 KiB

Open AccessEditor’s ChoiceArticle

Somatic Variants Acquired Later in Life Associated with Thoracic Aortic Aneurysms: JAK2 V617F

by Christina Waldron, Mohammad A. Zafar, Deqiong Ma, Hui Zhang, Daniel Dykas, Bulat A. Ziganshin, Andreea Popa, Alokkumar Jha, Jennifer M. Kwan and John A. Elefteriades

Genes 2024, 15(7), 883; https://doi.org/10.3390/genes15070883 - 5 Jul 2024

Cited by 1 | Viewed by 2174

Abstract

The JAK2 V617F somatic variant is a well-known driver of myeloproliferative neoplasms (MPN) associated with an increased risk for athero-thrombotic cardiovascular disease. Recent studies have demonstrated its role in the development of thoracic aortic aneurysm (TAA). However, limited clinical information and level of [...] Read more.

The JAK2 V617F somatic variant is a well-known driver of myeloproliferative neoplasms (MPN) associated with an increased risk for athero-thrombotic cardiovascular disease. Recent studies have demonstrated its role in the development of thoracic aortic aneurysm (TAA). However, limited clinical information and level of JAK2 V617F burden have been provided for a comprehensive evaluation of potential confounders. A retrospective genotype-first study was conducted to identify carriers of the JAK2 V617F variant from an internal exome sequencing database in Yale DNA Diagnostics Lab. Additionally, the overall incidence of somatic variants in the JAK2 gene across various tissue types in the healthy population was carried out based on reanalysis of SomaMutDB and data from the UK Biobank (UKBB) cohort to compare our dataset to the population prevalence of the variant. In our database of 12,439 exomes, 594 (4.8%) were found to have a thoracic aortic aneurysm (TAA), and 12 (0.049%) were found to have a JAK2 V617F variant. Among the 12 JAK2 V617F variant carriers, five had a TAA (42%), among whom four had an ascending TAA and one had a descending TAA, with a variant allele fraction ranging from 11.2% to 20%. Among these five patients, 60% were female, and average age at diagnosis was 70 (49–79). The mean ascending aneurysm size was 5.05 cm (range 4.6–5.5 cm), and four patients had undergone surgical aortic replacement or repair. UKBB data revealed a positive correlation between the JAK2 V617F somatic variant and aortic valve disease (effect size 0.0086, p = 0.85) and TAA (effect size = 0.004, p = 0.92), although not statistically significant. An unexpectedly high prevalence of TAA in our dataset (5/594, 0.84%) is greater than the prevalence reported before for the general population, supporting its association with TAA. JAK2 V617F may contribute a meaningful proportion of otherwise unexplained aneurysm patients. Additionally, it may imply a potential JAK2-specific disease mechanism in the developmental of TAA, which suggests a possible target of therapy that warrants further investigation. Full article

(This article belongs to the Special Issue Genetic and Genomic Research of Cardiovascular Diseases)

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9 pages, 496 KiB

Open AccessEditor’s ChoiceArticle

Comparing Cancer Risk Management between Females with Truncating CHEK2 1100delC versus Missense CHEK2 I157T Variants

by Diego Garmendia, Anne Weidner, Lindsay Venton and Tuya Pal

Genes 2024, 15(7), 881; https://doi.org/10.3390/genes15070881 - 5 Jul 2024

Cited by 1 | Viewed by 2183

Abstract

Breast cancer (BC) risks imparted by CHEK2 c.1100delC (“1100delC”) germline pathogenic/likely pathogenic variant (GPV) are 20–30%, compared to CHEK2 c.470T>C (“I157T”) GPV with <20%, leading to different breast screening recommendations through MRI. We compared cancer risk management (CRM) across these two GPVs. Study [...] Read more.

Breast cancer (BC) risks imparted by CHEK2 c.1100delC (“1100delC”) germline pathogenic/likely pathogenic variant (GPV) are 20–30%, compared to CHEK2 c.470T>C (“I157T”) GPV with <20%, leading to different breast screening recommendations through MRI. We compared cancer risk management (CRM) across these two GPVs. Study participants were adult females with an 1100delC or I157T GPV drawn from the Inherited Cancer Registry (ICARE) across the United States. Cancer history, clinical characteristics, and CRM were compared using chi-squared tests, t-tests, and logistic regression. Of 150 CHEK2 carriers, 40.7% had BC, with a mean age of 50. Comparing 1100delC and I157T GPVs, there were no differences in rates of (1) breast MRI among those with (65.2% versus 55.6% of 23 and 9; p = 0.612) and without (44.0% versus 44.8% of 50 and 29; p = 0.943) BC; (2) risk-reducing mastectomy among those with (50% versus 38.9% of 46 and 15; p = 0.501) and without (13.8% versus 6.5% of 58 and 31; p = 0.296) BC; and (3) risk-reducing salpingo-oophorectomy among those with (24.2% versus 22.2% of 45 and 18; p = 0.852) and without (17.5% versus 16.7% of 57 and 30; p = 0.918) BC. The results suggest over-screening with breast MRI among CHEK2 I157T GPV carriers and possible overuse of risk-reducing surgeries among CHEK2 carriers. Full article

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

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13 pages, 2603 KiB

Open AccessEditor’s ChoiceArticle

CrossMP: Enabling Cross-Modality Translation between Single-Cell RNA-Seq and Single-Cell ATAC-Seq through Web-Based Portal

by Zhen Lyu, Sabin Dahal, Shuai Zeng, Juexin Wang, Dong Xu and Trupti Joshi

Genes 2024, 15(7), 882; https://doi.org/10.3390/genes15070882 - 5 Jul 2024

Viewed by 2614

Abstract

In recent years, there has been a growing interest in profiling multiomic modalities within individual cells simultaneously. One such example is integrating combined single-cell RNA sequencing (scRNA-seq) data and single-cell transposase-accessible chromatin sequencing (scATAC-seq) data. Integrated analysis of diverse modalities has helped researchers [...] Read more.

In recent years, there has been a growing interest in profiling multiomic modalities within individual cells simultaneously. One such example is integrating combined single-cell RNA sequencing (scRNA-seq) data and single-cell transposase-accessible chromatin sequencing (scATAC-seq) data. Integrated analysis of diverse modalities has helped researchers make more accurate predictions and gain a more comprehensive understanding than with single-modality analysis. However, generating such multimodal data is technically challenging and expensive, leading to limited availability of single-cell co-assay data. Here, we propose a model for cross-modal prediction between the transcriptome and chromatin profiles in single cells. Our model is based on a deep neural network architecture that learns the latent representations from the source modality and then predicts the target modality. It demonstrates reliable performance in accurately translating between these modalities across multiple paired human scATAC-seq and scRNA-seq datasets. Additionally, we developed CrossMP, a web-based portal allowing researchers to upload their single-cell modality data through an interactive web interface and predict the other type of modality data, using high-performance computing resources plugged at the backend. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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20 pages, 8533 KiB

Open AccessEditor’s ChoiceArticle

The Development of a Fluorescent Microsatellite Marker Assay for the Pitaya Canker Pathogen (Neoscytalidium dimidiatum)

by Rui Li, Xi Li, Jingcheng Tang, Changping Xie and Jianan Wang

Genes 2024, 15(7), 885; https://doi.org/10.3390/genes15070885 - 5 Jul 2024

Viewed by 1383

Abstract

Pitaya canker, caused by Neoscytalidium dimidiatum, is a destructive disease that significantly threatens the safety of the pitaya industry. The authors of previous studies have mainly focused on its biological characteristics and chemical control. However, there are no molecular markers available thus [...] Read more.

Pitaya canker, caused by Neoscytalidium dimidiatum, is a destructive disease that significantly threatens the safety of the pitaya industry. The authors of previous studies have mainly focused on its biological characteristics and chemical control. However, there are no molecular markers available thus far that can be used for the population genetics study of this pathogen. In the present study, a draft genome of N. dimidiatum with a total length of 41.46 MB was assembled in which 9863 coding genes were predicted and annotated. In particular, the microsatellite sequences in the draft genome were investigated. To improve the successful screening rate of potentially polymorphic microsatellite makers, another five N. dimidiatum isolates were resequenced and assembled. A total of eight pairs of polymorphic microsatellite primers were screened out based on the polymorphic microsatellite loci after investigating the sequencing and resequencing assemblies of the six isolates. A total of thirteen representative isolates sampled from different pitaya plantations were genotyped in order to validate the polymorphism of the resulting eight markers. The results indicated that these markers were able to distinguish the isolates well. Lastly, a neighbor-joining tree of 35 isolates, sampled from different pitaya plantations located in different regions, was constructed according to the genotypes of the eight molecular markers. The developed tree indicated that these molecular markers had sufficient genotyping capabilities for our test panel of isolates. In summary, we developed a set of polymorphic microsatellite markers in the following study that can effectively genotype and distinguish N. dimidiatum isolates and be utilized in the population genetics study of N. dimidiatum. Full article

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

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18 pages, 8717 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genome of Megacarpaea megalocarpa and Comparative Analysis with Related Species from Brassicaceae

by Zhuo Zhang, Xiaojun Shi, Haowen Tian, Juan Qiu, Hanze Ma and Dunyan Tan

Genes 2024, 15(7), 886; https://doi.org/10.3390/genes15070886 - 5 Jul 2024

Cited by 1 | Viewed by 1247

Abstract

Megacarpaea megalocarpa, a perennial herbaceous species belonging to the Brassicaceae family, has potential medicinal value. We isolated and characterized the chloroplast (cp) genome of M. megalocarpa and compared it with closely related species. The chloroplast genome displayed a typical quadripartite structure, spanning [...] Read more.

Megacarpaea megalocarpa, a perennial herbaceous species belonging to the Brassicaceae family, has potential medicinal value. We isolated and characterized the chloroplast (cp) genome of M. megalocarpa and compared it with closely related species. The chloroplast genome displayed a typical quadripartite structure, spanning 154,877 bp, with an overall guanine–cytosine (GC) content of 36.20%. Additionally, this genome contained 129 genes, 105 simple sequence repeats (SSRs), and 48 long repeat sequences. Significantly, the ycf1 gene exhibited a high degree of polymorphism at the small single copy (SSC) region and the inverted repeat a (IRa) boundary. Despite this polymorphism, relative synonymous codon usage (RSCU) values were found to be similar across species, and no large segment rearrangements or inversions were detected. The large single copy (LSC) and SSC regions showed higher sequence variations and nucleotide polymorphisms compared to the IR region. Thirteen distinct hotspot regions were identified as potential molecular markers. Our selection pressure analysis revealed that the protein-coding gene rpl20 is subjected to different selection pressures in various species. Phylogenetic analysis positioned M. megalocarpa within the expanded lineage II of the Brassicaceae family. The estimated divergence time suggests that M. megalocarpa diverged approximately 4.97 million years ago. In summary, this study provides crucial baseline information for the molecular identification, phylogenetic relationships, conservation efforts, and utilization of wild resources in Megacarpaea. Full article

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

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16 pages, 1873 KiB

Open AccessEditor’s ChoiceArticle

Patterns in Genome-Wide Codon Usage Bias in Representative Species of Lycophytes and Ferns

by Piaoran Xu, Lijuan Zhang, Liping Lu, Yanli Zhu, Dandan Gao and Shanshan Liu

Genes 2024, 15(7), 887; https://doi.org/10.3390/genes15070887 - 5 Jul 2024

Cited by 2 | Viewed by 1511

Abstract

The latest research shows that ferns and lycophytes have distinct evolutionary lineages. The codon usage patterns of lycophytes and ferns have not yet been documented. To investigate the gene expression profiles across various plant lineages with respect to codon usage, analyze the disparities [...] Read more.

The latest research shows that ferns and lycophytes have distinct evolutionary lineages. The codon usage patterns of lycophytes and ferns have not yet been documented. To investigate the gene expression profiles across various plant lineages with respect to codon usage, analyze the disparities and determinants of gene evolution in primitive plant species, and identify appropriate exogenous gene expression platforms, the whole-genome sequences of four distinct species were retrieved from the NCBI database. The findings indicated that Ceratopteris richardii, Adiantum capillus-veneris, and Selaginella moellendorffii exhibited an elevated A/U content in their codon base composition and a tendency to end with A/U. Additionally, S. capillus-veneris had more C/G in its codons and a tendency to end with C/G. The ENC values derived from both ENC-plot and ENC-ratio analyses deviated significantly from the standard curves, suggesting that the codon usage preferences of these four species were primarily influenced by genetic mutations and natural selection, with natural selection exerting a more prominent influence. This finding was further supported by PR2-Plot, neutrality plot analysis, and COA. A combination of RSCU and ENC values was used as a reference criterion to rank the codons and further identify the optimal codons. The study identified 24 high-frequency codons in C. richardii, A. capillus-veneris, and Diphasiastrum complanatum, with no shared optimal codons among the four species. Arabidopsis thaliana and Ginkgo biloba exhibited similar codon preferences to the three species, except for S. moellendorffii. This research offers a theoretical framework at the genomic codon level for investigating the phylogenetic relationships between lycophytes and ferns, shedding light on gene codon optimization and its implications for genetic engineering in breeding. Full article

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

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11 pages, 7472 KiB

Open AccessEditor’s ChoiceCase Report

Myopic Macular Hole and Detachment after Gene Therapy in Atypical RPE65 Retinal Dystrophy: A Case Report

by Fabrizio Giansanti, Cristina Nicolosi, Dario Giorgio, Andrea Sodi, Dario Pasquale Mucciolo, Laura Pavese, Liliana Pollazzi, Gianni Virgili, Giulio Vicini, Ilaria Passerini, Elisabetta Pelo and Vittoria Murro

Genes 2024, 15(7), 879; https://doi.org/10.3390/genes15070879 - 4 Jul 2024

Viewed by 1594

Abstract

Purpose: To report a case of macular hole and detachment occurring after the subretinal injection of Voretigene Neparvovec (VN) in a patient affected by atypical RPE65 retinal dystrophy with high myopia and its successful surgical management. Case description: We report a case of [...] Read more.

Purpose: To report a case of macular hole and detachment occurring after the subretinal injection of Voretigene Neparvovec (VN) in a patient affected by atypical RPE65 retinal dystrophy with high myopia and its successful surgical management. Case description: We report a case of a 70-year-old man treated with VN in both eyes. The best corrected visual acuity (BCVA) was 0.7 LogMar in the right eye (RE) and 0.92 LogMar in the left eye (LE). Axial length was 29.60 mm in the RE and 30.28 mm in the LE. Both eyes were pseudophakic. In both eyes, fundus examination revealed high myopia, posterior staphyloma, and extended retinal atrophy areas at the posterior pole, circumscribing a central island of surviving retina. Both eyes were treated with VN subretinal injection, but a full-thickness macular hole and retinal detachment occurred in the LE three weeks after surgery. The patient underwent 23-gauge vitrectomy with internal limiting membrane (ILM) peeling and the inverted flap technique with sulfur hexafluoride (SF6) 20% tamponade. Postoperative follow-up showed that the macular hole was closed and the BCVA was maintained. Conclusions: Our experience suggests that patients with atypical RPE65 retinal dystrophy and high myopia undergoing VN subretinal injection require careful management to minimize the risk of macular hole and detachment occurrence and promptly detect and address these potential complications. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Disease Mechanisms in Eye Disorders)

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11 pages, 1032 KiB

Open AccessEditor’s ChoiceArticle

Chronic Adolescent Restraint Stress Downregulates miRNA-200a Expression in Male and Female C57BL/6J and BALB/cJ Mice

by Helen M. Kamens, Emma K. Anziano, William J. Horton and Sonia A. Cavigelli

Genes 2024, 15(7), 873; https://doi.org/10.3390/genes15070873 - 3 Jul 2024

Cited by 1 | Viewed by 1797

Abstract

Adolescence is a critical developmental period when the brain is plastic, and stress exposure can have lasting physiological consequences. One mechanism through which adolescent stress may have lasting effects is by altering microRNAs (miRNAs), leading to wide-scale gene expression changes. Three prior independent [...] Read more.

Adolescence is a critical developmental period when the brain is plastic, and stress exposure can have lasting physiological consequences. One mechanism through which adolescent stress may have lasting effects is by altering microRNAs (miRNAs), leading to wide-scale gene expression changes. Three prior independent studies used unbiased approaches (RNA sequencing or microarray) to identify miRNAs differentially expressed by chronic variable stress in male rodents. In all three studies, miRNA-200a was differentially expressed in areas of the brain associated with emotion regulation. The current study extends this research to determine if chronic non-variable adolescent stress downregulates miRNA-200a expression by looking at two strains (BALB/cJ and C57BL/6J) of male and female mice. We utilized a 14-day (2 h/day) restraint stress protocol and verified stress effects on adolescent body weight gain and circulating corticosterone concentrations relative to non-restraint controls. Mice were then left undisturbed until they were euthanized in adulthood, at which time brains were collected to measure miRNA-200a in the ventral hippocampus. Three weeks after adolescent stress ended, differences in body weight between groups were no longer significant; however, animals exposed to stress had less miRNA-200a expression in the ventral hippocampus than control animals. These data implicate miRNA-200a expression as a potential mechanism by which adolescent stress can have persistent impacts on multiple outcomes in both male and female mice. Full article

(This article belongs to the Section Neurogenomics)

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17 pages, 1008 KiB

Open AccessEditor’s ChoiceReview

SARS-CoV-2 Genomic Epidemiology Dashboards: A Review of Functionality and Technological Frameworks for the Public Health Response

by Nikita Sitharam, Houriiyah Tegally, Danilo de Castro Silva, Cheryl Baxter, Tulio de Oliveira and Joicymara S. Xavier

Genes 2024, 15(7), 876; https://doi.org/10.3390/genes15070876 - 3 Jul 2024

Cited by 1 | Viewed by 2851

Abstract

During the coronavirus disease 2019 (COVID-19) pandemic, the number and types of dashboards produced increased to convey complex information using digestible visualizations. The pandemic saw a notable increase in genomic surveillance data, which genomic epidemiology dashboards presented in an easily interpretable manner. These [...] Read more.

During the coronavirus disease 2019 (COVID-19) pandemic, the number and types of dashboards produced increased to convey complex information using digestible visualizations. The pandemic saw a notable increase in genomic surveillance data, which genomic epidemiology dashboards presented in an easily interpretable manner. These dashboards have the potential to increase the transparency between the scientists producing pathogen genomic data and policymakers, public health stakeholders, and the public. This scoping review discusses the data presented, functional and visual features, and the computational architecture of six publicly available SARS-CoV-2 genomic epidemiology dashboards. We found three main types of genomic epidemiology dashboards: phylogenetic, genomic surveillance, and mutational. We found that data were sourced from different databases, such as GISAID, GenBank, and specific country databases, and these dashboards were produced for specific geographic locations. The key performance indicators and visualization used were specific to the type of genomic epidemiology dashboard. The computational architecture of the dashboards was created according to the needs of the end user. The genomic surveillance of pathogens is set to become a more common tool used to track ongoing and future outbreaks, and genomic epidemiology dashboards are powerful and adaptable resources that can be used in the public health response. Full article

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

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14 pages, 7152 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Phylogenetic Analysis of the Chloroplast Genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor

by Li-Li Wu, Ying-Min Geng and Lan-Ping Zheng

Genes 2024, 15(7), 877; https://doi.org/10.3390/genes15070877 - 3 Jul 2024

Cited by 2 | Viewed by 1351

Abstract

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore [...] Read more.

This study sequenced the complete chloroplast genomes of Stephania japonica var. timoriensis and Stephania japonica var. discolor using the Illumina NovaSeq and PacBio RSII platforms. Following sequencing, the genomes were assembled, annotated, comparatively analyzed, and used to construct a phylogenetic tree to explore their phylogenetic positions. Results indicated that the chloroplast genomes of S. japonica var. timoriensis and S. japonica var. discolor both displayed a typical double-stranded circular tetrameric structure, measuring 157,609 and 157,748 bp in length, respectively. Each genome contained 130 annotated genes, with similar total GC content and relative codon usage patterns, showing a distinct preference for A/U at the third codon position. Simple sequence repeat analysis identified 207 and 211 repeats in S. japonica var. timoriensis and S. japonica var. discolor, respectively, primarily the A/T type. Boundary condition analysis indicated no significant expansion or contraction in the inverted repeat regions with consistent gene types and locations across both varieties. Nucleotide polymorphism analysis highlighted greater variation in the intergenic regions than in the coding sequences of Stephania chloroplast genomes. Phylogenetic analyses demonstrated that the species Stephania clustered into a distinct, well-supported clade. Notably, Stephania japonica, along with S. japonica var. discolor and S. japonica var. timoriensis, established a monophyletic lineage. Within this lineage, S. japonica and S. japonica var. discolor were closely related, with S. japonica var. timoriensis serving as their sister taxon. Full article

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

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