Genes

Article

15 pages, 1933 KiB

Open AccessEditor’s ChoiceArticle

Predicting Patterns of Distant Metastasis in Breast Cancer Patients following Local Regional Therapy Using Machine Learning

by Audrey Shiner, Alex Kiss, Khadijeh Saednia, Katarzyna J. Jerzak, Sonal Gandhi, Fang-I Lu, Urban Emmenegger, Lauren Fleshner, Andrew Lagree, Marie Angeli Alera, Mateusz Bielecki, Ethan Law, Brianna Law, Dylan Kam, Jonathan Klein, Christopher J. Pinard, Alex Shenfield, Ali Sadeghi-Naini and William T. Tran

Genes 2023, 14(9), 1768; https://doi.org/10.3390/genes14091768 - 7 Sep 2023

Cited by 7 | Viewed by 3258

Abstract

Up to 30% of breast cancer (BC) patients will develop distant metastases (DM), for which there is no cure. Here, statistical and machine learning (ML) models were developed to estimate the risk of site-specific DM following local-regional therapy. This retrospective study cohort included [...] Read more.

Up to 30% of breast cancer (BC) patients will develop distant metastases (DM), for which there is no cure. Here, statistical and machine learning (ML) models were developed to estimate the risk of site-specific DM following local-regional therapy. This retrospective study cohort included 175 patients diagnosed with invasive BC who later developed DM. Clinicopathological information was collected for analysis. Outcome variables were the first site of metastasis (brain, bone or visceral) and the time interval (months) to developing DM. Multivariate statistical analysis and ML-based multivariable gradient boosting machines identified factors associated with these outcomes. Machine learning models predicted the site of DM, demonstrating an area under the curve of 0.74, 0.75, and 0.73 for brain, bone and visceral sites, respectively. Overall, most patients (57%) developed bone metastases, with increased odds associated with estrogen receptor (ER) positivity. Human epidermal growth factor receptor-2 (HER2) positivity and non-anthracycline chemotherapy regimens were associated with a decreased risk of bone DM, while brain metastasis was associated with ER-negativity. Furthermore, non-anthracycline chemotherapy alone was a significant predictor of visceral metastasis. Here, clinicopathologic and treatment variables used in ML prediction models predict the first site of metastasis in BC. Further validation may guide focused patient-specific surveillance practices. Full article

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

► Show Figures

Figure 1

16 pages, 2600 KiB

Open AccessEditor’s ChoiceArticle

New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond

by Valentina Belli, Daniela Maiello, Concetta Di Lorenzo, Maria Furia, Rosario Vicidomini and Mimmo Turano

Genes 2023, 14(9), 1766; https://doi.org/10.3390/genes14091766 - 6 Sep 2023

Cited by 2 | Viewed by 1616

Abstract

The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl–prolyl cis–trans isomerase activity. This enzymatic [...] Read more.

The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl–prolyl cis–trans isomerase activity. This enzymatic function aids with the folding and activation of protein structures and often serves as a molecular regulatory switch for large multimolecular complexes, ensuring appropriate inter- and intra-molecular interactions. Here, we investigated the involvement of CypA in the nucleus, where it plays a crucial role in supporting the assembly and trafficking of heterogeneous ribonucleoproteins (RNPs). We reveal that CypA is enriched in the nucleolus, where it colocalizes with the pseudouridine synthase dyskerin, the catalytic component of the multifunctional H/ACA RNPs involved in the modification of cellular RNAs and telomere stability. We show that dyskerin, whose mutations cause the X-linked dyskeratosis (X-DC) and the Hoyeraal–Hreidarsson congenital ribosomopathies, can directly interact with CypA. These findings, together with the remark that substitution of four dyskerin prolines are known to cause X-DC pathogenic mutations, lead us to indicate this protein as a CypA client. The data presented here suggest that this chaperone can modulate dyskerin activity influencing all its partecipated RNPs. Full article

(This article belongs to the Special Issue Diagnosis and Therapies for Genetic Diseases)

► Show Figures

Figure 1

13 pages, 2074 KiB

Open AccessEditor’s ChoiceArticle

An Automated Prognostic Model for Pancreatic Ductal Adenocarcinoma

by Ioannis Vezakis, Antonios Vezakis, Sofia Gourtsoyianni, Vassilis Koutoulidis, Andreas A. Polydorou, George K. Matsopoulos and Dimitrios D. Koutsouris

Genes 2023, 14(9), 1742; https://doi.org/10.3390/genes14091742 - 31 Aug 2023

Cited by 8 | Viewed by 2371

Abstract

Pancreatic ductal adenocarcinoma (PDAC) constitutes a leading cause of cancer-related mortality despite advances in detection and treatment methods. While computed tomography (CT) serves as the current gold standard for initial evaluation of PDAC, its prognostic value remains limited, as it relies on diagnostic [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) constitutes a leading cause of cancer-related mortality despite advances in detection and treatment methods. While computed tomography (CT) serves as the current gold standard for initial evaluation of PDAC, its prognostic value remains limited, as it relies on diagnostic stage parameters encompassing tumor size, lymph node involvement, and metastasis. Radiomics have recently shown promise in predicting postoperative survival of PDAC patients; however, they rely on manual pancreas and tumor delineation by clinicians. In this study, we collected a dataset of pre-operative CT scans from a cohort of 40 PDAC patients to evaluate a fully automated pipeline for survival prediction. Employing nnU-Net trained on an external dataset, we generated automated pancreas and tumor segmentations. Subsequently, we extracted 854 radiomic features from each segmentation, which we narrowed down to 29 via feature selection. We then combined these features with the Tumor, Node, Metastasis (TNM) system staging parameters, as well as the patient’s age. We trained a random survival forest model to perform an overall survival prediction over time, as well as a random forest classifier for the binary classification of two-year survival, using repeated cross-validation for evaluation. Our results exhibited promise, with a mean C-index of 0.731 for survival modeling and a mean accuracy of 0.76 in two-year survival prediction, providing evidence of the feasibility and potential efficacy of a fully automated pipeline for PDAC prognostication. By eliminating the labor-intensive manual segmentation process, our streamlined pipeline demonstrates an efficient and accurate prognostication process, laying the foundation for future research endeavors. Full article

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

► Show Figures

Figure 1

16 pages, 5826 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Plant Homeodomain Transcription Factor Genes Involved in Flower Development and Multiple Abiotic Stress Response in Pepper

by Jinfen Wen, Minghua Deng, Kai Zhao, Huidan Zhou, Rui Wu, Mengjuan Li, Hong Cheng, Pingping Li, Ruihao Zhang and Junheng Lv

Genes 2023, 14(9), 1737; https://doi.org/10.3390/genes14091737 - 30 Aug 2023

Cited by 3 | Viewed by 1502

Abstract

Plant homeodomain (PHD) transcription factor genes are involved in plant development and in a plant’s response to stress. However, there are few reports about this gene family in peppers (Capsicum annuum L.). In this study, the pepper inbred line “Zunla-1” was used [...] Read more.

Plant homeodomain (PHD) transcription factor genes are involved in plant development and in a plant’s response to stress. However, there are few reports about this gene family in peppers (Capsicum annuum L.). In this study, the pepper inbred line “Zunla-1” was used as the reference genome, and a total of 43 PHD genes were identified, and systematic analysis was performed to study the chromosomal location, evolutionary relationship, gene structure, domains, and upstream cis-regulatory elements of the CaPHD genes. The fewest CaPHD genes were located on chromosome 4, while the most were on chromosome 3. Genes with similar gene structures and domains were clustered together. Expression analysis showed that the expression of CaPHD genes was quite different in different tissues and in response to various stress treatments. The expression of CaPHD17 was different in the early stage of flower bud development in the near-isogenic cytoplasmic male-sterile inbred and the maintainer inbred lines. It is speculated that this gene is involved in the development of male sterility in pepper. CaPHD37 was significantly upregulated in leaves and roots after heat stress, and it is speculated that CaPHD37 plays an important role in tolerating heat stress in pepper; in addition, CaPHD9, CaPHD10, CaPHD11, CaPHD17, CaPHD19, CaPHD20, and CaPHD43 were not sensitive to abiotic stress or hormonal factors. This study will provide the basis for further research into the function of CaPHD genes in plant development and responses to abiotic stresses and hormones. Full article

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

► Show Figures

Figure 1

18 pages, 5301 KiB

Open AccessEditor’s ChoiceArticle

One Step Closer to the Understanding of the Relationship IDR-LCR-Structure

by Mariane Gonçalves-Kulik, Friederike Schmid and Miguel A. Andrade-Navarro

Genes 2023, 14(9), 1711; https://doi.org/10.3390/genes14091711 - 28 Aug 2023

Cited by 8 | Viewed by 2100

Abstract

Intrinsically disordered regions (IDRs) in protein sequences are emerging as functionally important elements for interaction and regulation. While being generally flexible, we previously showed, by observation of experimentally obtained structures, that they contain regions of reduced sequence complexity that have an increased propensity [...] Read more.

Intrinsically disordered regions (IDRs) in protein sequences are emerging as functionally important elements for interaction and regulation. While being generally flexible, we previously showed, by observation of experimentally obtained structures, that they contain regions of reduced sequence complexity that have an increased propensity to form structure. Here we expand the universe of cases taking advantage of structural predictions by AlphaFold. Our studies focus on low complexity regions (LCRs) found within IDRs, where these LCRs have only one or two residue types (polyX and polyXY, respectively). In addition to confirming previous observations that polyE and polyEK have a tendency towards helical structure, we find a similar tendency for other LCRs such as polyQ and polyER, most of them including charged residues. We analyzed the position of polyXY containing IDRs within proteins, which allowed us to show that polyAG and polyAK accumulate at the N-terminal, with the latter showing increased helical propensity at that location. Functional enrichment analysis of polyXY with helical propensity indicated functions requiring interaction with RNA and DNA. Our work adds evidence of the function of LCRs in interaction-dependent structuring of disordered regions, encouraging the development of tools for the prediction of their dynamic structural properties. Full article

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

► Show Figures

Figure 1

12 pages, 7364 KiB

Open AccessEditor’s ChoiceArticle

Identification and Verification of Candidate miRNA Biomarkers with Application to Infection with Emiliania huxleyi Virus

by Enquan Zhang, Shumiao Zhang, Guiling Li, Zhengxiao Zhang and Jingwen Liu

Genes 2023, 14(9), 1716; https://doi.org/10.3390/genes14091716 - 28 Aug 2023

Cited by 2 | Viewed by 1718

Abstract

The interactions of Emiliania huxleyi and its specific lytic virus (EhV) have a profound influence on marine biogeochemical carbon–sulfur cycles and play a prominent role in global climate change. MicroRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential due to their [...] Read more.

The interactions of Emiliania huxleyi and its specific lytic virus (EhV) have a profound influence on marine biogeochemical carbon–sulfur cycles and play a prominent role in global climate change. MicroRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential due to their role in virus–host interactions. However, the application of miRNA signatures as diagnostic markers in marine viral infection has made limited progress. Based on our previous small-RNA sequencing data, one host miRNA biomarker that is upregulated in early infection and seven viral miRNA biomarkers that are upregulated in late infection were identified and verified using qRT-PCR and a receiver operating characteristic curve analysis in pure culture, mixed culture, and natural seawater culture. The host ehx-miR20-5p was able to significantly differentiate infection groups from the control in the middle (24 h post-infection, hpi) and late infection (48 hpi) phases, while seven virus-derived miRNA biomarkers could diagnose the early and late stages of EhV infection. Functional enrichment analysis showed that these miRNAs participated in numerous essential metabolic pathways, including gene transcription and translation, cell division-related pathways, protein-degradation-related processes, and lipid metabolism. Additionally, a dual-luciferase reporter assay confirmed the targeted relationship between a viral ehv-miR7-5p and the host dihydroceramide desaturase gene (hDCD). This finding suggests that the virus-derived miRNA has the ability to inhibit the host sphingolipid metabolism, which is a specific characteristic of EhV infection during the late stage. Our data revealed a cluster of potential miRNA biomarkers with significant regulatory functions that could be used to diagnose EhV infection, which has implications for assessing the infectious activity of EhV in a natural marine environment. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers, 2nd Edition)

► Show Figures

Figure 1

14 pages, 4526 KiB

Open AccessEditor’s ChoiceArticle

Optical Genome Mapping: Integrating Structural Variations for Precise Homologous Recombination Deficiency Score Calculation

by Nikhil Shri Sahajpal, Ashis K. Mondal, Ashutosh Vashisht, Harmanpreet Singh, Andy Wing Chun Pang, Daniel Saul, Omar Nivin, Benjamin Hilton, Barbara R. DuPont, Vamsi Kota, Natasha M. Savage, Alex R. Hastie, Alka Chaubey and Ravindra Kolhe

Genes 2023, 14(9), 1683; https://doi.org/10.3390/genes14091683 - 25 Aug 2023

Cited by 1 | Viewed by 2602

Abstract

Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence [...] Read more.

Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to measure and report HRD phenotypes. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and a 523-gene NGS panel for HRD score calculations. This retrospective study included the analysis of 196 samples, of which 10 were gliomas, 176 were hematological malignancy samples, and 10 were controls. The 10 gliomas were evaluated with both CMA and OGM, and 30 hematological malignancy samples were evaluated with both the NGS panel and OGM. To verify the scores in a larger cohort, 135 cases were evaluated with the NGS panel and 71 cases with OGM. The HRD scores were calculated using a combination of three HRD signatures that included loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST). In the ten glioma cases analyzed with OGM and CMA using the same DNA (to remove any tumor percentage bias), the HRD scores (mean ± SEM) were 13.2 (±4.2) with OGM compared to 3.7 (±1.4) with CMA. In the 30 hematological malignancy cases analyzed with OGM and the 523-gene NGS panel, the HRD scores were 7.6 (±2.2) with OGM compared to 2.6 (±0.8) with the 523-gene NGS panel. OGM detected 70.8% and 66.8% of additional variants that are considered HRD signatures in gliomas and hematological malignancies, respectively. The higher sensitivity of OGM to capture HRD signature variants might enable a more accurate and precise correlation with response to PARPi and platinum-based drugs. This study reveals HRD signatures that are cryptic to current standard of care (SOC) methods used for assessing the HRD phenotype and presents OGM as an attractive alternative with higher resolution and sensitivity to accurately assess the HRD phenotype. Full article

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

► Show Figures

Figure 1

19 pages, 6055 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study Reveals the Genetic Basis of Total Flavonoid Content in Brown Rice

by Haijian Xia, Xiaoying Pu, Xiaoyang Zhu, Xiaomeng Yang, Haifeng Guo, Henan Diao, Quan Zhang, Yulong Wang, Xingming Sun, Hongliang Zhang, Zhanying Zhang, Yawen Zeng and Zichao Li

Genes 2023, 14(9), 1684; https://doi.org/10.3390/genes14091684 - 25 Aug 2023

Cited by 2 | Viewed by 1845

Abstract

Flavonoids have anti-inflammatory, antioxidative, and anticarcinogenic effects. Breeding rice varieties rich in flavonoids can prevent chronic diseases such as cancer and cardio-cerebrovascular diseases. However, most of the genes reported are known to regulate flavonoid content in leaves or seedlings. To further elucidate the [...] Read more.

Flavonoids have anti-inflammatory, antioxidative, and anticarcinogenic effects. Breeding rice varieties rich in flavonoids can prevent chronic diseases such as cancer and cardio-cerebrovascular diseases. However, most of the genes reported are known to regulate flavonoid content in leaves or seedlings. To further elucidate the genetic basis of flavonoid content in rice grains and identify germplasm rich in flavonoids in grains, a set of rice core collections containing 633 accessions from 32 countries was used to determine total flavonoid content (TFC) in brown rice. We identified ten excellent germplasms with TFC exceeding 300 mg/100 g. Using a compressed mixed linear model, a total of 53 quantitative trait loci (QTLs) were detected through a genome-wide association study (GWAS). By combining linkage disequilibrium (LD) analysis, location of significant single nucleotide polymorphisms (SNPs), gene expression, and haplotype analysis, eight candidate genes were identified from two important QTLs (qTFC1-6 and qTFC9-7), among which LOC_Os01g59440 and LOC_Os09g24260 are the most likely candidate genes. We also analyzed the geographic distribution and breeding utilization of favorable haplotypes of the two genes. Our findings provide insights into the genetic basis of TFC in brown rice and could facilitate the breeding of flavonoid-rich varieties, which may be a prevention and adjuvant treatment for cancer and cardio-cerebrovascular diseases. Full article

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

► Show Figures

Figure 1

12 pages, 3020 KiB

Open AccessEditor’s ChoiceArticle

TERTmonitor—qPCR Detection of TERTp Mutations in Glioma

by João Paulo Brás, Tito Teles Jesus, Hugo Prazeres, Jorge Lima, Paula Soares and João Vinagre

Genes 2023, 14(9), 1693; https://doi.org/10.3390/genes14091693 - 25 Aug 2023

Cited by 3 | Viewed by 2172

Abstract

Telomerase promoter (TERTp) mutations are frequently observed in various types of tumours and commonly characterised by two specific hotspots located at positions −124 and −146 upstream of the start codon. They enhance TERTp activity, resulting in increased TERT expression. In central nervous system [...] Read more.

Telomerase promoter (TERTp) mutations are frequently observed in various types of tumours and commonly characterised by two specific hotspots located at positions −124 and −146 upstream of the start codon. They enhance TERTp activity, resulting in increased TERT expression. In central nervous system (CNS) tumours, they are integrated as biomarkers, aiding in the diagnosis and with a role in prognosis, where, in some settings, they are associated with aggressive behaviour. In this study, we evaluated the performance of TERTmonitor for TERTp genotyping in a series of 185 gliomas in comparison to the traditional method, Sanger sequencing. Against the gold-standard Sanger method, TERTmonitor performed with a 97.8% accuracy. Inaccuracy was mainly due to the over-detection of variants in negative cases (by Sanger) and the presence of variants that can modify the chemistry of the probe detection. The distribution of the mutations was comparable to other series, with the −124 being the most represented (38.92% for Sanger and TERTmonitor) and more prevalent in the higher-grade tumours, gliosarcoma (50.00%) and glioblastoma (52.6%). The non-matched cases are debatable, as we may be dealing with the reduced sensitivity of Sanger in detecting rare alleles, which strengthens the use of the TERTmonitor. With this study, we present a reliable and rapid potential tool for TERTp genotyping in gliomas. Full article

(This article belongs to the Section Genetic Diagnosis)

► Show Figures

Figure 1

18 pages, 3099 KiB

Open AccessEditor’s ChoiceArticle

SMRT Sequencing Enables High-Throughput Identification of Novel AAVs from Capsid Shuffling and Directed Evolution

by Widler Casy, Irvin T. Garza, Xin Chen, Thomas Dong, Yuhui Hu, Mohammed Kanchwala, Cynthia B. Trygg, Charles Shyng, Chao Xing, Bruce A. Bunnell, Stephen E. Braun and Steven J. Gray

Genes 2023, 14(8), 1660; https://doi.org/10.3390/genes14081660 - 21 Aug 2023

Cited by 1 | Viewed by 3534

Abstract

The use of AAV capsid libraries coupled with various selection strategies has proven to be a remarkable approach for generating novel AAVs with enhanced and desired features. The inability to reliably sequence the complete capsid gene in a high-throughput manner has been the [...] Read more.

The use of AAV capsid libraries coupled with various selection strategies has proven to be a remarkable approach for generating novel AAVs with enhanced and desired features. The inability to reliably sequence the complete capsid gene in a high-throughput manner has been the bottleneck of capsid engineering. As a result, many library strategies are confined to localized and modest alterations in the capsid, such as peptide insertions or single variable region (VR) alterations. The caveat of short reads by means of next-generation sequencing (NGS) hinders the diversity of capsid library construction, shifting the field away from whole-capsid modifications. We generated AAV capsid shuffled libraries of naturally occurring AAVs and applied directed evolution in both mice and non-human primates (NHPs), with the goal of yielding AAVs that are compatible across both species for translational applications. We recovered DNA from the tissues of injected animal and used single molecule real-time (SMRT) sequencing to identify variants enriched in the central nervous system (CNS). We provide insights and considerations for variant identification by comparing bulk tissue sequencing to that of isolated nuclei. Our work highlights the potential advantages of whole-capsid engineering, as well as indispensable methodological improvements for the analysis of recovered capsids, including the nuclei-enrichment step and SMRT sequencing. Full article

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

► Show Figures

Figure 1

19 pages, 4914 KiB

Open AccessEditor’s ChoiceArticle

StrainIQ: A Novel n-Gram-Based Method for Taxonomic Profiling of Human Microbiota at the Strain Level

by Sanjit Pandey, Nagavardhini Avuthu and Chittibabu Guda

Genes 2023, 14(8), 1647; https://doi.org/10.3390/genes14081647 - 18 Aug 2023

Cited by 2 | Viewed by 1959

Abstract

The emergence of next-generation sequencing (NGS) technology has greatly influenced microbiome research and led to the development of novel bioinformatics tools to deeply analyze metagenomics datasets. Identifying strain-level variations in microbial communities is important to understanding the onset and progression of diseases, host–pathogen [...] Read more.

The emergence of next-generation sequencing (NGS) technology has greatly influenced microbiome research and led to the development of novel bioinformatics tools to deeply analyze metagenomics datasets. Identifying strain-level variations in microbial communities is important to understanding the onset and progression of diseases, host–pathogen interrelationships, and drug resistance, in addition to designing new therapeutic regimens. In this study, we developed a novel tool called StrainIQ (strain identification and quantification) based on a new n-gram-based (series of n number of adjacent nucleotides in the DNA sequence) algorithm for predicting and quantifying strain-level taxa from whole-genome metagenomic sequencing data. We thoroughly evaluated our method using simulated and mock metagenomic datasets and compared its performance with existing methods. On average, it showed 85.8% sensitivity and 78.2% specificity on simulated datasets. It also showed higher specificity and sensitivity using n-gram models built from reduced reference genomes and on models with lower coverage sequencing data. It outperforms alternative approaches in genus- and strain-level prediction and strain abundance estimation. Overall, the results show that StrainIQ achieves high accuracy by implementing customized model-building and is an efficient tool for site-specific microbial community profiling. Full article

(This article belongs to the Section Bioinformatics)

► Show Figures

Figure 1

14 pages, 3508 KiB

Open AccessEditor’s ChoiceArticle

Refinement of Leishmania donovani Genome Annotations in the Light of Ribosome-Protected mRNAs Fragments (Ribo-Seq Data)

by Alejandro Sánchez-Salvador, Sandra González-de la Fuente, Begoña Aguado, Phillip A. Yates and Jose M. Requena

Genes 2023, 14(8), 1637; https://doi.org/10.3390/genes14081637 - 17 Aug 2023

Cited by 2 | Viewed by 2162

Abstract

Advances in next-generation sequencing methodologies have facilitated the assembly of an ever-increasing number of genomes. Gene annotations are typically conducted via specialized software, but the most accurate results require additional manual curation that incorporates insights derived from functional and bioinformatic analyses (e.g., transcriptomics, [...] Read more.

Advances in next-generation sequencing methodologies have facilitated the assembly of an ever-increasing number of genomes. Gene annotations are typically conducted via specialized software, but the most accurate results require additional manual curation that incorporates insights derived from functional and bioinformatic analyses (e.g., transcriptomics, proteomics, and phylogenetics). In this study, we improved the annotation of the Leishmania donovani (strain HU3) genome using publicly available data from the deep sequencing of ribosome-protected mRNA fragments (Ribo-Seq). As a result of this analysis, we uncovered 70 previously non-annotated protein-coding genes and improved the annotation of around 600 genes. Additionally, we present evidence for small upstream open reading frames (uORFs) in a significant number of transcripts, indicating their potential role in the translational regulation of gene expression. The bioinformatics pipelines developed for these analyses can be used to improve the genome annotations of other organisms for which Ribo-Seq data are available. The improvements provided by these studies will bring us closer to the ultimate goal of a complete and accurately annotated L. donovani genome and will enhance future transcriptomics, proteomics, and genetics studies. Full article

(This article belongs to the Special Issue Feature Papers in Microbial Genetics in 2023)

► Show Figures

Figure 1

14 pages, 1946 KiB

Open AccessEditor’s ChoiceArticle

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

by Sadia Afrin, Gregory W. Kirschen and Mostafa A. Borahay

Genes 2023, 14(8), 1625; https://doi.org/10.3390/genes14081625 - 15 Aug 2023

Cited by 3 | Viewed by 2829

Abstract

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction in obesity, including abnormal cellular proliferation, oxidative stress, and DNA damage. The present study aims to determine [...] Read more.

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction in obesity, including abnormal cellular proliferation, oxidative stress, and DNA damage. The present study aims to determine how adipocytes and adipocyte-secreted factors affect changes in MSCs in a manner that promotes the growth of uterine leiomyomas. Myometrial stem cells were isolated from the uteri of patients by fluorescence-activated cell sorting (FACS) using CD44/Stro1 antibodies. Enzyme-linked immunosorbent assay (ELISA), Western blot, and immunocytochemistry assays were performed on human adipocytes (SW872) co-cultured with MSCs and treated with leptin or adiponectin to examine the effects of proliferation, extracellular matrix (ECM) deposition, oxidative damage, and DNA damage. Co-culture with SW872 increased MSC proliferation compared to MSC culture alone, according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results. The expressions of PCNA and COL1A increased significantly with SW872 co-culture. In addition, the expression of these markers was increased after leptin treatment and decreased after adiponectin treatment in MSCs. The Wnt/β-catenin and TGF-β/SMAD signaling pathways promote proliferation and ECM deposition in uterine leiomyomas. The expression of Wnt4, β-catenin, TGFβ3, and pSMAD2/3 of MSCs was increased when co-cultured with adipocytes. We found that the co-culture of MSCs with adipocytes resulted in increased NOX4 expression, reactive oxygen species production, and γ-H2AX expression. Leptin acts by binding to its receptor (LEP-R), leading to signal transduction, resulting in the transcription of genes involved in cellular proliferation, angiogenesis, and glycolysis. In MSCs, co-culture with adipocytes increased the expression of LEP-R, pSTAT3/STAT3, and pERK1/2/ERK/12. Based on the above results, we suggest that obesity may mediate MSC initiation of tumorigenesis, resulting in leiomyomas. Full article

(This article belongs to the Topic Stem Cell Differentiation and Applications)

► Show Figures

Figure 1

21 pages, 2992 KiB

Open AccessEditor’s ChoiceArticle

Comparative Transcriptomic Analysis of Insecticide-Resistant Aedes aegypti from Puerto Rico Reveals Insecticide-Specific Patterns of Gene Expression

by Dieunel Derilus, Lucy Mackenzie Impoinvil, Ephantus J. Muturi, Janet McAllister, Joan Kenney, Steven E. Massey, Ryan Hemme, Linda Kothera and Audrey Lenhart

Genes 2023, 14(8), 1626; https://doi.org/10.3390/genes14081626 - 15 Aug 2023

Cited by 10 | Viewed by 3202

Abstract

Aedes aegypti transmits major arboviruses of public health importance, including dengue, chikungunya, Zika, and yellow fever. The use of insecticides represents the cornerstone of vector control; however, insecticide resistance in Ae. aegypti has become widespread. Understanding the molecular basis of insecticide resistance in [...] Read more.

Aedes aegypti transmits major arboviruses of public health importance, including dengue, chikungunya, Zika, and yellow fever. The use of insecticides represents the cornerstone of vector control; however, insecticide resistance in Ae. aegypti has become widespread. Understanding the molecular basis of insecticide resistance in this species is crucial to design effective resistance management strategies. Here, we applied Illumina RNA-Seq to study the gene expression patterns associated with resistance to three widely used insecticides (malathion, alphacypermethrin, and lambda-cyhalothrin) in Ae. aegypti populations from two sites (Manatí and Isabela) in Puerto Rico (PR). Cytochrome P450s were the most overexpressed detoxification genes across all resistant phenotypes. Some detoxification genes (CYP6Z7, CYP28A5, CYP9J2, CYP6Z6, CYP6BB2, CYP6M9, and two CYP9F2 orthologs) were commonly overexpressed in mosquitoes that survived exposure to all three insecticides (independent of geographical origin) while others including CYP6BY1 (malathion), GSTD1 (alpha-cypermethrin), CYP4H29 and GSTE6 (lambda-cyhalothrin) were uniquely overexpressed in mosquitoes that survived exposure to specific insecticides. The gene ontology (GO) terms associated with monooxygenase, iron binding, and passive transmembrane transporter activities were significantly enriched in four out of six resistant vs. susceptible comparisons while serine protease activity was elevated in all insecticide-resistant groups relative to the susceptible strain. Interestingly, cuticular-related protein genes (chinase and chitin) were predominantly downregulated, which was also confirmed in the functional enrichment analysis. This RNA-Seq analysis presents a detailed picture of the candidate detoxification genes and other pathways that are potentially associated with pyrethroid and organophosphate resistance in Ae. aegypti populations from PR. These results could inform development of novel molecular tools for detection of resistance-associated gene expression in this important arbovirus vector and guide the design and implementation of resistance management strategies. Full article

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

► Show Figures

Figure 1

22 pages, 2819 KiB

Open AccessEditor’s ChoiceArticle

Abundance and Diversification of Repetitive Elements in Decapoda Genomes

by Christelle Rutz, Lena Bonassin, Arnaud Kress, Caterina Francesconi, Ljudevit Luka Boštjančić, Dorine Merlat, Kathrin Theissinger and Odile Lecompte

Genes 2023, 14(8), 1627; https://doi.org/10.3390/genes14081627 - 15 Aug 2023

Cited by 4 | Viewed by 2527

Abstract

Repetitive elements are a major component of DNA sequences due to their ability to propagate through the genome. Characterization of Metazoan repetitive profiles is improving; however, current pipelines fail to identify a significant proportion of divergent repeats in non-model organisms. The Decapoda order, [...] Read more.

Repetitive elements are a major component of DNA sequences due to their ability to propagate through the genome. Characterization of Metazoan repetitive profiles is improving; however, current pipelines fail to identify a significant proportion of divergent repeats in non-model organisms. The Decapoda order, for which repeat content analyses are largely lacking, is characterized by extremely variable genome sizes that suggest an important presence of repetitive elements. Here, we developed a new standardized pipeline to annotate repetitive elements in non-model organisms, which we applied to twenty Decapoda and six other Crustacea genomes. Using this new tool, we identified 10% more repetitive elements than standard pipelines. Repetitive elements were more abundant in Decapoda species than in other Crustacea, with a very large number of highly repeated satellite DNA families. Moreover, we demonstrated a high correlation between assembly size and transposable elements and different repeat dynamics between Dendrobranchiata and Reptantia. The patterns of repetitive elements largely reflect the phylogenetic relationships of Decapoda and the distinct evolutionary trajectories within Crustacea. In summary, our results highlight the impact of repetitive elements on genome evolution in Decapoda and the value of our novel annotation pipeline, which will provide a baseline for future comparative analyses. Full article

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

► Show Figures

Figure 1

20 pages, 1680 KiB

Open AccessEditor’s ChoiceArticle

Cognitive–Behavioral Profile in Pediatric Patients with Syndrome 5p-; Genotype–Phenotype Correlationships

by Cristina Bel-Fenellós, Chantal Biencinto-López, Belén Sáenz-Rico, Adolfo Hernández, Ana Karen Sandoval-Talamantes, Jair Tenorio-Castaño, Pablo Lapunzina and Julián Nevado

Genes 2023, 14(8), 1628; https://doi.org/10.3390/genes14081628 - 15 Aug 2023

Cited by 6 | Viewed by 2110

Abstract

(1) Background: 5p minus Syndrome (S5p-) is a neurodevelopmental disorder caused by a deletion in the short arm of chromosome 5. Among the phenotypic characteristics of S5p-, the most characteristic and representative element is a monochromatic cry with a high-pitched tone reminiscent of [...] Read more.

(1) Background: 5p minus Syndrome (S5p-) is a neurodevelopmental disorder caused by a deletion in the short arm of chromosome 5. Among the phenotypic characteristics of S5p-, the most characteristic and representative element is a monochromatic cry with a high-pitched tone reminiscent of a cat’s meow. Individuals may also show great phenotypic heterogeneity and great genetic variability. Regarding cognitive–behavioral aspects of the syndrome, the studies are scarce and do not establish a general profile of the main cognitive–behavioral particularities that this syndrome presents. The main objective of this work was to describe the development profile of a cohort of 45 children with 5p minus Syndrome, concerning the biomedical, genetic, cognitive, and behavioral aspects. Establishing putative genotype–phenotype (cognitive–behavioral profiles) relationships in our cohort, from an interdisciplinary approach. (2) Methods: A selection of instruments of measures was selected for neuropsychological assessment (3) Results: In general, children with S5p- have a higher cognitive level than a communicative and motor level. Language difficulties, especially expressive ones, influence the frequency and severity of the most frequent behavioral problems in S5p. The most significant problem behavior of children with S5p-, especially girls, is self-harm. Compulsive behavior, limited preferences, and interest in monotony are significantly more frequent in subjects with better cognitive levels. We also find a significant correlation between the size of the loss of genetic material on 5p and the cognitive level of the subjects. (4) Conclusions: We described for the first time, the cognitive–behavioral profile of a cohort of minors with S5p-. Remarkably, it was found that language, especially of an expressive nature, modulates the most frequent behavioral aspects in subjects with lower cognitive levels, so it is essential to develop verbal or alternative communication strategies adjusted to these individuals. Full article

(This article belongs to the Special Issue Phenotypic Characterization and Genomic Methodology of Rare Diseases)

► Show Figures

Graphical abstract

14 pages, 3086 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Single-Nucleotide Polymorphism-Based Genomic Diversity and Runs of Homozygosity for Selection Signatures in Equine Breeds

by Anuradha Bhardwaj, Gitanjali Tandon, Yash Pal, Nitesh Kumar Sharma, Varij Nayan, Sonali Soni, Mir Asif Iquebal, Sarika Jaiswal, Ram Avatar Legha, Thirumala Rao Talluri, Tarun Kumar Bhattacharya, Dinesh Kumar, Anil Rai and B. N. Tripathi

Genes 2023, 14(8), 1623; https://doi.org/10.3390/genes14081623 - 14 Aug 2023

Cited by 1 | Viewed by 2015

Abstract

The horse, one of the most domesticated animals, has been used for several purposes, like transportation, hunting, in sport, or for agriculture-related works. Kathiawari, Marwari, Manipuri, Zanskari, Bhutia, Spiti, and Thoroughbred are the main breeds of horses, particularly due to their agroclimatic adaptation [...] Read more.

The horse, one of the most domesticated animals, has been used for several purposes, like transportation, hunting, in sport, or for agriculture-related works. Kathiawari, Marwari, Manipuri, Zanskari, Bhutia, Spiti, and Thoroughbred are the main breeds of horses, particularly due to their agroclimatic adaptation and role in any kind of strong physical activity, and these characteristics are majorly governed by genetic factors. The genetic diversity and phylogenetic relationship of these Indian equine breeds using microsatellite markers have been reported, but further studies exploring the SNP diversity and runs of homozygosity revealing the selection signature of breeds are still warranted. In our study, the identification of genes that play a vital role in muscle development is performed through SNP detection via the whole-genome sequencing approach. A total of 96 samples, categorized under seven breeds, and 620,721 SNPs were considered to ascertain the ROH patterns amongst all the seven breeds. Over 5444 ROH islands were mined, and the maximum number of ROHs was found to be present in Zanskari, while Thoroughbred was confined to the lowest number of ROHs. Gene enrichment of these ROH islands produced 6757 functional genes, with AGPAT1, CLEC4, and CFAP20 as important gene families. However, QTL annotation revealed that the maximum QTLs were associated with Wither’s height trait ontology that falls under the growth trait in all seven breeds. An Equine SNP marker database (EqSNPDb) was developed to catalogue ROHs for all these equine breeds for the flexible and easy chromosome-wise retrieval of ROH along with the genotype details of all the SNPs. Such a study can reveal breed divergence in different climatic and ecological conditions. Full article

(This article belongs to the Special Issue Molecular Genetics in Livestock Production and Disease Resistance)

► Show Figures

Figure 1

15 pages, 2712 KiB

Open AccessEditor’s ChoiceArticle

Hub Gene Mining and Co-Expression Network Construction of Low-Temperature Response in Maize of Seedling by WGCNA

by Tao Yu, Jianguo Zhang, Jingsheng Cao, Xuena Ma, Wenyue Li and Gengbin Yang

Genes 2023, 14(8), 1598; https://doi.org/10.3390/genes14081598 - 7 Aug 2023

Cited by 16 | Viewed by 2876

Abstract

Weighted gene co-expression network analysis (WGCNA) is a research method in systematic biology. It is widely used to identify gene modules related to target traits in multi-sample transcriptome data. In order to further explore the molecular mechanism of maize response to low-temperature stress [...] Read more.

Weighted gene co-expression network analysis (WGCNA) is a research method in systematic biology. It is widely used to identify gene modules related to target traits in multi-sample transcriptome data. In order to further explore the molecular mechanism of maize response to low-temperature stress at the seedling stage, B144 (cold stress tolerant) and Q319 (cold stress sensitive) provided by the Maize Research Institute of Heilongjiang Academy of Agricultural Sciences were used as experimental materials, and both inbred lines were treated with 5 °C for 0 h, 12 h, and 24 h, with the untreated material as a control. Eighteen leaf samples were used for transcriptome sequencing, with three biological replicates. Based on the above transcriptome data, co-expression networks of weighted genes associated with low-temperature-tolerance traits were constructed by WGCNA. Twelve gene modules significantly related to low-temperature tolerance at the seedling stage were obtained, and a number of hub genes involved in low-temperature stress regulation pathways were discovered from the four modules with the highest correlation with target traits. These results provide clues for further study on the molecular genetic mechanisms of low-temperature tolerance in maize at the seedling stage. Full article

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

► Show Figures

Figure 1

17 pages, 3952 KiB

Open AccessEditor’s ChoiceArticle

Morphological and Molecular Identification of Hard Ticks in Hainan Island, China

by Jitrawadee Intirach, Xin Lv, Qian Han, Zhi-Yue Lv and Tao Chen

Genes 2023, 14(8), 1592; https://doi.org/10.3390/genes14081592 - 6 Aug 2023

Cited by 21 | Viewed by 4191

Abstract

Ticks are small, blood-sucking arachnids, known vectors of various diseases, and found throughout the world. They are distributed basically in almost all regions of China. At present, there is not much information regarding tick species on Hainan Island. They were subjected to morphological [...] Read more.

Ticks are small, blood-sucking arachnids, known vectors of various diseases, and found throughout the world. They are distributed basically in almost all regions of China. At present, there is not much information regarding tick species on Hainan Island. They were subjected to morphological identification and imaging on an individual basis. Molecular phylogenetic analyses, based on cox1 and 16S rRNA genes, were utilized to identify the species and determine their approximate phylogenetic origin and genetic diversity. The genomic DNA of tick species was extracted, and cytochrome oxidase subunit 1 (cox1) and 16S ribosomal RNA (rRNA) genes were amplified and sequenced. The identification of five tick species, namely Rhipicephalus microplus, Rhipicephalus sanguineus, Rhipicephalus haemaphysaloides, Haemaphysalis cornigera and Haemaphysalis mageshimaensis, was carried out by morphological analysis. When employing the cox1 and 16S rRNA phylogenetic tree, all isolates of R. microplus from Hainan Island were classified as clade A and B, respectively. R. sanguineus was recognized as a member of the tropical lineage by phylogenetic analysis on the cox1 and 16S rRNA genes. Three phylogenetic groups of R. haemaphysaloides were recognized and found to be related closely to strains from China. H. cornigera and H. mageshimaensis formed one phylogenetic group, presumably from tick strains prevalent in Japan and China. The haplotype network analysis indicated that R. microplus is classed into 26 and 6 haplotypes, which correspond to cox1 and 16S rRNA gene assemblages, respectively. In addition, four cox1 haplotypes were detected in R. sanguineus. This is the first evidence that suggests genetic diversity, host range and geographical distribution of hard ticks in Hainan Island, China. Full article

(This article belongs to the Special Issue Vector Borne Infectious Diseases and Vectors: Biology, Genetics, Evolution, and Control)

► Show Figures

Figure 1

15 pages, 7808 KiB

Open AccessEditor’s ChoiceCommunication

Application of High-Resolution Melting and DNA Barcoding for Discrimination and Taxonomy Definition of Rocket Salad (Diplotaxis spp.) Species

by Pasquale Tripodi

Genes 2023, 14(8), 1594; https://doi.org/10.3390/genes14081594 - 6 Aug 2023

Cited by 2 | Viewed by 2154

Abstract

Nuclear and cytoplasmic DNA barcoding regions are useful for plant identification, breeding, and phylogenesis. In this study, the genetic diversity of 17 Diplotaxis species, was investigated with 5 barcode markers. The allelic variation was based on the sequences of chloroplast DNA markers including [...] Read more.

Nuclear and cytoplasmic DNA barcoding regions are useful for plant identification, breeding, and phylogenesis. In this study, the genetic diversity of 17 Diplotaxis species, was investigated with 5 barcode markers. The allelic variation was based on the sequences of chloroplast DNA markers including the spacer between trnL and trnF and tRNA-Phe gene (trnL-F), the rubisco (rbcl), the maturase K (matk), as well as the internal transcribed spacer (ITS) region of the nuclear ribosomal DNA. A highly polymorphic marker (HRM500) derived from a comparison of cytoplasmic genome sequences in Brassicaceae, was also included. Subsequently, a real-time PCR method coupled with HRM analysis was implemented to better resolve taxonomic relationships and identify assays suitable for species identification. Integration of the five barcode regions revealed a grouping of the species according to the common chromosomal set number. Clusters including species with n = 11 (D. duveryrieriana or cretacea, D. tenuifolia, D. simplex and D. acris), n = 8 (D. ibicensis, D. brevisiliqua and D. ilorcitana), and n = 9 (D. brachycarpa, D. virgata, D. assurgens, and D. berthautii) chromosomes were identified. Both phylogenetic analysis and the genetic structure of the collection identified D. siifolia as the most distant species. Previous studies emphasized this species’ extremely high glucosinolate content, particularly for glucobrassicin. High-resolution melting analysis showed specific curve patterns useful for the discrimination of the species, thus determining ITS1 as the best barcode for fingerprinting. Findings demonstrate that the approach used in this study is effective for taxa investigations and genetic diversity studies. Full article

(This article belongs to the Special Issue Phylogenetics, Genetics, and Breeding of Medicinal Plants)

► Show Figures

Figure 1

11 pages, 2861 KiB

Open AccessEditor’s ChoiceArticle

Examination of Factors Affecting Site-Directed RNA Editing by the MS2-ADAR1 Deaminase System

by Md Thoufic Anam Azad, Umme Qulsum and Toshifumi Tsukahara

Genes 2023, 14(8), 1584; https://doi.org/10.3390/genes14081584 - 4 Aug 2023

Cited by 1 | Viewed by 1783

Abstract

Adenosine deaminases acting on RNA (ADARs) have double-stranded RNA binding domains and a deaminase domain (DD). We used the MS2 system and specific guide RNAs to direct ADAR1-DD to target adenosines in the mRNA encoding-enhanced green fluorescence protein. Using this system in transfected [...] Read more.

Adenosine deaminases acting on RNA (ADARs) have double-stranded RNA binding domains and a deaminase domain (DD). We used the MS2 system and specific guide RNAs to direct ADAR1-DD to target adenosines in the mRNA encoding-enhanced green fluorescence protein. Using this system in transfected HEK-293 cells, we evaluated the effects of changing the length and position of the guide RNA on the efficiency of conversion of amber (TAG) and ochre (TAA) stop codons to tryptophan (TGG) in the target. Guide RNAs of 19, 21 and 23 nt were positioned upstream and downstream of the MS2-RNA, providing a total of six guide RNAs. The upstream guide RNAs were more functionally effective than the downstream guide RNAs, with the following hierarchy of efficiency: 21 nt > 23 nt > 19 nt. The highest editing efficiency was 16.6%. Off-target editing was not detected in the guide RNA complementary region but was detected 50 nt downstream of the target. The editing efficiency was proportional to the amount of transfected deaminase but inversely proportional to the amount of the transfected guide RNA. Our results suggest that specific RNA editing requires precise optimization of the ratio of enzyme, guide RNA, and target RNA. Full article

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

► Show Figures

Figure 1

12 pages, 2424 KiB

Open AccessEditor’s ChoiceArticle

Co-Occurrence of Germline Genomic Variants and Copy Number Variations in Hereditary Breast and Colorectal Cancer Patients

by Luiza Côrtes, Tatiane Ramos Basso, Rolando André Rios Villacis, Jeferson dos Santos Souza, Mads Malik Aagaard Jørgensen, Maria Isabel Achatz and Silvia Regina Rogatto

Genes 2023, 14(8), 1580; https://doi.org/10.3390/genes14081580 - 3 Aug 2023

Cited by 1 | Viewed by 2750

Abstract

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is an autosomal dominant disease associated with a high risk of developing breast, ovarian, and other malignancies. Lynch syndrome is caused by mutations in mismatch repair genes predisposing to colorectal and endometrial cancers, among others. A [...] Read more.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is an autosomal dominant disease associated with a high risk of developing breast, ovarian, and other malignancies. Lynch syndrome is caused by mutations in mismatch repair genes predisposing to colorectal and endometrial cancers, among others. A rare phenotype overlapping hereditary colorectal and breast cancer syndromes is poorly characterized. Three breast and colorectal cancer unrelated patients fulfilling clinical criteria for HBOC were tested by whole exome sequencing. A family history of colorectal cancer was reported in two patients (cases 2 and 3). Several variants and copy number variations were identified, which potentially contribute to the cancer risk or prognosis. All patients presented copy number imbalances encompassing PMS2 (two deletions and one duplication), a known gene involved in the DNA mismatch repair pathway. Two patients showed gains covering the POLE2 (cases 1 and 3), which is associated with DNA replication. Germline potentially damaging variants were found in PTCH1 (patient 3), MAT1A, and WRN (patient 2). Overall, concurrent genomic alterations were described that may increase the risk of cancer appearance in HBOC patients with breast and colorectal cancers. Full article

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

► Show Figures

Graphical abstract

13 pages, 1424 KiB

Open AccessEditor’s ChoiceArticle

Multiple Sclerosis Heritability Estimation on Sardinian Ascertained Extended Families Using Bayesian Liability Threshold Model

by Andrea Nova, Teresa Fazia, Valeria Saddi, Marialuisa Piras and Luisa Bernardinelli

Genes 2023, 14(8), 1579; https://doi.org/10.3390/genes14081579 - 2 Aug 2023

Cited by 1 | Viewed by 1825

Abstract

Heritability studies represent an important tool to investigate the main sources of variability for complex diseases, whose etiology involves both genetics and environmental factors. In this paper, we aimed to estimate multiple sclerosis (MS) narrow-sense heritability (h²), on a liability scale, [...] Read more.

Heritability studies represent an important tool to investigate the main sources of variability for complex diseases, whose etiology involves both genetics and environmental factors. In this paper, we aimed to estimate multiple sclerosis (MS) narrow-sense heritability (h²), on a liability scale, using extended families ascertained from affected probands sampled in the Sardinian province of Nuoro, Italy. We also investigated the sources of MS liability variability among shared environment effects, sex, and categorized year of birth (<1946, ≥1946). The latter can be considered a proxy for different early environmental exposures. To this aim, we implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. Our analysis highlighted categorized year of birth as the main explanatory factor, explaining ~70% of MS liability variability (median value = 0.69, 95% CI: 0.64, 0.73), while h² resulted near to 0% (median value = 0.03, 95% CI: 0.00, 0.09). By performing a year of birth-stratified analysis, we found a high h² only in individuals born on/after 1946 (median value = 0.82, 95% CI: 0.68, 0.93), meaning that the genetic variability acquired a high explanatory role only when focusing on this subpopulation. Overall, the results obtained highlighted early environmental exposures, in the Sardinian population, as a meaningful factor involved in MS to be further investigated. Full article

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

► Show Figures

Figure 1

16 pages, 2126 KiB

Open AccessEditor’s ChoiceArticle

Children with Chronic Immune Thrombocytopenia Exhibit High Expression of Human Endogenous Retroviruses TRIM28 and SETDB1

by Pier-Angelo Tovo, Ilaria Galliano, Emilia Parodi, Cristina Calvi, Stefano Gambarino, Francesco Licciardi, Maddalena Dini, Paola Montanari, Margherita Branca, Ugo Ramenghi and Massimiliano Bergallo

Genes 2023, 14(8), 1569; https://doi.org/10.3390/genes14081569 - 1 Aug 2023

Cited by 4 | Viewed by 2270

Abstract

Chronic immune thrombocytopenia (CITP) is an autoimmune disease whose underlying biologic mechanisms remain elusive. Human endogenous retroviruses (HERVs) derive from ancestral infections and constitute about 8% of our genome. A wealth of clinical and experimental studies highlights their pivotal pathogenetic role in autoimmune [...] Read more.

Chronic immune thrombocytopenia (CITP) is an autoimmune disease whose underlying biologic mechanisms remain elusive. Human endogenous retroviruses (HERVs) derive from ancestral infections and constitute about 8% of our genome. A wealth of clinical and experimental studies highlights their pivotal pathogenetic role in autoimmune diseases. Epigenetic mechanisms, such as those modulated by TRIM28 and SETDB1, are involved in HERV activation and regulation of immune response. We assessed, through a polymerase chain reaction real-time Taqman amplification assay, the transcription levels of pol genes of HERV-H, HERV-K, and HERV-W; env genes of Syncytin (SYN)1, SYN2, and HERV-W; as well as TRIM28 and SETDB1 in whole blood from 34 children with CITP and age-matched healthy controls (HC). The transcriptional levels of all HERV sequences, with the exception of HERV-W-env, were significantly enhanced in children with CITP as compared to HC. Patients on eltrombopag treatment exhibited lower expression of SYN1, SYN2, and HERV-W-env as compared to untreated patients. The mRNA concentrations of TRIM28 and SETDB1 were significantly higher and were positively correlated with those of HERVs in CITP patients. The over-expressions of HERVs and TRIM28/SETDB1 and their positive correlations in patients with CITP are suggestive clues of their contribution to the pathogenesis of the disease and support innovative interventions to inhibit HERV and TRIM28/SETDB1 expressions in patients unresponsive to standard therapies. Full article

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

► Show Figures

Figure 1

17 pages, 1516 KiB

Open AccessEditor’s ChoiceArticle

Weight Loss Is a Strong Predictor of Memory Disorder Independent of Genetic Influences

by Sunny Chen, Sara M. Sarasua, Nicole J. Davis, Jane M. DeLuca, Stephen M. Thielke and Chang-En Yu

Genes 2023, 14(8), 1563; https://doi.org/10.3390/genes14081563 - 31 Jul 2023

Cited by 7 | Viewed by 1742

Abstract

Background: Past studies identified a link between weight loss and dementia, but lacked consistent conclusions. We sought to establish this link by examining the weight change profiles before and after dementia diagnosis. Methods: Using data from the Health and Retirement Study (1996–2020), we [...] Read more.

Background: Past studies identified a link between weight loss and dementia, but lacked consistent conclusions. We sought to establish this link by examining the weight change profiles before and after dementia diagnosis. Methods: Using data from the Health and Retirement Study (1996–2020), we examined 13,123 participants. We conducted a nested case–control analysis to assess differences in biennial weight change profile while controlling for BMI, longevity polygenic risk scores, and APOE gene variants. Results: Participants with a memory disorder lost weight (−0.63%) biennially, whereas those without a diagnosis did not (+0.013%, p-value < 0.0001). Our case–control study shows a significant difference (p-value < 0.01) in pre-dementia % weight changes between the cases (−0.29%) and controls (0.19%), but not in post-dementia weight changes. The weight loss group have the highest risk (OR = 2.01; p-value < 0.0001) of developing a memory disorder compared to the stable weight and weight gain groups. The observations hold true after adjusting for BMI, longevity polygenic risk scores, and APOE variant in a multivariable model. Conclusions: We observe that weight loss in dementia is a physiological process independent of genetic factors associated with BMI and longevity. Pre-dementia weight loss may be an important prognostic criterion to assess a person’s risk of developing a memory disorder. Full article

(This article belongs to the Section Neurogenomics)

► Show Figures

Figure 1

29 pages, 2952 KiB

Open AccessEditor’s ChoiceArticle

The DEAD-Box RNA Helicase Ded1 Is Associated with Translating Ribosomes

by Hilal Yeter-Alat, Naïma Belgareh-Touzé, Emmeline Huvelle, Josette Banroques and N. Kyle Tanner

Genes 2023, 14(8), 1566; https://doi.org/10.3390/genes14081566 - 31 Jul 2023

Cited by 1 | Viewed by 2680

Abstract

DEAD-box RNA helicases are ATP-dependent RNA binding proteins and RNA-dependent ATPases that possess weak, nonprocessive unwinding activity in vitro, but they can form long-lived complexes on RNAs when the ATPase activity is inhibited. Ded1 is a yeast DEAD-box protein, the functional ortholog of [...] Read more.

DEAD-box RNA helicases are ATP-dependent RNA binding proteins and RNA-dependent ATPases that possess weak, nonprocessive unwinding activity in vitro, but they can form long-lived complexes on RNAs when the ATPase activity is inhibited. Ded1 is a yeast DEAD-box protein, the functional ortholog of mammalian DDX3, that is considered important for the scanning efficiency of the 48S pre-initiation complex ribosomes to the AUG start codon. We used a modified PAR-CLIP technique, which we call quicktime PAR-CLIP (qtPAR-CLIP), to crosslink Ded1 to 4-thiouridine-incorporated RNAs in vivo using UV light centered at 365 nm. The irradiation conditions are largely benign to the yeast cells and to Ded1, and we are able to obtain a high efficiency of crosslinking under physiological conditions. We find that Ded1 forms crosslinks on the open reading frames of many different mRNAs, but it forms the most extensive interactions on relatively few mRNAs, and particularly on mRNAs encoding certain ribosomal proteins and translation factors. Under glucose-depletion conditions, the crosslinking pattern shifts to mRNAs encoding metabolic and stress-related proteins, which reflects the altered translation. These data are consistent with Ded1 functioning in the regulation of translation elongation, perhaps by pausing or stabilizing the ribosomes through its ATP-dependent binding. Full article

(This article belongs to the Section RNA)

► Show Figures

Figure 1

13 pages, 4892 KiB

Open AccessEditor’s ChoiceArticle

High Atlastin 2-2 (ATL2-2) Expression Associates with Worse Prognosis in Estrogen-Receptor-Positive Breast Cancer

by Inga Reynisdottir, Adalgeir Arason, Edda S. Freysteinsdottir, Sigrun B. Kristjansdottir, Bylgja Hilmarsdottir, Gunnhildur A. Traustadottir, Oskar T. Johannsson, Bjarni A. Agnarsson and Rosa B. Barkardottir

Genes 2023, 14(8), 1559; https://doi.org/10.3390/genes14081559 - 29 Jul 2023

Cited by 2 | Viewed by 2375

Abstract

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in [...] Read more.

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in murine breast tissue. Thus, we analyzed whether ATL2 has a role in human breast cancer (BC) pathology. The expression of ATL2 variant ATL2-2 was analyzed in breast tumors from the BC cohorts of the TCGA, METABRIC, and two independent Icelandic cohorts, Cohort 1 and 2; its association with clinical, pathological, survival, and cellular pathways was explored. ATL2-2 mRNA and protein expression were higher in breast tumors than in normal tissue. ATL2-2 mRNA associated with tumor characteristics that indicate a worse prognosis. In METABRIC, high ATL2-2 mRNA levels were associated with shorter BC-specific survival (BCSS) in patients with estrogen-receptor-positive luminal breast tumors, which remained significant after correction for grade and tumor size (HR 1.334, CI 1.063–1.673). Tumors with high ATL2 mRNA showed an upregulation of hallmark pathways MYC targets v1, E2F targets, and G2M checkpoint genes. Taken together, the results suggest that high levels of ATL2-2 may support BC progression through key cancer driver pathways. Full article

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

► Show Figures

Graphical abstract

15 pages, 2863 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Profiling of Meat Quality Traits of Skeletal Muscles of the Chinese Indigenous Huai Pig and Duroc Pig

by Xiaojin Li, Liangyue Lu, Xinwei Tong, Ruidong Li, Erhui Jin, Man Ren, Yafei Gao, Youfang Gu and Shenghe Li

Genes 2023, 14(8), 1548; https://doi.org/10.3390/genes14081548 - 28 Jul 2023

Cited by 17 | Viewed by 2577

Abstract

The Huai pig is a well-known indigenous pig breed in China. The main advantages of Huai pigs over Western commercial pig breeds include a high intramuscular fat (IMF) content and good meat quality. There are significant differences in the meat quality traits of [...] Read more.

The Huai pig is a well-known indigenous pig breed in China. The main advantages of Huai pigs over Western commercial pig breeds include a high intramuscular fat (IMF) content and good meat quality. There are significant differences in the meat quality traits of the same muscle part or different muscle parts of the same variety. To investigate the potential genetic mechanism underlying the meat quality differences in different pig breeds or muscle groups, longissimus dorsi (LD), psoas major (PM), and biceps femoris (BF) muscle tissues were collected from two pig breeds (Huai and Duroc). There were significant differences in meat quality traits and amino acid content. We assessed the muscle transcriptomic profiles using high-throughput RNA sequencing. The IMF content in the LD, PM, and BF muscles of Huai pigs was significantly higher than that in Duroc pigs (p < 0.05). Similarly, the content of flavor amino acids in the three muscle groups was significantly higher in Huai pigs than that in Duroc pigs (p < 0.05). We identified 175, 110, and 86 differentially expressed genes (DEGs) between the LD, PM, and BF muscles of the Huai and Duroc pigs, respectively. The DEGs of the different pig breeds and muscle regions were significantly enriched in the biological processes and signaling pathways related to muscle fiber type, IMF deposition, lipid metabolism, PPAR signaling, cAMP signaling, amino acid metabolism, and ECM–receptor interaction. Our findings might help improve pork yield by using the obtained DEGs for marker-assisted selection and providing a theoretical reference for evaluating and improving pork quality. Full article

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

► Show Figures

Figure 1

23 pages, 4614 KiB

Open AccessEditor’s ChoiceArticle

Arabidopsis RAD16 Homologues Are Involved in UV Tolerance and Growth

by Linda Alrayes, Jake Stout and Dana Schroeder

Genes 2023, 14(8), 1552; https://doi.org/10.3390/genes14081552 - 28 Jul 2023

Cited by 3 | Viewed by 1649

Abstract

In plants, prolonged exposure to ultraviolet (UV) radiation causes harmful DNA lesions. Nucleotide excision repair (NER) is an important DNA repair mechanism that operates via two pathways: transcription coupled repair (TC-NER) and global genomic repair (GG-NER). In plants and mammals, TC-NER is initiated [...] Read more.

In plants, prolonged exposure to ultraviolet (UV) radiation causes harmful DNA lesions. Nucleotide excision repair (NER) is an important DNA repair mechanism that operates via two pathways: transcription coupled repair (TC-NER) and global genomic repair (GG-NER). In plants and mammals, TC-NER is initiated by the Cockayne Syndrome A and B (CSA/CSB) complex, whereas GG-NER is initiated by the Damaged DNA Binding protein 1/2 (DDB1/2) complex. In the yeast Saccharomyces cerevisiae (S. cerevisiae), GG-NER is initiated by the Radiation Sensitive 7 and 16, (RAD7/16) complex. Arabidopsis thaliana has two homologues of yeast RAD16, At1g05120 and At1g02670, which we named AtRAD16 and AtRAD16b, respectively. In this study, we characterized the roles of AtRAD16 and AtRAD16b. Arabidopsis rad16 and rad16b null mutants exhibited increased UV sensitivity. Moreover, AtRAD16 overexpression increased plant UV tolerance. Thus, AtRAD16 and AtRAD16b contribute to plant UV tolerance and growth. Additionally, we found physical interaction between AtRAD16 and AtRAD7. Thus, the Arabidopsis RAD7/16 complex is functional in plant NER. Furthermore, AtRAD16 makes a significant contribution to Arabidopsis UV tolerance compared to the DDB1/2 and the CSB pathways. This is the first time the role and interaction of DDB1/2, RAD7/16, and CSA/CSB components in a single system have been studied. Full article

(This article belongs to the Special Issue Gene Regulation of Abiotic Stress Responses in Plants)

► Show Figures

Figure 1

20 pages, 4494 KiB

Open AccessEditor’s ChoiceArticle

Mutations of BRCA1, BRCA2, and PALB2 Genes in Breast Tumor Tissue: Relationship with the Effectiveness of Neoadjuvant Chemotherapy and Disease Prognosis

by Matvey M. Tsyganov, Sofia S. Sorokovikova, Elizaveta A. Lutzkaya and Marina K. Ibragimova

Genes 2023, 14(8), 1554; https://doi.org/10.3390/genes14081554 - 28 Jul 2023

Cited by 2 | Viewed by 2203

Abstract

It has been shown that the loss of function of the BRCA1, BRCA2, and PALB2 genes due to a number of hereditary mutations or chromosomal aberrations can affect the effectiveness of chemotherapy treatment and disease prognosis in patients with various types [...] Read more.

It has been shown that the loss of function of the BRCA1, BRCA2, and PALB2 genes due to a number of hereditary mutations or chromosomal aberrations can affect the effectiveness of chemotherapy treatment and disease prognosis in patients with various types of cancer, and in particular in breast cancer. Thus, the aim of the work was to evaluate the predictive and prognostic potential of DNA copy number aberrations and mutations in the BRCA1, BRCA2, and PALB2 genes in breast tumors. Materials and Methods: The study included 66 patients with breast cancer. DNA copy number aberrations (CNA) were assessed by high-density CytoScanHD™ Array micro matrix analysis. Gene mutations were assessed by sequencing on the MiSeq™ Sequencing System using the Accel-Amplicon BRCA1, BRCA2, and PALB2 Panel. Results: It has been established that the presence of a normal copy number of PALB2 is associated with a lack of response to chemotherapy in Taxotere-containing treatment regimens (p = 0.05). In addition, the presence of a PALB2 deletion is associated with 100% metastatic survival rates (log-rank test p = 0.04). As a result of sequencing, 25 mutations were found in the BRCA1 gene, 42 mutations in BRCA2, and 27 mutations in the PALB2 gene. The effect of mutations on the effectiveness of treatment is controversial, but an effect on the survival of patients with breast cancer has been shown. So, in the presence of pathogenic mutations in the BRCA2 gene, 100% metastatic survival is observed (log-rank test p = 0.05), as well as in the elimination of PALB2 mutations during treatment (log-rank test p = 0.07). Conclusion: Currently, there is little data on the effect of chromosomal aberrations and mutations in the BRCA1/2 and PALB2 genes on the effectiveness of treatment and prognosis of the disease. At the same time, the study of these genes has great potential for testing focused on a personalized approach to the treatment of patients with breast cancer. Full article

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

► Show Figures

Figure 1

11 pages, 273 KiB

Open AccessEditor’s ChoiceArticle

Effects of the Trp64Arg Polymorphism in the ADRB3 Gene on Body Composition, Cardiorespiratory Fitness, and Physical Activity in Healthy Adults

by Natalia Potocka, Marzena Skrzypa, Maria Zadarko-Domaradzka, Zbigniew Barabasz, Beata Penar-Zadarko, Agata Sakowicz, Emilian Zadarko and Izabela Zawlik

Genes 2023, 14(8), 1541; https://doi.org/10.3390/genes14081541 - 27 Jul 2023

Cited by 4 | Viewed by 2469

Abstract

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied [...] Read more.

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults (N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath–Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference (p = 0.035), hip circumference (p = 0.029), BF (%) (p = 0.008), and BF (kg) (p = 0.010), BMI (p = 0.005), WHtR (p = 0.021), and BAI (p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components (p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake (p= 0.023) and oxygen pulse (p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise (p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise. Full article

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

11 pages, 293 KiB

Open AccessEditor’s ChoiceArticle

miR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study

by Emilia Burada, Maria-Magdalena Roșu, Raluca Elena Sandu, Florin Burada, Mihai Gabriel Cucu, Ioana Streață, Bianca Petre-Mandache, Gabriela Popescu-Hobeanu, Monica-Laura Cara, Anca-Maria Țucă, Elena Pinoșanu and Carmen Valeria Albu

Genes 2023, 14(8), 1543; https://doi.org/10.3390/genes14081543 - 27 Jul 2023

Cited by 2 | Viewed by 1731

Abstract

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, [...] Read more.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71–24.47; OR 2.30, 95% CI: 1.23–4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population. Full article

(This article belongs to the Section RNA)

11 pages, 1406 KiB

Open AccessEditor’s ChoiceArticle

Evidence for Two Soybean Looper Strains in the United States with Limited Capacity for Cross-Hybridization

by Rodney N. Nagoshi, Jeffrey A. Davis, Robert L. Meagher, Fred R. Musser, Graham P. Head, Hector Portillo and Henry Teran

Genes 2023, 14(7), 1509; https://doi.org/10.3390/genes14071509 - 24 Jul 2023

Cited by 2 | Viewed by 1590

Abstract

The noctuid moth soybean looper (SBL), Chrysodeixis includens (Walker) is an economically important pest of soybeans (Glycine max (L.) Merr.) in the southeastern United States. It has characteristics that are of particular concern for pest mitigation that include a broad host range, [...] Read more.

The noctuid moth soybean looper (SBL), Chrysodeixis includens (Walker) is an economically important pest of soybeans (Glycine max (L.) Merr.) in the southeastern United States. It has characteristics that are of particular concern for pest mitigation that include a broad host range, the capacity for annual long-distance flight, and resistance in some populations to important pesticides such as pyrethroids and chitin synthesis inhibitor. The biology of SBL in the United States resembles that of the fellow noctuid fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), a major pest of corn and several other crops. FAW exhibits a population structure in that it can be divided into two groups (host strains) that differ in their host preferences but are broadly sympatric and exhibit incomplete reproductive isolation. In this paper, strategies used to characterize the FAW strains were applied to SBL to assess the likelihood of population structure in the United States. Evidence is presented for two SBL strains that were defined phylogenetically and display differences in the proportions of a small set of genetic markers. The populations exhibit evidence of reproductive barriers sufficient to allow persistent asymmetry in the distribution of mitochondrial haplotypes. The identified molecular markers will facilitate studies characterizing the behaviors of these two populations, with relevance to pest mitigation and efforts to prevent further dispersal of the resistance traits. Full article

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

► Show Figures

Figure 1

17 pages, 1436 KiB

Open AccessEditor’s ChoiceArticle

by Flavia Privitera, Flavia Piccini, Maria Paola Recalcati, Silvia Presi, Silvia Mazzola and Paola Carrera

Genes 2023, 14(7), 1505; https://doi.org/10.3390/genes14071505 - 23 Jul 2023

Cited by 7 | Viewed by 2423

Abstract

The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC [...] Read more.

The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC gene (5q22.2) in the deletion predisposes them to tumoral syndromes (Familial Adenomatous Polyposis and Gardner syndrome). Although the development of gastrointestinal tract malignancies has been extensively described, the genetic causes underlying neurologic manifestations have never been investigated. In this study, we described a new patient with a 19.85 Mb interstitial deletion identified by array-CGH and compared the deletions and the phenotypes reported in other patients already described in the literature and the Decipher database. Overlapping deletions allowed us to highlight a common region in 5q22.1q23.1, identifying KCNN2 (5q22.3) as the most likely candidate gene contributing to the neurologic phenotype. Full article

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

► Show Figures

Figure 1

13 pages, 1779 KiB

Open AccessEditor’s ChoiceArticle

The Effect of DNA Methylation in the Development and Progression of Chronic Kidney Disease in the General Population: An Epigenome-Wide Association Study Using the Korean Genome and Epidemiology Study Database

by Ji-Eun Kim, Min-Jee Jo, Eunjung Cho, Shin-Young Ahn, Young-Joo Kwon, Jeong-An Gim and Gang-Jee Ko

Genes 2023, 14(7), 1489; https://doi.org/10.3390/genes14071489 - 21 Jul 2023

Cited by 3 | Viewed by 2160

Abstract

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function [...] Read more.

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development. Method: We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m² at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period (“CKD prediction” analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years (“kidney function slope” analysis). Results: In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2, CHCHD4, and AHR, were found to be significant in the CKD prediction analysis and related to a decline in kidney function. Conclusion: It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function. Full article

(This article belongs to the Special Issue Epigenetics: Mechanisms in Toxicology and Disease)

► Show Figures

Figure 1

11 pages, 3141 KiB

Open AccessEditor’s ChoiceArticle

ranchSATdb: A Genome-Wide Simple Sequence Repeat (SSR) Markers Database of Livestock Species for Mutant Germplasm Characterization and Improving Farm Animal Health

by Naveen Duhan, Simardeep Kaur and Rakesh Kaundal

Genes 2023, 14(7), 1481; https://doi.org/10.3390/genes14071481 - 20 Jul 2023

Cited by 3 | Viewed by 2360

Abstract

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource [...] Read more.

Microsatellites, also known as simple sequence repeats (SSRs), are polymorphic loci that play an important role in genome research, animal breeding, and disease control. Ranch animals are important components of agricultural landscape. The ranch animal SSR database, ranchSATdb, is a web resource which contains 15,520,263 putative SSR markers. This database provides a comprehensive tool for performing end-to-end marker selection, from SSRs prediction to generating marker primers and their cross-species feasibility, visualization of the resulting markers, and finding similarities between the genomic repeat sequences all in one place without the need to switch between other resources. The user-friendly online interface allows users to browse SSRs by genomic coordinates, repeat motif sequence, chromosome, motif type, motif frequency, and functional annotation. Users may enter their preferred flanking area around the repeat to retrieve the nucleotide sequence, they can investigate SSRs present in the genic or the genes between SSRs, they can generate custom primers, and they can also execute in silico validation of primers using electronic PCR. For customized sequences, an SSR prediction pipeline called miSATminer is also built. New species will be added to this website’s database on a regular basis throughout time. To improve animal health via genomic selection, we hope that ranchSATdb will be a useful tool for mapping quantitative trait loci (QTLs) and marker-assisted selection. The web-resource is freely accessible at https://bioinfo.usu.edu/ranchSATdb/. Full article

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

► Show Figures

Figure 1

12 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

by Dhouha Jamai, Raja Gargouri, Boulbaba Selmi and Abdelmajid Khabir

Genes 2023, 14(7), 1467; https://doi.org/10.3390/genes14071467 - 19 Jul 2023

Cited by 4 | Viewed by 1858

Abstract

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as [...] Read more.

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer. Full article

(This article belongs to the Special Issue Genetics and Genomics of Colorectal Cancer and Related Diseases)

► Show Figures

Figure 1

8 pages, 391 KiB

Open AccessEditor’s ChoiceArticle

Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients

by Takashi Higuchi, Shomi Oka, Hiroshi Furukawa, Kota Shimada, Atsushi Hashimoto, Akiko Komiya, Toshihiro Matsui, Naoshi Fukui and Shigeto Tohma

Genes 2023, 14(7), 1470; https://doi.org/10.3390/genes14071470 - 19 Jul 2023

Cited by 1 | Viewed by 1944

Abstract

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with [...] Read more.

Objectives: The prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients. Methods: HLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m²]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m²]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients. Results: There was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09–2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24–2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics. Conclusions: The present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear. Full article

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

► Show Figures

Figure 1

14 pages, 3267 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of the PYL Gene Family in Three Ipomoea Species and the Expression Profiling of IbPYL Genes during Abiotic Stress Response in Sweetpotato

by Lei Zhang, Weihan Song, Guosheng Xin, Mingku Zhu and Xiaoqing Meng

Genes 2023, 14(7), 1471; https://doi.org/10.3390/genes14071471 - 19 Jul 2023

Cited by 5 | Viewed by 1461

Abstract

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea [...] Read more.

Abscisic acid (ABA), a critical phytohormone that regulates plant development and stress response, is sensed by the ABA receptors PYR/PYL/RCAR (PYLs). The PYL genes have been widely studied in multiple plant species, while a systematic analysis of PYL genes in the genus Ipomoea remains unperformed. Here, a total of 13, 14, and 14 PYLs were identified in Ipomoea batatas, Ipomoea trifida, and Ipomoea triloba, respectively. Fragment duplication was speculated to play prominent roles in Ipomoea PYL gene expansions. These Ipomoea PYLs were classified into three subfamilies via phylogenetic analysis, which was supported by exon–intron structures and conserved motif analyses. Additionally, the interspecies collinearity analysis further depicted a potential evolutionary relationship between them. Moreover, qRT-PCR analysis showed that multiple IbPYLs are highly and differentially responsive to abiotic stress treatments, suggesting their potential roles in sweetpotato stress responses. Taken together, these data provide valuable insights into the PYLs in the genus Ipomoea, which may be useful for their further functional analysis of their defense against environmental changes. Full article

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

► Show Figures

Figure 1

12 pages, 2481 KiB

Open AccessEditor’s ChoiceArticle

The Responses of Alternative Splicing during Heat Stress in the Pacific White Shrimp Litopenaeus vannamei

by Xiaoxi Zhang, Xiaojun Zhang, Jianbo Yuan and Fuhua Li

Genes 2023, 14(7), 1473; https://doi.org/10.3390/genes14071473 - 19 Jul 2023

Cited by 13 | Viewed by 2471

Abstract

Heat tolerance is increasingly becoming a crucial trait for aquaculture species in the face of rapidly changing climate conditions. Alternative splicing (AS) is a vital mechanism within cells that modulates gene abundance and functional diversity, enabling organisms to effectively respond to diverse stressful [...] Read more.

Heat tolerance is increasingly becoming a crucial trait for aquaculture species in the face of rapidly changing climate conditions. Alternative splicing (AS) is a vital mechanism within cells that modulates gene abundance and functional diversity, enabling organisms to effectively respond to diverse stressful conditions, including thermal stress. However, it is still uncertain whether AS contributes to heat tolerance in shrimp. In this study, we conducted an extensive transcriptome analysis on the Pacific white shrimp, Litopenaeus vannamei, revealing a total of 1267, 987, and 130 differential AS events (DAS) in the gill, hepatopancreas, and muscle, respectively, following exposure to heat stress. Among all of the DAS events, exon skipping (ES) was the predominant form of splicing modification observed. Interestingly, a minor portion of DAS genes exhibited overlap across the three tissues, implying that heat stress exerts unique effects on various tissue types. Moreover, the functional enrichment analysis demonstrated that commonly identified DAS genes were primarily associated with the “spliceosome” pathway, indicating that the AS of splicing-related genes played a crucial role in the response to heat stress. Our findings also revealed that heat stress tended to induce longer mRNA isoforms through differential alternative 3′ splice site (A3SS) events. Notably, A3SS events exhibited the highest proportion of maintained open reading frames (ORFs) under heat stress. Interestingly, we observed a limited overlap between the genes exhibiting DAS and those showing differential gene expression (DEG), indicating that AS may function as a distinct regulatory mechanism independent of transcriptional regulation in response to heat stress. This is the first comprehensive study on AS in crustacea species under heat stress, which broadens our understanding of the regulatory mechanisms governing the crustaceans’ response to environmental stress, providing valuable insights for the aquaculture breeding of shrimp and other aquatic animals. Full article

(This article belongs to the Special Issue Penaeid Shrimp Genomics and Post-Genomics)

► Show Figures

Figure 1

15 pages, 6832 KiB

Open AccessEditor’s ChoiceArticle

Identification of the Light-Harvesting Chlorophyll a/b Binding Protein Gene Family in Peach (Prunus persica L.) and Their Expression under Drought Stress

by Li Wang, Jia Wei, Xingyun Shi, Weihong Qian, Jan Mehmood, Yiming Yin and Huijuan Jia

Genes 2023, 14(7), 1475; https://doi.org/10.3390/genes14071475 - 19 Jul 2023

Cited by 23 | Viewed by 2662

Abstract

In higher plants, light-harvesting chlorophyll a/b binding (Lhc) proteins play a vital role in photosynthetic processes and are widely involved in the regulation of plant growth, development, and response to abiotic stress. However, the Lhc gene family has not been well identified in [...] Read more.

In higher plants, light-harvesting chlorophyll a/b binding (Lhc) proteins play a vital role in photosynthetic processes and are widely involved in the regulation of plant growth, development, and response to abiotic stress. However, the Lhc gene family has not been well identified in peaches (Prunus persica L.). In this study, 19 PpLhc genes were identified in the peach genome database, which were unevenly distributed on all chromosomes. Phylogenetic analysis demonstrated that PpLhc proteins could be divided into three major subfamilies, each of whose members had different exon–intron structures but shared similar conserved motifs. A total of 17 different kinds of cis-regulatory elements were identified in the promoter regions of all PpLhc genes, which could be classified into three categories: plant growth and development, stress response, and phytohormone response. In addition, transcriptomic data analysis and RT-qPCR results revealed that the expression profiles of some PpLhc genes changed under drought treatment, suggesting the crucial roles of Lhc genes in the regulation of plant tolerance to drought stress. Taken together, these findings will provide valuable information for future functional studies of PpLhc genes, especially in response to drought stress. Full article

(This article belongs to the Special Issue Abiotic Stress in Land Plants: Molecular Genetics and Genomics)

► Show Figures

Figure 1

15 pages, 1447 KiB

Open AccessEditor’s ChoiceArticle

Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer

by Ricardo Cunha de Oliveira, Sávio Pinho dos Reis and Giovanna C. Cavalcante

Genes 2023, 14(7), 1465; https://doi.org/10.3390/genes14071465 - 18 Jul 2023

Cited by 8 | Viewed by 2627

Abstract

Although it has gained more attention in recent years, the relationship between breast cancer (BC) and mitochondrial oxidative phosphorylation (OXPHOS) is still not well understood. Importantly, Complex IV or Cytochrome C Oxidase (COX) of OXPHOS is one of the key players in mitochondrial [...] Read more.

Although it has gained more attention in recent years, the relationship between breast cancer (BC) and mitochondrial oxidative phosphorylation (OXPHOS) is still not well understood. Importantly, Complex IV or Cytochrome C Oxidase (COX) of OXPHOS is one of the key players in mitochondrial balance. An in silico investigation of mutations in structural genes of Complex IV was conducted in BC, comprising 2107 samples. Our findings show four variants (rs267606614, rs753969142, rs199476128 and rs267606884) with significant pathogenic potential. Moreover, we highlight nine genes (MT-CO1, MT-CO2, MT-CO3, CO4I2, COX5A, COX5B, COX6A2, COX6C and COX7B2) with a potential impact on BC. Full article

(This article belongs to the Special Issue mtDNA and Mitochondrial Stress Signaling in Cancers)

► Show Figures

Figure 1

17 pages, 1961 KiB

Open AccessEditor’s ChoiceArticle

Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis

by Alexandros Pontikas, Charalabos Antonatos, Evangelos Evangelou and Yiannis Vasilopoulos

Genes 2023, 14(7), 1456; https://doi.org/10.3390/genes14071456 - 17 Jul 2023

Cited by 4 | Viewed by 5350

Abstract

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the [...] Read more.

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways. Full article

(This article belongs to the Special Issue Genetics of Multifactorial Diseases)

► Show Figures

Figure 1

15 pages, 3940 KiB

Open AccessEditor’s ChoiceArticle

Mn-XRN1 Has an Inhibitory Effect on Ovarian Reproduction in Macrobrachium nipponense

by Tianyong Chen, Huwei Yuan, Hui Qiao, Sufei Jiang, Wenyi Zhang, Yiwei Xiong, Hongtuo Fu and Shubo Jin

Genes 2023, 14(7), 1454; https://doi.org/10.3390/genes14071454 - 16 Jul 2023

Cited by 1 | Viewed by 1826

Abstract

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1 [...] Read more.

XRN1 is an exoribonuclease that degrades mRNA in the cytoplasm along the 5′–3′ direction. A previous study indicated that it may be involved in the reproduction of Macrobrachium nipponense. Quantitative real-time PCR was used to detect the spatiotemporal expression pattern of Mn-XRN1. At the tissue level, Mn-XRN1 was significantly expressed in the ovary. During development, Mn-XRN1 was significantly expressed at the CS stage of the embryo, on the 10th day post-larval and in the O2 stage of ovarian reproduction. The in situ hybridization results showed the location of Mn-XRN1 in the ovary. The expression of Mn-VASA was significantly increased after in vivo injection of Mn-XRN1 dsRNA. This suggests that Mn-XRN1 negatively regulates the expression of Mn-VASA. Furthermore, we counted the number of M. nipponense at various stages of ovarian reproduction on different days after RNAi. The results showed that ovarian development was significantly accelerated. In general, the results of the present study indicate that Mn-XRN1 has an inhibitory effect on the ovarian maturation of M. nipponense. The inhibitory effect might be through negative regulation of Mn-VASA. Full article

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

► Show Figures

Figure 1

20 pages, 6461 KiB

Open AccessEditor’s ChoiceArticle

Shotgun Metagenomic Sequencing Reveals Virome Composition of Mosquitoes from a Transition Ecosystem of North-Northeast Brazil

by Carine Fortes Aragão, Sandro Patroca da Silva, Bruna Laís Sena do Nascimento, Fábio Silva da Silva, Joaquim Pinto Nunes Neto, Valéria Cristina Soares Pinheiro and Ana Cecília Ribeiro Cruz

Genes 2023, 14(7), 1443; https://doi.org/10.3390/genes14071443 - 14 Jul 2023

Cited by 12 | Viewed by 3192

Abstract

A wide diversity of pathogenic mosquito-borne viruses circulate in the Brazilian Amazon, and the intense deforestation can contribute to the spread of these viruses. In this context, this study aimed to investigate the viral diversity in mosquitoes of the genera Aedes, Culex [...] Read more.

A wide diversity of pathogenic mosquito-borne viruses circulate in the Brazilian Amazon, and the intense deforestation can contribute to the spread of these viruses. In this context, this study aimed to investigate the viral diversity in mosquitoes of the genera Aedes, Culex, Haemagogus, and Sabethes from a transition area between the Amazon, Cerrado, and Caatinga biomes in Brazil. Metagenomic high-throughput sequencing was used to characterize the virome of 20 mosquito pools. A total of 15 virus-like genomes were identified, comprising species genomically close to insect-specific viruses of the families Iflaviridae, Metaviridae, Lispiviridae, Rhabdoviridae, Xinmoviridae, and Parvoviridae and species of plant viruses of the families Solemoviridae, Virgaviridae, and Partitiviridae. However, sequences of viruses associated with human and animal diseases were not detected. Most of the recovered genomes were divergent from those previously described. These findings reveal that there are a large number of unknown viruses to be explored in the middle-north of Brazil. Full article

(This article belongs to the Special Issue Viral Genomics and Metagenomics)

► Show Figures

Figure 1

13 pages, 4384 KiB

Open AccessEditor’s ChoiceArticle

Dissection of the Genetic Basis of Resistance to Stem Rot in Cultivated Peanuts (Arachis hypogaea L.) through Genome-Wide Association Study

by Liying Yan, Wanduo Song, Zhihui Wang, Dongyang Yu, Hari Sudini, Yanping Kang, Yong Lei, Dongxin Huai, Yuning Chen, Xin Wang, Qianqian Wang and Boshou Liao

Genes 2023, 14(7), 1447; https://doi.org/10.3390/genes14071447 - 14 Jul 2023

Cited by 4 | Viewed by 2124

Abstract

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, [...] Read more.

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, resulting in significant yield losses. In this study, a panel of 202 peanut accessions was evaluated for their resistance to stem rot by inoculating plants in the field with A. rolfsii-infested oat grains in three environments. The mean disease index value of each environment for accessions in subsp. fasitigiate and subsp. hypogaea showed no significant difference. Accessions from southern China displayed the lowest disease index value compared to those from other ecological regions. We used whole-genome resequencing to analyze the genotypes of the accessions and to identify significant SNPs associated with stem rot resistance through genome-wide association study (GWAS). A total of 121 significant SNPs associated with stem rot resistance in peanut were identified, with phenotypic variation explained (PVE) ranging from 12.23% to 15.51%. A total of 27 candidate genes within 100 kb upstream and downstream of 23 significant SNPs were annotated, which have functions related to recognition, signal transduction, and defense response. These significant SNPs and candidate genes provide valuable information for further validation and molecular breeding to improve stem rot resistance in peanut. Full article

(This article belongs to the Special Issue Peanut Genetics and Omics)

► Show Figures

Figure 1

17 pages, 4928 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Potential Function Analysis of the SRS Gene Family in Brassica napus

by Ming Hu, Meili Xie, Xiaobo Cui, Junyan Huang, Xiaohui Cheng, Lijiang Liu, Shunping Yan, Shengyi Liu and Chaobo Tong

Genes 2023, 14(7), 1421; https://doi.org/10.3390/genes14071421 - 10 Jul 2023

Cited by 4 | Viewed by 2119

Abstract

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus ( [...] Read more.

SRS (SHI-related sequence) transcription factors play a crucial role in plant growth, development, and abiotic stress response. Although Brassica napus (B. napus) is one of the most important oil crops in the world, the role of SRS genes in B. napus (BnSRS) has not been well investigated. Therefore, we employed a bioinformatics approach to identify BnSRS genes from genomic data and investigated their characteristics, functions, and expression patterns, to gain a better understanding of how this gene family is involved in plant development and growth. The results revealed that there were 34 BnSRS gene family members in the genomic sequence of B. napus, unevenly distributed throughout the sequence. Based on the phylogenetic analysis, these BnSRS genes could be divided into four subgroups, with each group sharing comparable conserved motifs and gene structure. Analysis of the upstream promoter region showed that BnSRS genes may regulate hormone responses, biotic and abiotic stress response, growth, and development in B. napus. The protein-protein interaction analysis revealed the involvement of BnSRS genes in various biological processes and metabolic pathways. Our analysis of BnSRS gene expression showed that 23 BnSRS genes in the callus tissue exhibited a dominant expression pattern, suggesting their critical involvement in cell dedifferentiation, cell division, and tissue development. In addition, association analysis between genotype and agronomic traits revealed that BnSRS genes may be linked to some important agronomic traits in B. napus, suggesting that BnSRS genes were widely involved in the regulation of important agronomic traits (including C16.0, C18.0, C18.1, C18.2 C18.3, C20.1, C22.1, GLU, protein, TSW, and FFT). In this study, we predicted the evolutionary relationships and potential functions of BnSRS gene family members, providing a basis for the development of BnSRS gene functions which could facilitate targeted functional studies and genetic improvement for elite breeding in B. napus. Full article

(This article belongs to the Special Issue Genetics of Biotic and Abiotic Stress Response in Crops)

► Show Figures

Figure 1

26 pages, 23080 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genome-Wide Analysis of MicroRNAs and Their Target Genes in Roots of Contrasting Indica Rice Cultivars under Reproductive-Stage Drought

by Simardeep Kaur, Karishma Seem, Suresh Kumar, Rakesh Kaundal and Trilochan Mohapatra

Genes 2023, 14(7), 1390; https://doi.org/10.3390/genes14071390 - 1 Jul 2023

Cited by 7 | Viewed by 2502

Abstract

Recurrent occurrence of drought stress in varying intensity has become a common phenomenon in the present era of global climate change, which not only causes severe yield losses but also challenges the cultivation of rice. This raises serious concerns for sustainable food production [...] Read more.

Recurrent occurrence of drought stress in varying intensity has become a common phenomenon in the present era of global climate change, which not only causes severe yield losses but also challenges the cultivation of rice. This raises serious concerns for sustainable food production and global food security. The root of a plant is primarily responsible to perceive drought stress and acquire sufficient water for the survival/optimal growth of the plant under extreme climatic conditions. Earlier studies reported the involvement/important roles of microRNAs (miRNAs) in plants’ responses to environmental/abiotic stresses. A number (738) of miRNAs is known to be expressed in different tissues under varying environmental conditions in rice, but our understanding of the role, mode of action, and target genes of the miRNAs are still elusive. Using contrasting rice [IR-64 (reproductive-stage drought sensitive) and N-22 (drought-tolerant)] cultivars, imposed with terminal (reproductive-stage) drought stress, we demonstrate differential expression of 270 known and 91 novel miRNAs in roots of the contrasting rice cultivars in response to the stress. Among the known miRNAs, osamiR812, osamiR166, osamiR156, osamiR167, and osamiR396 were the most differentially expressed miRNAs between the rice cultivars. In the root of N-22, 18 known and 12 novel miRNAs were observed to be exclusively expressed, while only two known (zero novels) miRNAs were exclusively expressed in the roots of IR-64. The majority of the target gene(s) of the miRNAs were drought-responsive transcription factors playing important roles in flower, grain development, auxin signaling, root development, and phytohormone-crosstalk. The novel miRNAs identified in this study may serve as good candidates for the genetic improvement of rice for terminal drought stress towards developing climate-smart rice for sustainable food production. Full article

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

► Show Figures

Figure 1

15 pages, 1172 KiB

Open AccessEditor’s ChoiceArticle

Expression Profiling of the Slow Rusting Resistance Genes Lr34/Yr18 and Lr67/Yr46 in Common Wheat (Triticum aestivum L.) and Associated miRNAs Patterns

by Julia Spychała, Agnieszka Tomkowiak, Aleksandra Noweiska, Roksana Bobrowska, Jan Bocianowski, Michał Książkiewicz, Aleksandra Sobiech and Michał Tomasz Kwiatek

Genes 2023, 14(7), 1376; https://doi.org/10.3390/genes14071376 - 29 Jun 2023

Cited by 10 | Viewed by 2775

Abstract

The main efforts in common wheat (Triticum aestivum L.) breeding focus on yield, grain quality, and resistance to biotic and abiotic stresses. One of the major threats affecting global wheat cultivation and causing significant crop production losses are rust diseases, including leaf [...] Read more.

The main efforts in common wheat (Triticum aestivum L.) breeding focus on yield, grain quality, and resistance to biotic and abiotic stresses. One of the major threats affecting global wheat cultivation and causing significant crop production losses are rust diseases, including leaf rust caused by a biotrophic fungus Puccinia triticina Eriks. Genetically determined resistance to leaf rust has been characterized in young plants (seedling resistance) as well as in plants at the adult plant stage. At the seedling stage, resistance is controlled vertically by major R genes, conferring a race-specific response that is highly effective but usually short-lived due to the rapid evolution of potentially virulent fungi. In mature plants, horizontal adult plant resistance (APR) was described, which provides long-term protection against multiple races of pathogens. A better understanding of molecular mechanisms underlying the function of APR genes would enable the development of new strategies for resistance breeding in wheat. Therefore, in the present study we focused on early transcriptomic responses of two major wheat APR genes, Lr34 and Lr67, and three complementary miRNAs, tae-miR9653b, tae-miR9773 and tae-miR9677b, to inoculation with P. triticina. Plant material consisted of five wheat reference varieties, Artigas, NP846, Glenlea, Lerma Rojo and TX89D6435, containing the Lr34/Yr18 and Lr67/Yr46 resistance genes. Biotic stress was induced by inoculation with fungal spores under controlled conditions in a phytotron. Plant material consisted of leaf tissue sampled before inoculation as well as 6, 12, 24 and 48 h postinoculation (hpi). The APR gene expression was quantified using real-time PCR with two reference genes, whereas miRNA was quantified using droplet digital PCR. This paper describes the resistance response of APR genes to inoculation with races of leaf rust-causing fungi that occur in central Europe. The study revealed high variability of expression profiles between varieties and time-points, with the prevalence of downregulation for APR genes and upregulation for miRNAs during the development of an early defense response. Nevertheless, despite the downregulation initially observed, the expression of Lr34 and Lr67 genes in studied cultivars was significantly higher than in a control line carrying wild (susceptible) alleles. Full article

(This article belongs to the Special Issue Genetic and Genomic Approaches for Breeding in Wheat)

► Show Figures

Figure 1

12 pages, 1195 KiB

Open AccessEditor’s ChoiceArticle

A Novel KCNN2 Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis

by Maria d’Apolito, Caterina Ceccarini, Rosa Savino, Iolanda Adipietro, Ighli di Bari, Rosa Santacroce, Maria Curcetti, Giovanna D’Andrea, Anna-Irma Croce, Carla Cesarano, Anna Nunzia Polito and Maurizio Margaglione

Genes 2023, 14(7), 1380; https://doi.org/10.3390/genes14071380 - 29 Jun 2023

Cited by 10 | Viewed by 2332

Abstract

Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the [...] Read more.

Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (KCNN2) (NM_021614.3: c.1145G>A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The KCNN2 gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Article

Further Information

Guidelines

MDPI Initiatives

Follow MDPI