Genes

19 pages, 2576 KiB

Open AccessEditor’s ChoiceArticle

Species-Specific Quality Control, Assembly and Contamination Detection in Microbial Isolate Sequences with AQUAMIS

by Carlus Deneke, Holger Brendebach, Laura Uelze, Maria Borowiak, Burkhard Malorny and Simon H. Tausch

Genes 2021, 12(5), 644; https://doi.org/10.3390/genes12050644 - 26 Apr 2021

Cited by 45 | Viewed by 4118

Abstract

Sequencing of whole microbial genomes has become a standard procedure for cluster detection, source tracking, outbreak investigation and surveillance of many microorganisms. An increasing number of laboratories are currently in a transition phase from classical methods towards next generation sequencing, generating unprecedented amounts [...] Read more.

Sequencing of whole microbial genomes has become a standard procedure for cluster detection, source tracking, outbreak investigation and surveillance of many microorganisms. An increasing number of laboratories are currently in a transition phase from classical methods towards next generation sequencing, generating unprecedented amounts of data. Since the precision of downstream analyses depends significantly on the quality of raw data generated on the sequencing instrument, a comprehensive, meaningful primary quality control is indispensable. Here, we present AQUAMIS, a Snakemake workflow for an extensive quality control and assembly of raw Illumina sequencing data, allowing laboratories to automatize the initial analysis of their microbial whole-genome sequencing data. AQUAMIS performs all steps of primary sequence analysis, consisting of read trimming, read quality control (QC), taxonomic classification, de-novo assembly, reference identification, assembly QC and contamination detection, both on the read and assembly level. The results are visualized in an interactive HTML report including species-specific QC thresholds, allowing non-bioinformaticians to assess the quality of sequencing experiments at a glance. All results are also available as a standard-compliant JSON file, facilitating easy downstream analyses and data exchange. We have applied AQUAMIS to analyze ~13,000 microbial isolates as well as ~1000 in-silico contaminated datasets, proving the workflow’s ability to perform in high throughput routine sequencing environments and reliably predict contaminations. We found that intergenus and intragenus contaminations can be detected most accurately using a combination of different QC metrics available within AQUAMIS. Full article

(This article belongs to the Special Issue Applied Genomics: Bridging the Gap between R&D and Practical Implementations within Clinical and Public Health Settings)

► Show Figures

Figure 1

30 pages, 2881 KiB

Open AccessEditor’s ChoiceReview

The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD

by Emmanuel D. Dixon, Alexander D. Nardo, Thierry Claudel and Michael Trauner

Genes 2021, 12(5), 645; https://doi.org/10.3390/genes12050645 - 26 Apr 2021

Cited by 43 | Viewed by 6572

Abstract

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation [...] Read more.

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and modulation of inflammatory genes. The activity of nuclear receptors is key in maintaining metabolic flexibility. Their activity depends on the availability of endogenous ligands, like fatty acids or oxysterols, and their derivatives produced by the catabolic action of metabolic lipases, most of which are under the control of nuclear receptors. For example, adipose triglyceride lipase (ATGL) is activated by peroxisome proliferator-activated receptor γ (PPARγ) and conversely releases fatty acids as ligands for PPARα, therefore, demonstrating the interdependency of nuclear receptors and lipases. The diverse biological functions and importance of nuclear receptors in metabolic syndrome and NAFLD has led to substantial effort to target them therapeutically. This review summarizes recent findings on the roles of lipases and selected nuclear receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD. Full article

(This article belongs to the Special Issue Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation)

► Show Figures

Figure 1

21 pages, 3045 KiB

Open AccessEditor’s ChoiceArticle

Down-Regulation of SlGRAS10 in Tomato Confers Abiotic Stress Tolerance

by Sidra Habib, Yee Yee Lwin and Ning Li

Genes 2021, 12(5), 623; https://doi.org/10.3390/genes12050623 - 22 Apr 2021

Cited by 25 | Viewed by 2557

Abstract

Adverse environmental factors like salt stress, drought, and extreme temperatures, cause damage to plant growth, development, and crop yield. GRAS transcription factors (TFs) have numerous functions in biological processes. Some studies have reported that the GRAS protein family plays significant functions in plant [...] Read more.

Adverse environmental factors like salt stress, drought, and extreme temperatures, cause damage to plant growth, development, and crop yield. GRAS transcription factors (TFs) have numerous functions in biological processes. Some studies have reported that the GRAS protein family plays significant functions in plant growth and development under abiotic stresses. In this study, we demonstrated the functional characterization of a tomato SlGRAS10 gene under abiotic stresses such as salt stress and drought. Down-regulation of SlGRAS10 by RNA interference (RNAi) produced dwarf plants with smaller leaves, internode lengths, and enhanced flavonoid accumulation. We studied the effects of abiotic stresses on RNAi and wild-type (WT) plants. Moreover, SlGRAS10-RNAi plants were more tolerant to abiotic stresses (salt, drought, and Abscisic acid) than the WT plants. Down-regulation of SlGRAS10 significantly enhanced the expressions of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) to reduce the effects of reactive oxygen species (ROS) such as O²⁻ and H₂O₂. Malondialdehyde (MDA) and proline contents were remarkably high in SlGRAS10-RNAi plants. Furthermore, the expression levels of chlorophyll biosynthesis, flavonoid biosynthesis, and stress-related genes were also enhanced under abiotic stress conditions. Collectively, our conclusions emphasized the significant function of SlGRAS10 as a stress tolerate transcription factor in a certain variety of abiotic stress tolerance by enhancing osmotic potential, flavonoid biosynthesis, and ROS scavenging system in the tomato plant. Full article

(This article belongs to the Special Issue Genetics and Physiology of Multiple-Stress Tolerance in Crops)

► Show Figures

Figure 1

21 pages, 1115 KiB

Open AccessEditor’s ChoiceReview

Achromobacter xylosoxidans and Stenotrophomonas maltophilia: Emerging Pathogens Well-Armed for Life in the Cystic Fibrosis Patients’ Lung

by Quentin Menetrey, Pauline Sorlin, Estelle Jumas-Bilak, Raphaël Chiron, Chloé Dupont and Hélène Marchandin

Genes 2021, 12(5), 610; https://doi.org/10.3390/genes12050610 - 21 Apr 2021

Cited by 42 | Viewed by 4971

Abstract

In patients with cystic fibrosis (CF), the lung is a remarkable ecological niche in which the microbiome is subjected to important selective pressures. An inexorable colonization by bacteria of both endogenous and environmental origin is observed in most patients, leading to a vicious [...] Read more.

In patients with cystic fibrosis (CF), the lung is a remarkable ecological niche in which the microbiome is subjected to important selective pressures. An inexorable colonization by bacteria of both endogenous and environmental origin is observed in most patients, leading to a vicious cycle of infection–inflammation. In this context, long-term colonization together with competitive interactions among bacteria can lead to over-inflammation. While Pseudomonas aeruginosa and Staphylococcus aureus, the two pathogens most frequently identified in CF, have been largely studied for adaptation to the CF lung, in the last few years, there has been a growing interest in emerging pathogens of environmental origin, namely Achromobacter xylosoxidans and Stenotrophomonas maltophilia. The aim of this review is to gather all the current knowledge on the major pathophysiological traits, their supporting mechanisms, regulation and evolutionary modifications involved in colonization, virulence, and competitive interactions with other members of the lung microbiota for these emerging pathogens, with all these mechanisms being major drivers of persistence in the CF lung. Currently available research on A. xylosoxidans complex and S. maltophilia shows that these emerging pathogens share important pathophysiological features with well-known CF pathogens, making them important members of the complex bacterial community living in the CF lung. Full article

(This article belongs to the Special Issue Phenotypic Variability of Cystic Fibrosis: New Challenges)

► Show Figures

Figure 1

15 pages, 1149 KiB

Open AccessEditor’s ChoiceCommunication

Protective Role of a TMPRSS2 Variant on Severe COVID-19 Outcome in Young Males and Elderly Women

by Maria Monticelli, Bruno Hay Mele, Elisa Benetti, Chiara Fallerini, Margherita Baldassarri, Simone Furini, Elisa Frullanti, Francesca Mari, GEN-COVID Multicenter Study, Giuseppina Andreotti, Maria Vittoria Cubellis and Alessandra Renieri

Genes 2021, 12(4), 596; https://doi.org/10.3390/genes12040596 - 19 Apr 2021

Cited by 42 | Viewed by 5758

Abstract

The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in [...] Read more.

The protease encoded by the TMPRSS2 gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the TMPRSS2 sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.01) and six missense variants which may affect the protease activity according to PolyPhen-2 in HumVar-trained mode were identified. Among them, p.V197M (p.Val197Met) (rs12329760) emerges as a common variant that has a deleterious effect on the protease and a protective effect on the patients. Its role appears particularly relevant in two subgroups of patients—young males and elderly women—and among those affected by co-morbidities, where the variant frequency is higher among individuals who were mildly affected by the disease and did not need hospitalization or oxygen therapy than among those more severely affected, who required oxygen therapy, ventilation or intubation. This study provides useful information for the identification of patients at risk of developing a severe form of COVID-19, and encourages the usage of drugs affecting the expression of TMPRSS2 or inhibiting protein activity. Full article

(This article belongs to the Special Issue COVID-19 and Molecular Genetics)

► Show Figures

Graphical abstract

21 pages, 1852 KiB

Open AccessEditor’s ChoiceReview

Inosine in Biology and Disease

by Sundaramoorthy Srinivasan, Adrian Gabriel Torres and Lluís Ribas de Pouplana

Genes 2021, 12(4), 600; https://doi.org/10.3390/genes12040600 - 19 Apr 2021

Cited by 51 | Viewed by 10364

Abstract

The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post-transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of [...] Read more.

The nucleoside inosine plays an important role in purine biosynthesis, gene translation, and modulation of the fate of RNAs. The editing of adenosine to inosine is a widespread post-transcriptional modification in transfer RNAs (tRNAs) and messenger RNAs (mRNAs). At the wobble position of tRNA anticodons, inosine profoundly modifies codon recognition, while in mRNA, inosines can modify the sequence of the translated polypeptide or modulate the stability, localization, and splicing of transcripts. Inosine is also found in non-coding and exogenous RNAs, where it plays key structural and functional roles. In addition, molecular inosine is an important secondary metabolite in purine metabolism that also acts as a molecular messenger in cell signaling pathways. Here, we review the functional roles of inosine in biology and their connections to human health. Full article

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

► Show Figures

Figure 1

16 pages, 9573 KiB

Open AccessEditor’s ChoiceReview

Growth Restriction and Genomic Imprinting-Overlapping Phenotypes Support the Concept of an Imprinting Network

by Thomas Eggermann, Justin H. Davies, Maithé Tauber, Erica van den Akker, Anita Hokken-Koelega, Gudmundur Johansson and Irène Netchine

Genes 2021, 12(4), 585; https://doi.org/10.3390/genes12040585 - 17 Apr 2021

Cited by 21 | Viewed by 5095

Abstract

Intrauterine and postnatal growth disturbances are major clinical features of imprinting disorders, a molecularly defined group of congenital syndromes caused by molecular alterations affecting parentally imprinted genes. These genes are expressed monoallelically and in a parent-of-origin manner, and they have an impact on [...] Read more.

Intrauterine and postnatal growth disturbances are major clinical features of imprinting disorders, a molecularly defined group of congenital syndromes caused by molecular alterations affecting parentally imprinted genes. These genes are expressed monoallelically and in a parent-of-origin manner, and they have an impact on human growth and development. In fact, several genes with an exclusive expression from the paternal allele have been shown to promote foetal growth, whereas maternally expressed genes suppress it. The evolution of this correlation might be explained by the different interests of the maternal and paternal genomes, aiming for the conservation of maternal resources for multiple offspring versus extracting maximal maternal resources. Since not all imprinted genes in higher mammals show the same imprinting pattern in different species, the findings from animal models are not always transferable to human. Therefore, human imprinting disorders might serve as models to understand the complex regulation and interaction of imprinted loci. This knowledge is a prerequisite for the development of precise diagnostic tools and therapeutic strategies for patients affected by imprinting disorders. In this review we will specifically overview the current knowledge on imprinting disorders associated with growth retardation, and its increasing relevance in a personalised medicine direction and the need for a multidisciplinary therapeutic approach. Full article

(This article belongs to the Special Issue Genomic Imprinting and the Regulation of Growth and Metabolism)

► Show Figures

Figure 1

15 pages, 3226 KiB

Open AccessEditor’s ChoiceArticle

Deciphering the Monilinia fructicola Genome to Discover Effector Genes Possibly Involved in Virulence

by Laura Vilanova, Claudio A. Valero-Jiménez and Jan A.L. van Kan

Genes 2021, 12(4), 568; https://doi.org/10.3390/genes12040568 - 14 Apr 2021

Cited by 22 | Viewed by 2750

Abstract

Brown rot is the most economically important fungal disease of stone fruits and is primarily caused by Monilinia laxa and Monlinia fructicola. Both species co-occur in European orchards although M. fructicola is considered to cause the most severe yield losses in stone [...] Read more.

Brown rot is the most economically important fungal disease of stone fruits and is primarily caused by Monilinia laxa and Monlinia fructicola. Both species co-occur in European orchards although M. fructicola is considered to cause the most severe yield losses in stone fruit. This study aimed to generate a high-quality genome of M. fructicola and to exploit it to identify genes that may contribute to pathogen virulence. PacBio sequencing technology was used to assemble the genome of M. fructicola. Manual structural curation of gene models, supported by RNA-Seq, and functional annotation of the proteome yielded 10,086 trustworthy gene models. The genome was examined for the presence of genes that encode secreted proteins and more specifically effector proteins. A set of 134 putative effectors was defined. Several effector genes were cloned into Agrobacterium tumefaciens for transient expression in Nicotiana benthamiana plants, and some of them triggered necrotic lesions. Studying effectors and their biological properties will help to better understand the interaction between M. fructicola and its stone fruit host plants. Full article

(This article belongs to the Special Issue Omics Research of Pathogenic Microorganisms)

► Show Figures

Figure 1

14 pages, 312 KiB

Open AccessEditor’s ChoiceArticle

Deepening of In Silico Evaluation of SARS-CoV-2 Detection RT-qPCR Assays in the Context of New Variants

by Mathieu Gand, Kevin Vanneste, Isabelle Thomas, Steven Van Gucht, Arnaud Capron, Philippe Herman, Nancy H. C. Roosens and Sigrid C. J. De Keersmaecker

Genes 2021, 12(4), 565; https://doi.org/10.3390/genes12040565 - 13 Apr 2021

Cited by 23 | Viewed by 3644

Abstract

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set [...] Read more.

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set of primers and probe. It is important to frequently evaluate the performance of these tests and this can be done first by an in silico approach. Previously, we reported some mismatches between the oligonucleotides of publicly available RT-qPCR assays and SARS-CoV-2 genomes collected from GISAID and NCBI, potentially impacting proper detection of the virus. In the present study, 11 primers and probe sets investigated during the first study were evaluated again with 84,305 new SARS-CoV-2 unique genomes collected between June 2020 and January 2021. The lower inclusivity of the China CDC assay targeting the gene N has continued to decrease with new mismatches detected, whereas the other evaluated assays kept their inclusivity above 99%. Additionally, some mutations specific to new SARS-CoV-2 variants of concern were found to be located in oligonucleotide annealing sites. This might impact the strategy to be considered for future SARS-CoV-2 testing. Given the potential threat of the new variants, it is crucial to assess if they can still be correctly targeted by the primers and probes of the RT-qPCR assays. Our study highlights that considering the evolution of the virus and the emergence of new variants, an in silico (re-)evaluation should be performed on a regular basis. Ideally, this should be done for all the RT-qPCR assays employed for SARS-CoV-2 detection, including also commercial tests, although the primer and probe sequences used in these kits are rarely disclosed, which impedes independent performance evaluation. Full article

(This article belongs to the Special Issue COVID-19 and Molecular Genetics)

15 pages, 682 KiB

Open AccessEditor’s ChoiceReview

Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine

by Afsoon Sepahzad, Deborah J. Morris-Rosendahl and Jane C. Davies

Genes 2021, 12(4), 562; https://doi.org/10.3390/genes12040562 - 13 Apr 2021

Cited by 21 | Viewed by 4519

Abstract

Our understanding of cystic fibrosis (CF) has grown exponentially since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989. With evolving genetic and genomic tools, we have come to better understand the role of CFTR genotypes in [...] Read more.

Our understanding of cystic fibrosis (CF) has grown exponentially since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989. With evolving genetic and genomic tools, we have come to better understand the role of CFTR genotypes in the pathophysiology of the disease. This, in turn, has paved the way for the development of modulator therapies targeted at mutations in the CFTR, which are arguably one of the greatest advances in the treatment of CF. These modulator therapies, however, do not target all the mutations in CFTR that are seen in patients with CF and, furthermore, a variation in response is seen in patients with the same genotype who are taking modulator therapies. There is growing evidence to support the role of non-CFTR modifiers, both genetic and environmental, in determining the variation seen in CF morbidity and mortality and also in the response to existing therapies. This review focusses on key findings from studies using candidate gene and genome-wide approaches to identify CF modifier genes of lung disease in cystic fibrosis and considers the interaction between modifiers and the response to modulator therapies. As the use of modulator therapies expands and we gain data around outcomes, it will be of great interest to investigate this interaction further. Going forward, it will also be crucial to better understand the relative influence of genomic versus environmental factors. With this understanding, we can truly begin to deliver personalised care by better profiling the likely disease phenotype for each patient and their response to treatment. Full article

(This article belongs to the Special Issue Phenotypic Variability of Cystic Fibrosis: New Challenges)

► Show Figures

Figure 1

21 pages, 6386 KiB

Open AccessEditor’s ChoiceArticle

OTUs and ASVs Produce Comparable Taxonomic and Diversity from Shrimp Microbiota 16S Profiles Using Tailored Abundance Filters

by Rodrigo García-López, Fernanda Cornejo-Granados, Alonso A. Lopez-Zavala, Andrés Cota-Huízar, Rogerio R. Sotelo-Mundo, Bruno Gómez-Gil and Adrian Ochoa-Leyva

Genes 2021, 12(4), 564; https://doi.org/10.3390/genes12040564 - 13 Apr 2021

Cited by 24 | Viewed by 6759

Abstract

The interplay between shrimp immune system, its environment, and microbiota contributes to the organism’s homeostasis and optimal production. The metagenomic composition is typically studied using 16S rDNA profiling by clustering amplicon sequences into operational taxonomic units (OTUs) and, more recently, amplicon sequence variants [...] Read more.

The interplay between shrimp immune system, its environment, and microbiota contributes to the organism’s homeostasis and optimal production. The metagenomic composition is typically studied using 16S rDNA profiling by clustering amplicon sequences into operational taxonomic units (OTUs) and, more recently, amplicon sequence variants (ASVs). Establish the compatibility of the taxonomy, α, and β diversity described by both methods is necessary to compare past and future shrimp microbiota studies. Here, we used identical sequences to survey the V3 16S hypervariable-region using 97% and 99% OTUs and ASVs to assess the hepatopancreas and intestine microbiota of L. vannamei from two ponds under standardized rearing conditions. We found that applying filters to retain clusters >0.1% of the total abundance per sample enabled a consistent taxonomy comparison while preserving >94% of the total reads. The three sets turned comparable at the family level, whereas the 97% identity OTU set produced divergent genus and species profiles. Interestingly, the detection of organ and pond variations was robust to the clustering method’s choice, producing comparable α and β-diversity profiles. For comparisons on shrimp microbiota between past and future studies, we strongly recommend that ASVs be compared at the family level to 97% identity OTUs or use 99% identity OTUs, both using tailored frequency filters. Full article

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

► Show Figures

Graphical abstract

17 pages, 3284 KiB

Open AccessEditor’s ChoiceArticle

Allelic Diversity at Abiotic Stress Responsive Genes in Relationship to Ecological Drought Indices for Cultivated Tepary Bean, Phaseolus acutifolius A. Gray, and Its Wild Relatives

by María A. Buitrago-Bitar, Andrés J. Cortés, Felipe López-Hernández, Jorge M. Londoño-Caicedo, Jaime E. Muñoz-Florez, L. Carmenza Muñoz and Matthew Wohlgemuth Blair

Genes 2021, 12(4), 556; https://doi.org/10.3390/genes12040556 - 12 Apr 2021

Cited by 36 | Viewed by 4546

Abstract

Some of the major impacts of climate change are expected in regions where drought stress is already an issue. Grain legumes are generally drought susceptible. However, tepary bean and its wild relatives within Phaseolus acutifolius or P. parvifolius are from arid areas between [...] Read more.

Some of the major impacts of climate change are expected in regions where drought stress is already an issue. Grain legumes are generally drought susceptible. However, tepary bean and its wild relatives within Phaseolus acutifolius or P. parvifolius are from arid areas between Mexico and the United States. Therefore, we hypothesize that these bean accessions have diversity signals indicative of adaptation to drought at key candidate genes such as: Asr2, Dreb2B, and ERECTA. By sequencing alleles of these genes and comparing to estimates of drought tolerance indices from climate data for the collection site of geo-referenced, tepary bean accessions, we determined the genotype x environmental association (GEA) of each gene. Diversity analysis found that cultivated and wild P. acutifolius were intermingled with var. tenuifolius and P. parvifolius, signifying that allele diversity was ample in the wild and cultivated clade over a broad sense (sensu lato) evaluation. Genes Dreb2B and ERECTA harbored signatures of directional selection, represented by six SNPs correlated with the environmental drought indices. This suggests that wild tepary bean is a reservoir of novel alleles at genes for drought tolerance, as expected for a species that originated in arid environments. Our study corroborated that candidate gene approach was effective for marker validation across a broad genetic base of wild tepary accessions. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Plant Crop-Wild Complexes: From Fundamental to Applied Research)

► Show Figures

Figure 1

16 pages, 312 KiB

Open AccessEditor’s ChoiceArticle

Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test

by Ana Arteche-López, Maria José Gómez Rodríguez, Maria Teresa Sánchez Calvin, Juan Francisco Quesada-Espinosa, Jose Miguel Lezana Rosales, Carmen Palma Milla, Irene Gómez-Manjón, Irene Hidalgo Mayoral, Rubén Pérez de la Fuente, Arancha Díaz de Bustamante, María Teresa Darnaude, Belén Gil-Fournier, Soraya Ramiro León, Patricia Ramos Gómez, Olalla Sierra Tomillo, Alexandra Juárez Rufián, Maria Isabel Arranz Cano, Rebeca Villares Alonso, Pablo Morales-Pérez, Alejandro Segura-Tudela, Ana Camacho, Noemí Nuñez, Rogelio Simón, Marta Moreno-García and Maria Isabel Alvarez-Mora Show full author list Hide full author list

Genes 2021, 12(4), 560; https://doi.org/10.3390/genes12040560 - 12 Apr 2021

Cited by 20 | Viewed by 4436

Abstract

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and [...] Read more.

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome. Full article

(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)

16 pages, 10042 KiB

Open AccessEditor’s ChoiceArticle

Kinetics and Topology of DNA Associated with Circulating Extracellular Vesicles Released during Exercise

by Elmo W. I. Neuberger, Barlo Hillen, Katharina Mayr, Perikles Simon, Eva-Maria Krämer-Albers and Alexandra Brahmer

Genes 2021, 12(4), 522; https://doi.org/10.3390/genes12040522 - 2 Apr 2021

Cited by 22 | Viewed by 3293

Abstract

Although it is widely accepted that cancer-derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed [...] Read more.

Although it is widely accepted that cancer-derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed to characterize the kinetics and localization of DNA associated with EVs. EVs were separated from human plasma using size exclusion chromatography or immuno-affinity capture for CD9⁺, CD63⁺, and CD81⁺ EVs. DNA was quantified with an ultra-sensitive qPCR assay targeting repetitive LINE elements, with or without DNase digestion. This model shows that a minute part of circulating cell-free DNA is associated with EVs. During rest and following exercise, only 0.12% of the total cfDNA occurs in association with CD9⁺/CD63⁺/CD81⁺EVs. DNase digestion experiments indicate that the largest part of EV associated DNA is sensitive to DNase digestion and only ~20% are protected within the lumen of the separated EVs. A single bout of running or cycling exercise increases the levels of EVs, cfDNA, and EV-associated DNA. While EV surface DNA is increasing, DNAse-resistant DNA remains at resting levels, indicating that EVs released during exercise (ExerVs) do not contain DNA. Consequently, DNA is largely associated with the outer surface of circulating EVs. ExerVs recruit cfDNA to their corona, but do not carry DNA in their lumen. Full article

(This article belongs to the Special Issue Nucleic Acids within Extracellular Vesicles: Functional Role in Health and Disease)

► Show Figures

Figure 1

8 pages, 1033 KiB

Open AccessEditor’s ChoiceCase Report

MCAT Mutations Cause Nuclear LHON-like Optic Neuropathy

by Sylvie Gerber, Christophe Orssaud, Josseline Kaplan, Catrine Johansson and Jean-Michel Rozet

Genes 2021, 12(4), 521; https://doi.org/10.3390/genes12040521 - 2 Apr 2021

Cited by 24 | Viewed by 2616

Abstract

Pathological variants in the nuclear malonyl-CoA-acyl carrier protein transacylase (MCAT) gene, which encodes a mitochondrial protein involved in fatty-acid biogenesis, have been reported in two siblings from China affected by insidious optic nerve degeneration in childhood, leading to blindness in the [...] Read more.

Pathological variants in the nuclear malonyl-CoA-acyl carrier protein transacylase (MCAT) gene, which encodes a mitochondrial protein involved in fatty-acid biogenesis, have been reported in two siblings from China affected by insidious optic nerve degeneration in childhood, leading to blindness in the first decade of life. After analysing 51 families with negative molecular diagnostic tests, from a cohort of 200 families with hereditary optic neuropathy (HON), we identified two novel MCAT mutations in a female patient who presented with acute, sudden, bilateral, yet asymmetric, central visual loss at the age of 20. This presentation is consistent with a Leber hereditary optic neuropathy (LHON)-like phenotype, whose existence and association with NDUFS2 and DNAJC30 has only recently been described. Our findings reveal a wider phenotypic presentation of MCAT mutations, and a greater genetic heterogeneity of nuclear LHON-like phenotypes. Although MCAT pathological variants are very uncommon, this gene should be investigated in HON patients, irrespective of disease presentation. Full article

(This article belongs to the Special Issue Genetics in Ophthalmology)

► Show Figures

Figure 1

14 pages, 312 KiB

Open AccessEditor’s ChoiceReview

Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review

by Ivonne Bedei, Aline Wolter, Axel Weber, Fabrizio Signore and Roland Axt-Fliedner

Genes 2021, 12(4), 501; https://doi.org/10.3390/genes12040501 - 29 Mar 2021

Cited by 34 | Viewed by 8347

Abstract

In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, [...] Read more.

In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, several advances have been made. First trimester screening, combining maternal age, maternal serum parameters and ultrasound findings, emerged in the 1990s with a detection rate (DR) of around 90–95% and a false positive rate (FPR) of around 5%, also looking for trisomy 13 and 18. With the development of high-resolution ultrasound, around 50% of fetal anomalies are now detected in the first trimester. Non-invasive prenatal testing (NIPT) for trisomy 21, 13 and 18 is a highly efficient screening method and has been applied as a first-line or a contingent screening approach all over the world since 2012, in some countries without a systematic screening program. Concomitant with the rise in technology, the possibility of screening for other genetic conditions by analysis of cfDNA, such as sex chromosome anomalies (SCAs), rare autosomal anomalies (RATs) and microdeletions and duplications, is offered by different providers to an often not preselected population of pregnant women. Most of the research in the field is done by commercial providers, and some of the tests are on the market without validated data on test performance. This raises difficulties in the counseling process and makes it nearly impossible to obtain informed consent. In parallel with the advent of new screening technologies, an expansion of diagnostic methods has begun to be applied after invasive procedures. The karyotype has been the gold standard for decades. Chromosomal microarrays (CMAs) able to detect deletions and duplications on a submicroscopic level have replaced the conventional karyotyping in many countries. Sequencing methods such as whole exome sequencing (WES) and whole genome sequencing (WGS) tremendously amplify the diagnostic yield in fetuses with ultrasound anomalies. Full article

(This article belongs to the Special Issue Genetic Research in Fetal Medicine)

25 pages, 8475 KiB

Open AccessEditor’s ChoiceReview

Whole-Body Regeneration in Sponges: Diversity, Fine Mechanisms, and Future Prospects

by Alexander Ereskovsky, Ilya E. Borisenko, Fyodor V. Bolshakov and Andrey I. Lavrov

Genes 2021, 12(4), 506; https://doi.org/10.3390/genes12040506 - 29 Mar 2021

Cited by 26 | Viewed by 5551

Abstract

While virtually all animals show certain abilities for regeneration after an injury, these abilities vary greatly among metazoans. Porifera (Sponges) is basal metazoans characterized by a wide variety of different regenerative processes, including whole-body regeneration (WBR). Considering phylogenetic position and unique body organization, [...] Read more.

While virtually all animals show certain abilities for regeneration after an injury, these abilities vary greatly among metazoans. Porifera (Sponges) is basal metazoans characterized by a wide variety of different regenerative processes, including whole-body regeneration (WBR). Considering phylogenetic position and unique body organization, sponges are highly promising models, as they can shed light on the origin and early evolution of regeneration in general and WBR in particular. The present review summarizes available data on the morphogenetic and cellular mechanisms accompanying different types of WBR in sponges. Sponges show a high diversity of WBR, which principally could be divided into (1) WBR from a body fragment and (2) WBR by aggregation of dissociated cells. Sponges belonging to different phylogenetic clades and even to different species and/or differing in the anatomical structure undergo different morphogeneses after similar operations. A common characteristic feature of WBR in sponges is the instability of the main body axis: a change of the organism polarity is described during all types of WBR. The cellular mechanisms of WBR are different across sponge classes, while cell dedifferentiations and transdifferentiations are involved in regeneration processes in all sponges. Data considering molecular regulation of WBR in sponges are extremely scarce. However, the possibility to achieve various types of WBR ensured by common morphogenetic and cellular basis in a single species makes sponges highly accessible for future comprehensive physiological, biochemical, and molecular studies of regeneration processes. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

► Show Figures

Graphical abstract

23 pages, 2745 KiB

Open AccessEditor’s ChoiceReview

Diverse Regulation but Conserved Function: SOX9 in Vertebrate Sex Determination

by Brittany Vining, Zhenhua Ming, Stefan Bagheri-Fam and Vincent Harley

Genes 2021, 12(4), 486; https://doi.org/10.3390/genes12040486 - 26 Mar 2021

Cited by 29 | Viewed by 7747

Abstract

Sex determination occurs early during embryogenesis among vertebrates. It involves the differentiation of the bipotential gonad to ovaries or testes by a fascinating diversity of molecular switches. In most mammals, the switch is SRY (sex determining region Y); in other vertebrates it could [...] Read more.

Sex determination occurs early during embryogenesis among vertebrates. It involves the differentiation of the bipotential gonad to ovaries or testes by a fascinating diversity of molecular switches. In most mammals, the switch is SRY (sex determining region Y); in other vertebrates it could be one of a variety of genes including Dmrt1 or dmy. Downstream of the switch gene, SOX9 upregulation is a central event in testes development, controlled by gonad-specific enhancers across the 2 Mb SOX9 locus. SOX9 is a ‘hub’ gene of gonadal development, regulated positively in males and negatively in females. Despite this diversity, SOX9 protein sequence and function among vertebrates remains highly conserved. This article explores the cellular, morphological, and genetic mechanisms initiated by SOX9 for male gonad differentiation. Full article

(This article belongs to the Special Issue Evolution and Development of Testis)

► Show Figures

Figure 1

17 pages, 2263 KiB

Open AccessEditor’s ChoiceReview

The Diversity and Evolution of Sex Chromosomes in Frogs

by Wen-Juan Ma and Paris Veltsos

Genes 2021, 12(4), 483; https://doi.org/10.3390/genes12040483 - 26 Mar 2021

Cited by 26 | Viewed by 6281

Abstract

Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between [...] Read more.

Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between homomorphic and heteromorphic states, as well as between sex-determination systems. Most (~75%) anurans have homomorphic sex chromosomes, with XY systems being three times more common than ZW systems. Most remaining anurans (~25%) have heteromorphic sex chromosomes, with XY and ZW systems almost equally represented. There are Y-autosome fusions in 11 species, and no W-/Z-/X-autosome fusions are known. The phylogeny represents at least 19 transitions between sex-determination systems and at least 16 cases of independent evolution of heteromorphic sex chromosomes from homomorphy, the likely ancestral state. Five lineages mostly have heteromorphic sex chromosomes, which might have evolved due to demographic and sexual selection attributes of those lineages. Males do not recombine over most of their genome, regardless of which is the heterogametic sex. Nevertheless, telomere-restricted recombination between ZW chromosomes has evolved at least once. More comparative genomic studies are needed to understand the evolutionary trajectories of sex chromosomes among frog lineages, especially in the ZW systems. Full article

(This article belongs to the Special Issue Vertebrate Karyotype Evolution: How Far Have We Come, and Where Are We Going?)

► Show Figures

Figure 1

33 pages, 854 KiB

Open AccessEditor’s ChoiceReview

Kabuki Syndrome—Clinical Review with Molecular Aspects

by Snir Boniel, Krystyna Szymańska, Robert Śmigiel and Krzysztof Szczałuba

Genes 2021, 12(4), 468; https://doi.org/10.3390/genes12040468 - 25 Mar 2021

Cited by 47 | Viewed by 18127

Abstract

Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large [...] Read more.

Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in KMT2D or KDM6A. Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals. Full article

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

► Show Figures

Figure 1

21 pages, 3869 KiB

Open AccessEditor’s ChoiceArticle

Regulation of DNA (de)Methylation Positively Impacts Seed Germination during Seed Development under Heat Stress

by Jaiana Malabarba, David Windels, Wenjia Xu and Jerome Verdier

Genes 2021, 12(3), 457; https://doi.org/10.3390/genes12030457 - 23 Mar 2021

Cited by 22 | Viewed by 4754

Abstract

Seed development needs the coordination of multiple molecular mechanisms to promote correct tissue development, seed filling, and the acquisition of germination capacity, desiccation tolerance, longevity, and dormancy. Heat stress can negatively impact these processes and upon the increase of global mean temperatures, global [...] Read more.

Seed development needs the coordination of multiple molecular mechanisms to promote correct tissue development, seed filling, and the acquisition of germination capacity, desiccation tolerance, longevity, and dormancy. Heat stress can negatively impact these processes and upon the increase of global mean temperatures, global food security is threatened. Here, we explored the impact of heat stress on seed physiology, morphology, gene expression, and methylation on three stages of seed development. Notably, Arabidopsis Col-0 plants under heat stress presented a decrease in germination capacity as well as a decrease in longevity. We observed that upon mild stress, gene expression and DNA methylation were moderately affected. Nevertheless, upon severe heat stress during seed development, gene expression was intensively modified, promoting heat stress response mechanisms including the activation of the ABA pathway. By analyzing candidate epigenetic markers using the mutants’ physiological assays, we observed that the lack of DNA demethylation by the ROS1 gene impaired seed germination by affecting germination-related gene expression. On the other hand, we also observed that upon severe stress, a large proportion of differentially methylated regions (DMRs) were located in the promoters and gene sequences of germination-related genes. To conclude, our results indicate that DNA (de)methylation could be a key regulatory process to ensure proper seed germination of seeds produced under heat stress. Full article

(This article belongs to the Special Issue Seeds and Epigenetics)

► Show Figures

Graphical abstract

24 pages, 1008 KiB

Open AccessEditor’s ChoiceReview

Decipher the Glioblastoma Microenvironment: The First Milestone for New Groundbreaking Therapeutic Strategies

by Giuseppe Nicolò Fanelli, Dario Grassini, Valerio Ortenzi, Francesco Pasqualetti, Nicola Montemurro, Paolo Perrini, Antonio Giuseppe Naccarato and Cristian Scatena

Genes 2021, 12(3), 445; https://doi.org/10.3390/genes12030445 - 20 Mar 2021

Cited by 67 | Viewed by 6079

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists [...] Read more.

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM’s microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM’s tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells’ immune-mediated destruction. Though literature data suggest that distinct GBM’s subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM’s microenvironment may lead to novel therapeutic opportunities to improve patients’ outcomes. This review will elucidate the GBM’s microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Solid Tumors)

► Show Figures

Figure 1

16 pages, 1546 KiB

Open AccessEditor’s ChoiceReview

The PARP Way to Epigenetic Changes

by Simone Ummarino, Clinton Hausman and Annalisa Di Ruscio

Genes 2021, 12(3), 446; https://doi.org/10.3390/genes12030446 - 20 Mar 2021

Cited by 24 | Viewed by 4565

Abstract

ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes that catalyze the addition of ADP ribose units from “nicotinamide adenine dinucleotide-donor molecules” to their target substrates. This reaction known as PARylation modulates essential cellular [...] Read more.

ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes that catalyze the addition of ADP ribose units from “nicotinamide adenine dinucleotide-donor molecules” to their target substrates. This reaction known as PARylation modulates essential cellular processes including DNA damage response, chromatin remodeling, DNA methylation and gene expression. Herein, we discuss emerging roles of PARP1 in chromatin remodeling and epigenetic regulation, focusing on its therapeutic implications for cancer treatment and beyond. Full article

(This article belongs to the Special Issue Advances in Tumor Epigenetics Research)

► Show Figures

Figure 1

29 pages, 3524 KiB

Open AccessEditor’s ChoiceReview

Molecular Regulation of Lipogenesis, Adipogenesis and Fat Deposition in Chicken

by Sara Nematbakhsh, Chong Pei Pei, Jinap Selamat, Noordiana Nordin, Lokman Hakim Idris and Ahmad Faizal Abdull Razis

Genes 2021, 12(3), 414; https://doi.org/10.3390/genes12030414 - 13 Mar 2021

Cited by 48 | Viewed by 6641

Abstract

In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer’s health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic [...] Read more.

In the poultry industry, excessive fat deposition is considered an undesirable factor, affecting feed efficiency, meat production cost, meat quality, and consumer’s health. Efforts to reduce fat deposition in economically important animals, such as chicken, can be made through different strategies; including genetic selection, feeding strategies, housing, and environmental strategies, as well as hormone supplementation. Recent investigations at the molecular level have revealed the significant role of the transcriptional and post-transcriptional regulatory networks and their interaction on modulating fat metabolism in chickens. At the transcriptional level, different transcription factors are known to regulate the expression of lipogenic and adipogenic genes through various signaling pathways, affecting chicken fat metabolism. Alternatively, at the post-transcriptional level, the regulatory mechanism of microRNAs (miRNAs) on lipid metabolism and deposition has added a promising dimension to understand the structural and functional regulatory mechanism of lipid metabolism in chicken. Therefore, this review focuses on the progress made in unraveling the molecular function of genes, transcription factors, and more notably significant miRNAs responsible for regulating adipogenesis, lipogenesis, and fat deposition in chicken. Moreover, a better understanding of the molecular regulation of lipid metabolism will give researchers novel insights to use functional molecular markers, such as miRNAs, for selection against excessive fat deposition to improve chicken production efficiency and meat quality. Full article

(This article belongs to the Special Issue Poultry Genetics, Breeding and Biotechnology)

► Show Figures

Figure 1

11 pages, 1976 KiB

Open AccessEditor’s ChoiceCommentary

Optical Genome Mapping as a Next-Generation Cytogenomic Tool for Detection of Structural and Copy Number Variations for Prenatal Genomic Analyses

by Nikhil Shri Sahajpal, Hayk Barseghyan, Ravindra Kolhe, Alex Hastie and Alka Chaubey

Genes 2021, 12(3), 398; https://doi.org/10.3390/genes12030398 - 11 Mar 2021

Cited by 57 | Viewed by 18728

Abstract

Global medical associations (ACOG, ISUOG, ACMG) recommend diagnostic prenatal testing for the detection and prevention of genetic disorders. Historically, cytogenetic methods such as karyotype analysis, fluorescent in situ hybridization (FISH) and chromosomal microarray (CMA) are utilized worldwide to diagnose common syndromes. However, the [...] Read more.

Global medical associations (ACOG, ISUOG, ACMG) recommend diagnostic prenatal testing for the detection and prevention of genetic disorders. Historically, cytogenetic methods such as karyotype analysis, fluorescent in situ hybridization (FISH) and chromosomal microarray (CMA) are utilized worldwide to diagnose common syndromes. However, the limitations of each of these methods, either performed in tandem or simultaneously, demonstrates the need of a revolutionary technology that can alleviate the need for multiple technologies. Optical genome mapping (OGM) is a novel method that fills this void by being able to detect all classes of structural variations (SVs), including copy number variations (CNVs). OGM is being adopted by laboratories as a tool for both postnatal constitutional genetic disorders and hematological malignancies. This commentary highlights the potential for OGM to become a standard of care in prenatal genetic testing based on its capability to comprehensively identify large balanced and unbalanced SVs (currently the strength of karyotyping and metaphase FISH), CNVs (by CMA), repeat contraction disorders (by Southern blotting) and multiple repeat expansion disorders (by PCR-based methods or Southern blotting). Next-generation sequencing (NGS) methods are excellent at detecting sequence variants, but they are unable to accurately resolve repeat regions of the genome, which limits their ability to detect all classes of SVs. Notably, multiple molecular methods are used to identify repeat expansion and contraction disorders in routine clinical laboratories around the world. With non-invasive prenatal testing (NIPT) becoming the standard of care screening assay for all global pregnancies, we anticipate that OGM can provide a high-resolution, cytogenomic assay to be employed following a positive NIPT screen or for high-risk pregnancies with an abnormal ultrasound. Accurate detection of all types of genetic disorders by OGM, such as liveborn aneuploidies, sex chromosome anomalies, microdeletion/microduplication syndromes, repeat expansion/contraction disorders is key to reducing the global burden of genetic disorders. Full article

(This article belongs to the Special Issue Advances in Prenatal Genetic Screening and Diagnosis Technologies)

► Show Figures

Figure 1

14 pages, 1461 KiB

Open AccessEditor’s ChoiceArticle

Maternal Vitamin and Mineral Supplementation and Rate of Maternal Weight Gain Affects Placental Expression of Energy Metabolism and Transport-Related Genes

by Wellison J. S. Diniz, Lawrence P. Reynolds, Pawel P. Borowicz, Alison K. Ward, Kevin K. Sedivec, Kacie L. McCarthy, Cierrah J. Kassetas, Friederike Baumgaertner, James D. Kirsch, Sheri T. Dorsam, Tammi L. Neville, J. Chris Forcherio, Ronald R. Scott, Joel S. Caton and Carl R. Dahlen

Genes 2021, 12(3), 385; https://doi.org/10.3390/genes12030385 - 9 Mar 2021

Cited by 25 | Viewed by 3105

Abstract

Maternal nutrients are essential for proper fetal and placental development and function. However, the effects of vitamin and mineral supplementation under two rates of maternal weight gain on placental genome-wide gene expression have not been investigated so far. Furthermore, biological processes and pathways [...] Read more.

Maternal nutrients are essential for proper fetal and placental development and function. However, the effects of vitamin and mineral supplementation under two rates of maternal weight gain on placental genome-wide gene expression have not been investigated so far. Furthermore, biological processes and pathways in the placenta that act in response to early maternal nutrition are yet to be elucidated. Herein, we examined the impact of maternal vitamin and mineral supplementation (from pre-breeding to day 83 post-breeding) and two rates of gain during the first 83 days of pregnancy on the gene expression of placental caruncles (CAR; maternal placenta) and cotyledons (COT; fetal placenta) of crossbred Angus beef heifers. We identified 267 unique differentially expressed genes (DEG). Among the DEGs from CAR, we identified ACAT2, SREBF2, and HMGCCS1 that underlie the cholesterol biosynthesis pathway. Furthermore, the transcription factors PAX2 and PAX8 were over-represented in biological processes related to kidney organogenesis. The DEGs from COT included SLC2A1, SLC2A3, SLC27A4, and INSIG1. Our over-representation analysis retrieved biological processes related to nutrient transport and ion homeostasis, whereas the pathways included insulin secretion, PPAR signaling, and biosynthesis of amino acids. Vitamin and mineral supplementation and rate of gain were associated with changes in gene expression, biological processes, and KEGG pathways in beef cattle placental tissues. Full article

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

► Show Figures

Figure 1

32 pages, 1466 KiB

Open AccessEditor’s ChoiceReview

The Role of Epigenetics in Congenital Heart Disease

by Tingsen Benson Lim, Sik Yin Roger Foo and Ching Kit Chen

Genes 2021, 12(3), 390; https://doi.org/10.3390/genes12030390 - 9 Mar 2021

Cited by 28 | Viewed by 9511

Abstract

Congenital heart disease (CHD) is the most common birth defect among newborns worldwide and contributes to significant infant morbidity and mortality. Owing to major advances in medical and surgical management, as well as improved prenatal diagnosis, the outcomes for these children with CHD [...] Read more.

Congenital heart disease (CHD) is the most common birth defect among newborns worldwide and contributes to significant infant morbidity and mortality. Owing to major advances in medical and surgical management, as well as improved prenatal diagnosis, the outcomes for these children with CHD have improved tremendously so much so that there are now more adults living with CHD than children. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. For this reason, the complex process of cardiogenesis, which is governed by multiple interlinked and dose-dependent pathways, is a well investigated process. In addition to the sequence of the genome, the contribution of epigenetics to cardiogenesis is increasingly recognized. Significant progress has been made dissecting the epigenome of the heart and identified associations with cardiovascular diseases. The role of epigenetic regulation in cardiac development/cardiogenesis, using tissue and animal models, has been well reviewed. Here, we curate the current literature based on studies in humans, which have revealed associated and/or causative epigenetic factors implicated in CHD. We sought to summarize the current knowledge on the functional role of epigenetics in cardiogenesis as well as in distinct CHDs, with an aim to provide scientists and clinicians an overview of the abnormal cardiogenic pathways affected by epigenetic mechanisms, for a better understanding of their impact on the developing fetal heart, particularly for readers interested in CHD research. Full article

(This article belongs to the Special Issue Advances in Prenatal Genetic Screening and Diagnosis Technologies)

► Show Figures

Figure 1

14 pages, 1814 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome Sequencing in the Evaluation of Fetal Structural Anomalies: A Parallel Test with Chromosomal Microarray Plus Whole Exome Sequencing

by Jia Zhou, Ziying Yang, Jun Sun, Lipei Liu, Xinyao Zhou, Fengxia Liu, Ya Xing, Shuge Cui, Shiyi Xiong, Xiaoyu Liu, Yingjun Yang, Xiuxiu Wei, Gang Zou, Zhonghua Wang, Xing Wei, Yaoshen Wang, Yun Zhang, Saiying Yan, Fengyu Wu, Fanwei Zeng, Jian Wang, Tao Duan, Zhiyu Peng and Luming Sun Show full author list Hide full author list

Genes 2021, 12(3), 376; https://doi.org/10.3390/genes12030376 - 6 Mar 2021

Cited by 37 | Viewed by 4982

Abstract

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome [...] Read more.

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies. Full article

(This article belongs to the Special Issue Advances in Prenatal Genetic Screening and Diagnosis Technologies)

► Show Figures

Figure 1

22 pages, 1000 KiB

Open AccessEditor’s ChoiceReview

Circadian Clock Components Offer Targets for Crop Domestication and Improvement

by C. Robertson McClung

Genes 2021, 12(3), 374; https://doi.org/10.3390/genes12030374 - 6 Mar 2021

Cited by 24 | Viewed by 4372

Abstract

During plant domestication and improvement, farmers select for alleles present in wild species that improve performance in new selective environments associated with cultivation and use. The selected alleles become enriched and other alleles depleted in elite cultivars. One important aspect of crop improvement [...] Read more.

During plant domestication and improvement, farmers select for alleles present in wild species that improve performance in new selective environments associated with cultivation and use. The selected alleles become enriched and other alleles depleted in elite cultivars. One important aspect of crop improvement is expansion of the geographic area suitable for cultivation; this frequently includes growth at higher or lower latitudes, requiring the plant to adapt to novel photoperiodic environments. Many crops exhibit photoperiodic control of flowering and altered photoperiodic sensitivity is commonly required for optimal performance at novel latitudes. Alleles of a number of circadian clock genes have been selected for their effects on photoperiodic flowering in multiple crops. The circadian clock coordinates many additional aspects of plant growth, metabolism and physiology, including responses to abiotic and biotic stresses. Many of these clock-regulated processes contribute to plant performance. Examples of selection for altered clock function in tomato demonstrate that with domestication, the phasing of the clock is delayed with respect to the light–dark cycle and the period is lengthened; this modified clock is associated with increased chlorophyll content in long days. These and other data suggest the circadian clock is an attractive target during breeding for crop improvement. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Circadian Clock Function in Plants)

► Show Figures

Figure 1

17 pages, 366 KiB

Open AccessEditor’s ChoiceReview

Ophthalmologic Manifestations of Primary Sjögren’s Syndrome

by Anna Maria Roszkowska, Giovanni William Oliverio, Emanuela Aragona, Leandro Inferrera, Alice Antonella Severo, Federica Alessandrello, Rosaria Spinella, Elisa Imelde Postorino and Pasquale Aragona

Genes 2021, 12(3), 365; https://doi.org/10.3390/genes12030365 - 4 Mar 2021

Cited by 25 | Viewed by 3527

Abstract

Sjögren’s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with [...] Read more.

Sjögren’s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics. Full article

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

20 pages, 772 KiB

Open AccessEditor’s ChoiceReview

Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

by Ivana Martins, Ilda Patrícia Ribeiro, Joana Jorge, Ana Cristina Gonçalves, Ana Bela Sarmento-Ribeiro, Joana Barbosa Melo and Isabel Marques Carreira

Genes 2021, 12(3), 349; https://doi.org/10.3390/genes12030349 - 27 Feb 2021

Cited by 90 | Viewed by 6966

Abstract

The minimally—or non-invasive detection of circulating tumor-derived components in biofluids, such as blood, liquid biopsy is a revolutionary approach with significant potential for the management of cancer. Genomic and transcriptomic alterations can be accurately detected through liquid biopsies, which provide a more comprehensive [...] Read more.

The minimally—or non-invasive detection of circulating tumor-derived components in biofluids, such as blood, liquid biopsy is a revolutionary approach with significant potential for the management of cancer. Genomic and transcriptomic alterations can be accurately detected through liquid biopsies, which provide a more comprehensive characterization of the heterogeneous tumor profile than tissue biopsies alone. Liquid biopsies could assist diagnosis, prognosis, and treatment selection, and hold great potential to complement current surveilling strategies to monitor disease evolution and treatment response in real-time. In particular, these are able to detect minimal residual disease, to predict progression, and to identify mechanisms of resistance, allowing to re-orient treatment strategies in a timelier manner. In this review we gathered current knowledge regarding the role and potential of liquid biopsies for the diagnosis and follow-up of cancer patients. The presented findings emphasize the strengths of liquid biopsies, revealing their chance of improving the diagnosis and monitoring of several tumor types in the near future. However, despite growing evidence supporting their value as a management tool in oncology, some limitations still need to be overcome for their implementation in the routine clinical setting. Full article

(This article belongs to the Special Issue Application of Genomic Technology in Disease Outcome Prediction)

► Show Figures

Figure 1

20 pages, 421 KiB

Open AccessEditor’s ChoicePerspective

The Regulation of RNA Modification Systems: The Next Frontier in Epitranscriptomics?

by Matthias R. Schaefer

Genes 2021, 12(3), 345; https://doi.org/10.3390/genes12030345 - 26 Feb 2021

Cited by 24 | Viewed by 3874

Abstract

RNA modifications, long considered to be molecular curiosities embellishing just abundant and non-coding RNAs, have now moved into the focus of both academic and applied research. Dedicated research efforts (epitranscriptomics) aim at deciphering the underlying principles by determining RNA modification landscapes and investigating [...] Read more.

RNA modifications, long considered to be molecular curiosities embellishing just abundant and non-coding RNAs, have now moved into the focus of both academic and applied research. Dedicated research efforts (epitranscriptomics) aim at deciphering the underlying principles by determining RNA modification landscapes and investigating the molecular mechanisms that establish, interpret and modulate the information potential of RNA beyond the combination of four canonical nucleotides. This has resulted in mapping various epitranscriptomes at high resolution and in cataloguing the effects caused by aberrant RNA modification circuitry. While the scope of the obtained insights has been complex and exciting, most of current epitranscriptomics appears to be stuck in the process of producing data, with very few efforts to disentangle cause from consequence when studying a specific RNA modification system. This article discusses various knowledge gaps in this field with the aim to raise one specific question: how are the enzymes regulated that dynamically install and modify RNA modifications? Furthermore, various technologies will be highlighted whose development and use might allow identifying specific and context-dependent regulators of epitranscriptomic mechanisms. Given the complexity of individual epitranscriptomes, determining their regulatory principles will become crucially important, especially when aiming at modifying specific aspects of an epitranscriptome both for experimental and, potentially, therapeutic purposes. Full article

(This article belongs to the Special Issue Functions and Dynamics of RNA Modifications)

18 pages, 11313 KiB

Open AccessEditor’s ChoiceArticle

Complete Mitochondrial DNA Genome of Nine Species of Sharks and Rays and Their Phylogenetic Placement among Modern Elasmobranchs

by Vasiliki Kousteni, Sofia Mazzoleni, Katerina Vasileiadou and Michail Rovatsos

Genes 2021, 12(3), 324; https://doi.org/10.3390/genes12030324 - 24 Feb 2021

Cited by 34 | Viewed by 5655

Abstract

Chondrichthyes occupy a key position in the phylogeny of vertebrates. The complete sequence of the mitochondrial genome (mitogenome) of four species of sharks and five species of rays was obtained by whole genome sequencing (DNA-seq) in the Illumina HiSeq2500 platform. The arrangement and [...] Read more.

Chondrichthyes occupy a key position in the phylogeny of vertebrates. The complete sequence of the mitochondrial genome (mitogenome) of four species of sharks and five species of rays was obtained by whole genome sequencing (DNA-seq) in the Illumina HiSeq2500 platform. The arrangement and features of the genes in the assembled mitogenomes were identical to those found in vertebrates. Both Maximum Likelihood (ML) and Bayesian Inference (BI) analyses were used to reconstruct the phylogenetic relationships among 172 species (including 163 mitogenomes retrieved from GenBank) based on the concatenated dataset of 13 individual protein coding genes. Both ML and BI analyses did not support the “Hypnosqualea” hypothesis and confirmed the monophyly of sharks and rays. The broad notion in shark phylogeny, namely the division of sharks into Galeomorphii and Squalomorphii and the monophyly of the eight shark orders, was also supported. The phylogenetic placement of all nine species sequenced in this study produced high statistical support values. The present study expands our knowledge on the systematics, genetic differentiation, and conservation genetics of the species studied, and contributes to our understanding of the evolutionary history of Chondrichthyes. Full article

(This article belongs to the Special Issue Molecular Evolution of the Mitochondrial DNA in Animals)

► Show Figures

Figure 1

19 pages, 1076 KiB

Open AccessEditor’s ChoiceReview

Post-Translational Mechanisms of Plant Circadian Regulation

by Jiapei Yan, Yeon Jeong Kim and David E. Somers

Genes 2021, 12(3), 325; https://doi.org/10.3390/genes12030325 - 24 Feb 2021

Cited by 24 | Viewed by 4195

Abstract

The molecular components of the circadian system possess the interesting feature of acting together to create a self-sustaining oscillator, while at the same time acting individually, and in complexes, to confer phase-specific circadian control over a wide range of physiological and developmental outputs. [...] Read more.

The molecular components of the circadian system possess the interesting feature of acting together to create a self-sustaining oscillator, while at the same time acting individually, and in complexes, to confer phase-specific circadian control over a wide range of physiological and developmental outputs. This means that many circadian oscillator proteins are simultaneously also part of the circadian output pathway. Most studies have focused on transcriptional control of circadian rhythms, but work in plants and metazoans has shown the importance of post-transcriptional and post-translational processes within the circadian system. Here we highlight recent work describing post-translational mechanisms that impact both the function of the oscillator and the clock-controlled outputs. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Circadian Clock Function in Plants)

► Show Figures

Figure 1

25 pages, 9434 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis, Characterization and Evolutionary Study of Dirigent Gene Family in Cucurbitaceae and Expression of Novel Dirigent Peptide against Powdery Mildew Stress

by Vivek Yadav, Zhongyuan Wang, Xiaozhen Yang, Chunhua Wei, Xuan Changqing and Xian Zhang

Genes 2021, 12(3), 326; https://doi.org/10.3390/genes12030326 - 24 Feb 2021

Cited by 17 | Viewed by 2870

Abstract

Dirigent (DIR) proteins are induced under various stress conditions and involved in sterio- and regio-selective coupling of monolignol. A striking lack of information about dirigent genes in cucurbitaceae plants underscores the importance of functional characterization. In this study, 112 DIR genes were identified [...] Read more.

Dirigent (DIR) proteins are induced under various stress conditions and involved in sterio- and regio-selective coupling of monolignol. A striking lack of information about dirigent genes in cucurbitaceae plants underscores the importance of functional characterization. In this study, 112 DIR genes were identified in six species, and 61 genes from major cultivated species were analyzed. DIRs were analyzed using various bioinformatics tools and complemented by expression profiling. Phylogenetic analysis segregated the putative DIRs into six distinctively known subgroups. Chromosomal mapping revealed uneven distribution of genes, whereas synteny analysis exhibited that duplication events occurred during gene evolution. Gene structure analysis suggested the gain of introns during gene diversification. Gene ontology (GO) enrichment analysis indicates the participation of proteins in lignification and pathogen resistance activities. We also determined their organ-specific expression levels in three species revealing preferential expression in root and leaves. Furthermore, the number of CmDIR (CmDIR1, 6, 7 and 12) and ClDIR (ClDIR2, 5, 8, 9 and 17) genes exhibited higher expression in resistant cultivars after powdery mildew (PM) inoculation. In summary, based on the expression and in-silico analysis, we propose a role of DIRs in disease resistance mechanisms. Full article

(This article belongs to the Special Issue Powdery Mildew Resistance Genetics)

► Show Figures

Figure 1

16 pages, 1550 KiB

Open AccessEditor’s ChoiceReview

Sex Determination and Differentiation in Decapod and Cladoceran Crustaceans: An Overview of Endocrine Regulation

by Kenji Toyota, Hitoshi Miyakawa, Chizue Hiruta, Tomomi Sato, Hidekazu Katayama, Tsuyoshi Ohira and Taisen Iguchi

Genes 2021, 12(2), 305; https://doi.org/10.3390/genes12020305 - 21 Feb 2021

Cited by 30 | Viewed by 5434

Abstract

Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are [...] Read more.

Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are particularly diverse among the Arthropoda and contain a wide variety of commercially important fishery species such as shrimps, lobsters and crabs (Order Decapoda), and keystone species of aquatic ecosystems such as water fleas (Order Branchiopoda). In terms of decapod sex determination and differentiation, previous approaches have attempted to elucidate their molecular components, to establish mono-sex breeding technology. Here, we overview reports describing the physiological functions of sex hormones regulating masculinization and feminization, and gene discovery by transcriptomics in decapod species. Moreover, this review summarizes the recent progresses of studies on the juvenile hormone-driven sex determination system of the branchiopod genus Daphnia, and then compares sex determination and endocrine systems between decapods and branchiopods. This review provides not only substantial insights for aquaculture research, but also the opportunity to re-organize the current and future trends of this field. Full article

(This article belongs to the Special Issue The Evolution of Sexual Development in Arthropods)

► Show Figures

Figure 1

20 pages, 1678 KiB

Open AccessEditor’s ChoiceReview

Analysis of RNA Modifications by Second- and Third-Generation Deep Sequencing: 2020 Update

by Yuri Motorin and Virginie Marchand

Genes 2021, 12(2), 278; https://doi.org/10.3390/genes12020278 - 16 Feb 2021

Cited by 37 | Viewed by 6279

Abstract

The precise mapping and quantification of the numerous RNA modifications that are present in tRNAs, rRNAs, ncRNAs/miRNAs, and mRNAs remain a major challenge and a top priority of the epitranscriptomics field. After the keystone discoveries of massive m⁶A methylation in mRNAs, [...] Read more.

The precise mapping and quantification of the numerous RNA modifications that are present in tRNAs, rRNAs, ncRNAs/miRNAs, and mRNAs remain a major challenge and a top priority of the epitranscriptomics field. After the keystone discoveries of massive m⁶A methylation in mRNAs, dozens of deep sequencing-based methods and protocols were proposed for the analysis of various RNA modifications, allowing us to considerably extend the list of detectable modified residues. Many of the currently used methods rely on the particular reverse transcription signatures left by RNA modifications in cDNA; these signatures may be naturally present or induced by an appropriate enzymatic or chemical treatment. The newest approaches also include labeling at RNA abasic sites that result from the selective removal of RNA modification or the enhanced cleavage of the RNA ribose-phosphate chain (perhaps also protection from cleavage), followed by specific adapter ligation. Classical affinity/immunoprecipitation-based protocols use either antibodies against modified RNA bases or proteins/enzymes, recognizing RNA modifications. In this survey, we review the most recent achievements in this highly dynamic field, including promising attempts to map RNA modifications by the direct single-molecule sequencing of RNA by nanopores. Full article

(This article belongs to the Special Issue Functions and Dynamics of RNA Modifications)

► Show Figures

Figure 1

23 pages, 2058 KiB

Open AccessEditor’s ChoiceReview

HMGA2 as a Critical Regulator in Cancer Development

by Behzad Mansoori, Ali Mohammadi, Henrik J. Ditzel, Pascal H. G. Duijf, Vahid Khaze, Morten F. Gjerstorff and Behzad Baradaran

Genes 2021, 12(2), 269; https://doi.org/10.3390/genes12020269 - 13 Feb 2021

Cited by 95 | Viewed by 9767

Abstract

The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of [...] Read more.

The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes. Full article

(This article belongs to the Special Issue Transcription Factors in Cancer Progression)

► Show Figures

Figure 1

17 pages, 3585 KiB

Open AccessEditor’s ChoiceArticle

miR-34a and miR-200c Have an Additive Tumor-Suppressive Effect on Breast Cancer Cells and Patient Prognosis

by Behzad Mansoori, Nicola Silvestris, Ali Mohammadi, Vahid Khaze, Elham Baghbani, Ahad Mokhtarzadeh, Dariush Shanehbandi, Afshin Derakhshani, Pascal H. G. Duijf and Behzad Baradaran

Genes 2021, 12(2), 267; https://doi.org/10.3390/genes12020267 - 12 Feb 2021

Cited by 27 | Viewed by 3408

Abstract

Breast cancer is the most common women’s malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles [...] Read more.

Breast cancer is the most common women’s malignancy in the world and, for subgroups of patients, treatment outcomes remain poor. Thus, more effective therapeutic strategies are urgently needed. MicroRNAs (miRNAs) have emerged as promising therapeutic tools and targets, as they play significant roles in regulating key cellular processes by suppressing gene expression. However, additive opportunities involving miRNAs have been underexplored. For example, both miR-34a and miR-200c individually suppress the development of different types of cancer, but the cellular effects of their combined actions remain unknown. Here, we show that miR-34a and miR-200c levels are reduced in breast tumors compared to adjacent normal tissues and that this additively predicts poor patient survival. In addition, in cell lines, miR-34a and miR-200c additively induce apoptosis and cell cycle arrest, while also inhibiting proliferation, invasion, migration, stemness and epithelial-to-mesenchymal transition (EMT). Mechanistically, both miRNA-34a and miR-200c directly target HIF1-α and subsequently downregulate VEGFR, MMP9 and CXCR4, although combined miRNA-34a and miR-200c delivery suppresses mouse xenograft tumor development as effectively as individual delivery. We establish a model, supported by in vitro and clinical data, which collectively suggest that the co-delivery of miR-34a and miR-200c represents a promising novel therapeutic strategy for breast cancer patients. Full article

(This article belongs to the Special Issue Transcription Factors in Cancer Progression)

► Show Figures

Figure 1

16 pages, 6533 KiB

Open AccessEditor’s ChoiceArticle

Two Expansin Genes, AtEXPA4 and AtEXPB5, Are Redundantly Required for Pollen Tube Growth and AtEXPA4 Is Involved in Primary Root Elongation in Arabidopsis thaliana

by Weimiao Liu, Liai Xu, Hui Lin and Jiashu Cao

Genes 2021, 12(2), 249; https://doi.org/10.3390/genes12020249 - 10 Feb 2021

Cited by 30 | Viewed by 2801

Abstract

The growth of plant cells is inseparable from relaxation and expansion of cell walls. Expansins are a class of cell wall binding proteins, which play important roles in the relaxation of cell walls. Although there are many members in expansin gene family, the [...] Read more.

The growth of plant cells is inseparable from relaxation and expansion of cell walls. Expansins are a class of cell wall binding proteins, which play important roles in the relaxation of cell walls. Although there are many members in expansin gene family, the functions of most expansin genes in plant growth and development are still poorly understood. In this study, the functions of two expansin genes, AtEXPA4 and AtEXPB5 were characterized in Arabidopsis thaliana. AtEXPA4 and AtEXPB5 displayed consistent expression patterns in mature pollen grains and pollen tubes, but AtEXPA4 also showed a high expression level in primary roots. Two single mutants, atexpa4 and atexpb5, showed normal reproductive development, whereas atexpa4atexpb5 double mutant was defective in pollen tube growth. Moreover, AtEXPA4 overexpression enhanced primary root elongation, on the contrary, knocking out AtEXPA4 made the growth of primary root slower. Our results indicated that AtEXPA4 and AtEXPB5 were redundantly involved in pollen tube growth and AtEXPA4 was required for primary root elongation. Full article

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

► Show Figures

Figure 1

31 pages, 2533 KiB

Open AccessEditor’s ChoiceReview

Molecular Aspects of Regeneration Mechanisms in Holothurians

by Igor Yu. Dolmatov

Genes 2021, 12(2), 250; https://doi.org/10.3390/genes12020250 - 10 Feb 2021

Cited by 26 | Viewed by 3359

Abstract

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and [...] Read more.

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation). Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

► Show Figures

Figure 1

24 pages, 989 KiB

Open AccessEditor’s ChoiceReview

Mitochondrial Dynamics: Molecular Mechanisms, Related Primary Mitochondrial Disorders and Therapeutic Approaches

by Michela Di Nottia, Daniela Verrigni, Alessandra Torraco, Teresa Rizza, Enrico Bertini and Rosalba Carrozzo

Genes 2021, 12(2), 247; https://doi.org/10.3390/genes12020247 - 10 Feb 2021

Cited by 27 | Viewed by 4719

Abstract

Mitochondria do not exist as individual entities in the cell—conversely, they constitute an interconnected community governed by the constant and opposite process of fission and fusion. The mitochondrial fission leads to the formation of smaller mitochondria, promoting the biogenesis of new organelles. On [...] Read more.

Mitochondria do not exist as individual entities in the cell—conversely, they constitute an interconnected community governed by the constant and opposite process of fission and fusion. The mitochondrial fission leads to the formation of smaller mitochondria, promoting the biogenesis of new organelles. On the other hand, following the fusion process, mitochondria appear as longer and interconnected tubules, which enhance the communication with other organelles. Both fission and fusion are carried out by a small number of highly conserved guanosine triphosphatase proteins and their interactors. Disruption of this equilibrium has been associated with several pathological conditions, ranging from cancer to neurodegeneration, and mutations in genes involved in mitochondrial fission and fusion have been reported to be the cause of a subset of neurogenetic disorders. Full article

(This article belongs to the Special Issue Alterations in mtDNA and Mitochondrial Quality Control)

► Show Figures

Figure 1

18 pages, 4853 KiB

Open AccessEditor’s ChoiceArticle

Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events

by Michel-Edwar Mickael, Norwin Kubick, Pavel Klimovich, Patrick Henckell Flournoy, Irmina Bieńkowska and Mariusz Sacharczuk

Genes 2021, 12(2), 254; https://doi.org/10.3390/genes12020254 - 10 Feb 2021

Cited by 16 | Viewed by 3217

Abstract

Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a [...] Read more.

Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system. Full article

(This article belongs to the Special Issue The Immune Response in the Time of Omics Research)

► Show Figures

Figure 1

13 pages, 3717 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genomic Analysis of Lactiplantibacillus plantarum Isolated from Different Niches

by Bingyong Mao, Ruimin Yin, Xiaoshu Li, Shumao Cui, Hao Zhang, Jianxin Zhao and Wei Chen

Genes 2021, 12(2), 241; https://doi.org/10.3390/genes12020241 - 8 Feb 2021

Cited by 33 | Viewed by 3473

Abstract

Lactiplantibacillus plantarum can adapt to a variety of niches and is widely distributed in many sources. We used comparative genomics to explore the differences in the genome and in the physiological characteristics of L. plantarum isolated from pickles, fermented sauce, and human feces. [...] Read more.

Lactiplantibacillus plantarum can adapt to a variety of niches and is widely distributed in many sources. We used comparative genomics to explore the differences in the genome and in the physiological characteristics of L. plantarum isolated from pickles, fermented sauce, and human feces. The relationships between genotypes and phenotypes were analyzed to address the effects of isolation source on the genetic variation of L. plantarum. The comparative genomic results indicate that the numbers of unique genes in the different strains were niche-dependent. L. plantarum isolated from fecal sources generally had more strain-specific genes than L. plantarum isolated from pickles. The phylogenetic tree and average nucleotide identity (ANI) results indicate that L. plantarum in pickles and fermented sauce clustered independently, whereas the fecal L. plantarum was distributed more uniformly in the phylogenetic tree. The pan-genome curve indicated that the L. plantarum exhibited high genomic diversity. Based on the analysis of the carbohydrate active enzyme and carbohydrate-use abilities, we found that L. plantarum strains isolated from different sources exhibited different expression of the Glycoside Hydrolases (GH) and Glycosyl Transferases (GT) families and that the expression patterns of carbohydrate active enzymes were consistent with the evolution relationships of the strains. L. plantarum strains exhibited niche-specific characteristicsand the results provided better understating on genetics of this species. Full article

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

► Show Figures

Figure 1

33 pages, 2324 KiB

Open AccessEditor’s ChoiceReview

Epigenetics: New Insights into Mammary Gland Biology

by Elitsa Ivanova, Sandrine Le Guillou, Cathy Hue-Beauvais and Fabienne Le Provost

Genes 2021, 12(2), 231; https://doi.org/10.3390/genes12020231 - 5 Feb 2021

Cited by 23 | Viewed by 4472

Abstract

The mammary gland undergoes important anatomical and physiological changes from embryogenesis through puberty, pregnancy, lactation and involution. These steps are under the control of a complex network of molecular factors, in which epigenetic mechanisms play a role that is increasingly well described. Recently, [...] Read more.

The mammary gland undergoes important anatomical and physiological changes from embryogenesis through puberty, pregnancy, lactation and involution. These steps are under the control of a complex network of molecular factors, in which epigenetic mechanisms play a role that is increasingly well described. Recently, studies investigating epigenetic modifications and their impacts on gene expression in the mammary gland have been performed at different physiological stages and in different mammary cell types. This has led to the establishment of a role for epigenetic marks in milk component biosynthesis. This review aims to summarize the available knowledge regarding the involvement of the four main molecular mechanisms in epigenetics: DNA methylation, histone modifications, polycomb protein activity and non-coding RNA functions. Full article

(This article belongs to the Special Issue Gene Analysis of Mammary Gland Development and Breast Cancers)

► Show Figures

Figure 1

26 pages, 2066 KiB

Open AccessEditor’s ChoiceReview

The Genetic Basis of Tomato Aroma

by Matteo Martina, Yury Tikunov, Ezio Portis and Arnaud G. Bovy

Genes 2021, 12(2), 226; https://doi.org/10.3390/genes12020226 - 4 Feb 2021

Cited by 40 | Viewed by 7530

Abstract

Tomato (Solanum lycopersicum L.) aroma is determined by the interaction of volatile compounds (VOCs) released by the tomato fruits with receptors in the nose, leading to a sensorial impression, such as “sweet”, “smoky”, or “fruity” aroma. Of the more than 400 VOCs [...] Read more.

Tomato (Solanum lycopersicum L.) aroma is determined by the interaction of volatile compounds (VOCs) released by the tomato fruits with receptors in the nose, leading to a sensorial impression, such as “sweet”, “smoky”, or “fruity” aroma. Of the more than 400 VOCs released by tomato fruits, 21 have been reported as main contributors to the perceived tomato aroma. These VOCs can be grouped in five clusters, according to their biosynthetic origins. In the last decades, a vast array of scientific studies has investigated the genetic component of tomato aroma in modern tomato cultivars and their relatives. In this paper we aim to collect, compare, integrate and summarize the available literature on flavour-related QTLs in tomato. Three hundred and fifty nine (359) QTLs associated with tomato fruit VOCs were physically mapped on the genome and investigated for the presence of potential candidate genes. This review makes it possible to (i) pinpoint potential donors described in literature for specific traits, (ii) highlight important QTL regions by combining information from different populations, and (iii) pinpoint potential candidate genes. This overview aims to be a valuable resource for researchers aiming to elucidate the genetics underlying tomato flavour and for breeders who aim to improve tomato aroma. Full article

(This article belongs to the Special Issue Tomato Genetics)

► Show Figures

Figure 1

22 pages, 1211 KiB

Open AccessEditor’s ChoiceReview

Hashimoto’s Thyroiditis and Graves’ Disease in Genetic Syndromes in Pediatric Age

by Celeste Casto, Giorgia Pepe, Alessandra Li Pomi, Domenico Corica, Tommaso Aversa and Malgorzata Wasniewska

Genes 2021, 12(2), 222; https://doi.org/10.3390/genes12020222 - 4 Feb 2021

Cited by 23 | Viewed by 6690

Abstract

Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), are the most common cause of acquired thyroid disorder during childhood and adolescence. Our purpose was to assess the main features of AITDs when they occur in association with genetic syndromes. [...] Read more.

Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), are the most common cause of acquired thyroid disorder during childhood and adolescence. Our purpose was to assess the main features of AITDs when they occur in association with genetic syndromes. We conducted a systematic review of the literature, covering the last 20 years, through MEDLINE via PubMed and EMBASE databases, in order to identify studies focused on the relation between AITDs and genetic syndromes in children and adolescents. From the 1654 references initially identified, 90 articles were selected for our final evaluation. Turner syndrome, Down syndrome, Klinefelter syndrome, neurofibromatosis type 1, Noonan syndrome, 22q11.2 deletion syndrome, Prader–Willi syndrome, Williams syndrome and 18q deletion syndrome were evaluated. Our analysis confirmed that AITDs show peculiar phenotypic patterns when they occur in association with some genetic disorders, especially chromosomopathies. To improve clinical practice and healthcare in children and adolescents with genetic syndromes, an accurate screening and monitoring of thyroid function and autoimmunity should be performed. Furthermore, maintaining adequate thyroid hormone levels is important to avoid aggravating growth and cognitive deficits that are not infrequently present in the syndromes analyzed. Full article

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

► Show Figures

Figure 1

15 pages, 961 KiB

Open AccessEditor’s ChoiceReview

Eicosanoid Signaling in Insect Immunology: New Genes and Unresolved Issues

by Yonggyun Kim and David Stanley

Genes 2021, 12(2), 211; https://doi.org/10.3390/genes12020211 - 1 Feb 2021

Cited by 44 | Viewed by 3959

Abstract

This paper is focused on eicosanoid signaling in insect immunology. We begin with eicosanoid biosynthesis through the actions of phospholipase A₂, responsible for hydrolyzing the C18 polyunsaturated fatty acid, linoleic acid (18:2n-6), from cellular phospholipids, which is subsequently converted into arachidonic [...] Read more.

This paper is focused on eicosanoid signaling in insect immunology. We begin with eicosanoid biosynthesis through the actions of phospholipase A₂, responsible for hydrolyzing the C18 polyunsaturated fatty acid, linoleic acid (18:2n-6), from cellular phospholipids, which is subsequently converted into arachidonic acid (AA; 20:4n-6) via elongases and desaturases. The synthesized AA is then oxygenated into one of three groups of eicosanoids, prostaglandins (PGs), epoxyeicosatrienoic acids (EETs) and lipoxygenase products. We mark the distinction between mammalian cyclooxygenases and insect peroxynectins, both of which convert AA into PGs. One PG, PGI₂ (also called prostacyclin), is newly discovered in insects, as a negative regulator of immune reactions and a positive signal in juvenile development. Two new elements of insect PG biology are a PG dehydrogenase and a PG reductase, both of which enact necessary PG catabolism. EETs, which are produced from AA via cytochrome P450s, also act in immune signaling, acting as pro-inflammatory signals. Eicosanoids signal a wide range of cellular immune reactions to infections, invasions and wounding, including nodulation, cell spreading, hemocyte migration and releasing prophenoloxidase from oenocytoids, a class of lepidopteran hemocytes. We briefly review the relatively scant knowledge on insect PG receptors and note PGs also act in gut immunity and in humoral immunity. Detailed new information on PG actions in mosquito immunity against the malarial agent, Plasmodium berghei, has recently emerged and we treat this exciting new work. The new findings on eicosanoid actions in insect immunity have emerged from a very broad range of research at the genetic, cellular and organismal levels, all taking place at the international level. Full article

(This article belongs to the Special Issue Evolutionary Genetics of Insect Innate Immunity)

► Show Figures

Figure 1

21 pages, 696 KiB

Open AccessEditor’s ChoiceReview

Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing

by Aleksandra Majchrzak-Celińska, Anna Warych and Mikołaj Szoszkiewicz

Genes 2021, 12(2), 208; https://doi.org/10.3390/genes12020208 - 31 Jan 2021

Cited by 62 | Viewed by 6320

Abstract

Cancer development involves both genetic and epigenetic alterations. Aberrant epigenetic modifications are reversible, allowing excellent opportunities for therapeutic intervention. Nowadays, several epigenetic drugs are used worldwide to treat, e.g., myelodysplastic syndromes and leukemias. However, overcoming resistance and widening the therapeutic profiles are the [...] Read more.

Cancer development involves both genetic and epigenetic alterations. Aberrant epigenetic modifications are reversible, allowing excellent opportunities for therapeutic intervention. Nowadays, several epigenetic drugs are used worldwide to treat, e.g., myelodysplastic syndromes and leukemias. However, overcoming resistance and widening the therapeutic profiles are the most important challenges faced by traditional epigenetic drugs. Recently, novel approaches to epigenetic therapies have been proposed. Next-generation epigenetic drugs, with longer half-life and better bioavailability, are being developed and tested. Since epigenetic phenomena are interdependent, treatment modalities include co-administration of two different epigenetic drugs. In order to sensitize cancer cells to chemotherapy, epigenetic drugs are administered prior to chemotherapy, or both epigenetic drug and chemotherapy are used together to achieve synergistic effects and maximize treatment efficacy. The combinations of epigenetic drug with immunotherapy are being tested, because they have proved to enhance antitumor immune responses. The next approach involves targeting the metabolic causes of epigenetic changes, i.e., enzymes which, when mutated, produce oncometabolites. Finally, epigenome editing makes it possible to modify individual chromatin marks at a defined region with unprecedented specificity and efficiency. This review summarizes the above attempts in fulfilling the promise of epigenetic drugs in the effective cancer treatment. Full article

(This article belongs to the Special Issue Cancer Epigenetics-Recent Developments in Epigenetic Diagnostics and Therapy)

► Show Figures

Figure 1

27 pages, 4255 KiB

Open AccessEditor’s ChoiceArticle

Long-Term Waterlogging as Factor Contributing to Hypoxia Stress Tolerance Enhancement in Cucumber: Comparative Transcriptome Analysis of Waterlogging Sensitive and Tolerant Accessions

by Kinga Kęska, Michał Wojciech Szcześniak, Izabela Makałowska and Małgorzata Czernicka

Genes 2021, 12(2), 189; https://doi.org/10.3390/genes12020189 - 28 Jan 2021

Cited by 28 | Viewed by 3485

Abstract

Waterlogging (WL), excess water in the soil, is a phenomenon often occurring during plant cultivation causing low oxygen levels (hypoxia) in the soil. The aim of this study was to identify candidate genes involved in long-term waterlogging tolerance in cucumber using RNA sequencing. [...] Read more.

Waterlogging (WL), excess water in the soil, is a phenomenon often occurring during plant cultivation causing low oxygen levels (hypoxia) in the soil. The aim of this study was to identify candidate genes involved in long-term waterlogging tolerance in cucumber using RNA sequencing. Here, we also determined how waterlogging pre-treatment (priming) influenced long-term memory in WL tolerant (WL-T) and WL sensitive (WL-S) i.e., DH2 and DH4 accessions, respectively. This work uncovered various differentially expressed genes (DEGs) activated in the long-term recovery in both accessions. De novo assembly generated 36,712 transcripts with an average length of 2236 bp. The results revealed that long-term waterlogging had divergent impacts on gene expression in WL-T DH2 and WL-S DH4 cucumber accessions: after 7 days of waterlogging, more DEGs in comparison to control conditions were identified in WL-S DH4 (8927) than in WL-T DH2 (5957). Additionally, 11,619 and 5007 DEGs were identified after a second waterlogging treatment in the WL-S and WL-T accessions, respectively. We identified genes associated with WL in cucumber that were especially related to enhanced glycolysis, adventitious roots development, and amino acid metabolism. qRT-PCR assay for hypoxia marker genes i.e., alcohol dehydrogenase (adh), 1-aminocyclopropane-1-carboxylate oxidase (aco) and long chain acyl-CoA synthetase 6 (lacs6) confirmed differences in response to waterlogging stress between sensitive and tolerant cucumbers and effectiveness of priming to enhance stress tolerance. Full article

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

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI