Genes

18 pages, 3348 KiB

Open AccessEditor’s ChoiceArticle

Altered Mitochondrial Quality Control in Rats with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Induced by High-Fat Feeding

by Federica Cioffi, Antonia Giacco, Giuseppe Petito, Rita de Matteis, Rosalba Senese, Assunta Lombardi, Pieter de Lange, Maria Moreno, Fernando Goglia, Antonia Lanni and Elena Silvestri

Genes 2022, 13(2), 315; https://doi.org/10.3390/genes13020315 - 8 Feb 2022

Cited by 22 | Viewed by 2977

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) is defined as the presence of hepatic steatosis in addition to one of three metabolic conditions: overweight/obesity, type 2 diabetes mellitus, or metabolic dysregulation. Chronic exposure to excess dietary fatty acids may cause hepatic steatosis and metabolic [...] Read more.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is defined as the presence of hepatic steatosis in addition to one of three metabolic conditions: overweight/obesity, type 2 diabetes mellitus, or metabolic dysregulation. Chronic exposure to excess dietary fatty acids may cause hepatic steatosis and metabolic disturbances. The alteration of the quality of mitochondria is one of the factors that could contribute to the metabolic dysregulation of MAFDL. This study was designed to determine, in a rodent model of MAFLD, the effects of a long-term high-fat diet (HFD) on some hepatic processes that characterize mitochondrial quality control, such as biogenesis, dynamics, and mitophagy. To mimic the human manifestation of MAFLD, the rats were exposed to both an HFD and a housing temperature within the rat thermoneutral zone (28–30 °C). After 14 weeks of the HFD, the rats showed significant fat deposition and liver steatosis. Concomitantly, some important factors related to the hepatic mitochondrial quality were markedly affected, such as increased mitochondrial reactive oxygen species (ROS) production and mitochondrial DNA (mtDNA) damage; reduced mitochondrial biogenesis, mtDNA copy numbers, mtDNA repair, and mitochondrial fusion. HFD-fed rats also showed an impaired mitophagy. Overall, the obtained data shed new light on the network of different processes contributing to the failure of mitochondrial quality control as a central event for mitochondrial dysregulation in MAFLD. Full article

(This article belongs to the Collection Genotype-Phenotype Study in Disease)

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19 pages, 862 KiB

Open AccessEditor’s ChoiceReview

A Review on CYP11A1, CYP17A1, and CYP19A1 Polymorphism Studies: Candidate Susceptibility Genes for Polycystic Ovary Syndrome (PCOS) and Infertility

by Roozbeh Heidarzadehpilehrood, Maryam Pirhoushiaran, Rasoul Abdollahzadeh, Malina Binti Osman, Maryam Sakinah, Norshariza Nordin and Habibah Abdul Hamid

Genes 2022, 13(2), 302; https://doi.org/10.3390/genes13020302 - 5 Feb 2022

Cited by 52 | Viewed by 5854

Abstract

Polycystic ovary syndrome is a multifactorial condition associated with reproductive and endocrine organs and might cause infertility and metabolic abnormalities in childbearing age. PCOS seems to be a multifactorial disorder resulting from the combination of several genetic and environmental factors. Little research has [...] Read more.

Polycystic ovary syndrome is a multifactorial condition associated with reproductive and endocrine organs and might cause infertility and metabolic abnormalities in childbearing age. PCOS seems to be a multifactorial disorder resulting from the combination of several genetic and environmental factors. Little research has been conducted to date on the impact of polymorphisms in infertility. We aim to review the appearance of polymorphisms in females of diverse ethnicities and their effect on infertility in the population with polycystic ovary syndrome. There have been numerous reports of the importance of the steroidogenesis pathway and genetic variants in PCOS pathogenesis. The most important genes that play a role in the aetiology of PCOS are CYP11A1, CYP17A1, and CYP19A1. We evaluated the occurrence of polymorphisms in various ethnicities in the CYP11A1, CYP17A1, and CYP19A1 genes and their efficacy on increasing PCOS risk with infertility. Our findings revealed that polymorphisms in various ethnicities are associated with the risk of PCOS with infertility. Although conflicting results regarding CYP11A1, CYP17A1, and CYP19A1 polymorphisms and their influence on PCOS with infertility have been reported in a small number of papers, the authors feel this may be attributable to the sample size and ethnic composition of the examined populations. In conclusion, our study strongly suggests that the CYP11A1, CYP17A1, and CYP19A1 genes might significantly enhance the probability of developing PCOS with infertility. Full article

(This article belongs to the Special Issue Genetics and Genomics in Hereditary Endocrine Disorders)

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24 pages, 14876 KiB

Open AccessEditor’s ChoiceReview

From Copper Tolerance to Resistance in Pseudomonas aeruginosa towards Patho-Adaptation and Hospital Success

by Maxine Virieux-Petit, Florence Hammer-Dedet, Fabien Aujoulat, Estelle Jumas-Bilak and Sara Romano-Bertrand

Genes 2022, 13(2), 301; https://doi.org/10.3390/genes13020301 - 4 Feb 2022

Cited by 20 | Viewed by 3898

Abstract

The hospital environment constitutes a reservoir of opportunistic pathogens responsible for healthcare-associated infections (HCAI) such as Pseudomonas aeruginosa (Pa). Pa persistence within technological niches, the increasing emergence of epidemic high-risk clones in HCAI, the epidemiological link between plumbing strains and clinical [...] Read more.

The hospital environment constitutes a reservoir of opportunistic pathogens responsible for healthcare-associated infections (HCAI) such as Pseudomonas aeruginosa (Pa). Pa persistence within technological niches, the increasing emergence of epidemic high-risk clones in HCAI, the epidemiological link between plumbing strains and clinical strains, make it a major nosocomial pathogen. Therefore, understanding the mechanisms of Pa adaptation to hospital water systems would be useful in preventing HCAI. This review deciphers how copper resistance contributes to Pa adaptation and persistence in a hospital environment, especially within copper water systems, and ultimately to its success as a causative agent of HCAI. Numerous factors are involved in copper homeostasis in Pa, among which active efflux conferring copper tolerance, and copper-binding proteins regulating the copper compartmentalization between periplasm and cytoplasm. The functional harmony of copper homeostasis is regulated by several transcriptional regulators. The genomic island GI-7 appeared as especially responsible for the copper resistance in Pa. Mechanisms of copper and antibiotic cross-resistance and co-resistance are also identified, with potential co-regulation processes between them. Finally, copper resistance of Pa confers selective advantages in colonizing and persisting in hospital environments but also appears as an asset at the host/pathogen interface that helps in HCAI occurrence. Full article

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

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15 pages, 7536 KiB

Open AccessEditor’s ChoiceArticle

Expanding Phenotype of Poirier–Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients

by Alessandro Orsini, Andrea Santangelo, Francesca Bravin, Alice Bonuccelli, Diego Peroni, Roberta Battini, Thomas Foiadelli, Veronica Bertini, Angelo Valetto, Michele Iacomino, Vincenzo Nigro, Anna Laura Torella, Marcello Scala, Valeria Capra, Maria Stella Vari, Anna Fetta, Veronica Di Pisa, Francesca Montanari, Roberta Epifanio, Paolo Bonanni, Roberto Giorda, Francesca Operto, Grazia Pastorino, Esra Sarigecili, Esra Sardaroglu, Cetin Okuyaz, Sevgan Bozdogan, Luciana Musante, Flavio Faletra, Caterina Zanus, Alessandro Ferretti, Federico Vigevano, Pasquale Striano and Duccio Maria Cordelli Show full author list Hide full author list

Genes 2022, 13(2), 276; https://doi.org/10.3390/genes13020276 - 30 Jan 2022

Cited by 13 | Viewed by 4704

Abstract

Background: Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack [...] Read more.

Background: Poirier–Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. Methods: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. Results: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. Conclusion: Although it was not possible to assess a genotype–phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene. Full article

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

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20 pages, 24360 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of CCD Gene Family in Six Cucurbitaceae Species and Its Expression Profiles in Melon

by Denghu Cheng, Zhongyuan Wang, Shiyu Li, Juan Zhao, Chunhua Wei and Yong Zhang

Genes 2022, 13(2), 262; https://doi.org/10.3390/genes13020262 - 28 Jan 2022

Cited by 13 | Viewed by 3563

Abstract

The carotenoid cleavage dioxygenase (CCD) gene family in plants comprises two subfamilies: CCD and 9-cis-epoxycarotenoid dioxygenase (NCED). Genes in the NCED subfamily are mainly involved in plant responses to abiotic stresses such as salt, low temperature, and drought. Members of the NCED subfamily [...] Read more.

The carotenoid cleavage dioxygenase (CCD) gene family in plants comprises two subfamilies: CCD and 9-cis-epoxycarotenoid dioxygenase (NCED). Genes in the NCED subfamily are mainly involved in plant responses to abiotic stresses such as salt, low temperature, and drought. Members of the NCED subfamily are the most important rate-limiting enzymes in the biosynthesis of abscisic acid (ABA). In the present study, genome-wide analysis was performed to identify CCD gene members in six Cucurbitaceae species, including watermelon (Citrullus lanatus), melon (Cucumis melo), cucumber (C.sativus), pumpkin (Cucurbita moschata), bottle gourd (Lagenaria siceraria), and wax gourd (Benincasa hispida). A total of 10, 9, 9, 13, 8, 8 CCD genes were identified in the six species, respectively, and these genes were unevenly distributed in different chromosomes. Phylogenetic analysis showed that CCD genes of the six species clustered into two subfamilies: CCD and NCED, with five and three independent clades, respectively. The number of exons ranged from 1 to 15, and the number of motifs were set to 15 at most. The cis-acting elements analysis showed that a lot of the cis-acting elements were implicated in stress and hormone response. Melon seedlings were treated with salt, low temperature, drought, and ABA, and then tissue-specific analysis of CCDs expression were performed on the root, stem, upper leaf, middle leaf, female flower, male flower, and tendril of melon. The results showed that genes in CCD family exhibited various expression patterns. Different CCD genes of melon showed different degrees of response to abiotic stress. This study presents a comprehensive analysis of CCD gene family in six species of Cucurbitaceae, providing a strong foundation for future studies on specific genes in this family. Full article

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

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17 pages, 638 KiB

Open AccessEditor’s ChoiceReview

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

by Harry Wilton-Clark and Toshifumi Yokota

Genes 2022, 13(2), 257; https://doi.org/10.3390/genes13020257 - 28 Jan 2022

Cited by 19 | Viewed by 6627

Abstract

Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few [...] Read more.

Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy. Full article

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

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19 pages, 16013 KiB

Open AccessEditor’s ChoiceArticle

Genomic Analysis of Resistance to Fall Armyworm (Spodoptera frugiperda) in CIMMYT Maize Lines

by Isaac Kamweru, Bruce Y. Anani, Yoseph Beyene, Dan Makumbi, Victor O. Adetimirin, Boddupalli M. Prasanna and Manje Gowda

Genes 2022, 13(2), 251; https://doi.org/10.3390/genes13020251 - 28 Jan 2022

Cited by 15 | Viewed by 3731

Abstract

The recent invasion, rapid spread, and widescale destruction of the maize crop by the fall armyworm (FAW; Spodoptera frugiperda (J.E. Smith)) is likely to worsen the food insecurity situation in Africa. In the present study, a set of 424 maize lines were screened [...] Read more.

The recent invasion, rapid spread, and widescale destruction of the maize crop by the fall armyworm (FAW; Spodoptera frugiperda (J.E. Smith)) is likely to worsen the food insecurity situation in Africa. In the present study, a set of 424 maize lines were screened for their responses to FAW under artificial infestation to dissect the genetic basis of resistance. All lines were evaluated for two seasons under screen houses and genotyped with the DArTseq platform. Foliar damage was rated on a scale of 1 (highly resistant) to 9 (highly susceptible) and scored at 7, 14, and 21 days after artificial infestation. Analyses of variance revealed significant genotypic and genotype by environment interaction variances for all traits. Heritability estimates for leaf damage scores were moderately high and ranged from 0.38 to 0.58. Grain yield was negatively correlated with a high magnitude to foliar damage scores, ear rot, and ear damage traits. The genome-wide association study (GWAS) revealed 56 significant marker–trait associations and the predicted functions of the putative candidate genes varied from a defense response to several genes of unknown function. Overall, the study revealed that native genetic resistance to FAW is quantitative in nature and is controlled by many loci with minor effects. Full article

(This article belongs to the Special Issue Research on Tropical Food Crop Genomics)

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14 pages, 16528 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Study of Root System Architecture in Maize

by Bin Wu, Wei Ren, Longfei Zhao, Qiang Li, Jiazheng Sun, Fanjun Chen and Qingchun Pan

Genes 2022, 13(2), 181; https://doi.org/10.3390/genes13020181 - 28 Jan 2022

Cited by 16 | Viewed by 3568

Abstract

Roots are important plant organs for the absorption of water and nutrients. To date, there have been few genome-wide association studies of maize root system architecture (RSA) in the field. The genetic basis of maize RSA is poorly understood, and the maize RSA-related [...] Read more.

Roots are important plant organs for the absorption of water and nutrients. To date, there have been few genome-wide association studies of maize root system architecture (RSA) in the field. The genetic basis of maize RSA is poorly understood, and the maize RSA-related genes that have been cloned are very limited. Here, 421 maize inbred lines of an association panel were planted to measure the root systems at the maturity stage, and a genome-wide association study was performed. There was a strong correlation among eight RSA traits, and the RSA traits were highly correlated with the aboveground plant architecture traits (e.g., plant height and ear leaf length, r = 0.13–0.25, p < 0.05). The RSA traits of the stiff stalk subgroup (SS) showed lower values than those of the non-stiff stalk subgroup (NSS) and tropical/subtropical subgroup (TST). Using the RSA traits, the genome-wide association study identified 63 SNPs and 189 candidate genes. Among them, nine candidate genes co-localized between RSA and aboveground architecture traits. A further co-expression analysis identified 88 candidate genes having high confidence levels. Furthermore, we identified four highly reliable RSA candidate genes, GRMZM2G099797, GRMZM2G354338, GRMZM2G085042, and GRMZM5G812926. This research provides theoretical support for the genetic improvement of maize root systems, and it identified candidate genes that may act as genetic resources for breeding. Full article

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

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15 pages, 2838 KiB

Open AccessEditor’s ChoiceReview

MicroRNA Interrelated Epithelial Mesenchymal Transition (EMT) in Glioblastoma

by Botle Precious Setlai, Rodney Hull, Rui Manuel Reis, Cyril Agbor, Melvin Anyasi Ambele, Thanyani Victor Mulaudzi and Zodwa Dlamini

Genes 2022, 13(2), 244; https://doi.org/10.3390/genes13020244 - 27 Jan 2022

Cited by 18 | Viewed by 5008

Abstract

MicroRNAs (miRNA) are small non-coding RNAs that are 20–23 nucleotides in length, functioning as regulators of oncogenes or tumor suppressor genes. They are molecular modulators that regulate gene expression by suppressing gene translation through gene silencing/degradation, or by promoting translation of messenger RNA [...] Read more.

MicroRNAs (miRNA) are small non-coding RNAs that are 20–23 nucleotides in length, functioning as regulators of oncogenes or tumor suppressor genes. They are molecular modulators that regulate gene expression by suppressing gene translation through gene silencing/degradation, or by promoting translation of messenger RNA (mRNA) into proteins. Circulating miRNAs have attracted attention as possible prognostic markers of cancer, which could aid in the early detection of the disease. Epithelial to mesenchymal transition (EMT) has been implicated in tumorigenic processes, primarily by promoting tumor invasiveness and metastatic activity; this is a process that could be manipulated to halt or prevent brain metastasis. Studies show that miRNAs influence the function of EMT in glioblastomas. Thus, miRNA-related EMT can be exploited as a potential therapeutic target in glioblastomas. This review points out the interrelation between miRNA and EMT signatures, and how they can be used as reliable molecular signatures for diagnostic purposes or targeted therapy in glioblastomas. Full article

(This article belongs to the Special Issue Non-coding RNAs in Human Health and Diseases)

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18 pages, 6584 KiB

Open AccessEditor’s ChoiceArticle

Identification of a Four-Gene Signature Associated with the Prognosis Prediction of Lung Adenocarcinoma Based on Integrated Bioinformatics Analysis

by Yuan Wu, Lingge Yang, Long Zhang, Xinjie Zheng, Huan Xu, Kai Wang and Xianwu Weng

Genes 2022, 13(2), 238; https://doi.org/10.3390/genes13020238 - 27 Jan 2022

Cited by 14 | Viewed by 3165

Abstract

Lung adenocarcinoma (LUAD) is often diagnosed at an advanced stage, so it is necessary to identify potential biomarkers for the early diagnosis and prognosis of LUAD. In our study, a gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) in [...] Read more.

Lung adenocarcinoma (LUAD) is often diagnosed at an advanced stage, so it is necessary to identify potential biomarkers for the early diagnosis and prognosis of LUAD. In our study, a gene co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) in order to obtain the key modules and genes correlated with LUAD prognosis. Four hub genes (HLF, CHRDL1, SELENBP1, and TMEM163) were screened out using least absolute shrinkage and selection operator (LASSO)–Cox regression analysis; then, a prognostic model was established for predicting overall survival (OS) based on these four hub genes..Furthermore, the prognostic values of this four-gene signature were verified in four validation sets (GSE26939, GSE31210, GSE72094, and TCGA-LUAD) as well as in the GEPIA database. To assess the prognostic values of hub genes, receiver operating characteristic (ROC) curves were constructed and a nomogram was created. We found that a higher expression of four hub genes was associated with a lower risk of patient death. In a training set, it was demonstrated that this four-gene signature was a better prognostic factor than clinical factors such as age and stage of disease. Moreover, our results revealed that these four genes were suppressor factors of LUAD and that their high expression was associated with a lower risk of death. In summary, we demonstrated that this four-gene signature could be a potential prognostic factor for LUAD patients. These findings provide a theoretical basis for exploring potential biomarkers for LUAD prognosis prediction in the future. Full article

(This article belongs to the Section Bioinformatics)

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18 pages, 1282 KiB

Open AccessEditor’s ChoiceArticle

miRNome Profiling Detects miR-101-3p and miR-142-5p as Putative Blood Biomarkers of Frailty Syndrome

by Giulia Carini, Jessica Mingardi, Francesco Bolzetta, Alberto Cester, Andrea Bolner, Giampietro Nordera, Luca La Via, Alessandro Ieraci, Isabella Russo, Stefania Maggi, Stefano Calza, Maurizio Popoli, Nicola Veronese, Laura Musazzi and Alessandro Barbon

Genes 2022, 13(2), 231; https://doi.org/10.3390/genes13020231 - 26 Jan 2022

Cited by 11 | Viewed by 4028

Abstract

Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this [...] Read more.

Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty. Full article

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

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21 pages, 3129 KiB

Open AccessEditor’s ChoiceReview

The Ecology and Evolution of the Baker’s Yeast Saccharomyces cerevisiae

by Feng-Yan Bai, Da-Yong Han, Shou-Fu Duan and Qi-Ming Wang

Genes 2022, 13(2), 230; https://doi.org/10.3390/genes13020230 - 26 Jan 2022

Cited by 24 | Viewed by 9977

Abstract

The baker’s yeast Saccharomyces cerevisiae has become a powerful model in ecology and evolutionary biology. A global effort on field survey and population genetics and genomics of S. cerevisiae in past decades has shown that the yeast distributes ubiquitously in nature with clearly [...] Read more.

The baker’s yeast Saccharomyces cerevisiae has become a powerful model in ecology and evolutionary biology. A global effort on field survey and population genetics and genomics of S. cerevisiae in past decades has shown that the yeast distributes ubiquitously in nature with clearly structured populations. The global genetic diversity of S. cerevisiae is mainly contributed by strains from Far East Asia, and the ancient basal lineages of the species have been found only in China, supporting an ‘out-of-China’ origin hypothesis. The wild and domesticated populations are clearly separated in phylogeny and exhibit hallmark differences in sexuality, heterozygosity, gene copy number variation (CNV), horizontal gene transfer (HGT) and introgression events, and maltose utilization ability. The domesticated strains from different niches generally form distinct lineages and harbor lineage-specific CNVs, HGTs and introgressions, which contribute to their adaptations to specific fermentation environments. However, whether the domesticated lineages originated from a single, or multiple domestication events is still hotly debated and the mechanism causing the diversification of the wild lineages remains to be illuminated. Further worldwide investigations on both wild and domesticated S. cerevisiae, especially in Africa and West Asia, will be helpful for a better understanding of the natural and domestication histories and evolution of S. cerevisiae. Full article

(This article belongs to the Special Issue Population Genetics of Fungi)

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25 pages, 3876 KiB

Open AccessEditor’s ChoiceArticle

Y-Chromosomal Insights into Breeding History and Sire Line Genealogies of Arabian Horses

by Viktoria Remer, Elif Bozlak, Sabine Felkel, Lara Radovic, Doris Rigler, Gertrud Grilz-Seger, Monika Stefaniuk-Szmukier, Monika Bugno-Poniewierska, Samantha Brooks, Donald C. Miller, Douglas F. Antczak, Raheleh Sadeghi, Gus Cothran, Rytis Juras, Anas M. Khanshour, Stefan Rieder, Maria C. Penedo, Gudrun Waiditschka, Liliya Kalinkova, Valery V. Kalashnikov, Alexander M. Zaitsev, Saria Almarzook, Monika Reißmann, Gudrun A. Brockmann, Gottfried Brem and Barbara Wallner Show full author list Hide full author list

Genes 2022, 13(2), 229; https://doi.org/10.3390/genes13020229 - 26 Jan 2022

Cited by 18 | Viewed by 8381

Abstract

The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data [...] Read more.

The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data of 157 males from several breeds. Y-chromosomal haplotypes specific for Arabian horses were inferred by genotyping a collection of 145 males representing most Arabian sire lines that are active around the globe. These lines formed three discrete haplogroups, and the same haplogroups were detected in Arabian populations native to the Middle East. The Arabian haplotypes were clearly distinct from the ones detected in Akhal Tekes, Turkoman horses, and the progeny of two Thoroughbred foundation sires. However, a haplotype introduced into the English Thoroughbred by the stallion Byerley Turk (1680), was shared among Arabians, Turkomans, and Akhal Tekes, which opens a discussion about the historic connections between Oriental horse types. Furthermore, we genetically traced Arabian sire line breeding in the Western World over the past 200 years. This confirmed a strong selection for relatively few male lineages and uncovered incongruences to written pedigree records. Overall, we demonstrate how fine-scaled Y-analysis contributes to a better understanding of the historical development of horse breeds. Full article

(This article belongs to the Special Issue Animal Domestication and Breeding)

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15 pages, 2210 KiB

Open AccessEditor’s ChoiceArticle

Evaluation and Genetic Analysis of Parthenocarpic Germplasms in Cucumber

by Chenxing Gou, Pinyu Zhu, Yongjiao Meng, Fan Yang, Yan Xu, Pengfei Xia, Jinfeng Chen and Ji Li

Genes 2022, 13(2), 225; https://doi.org/10.3390/genes13020225 - 25 Jan 2022

Cited by 15 | Viewed by 4008

Abstract

Parthenocarpy is an important agronomic trait in cucumber (Cucumis sativus L.) production. However, the systematic identification of parthenocarpic germplasms from national gene banks for cucumber improvement remains an international challenge. In this study, 201 cucumber lines were investigated, including different ecotypes. The [...] Read more.

Parthenocarpy is an important agronomic trait in cucumber (Cucumis sativus L.) production. However, the systematic identification of parthenocarpic germplasms from national gene banks for cucumber improvement remains an international challenge. In this study, 201 cucumber lines were investigated, including different ecotypes. The percentages of parthenocarpic fruit set (PFS) and parthenocarpic fruit expansion (PFE) were evaluated in three experiments. In natural populations, the PFS rates fit a normal distribution, while PFE rates showed a skewed distribution, suggesting that both PFS and PFE rates are typical quantitative traits. Genetic analysis showed that parthenocarpy in different ecotypes was inherited in a similar incompletely dominant manner. A total of 5324 single nucleotide polymorphisms (SNPs) associated with parthenocarpy were detected in a Genome-wide association study (GWAS) of parthenocarpy in the 31 cucumber lines, from which six parthenocarpic loci, including two novel loci (Pfs1.1 and Pfs4.1), were identified. Consequently, fifteen of the elite lines that were screened presented relatively stronger parthenocarpy ability (PFS > 90%, PFE > 50%), among which six cucumber lines (18007s, 18008s, 18022s, 18076s, 18099s, and 18127s) exhibited weak first-fruit inhibition. Three lines (18011s, 18018s, and 18019s) were screened for super ovary parthenocarpy, which showed more attractive performance. Four low-temperature-enhanced parthenocarpy lines (18018s, 18022s, 18029s, and 18012s) were identified, which were suited for breeding for counter-season production. Our approaches could help increase efficiency and lead to parthenocarpy improvements for modern cucumber cultivars. Full article

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

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15 pages, 1946 KiB

Open AccessEditor’s ChoiceReview

Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes

by Takeshi Sakuno and Yasushi Hiraoka

Genes 2022, 13(2), 200; https://doi.org/10.3390/genes13020200 - 22 Jan 2022

Cited by 12 | Viewed by 6458

Abstract

Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role [...] Read more.

Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role in the regulation of the processes required for recombination. In particular, the Rec8 subunit of the meiotic cohesin complex, which is conserved in a wide range of eukaryotes, has been analyzed for its function in modulating chromosomal architecture during the pairing and recombination of homologous chromosomes in meiosis. Here, we review the current understanding of Rec8 cohesin as a structural platform for meiotic chromosomes. Full article

(This article belongs to the Special Issue Genetics of Meiotic Chromosome Dynamics)

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16 pages, 4221 KiB

Open AccessEditor’s ChoiceArticle

Oligo-FISH Can Identify Chromosomes and Distinguish Hippophaë rhamnoides L. Taxa

by Xiaomei Luo, Juncheng Liu and Zhoujian He

Genes 2022, 13(2), 195; https://doi.org/10.3390/genes13020195 - 22 Jan 2022

Cited by 12 | Viewed by 3046

Abstract

Oligo-fluorescence in situ hybridization (FISH) facilitates precise chromosome identification and comparative cytogenetic analysis. Detection of autosomal chromosomes of Hippophaë rhamnoides has not been achieved using oligonucleotide sequences. Here, the chromosomes of five H. rhamnoides taxa in the mitotic metaphase and mitotic metaphase to [...] Read more.

Oligo-fluorescence in situ hybridization (FISH) facilitates precise chromosome identification and comparative cytogenetic analysis. Detection of autosomal chromosomes of Hippophaë rhamnoides has not been achieved using oligonucleotide sequences. Here, the chromosomes of five H. rhamnoides taxa in the mitotic metaphase and mitotic metaphase to anaphase were detected using the oligo-FISH probes (AG₃T₃)₃, 5S rDNA, and (TTG)₆. In total, 24 small chromosomes were clearly observed in the mitotic metaphase (0.89–3.03 μm), whereas 24–48 small chromosomes were observed in the mitotic metaphase to anaphase (0.94–3.10 μm). The signal number and intensity of (AG₃T₃)₃, 5S rDNA, and (TTG)₆ in the mitotic metaphase to anaphase chromosomes were nearly consistent with those in the mitotic metaphase chromosomes when the two split chromosomes were integrated as one unit. Of note, 14 chromosomes (there is a high chance that sex chromosomes are included) were exclusively identified by (AG₃T₃)₃, 5S rDNA, and (TTG)₆. The other 10 also showed a terminal signal with (AG₃T₃)₃. Moreover, these oligo-probes were able to distinguish one wild H. rhamnoides taxon from four H. rhamnoides taxa. These chromosome identification and taxa differentiation data will help in elucidating visual and elaborate physical mapping and guide breeders’ utilization of wild resources of H. rhamnoides. Full article

(This article belongs to the Special Issue Tree Genetics and Improvement)

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9 pages, 3104 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Different Cleaning Strategies for Removal of Contaminating DNA Molecules

by Martina Nilsson, Hanne De Maeyer and Marie Allen

Genes 2022, 13(1), 162; https://doi.org/10.3390/genes13010162 - 17 Jan 2022

Cited by 17 | Viewed by 7520

Abstract

Decontamination strategies and their efficiencies are crucial when performing routine forensic analysis, and many factors influence the choice of agent to use. In this study, the effects of ten different cleaning strategies were evaluated to compare their ability to remove contaminating DNA molecules. [...] Read more.

Decontamination strategies and their efficiencies are crucial when performing routine forensic analysis, and many factors influence the choice of agent to use. In this study, the effects of ten different cleaning strategies were evaluated to compare their ability to remove contaminating DNA molecules. Cell-free DNA or blood was deposited on three surfaces (plastic, metal, and wood) and decontaminated with various treatments. The quantities of recovered DNA, obtained by swabbing the surfaces after cleaning using the different strategies, was analyzed by real-time PCR. Large differences in the DNA removal efficiencies were observed between different cleaning strategies, as well as between different surfaces. The most efficient cleaning strategies for cell-free DNA were the different sodium hypochlorite solutions and Trigene^®, for which a maximum of 0.3% DNA was recovered on all three surfaces. For blood, a maximum of 0.8% of the deposited DNA was recovered after using Virkon^® for decontamination. The recoveries after using these cleaning strategies correspond to DNA from only a few cells, out of 60 ng of cell-free DNA or thousands of deposited blood cells. Full article

(This article belongs to the Special Issue Advances in Forensic Genetics)

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18 pages, 1900 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Drought, Low Nitrogen Stress, and Ultraviolet-B Radiation Effects on Growth, Development, and Physiology of Sweetpotato Cultivars during Early Season

by Purushothaman Ramamoorthy, Raju Bheemanahalli, Stephen L. Meyers, Mark W. Shankle and Kambham Raja Reddy

Genes 2022, 13(1), 156; https://doi.org/10.3390/genes13010156 - 16 Jan 2022

Cited by 17 | Viewed by 3366

Abstract

Drought, ultraviolet-B (UV-B), and nitrogen stress are significant constraints for sweetpotato productivity. Their impact on plant growth and development can be acute, resulting in low productivity. Identifying phenotypes that govern stress tolerance in sweetpotatoes is highly desirable to develop elite cultivars with better [...] Read more.

Drought, ultraviolet-B (UV-B), and nitrogen stress are significant constraints for sweetpotato productivity. Their impact on plant growth and development can be acute, resulting in low productivity. Identifying phenotypes that govern stress tolerance in sweetpotatoes is highly desirable to develop elite cultivars with better yield. Ten sweetpotato cultivars were grown under nonstress (100% replacement of evapotranspiration (ET)), drought-stress (50% replacement of ET), UV-B (10 kJ), and low-nitrogen (20% LN) conditions. Various shoot and root morphological, physiological, and gas-exchange traits were measured at the early stage of the crop growth to assess its performance and association with the storage root number. All three stress factors caused significant changes in the physiological and root- and shoot-related traits. Drought stress reduced most shoot developmental traits (29%) to maintain root growth. UV-B stress increased the accumulation of plant pigments and decreased the photosynthetic rate. Low-nitrogen treatment decreased shoot growth (11%) and increased the root traits (18%). The highly stable and productive cultivars under all four treatments were identified using multitrait stability index analysis and weighted average of absolute scores (WAASB) analyses. Further, based on the total stress response indices, ‘Evangeline’, ‘O’Henry’, and ‘Beauregard B-14’ were identified as vigorous under drought; ‘Evangeline’, ‘Orleans’, and ‘Covington’ under UV-B; and ‘Bonita’, ‘Orleans’, and ‘Beauregard B-14’ cultivars showed greater tolerance to low nitrogen. The cultivars ‘Vardaman’ and ‘NC05-198’ recorded a low tolerance index across stress treatments. This information could help determine which plant phenotypes are desirable under stress treatment for better productivity. The cultivars identified as tolerant, sensitive, and well-adapted within and across stress treatments can be used as source materials for abiotic stress tolerance breeding programs. Full article

(This article belongs to the Special Issue Genetic Diversity of Plant Tolerance to Environmental Restraints)

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8 pages, 658 KiB

Open AccessEditor’s ChoiceReview

All Ways Lead to Rome—Meiotic Stabilization Can Take Many Routes in Nascent Polyploid Plants

by Adrián Gonzalo

Genes 2022, 13(1), 147; https://doi.org/10.3390/genes13010147 - 15 Jan 2022

Cited by 12 | Viewed by 4082

Abstract

Newly formed polyploids often show extensive meiotic defects, resulting in aneuploid gametes, and thus reduced fertility. However, while many neopolyploids are meiotically unstable, polyploid lineages that survive in nature are generally stable and fertile; thus, those lineages that survive are those that are [...] Read more.

Newly formed polyploids often show extensive meiotic defects, resulting in aneuploid gametes, and thus reduced fertility. However, while many neopolyploids are meiotically unstable, polyploid lineages that survive in nature are generally stable and fertile; thus, those lineages that survive are those that are able to overcome these challenges. Several genes that promote polyploid stabilization are now known in plants, allowing speculation on the evolutionary origin of these meiotic adjustments. Here, I discuss results that show that meiotic stability can be achieved through the differentiation of certain alleles of certain genes between ploidies. These alleles, at least sometimes, seem to arise by novel mutation, while standing variation in either ancestral diploids or related polyploids, from which alleles can introgress, may also contribute. Growing evidence also suggests that the coevolution of multiple interacting genes has contributed to polyploid stabilization, and in allopolyploids, the return of duplicated genes to single copies (genome fractionation) may also play a role in meiotic stabilization. There is also some evidence that epigenetic regulation may be important, which can help explain why some polyploid lineages can partly stabilize quite rapidly. Full article

(This article belongs to the Special Issue Genetics of Meiotic Chromosome Dynamics)

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22 pages, 2282 KiB

Open AccessEditor’s ChoiceArticle

Molecular Responses to Thermal and Osmotic Stress in Arctic Intertidal Mussels (Mytilus edulis): The Limits of Resilience

by Nicholas J. Barrett, Jakob Thyrring, Elizabeth M. Harper, Mikael K. Sejr, Jesper G. Sørensen, Lloyd S. Peck and Melody S. Clark

Genes 2022, 13(1), 155; https://doi.org/10.3390/genes13010155 - 15 Jan 2022

Cited by 15 | Viewed by 4322

Abstract

Increases in Arctic temperatures have accelerated melting of the Greenland icesheet, exposing intertidal organisms, such as the blue mussel Mytilus edulis, to high air temperatures and low salinities in summer. However, the interaction of these combined stressors is poorly described at the transcriptional [...] Read more.

Increases in Arctic temperatures have accelerated melting of the Greenland icesheet, exposing intertidal organisms, such as the blue mussel Mytilus edulis, to high air temperatures and low salinities in summer. However, the interaction of these combined stressors is poorly described at the transcriptional level. Comparing expression profiles of M. edulis from experimentally warmed (30 °C and 33 °C) animals kept at control (23‰) and low salinities (15‰) revealed a significant lack of enrichment for Gene Ontology terms (GO), indicating that similar processes were active under all conditions. However, there was a progressive increase in the abundance of upregulated genes as each stressor was applied, with synergistic increases at 33 °C and 15‰, suggesting combined stressors push the animal towards their tolerance thresholds. Further analyses comparing the effects of salinity alone (23‰, 15‰ and 5‰) showed high expression of stress and osmoregulatory marker genes at the lowest salinity, implying that the cell is carrying out intracellular osmoregulation to maintain the cytosol as hyperosmotic. Identification of aquaporins and vacuolar-type ATPase transcripts suggested the cell may use fluid-filled cavities to excrete excess intracellular water, as previously identified in embryonic freshwater mussels. These results indicate that M. edulis has considerable resilience to heat stress and highly efficient mechanisms to acclimatise to lowered salinity in a changing world. Full article

(This article belongs to the Special Issue Polar Genomics)

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13 pages, 2058 KiB

Open AccessEditor’s ChoiceReview

LncRNAs and the Angiogenic Switch in Cancer: Clinical Significance and Therapeutic Opportunities

by Peace Mabeta, Rodney Hull and Zodwa Dlamini

Genes 2022, 13(1), 152; https://doi.org/10.3390/genes13010152 - 15 Jan 2022

Cited by 17 | Viewed by 2891

Abstract

Angiogenesis is one of the hallmarks of cancer, and the establishment of new blood vessels is vital to allow for a tumour to grow beyond 1–2 mm in size. The angiogenic switch is the term given to the point where the number or [...] Read more.

Angiogenesis is one of the hallmarks of cancer, and the establishment of new blood vessels is vital to allow for a tumour to grow beyond 1–2 mm in size. The angiogenic switch is the term given to the point where the number or activity of the pro-angiogenic factors exceeds that of the anti-angiogenic factors, resulting in the angiogenic process proceeding, giving rise to new blood vessels accompanied by increased tumour growth, metastasis, and potential drug resistance. Long noncoding ribonucleic acids (lncRNAs) have been found to play a role in the angiogenic switch by regulating gene expression, transcription, translation, and post translation modification. In this regard they play both anti-angiogenic and pro-angiogenic roles. The expression levels of the pro-angiogenic lncRNAs have been found to correlate with patient survival. These lncRNAs are also potential drug targets for the development of therapies that will inhibit or modify tumour angiogenesis. Here we review the roles of lncRNAs in regulating the angiogenic switch. We cover specific examples of both pro and anti-angiogenic lncRNAs and discuss their potential use as both prognostic biomarkers and targets for the development of future therapies. Full article

(This article belongs to the Special Issue Non-coding RNAs in Human Health and Diseases)

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28 pages, 5592 KiB

Open AccessEditor’s ChoiceArticle

Effects of BPA, BPS, and BPF on Oxidative Stress and Antioxidant Enzyme Expression in Bovine Oocytes and Spermatozoa

by Mimi Nguyen, Reem Sabry, Ola S. Davis and Laura A. Favetta

Genes 2022, 13(1), 142; https://doi.org/10.3390/genes13010142 - 14 Jan 2022

Cited by 26 | Viewed by 3924

Abstract

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes—COCs) and male (spermatozoa), oxidative stress [...] Read more.

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes—COCs) and male (spermatozoa), oxidative stress was measured by CM-H₂DCFDA assay and key ROS scavengers (SOD1, SOD2, GPX1, GPX4, CAT) were quantified at the mRNA and protein levels using qPCR and Western blot (COCs)/immunofluorescence (sperm). Either gamete was treated in five groups: control, vehicle, and 0.05 mg/mL of BPA, BPS, or BPF. Our results show elevated ROS in BPA-treated COCs but decreased production in BPS- and BPF-treated spermatozoa. Additionally, both mRNA and protein expression of SOD2, GPX1, and GPX4 were decreased in BPA-treated COCs (p < 0.05). In sperm, motility (p < 0.03), but not morphology, was significantly altered by bisphenols. SOD1 mRNA expression was significantly increased, while GPX4 was significantly reduced. These results support BPA’s ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm. However, BPS and BPF likely act through different mechanisms. Full article

(This article belongs to the Special Issue Effect of Toxicants on Oocyte Quality and Embryo Development)

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52 pages, 3921 KiB

Open AccessEditor’s ChoiceReview

Wnt Pathway Extracellular Components and Their Essential Roles in Bone Homeostasis

by Núria Martínez-Gil, Nerea Ugartondo, Daniel Grinberg and Susanna Balcells

Genes 2022, 13(1), 138; https://doi.org/10.3390/genes13010138 - 13 Jan 2022

Cited by 18 | Viewed by 4725

Abstract

The Wnt pathway is involved in several processes essential for bone development and homeostasis. For proper functioning, the Wnt pathway is tightly regulated by numerous extracellular elements that act by both activating and inhibiting the pathway at different moments. This review aims to [...] Read more.

The Wnt pathway is involved in several processes essential for bone development and homeostasis. For proper functioning, the Wnt pathway is tightly regulated by numerous extracellular elements that act by both activating and inhibiting the pathway at different moments. This review aims to describe, summarize and update the findings regarding the extracellular modulators of the Wnt pathway, including co-receptors, ligands and inhibitors, in relation to bone homeostasis, with an emphasis on the animal models generated, the diseases associated with each gene and the bone processes in which each member is involved. The precise knowledge of all these elements will help us to identify possible targets that can be used as a therapeutic target for the treatment of bone diseases such as osteoporosis. Full article

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

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17 pages, 4295 KiB

Open AccessEditor’s ChoiceArticle

Identification and Characterization of Wall-Associated Kinase (WAK) and WAK-like (WAKL) Gene Family in Juglans regia and Its Wild Related Species Juglans mandshurica

by Mengdi Li, Jiayu Ma, Hengzhao Liu, Mengwei Ou, Hang Ye and Peng Zhao

Genes 2022, 13(1), 134; https://doi.org/10.3390/genes13010134 - 12 Jan 2022

Cited by 18 | Viewed by 2930

Abstract

Wall-associated kinase (WAK) and WAK-like kinase (WAKL) are receptor-like kinases (RLKs), which play important roles in signal transduction between the cell wall and the cytoplasm in plants. WAK/WAKLs have been studied in many plants, but were rarely studied in the important economic walnut [...] Read more.

Wall-associated kinase (WAK) and WAK-like kinase (WAKL) are receptor-like kinases (RLKs), which play important roles in signal transduction between the cell wall and the cytoplasm in plants. WAK/WAKLs have been studied in many plants, but were rarely studied in the important economic walnut tree. In this study, 27 and 14 WAK/WAKL genes were identified in Juglans regia and its wild related species Juglans mandshurica, respectively. We found tandem duplication might play a critical role in the expansion of WAK/WAKL gene family in J. regia, and most of the WAK/WAKL homologous pairs underwent purified selection during evolution. All WAK/WAKL proteins have the extracellular WAK domain and the cytoplasmic protein kinase domain, and the latter was more conserved than the former. Cis-acting elements analysis showed that WAK/WAKL might be involved in plant growth and development, plant response to abiotic stress and hormones. Gene expression pattern analysis further indicated that most WAK/WAKL genes in J. regia might play a role in the development of leaves and be involved in plant response to biotic stress. Our study provides a new perspective for the evolutionary analysis of gene families in tree species and also provides potential candidate genes for studying WAK/WAKL gene function in walnuts. Full article

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

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19 pages, 3098 KiB

Open AccessEditor’s ChoiceArticle

Ancient DNA Methods Improve Forensic DNA Profiling of Korean War and World War II Unknowns

by Elena I. Zavala, Jacqueline Tyler Thomas, Kimberly Sturk-Andreaggi, Jennifer Daniels-Higginbotham, Kerriann K. Meyers, Suzanne Barrit-Ross, Ayinuer Aximu-Petri, Julia Richter, Birgit Nickel, Gregory E. Berg, Timothy P. McMahon, Matthias Meyer and Charla Marshall

Genes 2022, 13(1), 129; https://doi.org/10.3390/genes13010129 - 11 Jan 2022

Cited by 24 | Viewed by 7477

Abstract

The integration of massively parallel sequencing (MPS) technology into forensic casework has been of particular benefit to the identification of unknown military service members. However, highly degraded or chemically treated skeletal remains often fail to provide usable DNA profiles, even with sensitive mitochondrial [...] Read more.

The integration of massively parallel sequencing (MPS) technology into forensic casework has been of particular benefit to the identification of unknown military service members. However, highly degraded or chemically treated skeletal remains often fail to provide usable DNA profiles, even with sensitive mitochondrial (mt) DNA capture and MPS methods. In parallel, the ancient DNA field has developed workflows specifically for degraded DNA, resulting in the successful recovery of nuclear DNA and mtDNA from skeletal remains as well as sediment over 100,000 years old. In this study we use a set of disinterred skeletal remains from the Korean War and World War II to test if ancient DNA extraction and library preparation methods improve forensic DNA profiling. We identified an ancient DNA extraction protocol that resulted in the recovery of significantly more human mtDNA fragments than protocols previously used in casework. In addition, utilizing single-stranded rather than double-stranded library preparation resulted in increased attainment of reportable mtDNA profiles. This study emphasizes that the combination of ancient DNA extraction and library preparation methods evaluated here increases the success rate of DNA profiling, and likelihood of identifying historical remains. Full article

(This article belongs to the Special Issue Advances in Forensic Genetics)

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19 pages, 402 KiB

Open AccessEditor’s ChoiceReview

Role of Actionable Genes in Pursuing a True Approach of Precision Medicine in Monogenic Diabetes

by Antonella Marucci, Irene Rutigliano, Grazia Fini, Serena Pezzilli, Claudia Menzaghi, Rosa Di Paola and Vincenzo Trischitta

Genes 2022, 13(1), 117; https://doi.org/10.3390/genes13010117 - 9 Jan 2022

Cited by 9 | Viewed by 3377

Abstract

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1–5% of patients with diabetes. [...] Read more.

Monogenic diabetes is a genetic disorder caused by one or more variations in a single gene. It encompasses a broad spectrum of heterogeneous conditions, including neonatal diabetes, maturity onset diabetes of the young (MODY) and syndromic diabetes, affecting 1–5% of patients with diabetes. Some of these variants are harbored by genes whose altered function can be tackled by specific actions (“actionable genes”). In suspected patients, molecular diagnosis allows the implementation of effective approaches of precision medicine so as to allow individual interventions aimed to prevent, mitigate or delay clinical outcomes. This review will almost exclusively concentrate on the clinical strategy that can be specifically pursued in carriers of mutations in “actionable genes”, including ABCC8, KCNJ11, GCK, HNF1A, HNF4A, HNF1B, PPARG, GATA4 and GATA6. For each of them we will provide a short background on what is known about gene function and dysfunction. Then, we will discuss how the identification of their mutations in individuals with this form of diabetes, can be used in daily clinical practice to implement specific monitoring and treatments. We hope this article will help clinical diabetologists carefully consider who of their patients deserves timely genetic testing for monogenic diabetes. Full article

(This article belongs to the Special Issue Pharmacogenomics: Precision Medicine and Drug Response)

14 pages, 2034 KiB

Open AccessEditor’s ChoiceArticle

Unlocking the Complete Chloroplast Genome of a Native Tree Species from the Amazon Basin, Capirona (Calycophyllum Spruceanum, Rubiaceae), and Its Comparative Analysis with Other Ixoroideae Species

by Carla L. Saldaña, Pedro Rodriguez-Grados, Julio C. Chávez-Galarza, Shefferson Feijoo, Juan Carlos Guerrero-Abad, Héctor V. Vásquez, Jorge L. Maicelo, Jorge H. Jhoncon and Carlos I. Arbizu

Genes 2022, 13(1), 113; https://doi.org/10.3390/genes13010113 - 7 Jan 2022

Cited by 11 | Viewed by 3642

Abstract

Capirona (Calycophyllum spruceanum Benth.) belongs to subfamily Ixoroideae, one of the major lineages in the Rubiaceae family, and is an important timber tree. It originated in the Amazon Basin and has widespread distribution in Bolivia, Peru, Colombia, and Brazil. In this study, [...] Read more.

Capirona (Calycophyllum spruceanum Benth.) belongs to subfamily Ixoroideae, one of the major lineages in the Rubiaceae family, and is an important timber tree. It originated in the Amazon Basin and has widespread distribution in Bolivia, Peru, Colombia, and Brazil. In this study, we obtained the first complete chloroplast (cp) genome of capirona from the department of Madre de Dios located in the Peruvian Amazon. High-quality genomic DNA was used to construct libraries. Pair-end clean reads were obtained by PE 150 library and the Illumina HiSeq 2500 platform. The complete cp genome of C. spruceanum has a 154,480 bp in length with typical quadripartite structure, containing a large single copy (LSC) region (84,813 bp) and a small single-copy (SSC) region (18,101 bp), separated by two inverted repeat (IR) regions (25,783 bp). The annotation of C. spruceanum cp genome predicted 87 protein-coding genes (CDS), 8 ribosomal RNA (rRNA) genes, 37 transfer RNA (tRNA) genes, and one pseudogene. A total of 41 simple sequence repeats (SSR) of this cp genome were divided into mononucleotides (29), dinucleotides (5), trinucleotides (3), and tetranucleotides (4). Most of these repeats were distributed in the noncoding regions. Whole chloroplast genome comparison with the other six Ixoroideae species revealed that the small single copy and large single copy regions showed more divergence than inverted regions. Finally, phylogenetic analyses resolved that C. spruceanum is a sister species to Emmenopterys henryi and confirms its position within the subfamily Ixoroideae. This study reports for the first time the genome organization, gene content, and structural features of the chloroplast genome of C. spruceanum, providing valuable information for genetic and evolutionary studies in the genus Calycophyllum and beyond. Full article

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

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16 pages, 4193 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization and Target Prediction of Candidate miRNAs Related to Abiotic Stress Responses and/or Storage Root Development in Sweet Potato

by Li Sun, Yiyu Yang, Hong Pan, Jiahao Zhu, Mingku Zhu, Tao Xu, Zongyun Li and Tingting Dong

Genes 2022, 13(1), 110; https://doi.org/10.3390/genes13010110 - 6 Jan 2022

Cited by 12 | Viewed by 2362

Abstract

Sweet potato is a tuberous root crop with strong environmental stress resistance. It is beneficial to study its storage root formation and stress responses to identify sweet potato stress- and storage-root-thickening-related regulators. Here, six conserved miRNAs (miR156g, miR157d, miR158a-3p, miR161.1, miR167d and miR397a) [...] Read more.

Sweet potato is a tuberous root crop with strong environmental stress resistance. It is beneficial to study its storage root formation and stress responses to identify sweet potato stress- and storage-root-thickening-related regulators. Here, six conserved miRNAs (miR156g, miR157d, miR158a-3p, miR161.1, miR167d and miR397a) and six novel miRNAs (novel 104, novel 120, novel 140, novel 214, novel 359 and novel 522) were isolated and characterized in sweet potato. Tissue-specific expression patterns suggested that miR156g, miR157d, miR158a-3p, miR167d, novel 359 and novel 522 exhibited high expression in fibrous roots or storage roots and were all upregulated in response to storage-root-related hormones (indole acetic acid, IAA; zeaxanthin, ZT; abscisic acid, ABA; and gibberellin, GAs). The expression of miR156g, miR158a-3p, miR167d, novel 120 and novel 214 was induced or reduced dramatically by salt, dehydration and cold or heat stresses. Moreover, these miRNAs were all upregulated by ABA, a crucial hormone modulator in regulating abiotic stresses. Additionally, the potential targets of the twelve miRNAs were predicted and analyzed. Above all, these results indicated that these miRNAs might play roles in storage root development and/or stress responses in sweet potato as well as provided valuable information for the further investigation of the roles of miRNA in storage root development and stress responses. Full article

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

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18 pages, 499 KiB

Open AccessEditor’s ChoicePerspective

Genome Chaos, Information Creation, and Cancer Emergence: Searching for New Frameworks on the 50th Anniversary of the “War on Cancer”

by Julie Heng and Henry H. Heng

Genes 2022, 13(1), 101; https://doi.org/10.3390/genes13010101 - 31 Dec 2021

Cited by 35 | Viewed by 4930

Abstract

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national “war on cancer.” Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, [...] Read more.

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national “war on cancer.” Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, primarily through the characterization of cancer genes and the phenotypes associated with their pathways. Despite millions of publications and the overwhelming volume data generated from the Cancer Genome Project, clinical benefits are still lacking. In fact, the massive, diverse data also unexpectedly challenge the current somatic gene mutation theory of cancer, as well as the initial rationales behind sequencing so many cancer samples. Therefore, what should we do next? Should we continue to sequence more samples and push for further molecular characterizations, or should we take a moment to pause and think about the biological meaning of the data we have, integrating new ideas in cancer biology? On this special anniversary, we implore that it is time for the latter. We review the Genome Architecture Theory, an alternative conceptual framework that departs from gene-based theories. Specifically, we discuss the relationship between genes, genomes, and information-based platforms for future cancer research. This discussion will reinforce some newly proposed concepts that are essential for advancing cancer research, including two-phased cancer evolution (which reconciles evolutionary contributions from karyotypes and genes), stress-induced genome chaos (which creates new system information essential for macroevolution), the evolutionary mechanism of cancer (which unifies diverse molecular mechanisms to create new karyotype coding during evolution), and cellular adaptation and cancer emergence (which explains why cancer exists in the first place). We hope that these ideas will usher in new genomic and evolutionary conceptual frameworks and strategies for the next 50 years of cancer research. Full article

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

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15 pages, 300 KiB

Open AccessEditor’s ChoiceReview

Ischemic Stroke Genetics: What Is New and How to Apply It in Clinical Practice?

by Aleksandra Ekkert, Aleksandra Šliachtenko, Julija Grigaitė, Birutė Burnytė, Algirdas Utkus and Dalius Jatužis

Genes 2022, 13(1), 48; https://doi.org/10.3390/genes13010048 - 24 Dec 2021

Cited by 33 | Viewed by 8695

Abstract

The etiology of ischemic stroke is multifactorial. Although receiving less emphasis, genetic causes make a significant contribution to ischemic stroke genesis, especially in early-onset stroke. Several stroke classification systems based on genetic information corresponding to various stroke phenotypes were proposed. Twin and family [...] Read more.

The etiology of ischemic stroke is multifactorial. Although receiving less emphasis, genetic causes make a significant contribution to ischemic stroke genesis, especially in early-onset stroke. Several stroke classification systems based on genetic information corresponding to various stroke phenotypes were proposed. Twin and family history studies, as well as candidate gene approach, are common methods to discover genetic causes of stroke, however, both have their own limitations. Genome-wide association studies and next generation sequencing are more efficient, promising and increasingly used for daily diagnostics. Some monogenic disorders, despite covering only about 7% of stroke etiology, may cause well-known clinical manifestations that include stroke. Polygenic disorders are more frequent, causing about 38% of all ischemic strokes, and their identification is a rapidly developing field of modern stroke genetics. Current advances in human genetics provide opportunity for personalized prevention of stroke and novel treatment possibilities. Genetic risk scores (GRS) and extended polygenic risk scores (PRS) estimate cumulative contribution of known genetic factors to a specific outcome of stroke. Combining those scores with clinical information and risk factor profiles might result in better primary stroke prevention. Some authors encourage the use of stroke gene panels for stroke risk evaluation and further stroke research. Moreover, new biomarkers for stroke genetic causes and novel targets for gene therapy are on the horizon. In this article, we summarize the latest evidence and perspectives of ischemic stroke genetics that could be of interest to the practitioner and useful for day-to-day clinical work. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Modification in the Brain)

17 pages, 959 KiB

Open AccessEditor’s ChoiceReview

Two-Component Systems of S. aureus: Signaling and Sensing Mechanisms

by Lisa Bleul, Patrice Francois and Christiane Wolz

Genes 2022, 13(1), 34; https://doi.org/10.3390/genes13010034 - 23 Dec 2021

Cited by 33 | Viewed by 6563

Abstract

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms [...] Read more.

Staphylococcus aureus encodes 16 two-component systems (TCSs) that enable the bacteria to sense and respond to changing environmental conditions. Considering the function of these TCSs in bacterial survival and their potential role as drug targets, it is important to understand the exact mechanisms underlying signal perception. The differences between the sensing of appropriate signals and the transcriptional activation of the TCS system are often not well described, and the signaling mechanisms are only partially understood. Here, we review present insights into which signals are sensed by histidine kinases in S. aureus to promote appropriate gene expression in response to diverse environmental challenges. Full article

(This article belongs to the Special Issue Genetics, Genomics and Pathogenesis of Staphylococcus aureus)

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13 pages, 9753 KiB

Open AccessEditor’s ChoiceArticle

Detection of A-to-I RNA Editing in SARS-COV-2

by Ernesto Picardi, Luigi Mansi and Graziano Pesole

Genes 2022, 13(1), 41; https://doi.org/10.3390/genes13010041 - 23 Dec 2021

Cited by 26 | Viewed by 3545

Abstract

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments [...] Read more.

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions. Full article

(This article belongs to the Section Bioinformatics)

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23 pages, 815 KiB

Open AccessEditor’s ChoiceReview

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences

by Irene Peral-Sanchez, Batoul Hojeij, Diego A. Ojeda, Régine P. M. Steegers-Theunissen and Sandrine Willaime-Morawek

Genes 2022, 13(1), 31; https://doi.org/10.3390/genes13010031 - 23 Dec 2021

Cited by 27 | Viewed by 10757

Abstract

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can [...] Read more.

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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18 pages, 1243 KiB

Open AccessEditor’s ChoiceReview

Genetics and Epigenetics in Allergic Rhinitis

by Bo Yoon Choi, Munsoo Han, Ji Won Kwak and Tae Hoon Kim

Genes 2021, 12(12), 2004; https://doi.org/10.3390/genes12122004 - 17 Dec 2021

Cited by 39 | Viewed by 8720

Abstract

The pathogenesis of allergic rhinitis is associated with genetic, environmental, and epigenetic factors. Genotyping of single nucleotide polymorphisms (SNPs) is an advanced technique in the field of molecular genetics that is closely correlated with genome-wide association studies (GWASs) in large population groups with [...] Read more.

The pathogenesis of allergic rhinitis is associated with genetic, environmental, and epigenetic factors. Genotyping of single nucleotide polymorphisms (SNPs) is an advanced technique in the field of molecular genetics that is closely correlated with genome-wide association studies (GWASs) in large population groups with allergic diseases. Many recent studies have paid attention to the role of epigenetics, including alteration of DNA methylation, histone acetylation, and miRNA levels in the pathogenesis of allergic rhinitis. In this review article, genetics and epigenetics of allergic rhinitis, including information regarding functions and significance of previously known and newly-discovered genes, are summarized. Directions for future genetic and epigenetic studies of allergic rhinitis are also proposed. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Allergy Diseases)

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22 pages, 1337 KiB

Open AccessEditor’s ChoiceReview

Role of Basal ABA in Plant Growth and Development

by Benjamin P. Brookbank, Jasmin Patel, Sonia Gazzarrini and Eiji Nambara

Genes 2021, 12(12), 1936; https://doi.org/10.3390/genes12121936 - 30 Nov 2021

Cited by 81 | Viewed by 8726

Abstract

Abscisic acid (ABA) regulates various aspects of plant physiology, including promoting seed dormancy and adaptive responses to abiotic and biotic stresses. In addition, ABA plays an im-portant role in growth and development under non-stressed conditions. This review summarizes phenotypes of ABA biosynthesis and [...] Read more.

Abscisic acid (ABA) regulates various aspects of plant physiology, including promoting seed dormancy and adaptive responses to abiotic and biotic stresses. In addition, ABA plays an im-portant role in growth and development under non-stressed conditions. This review summarizes phenotypes of ABA biosynthesis and signaling mutants to clarify the roles of basal ABA in growth and development. The promotive and inhibitive actions of ABA in growth are characterized by stunted and enhanced growth of ABA-deficient and insensitive mutants, respectively. Growth regulation by ABA is both promotive and inhibitive, depending on the context, such as concentrations, tissues, and environmental conditions. Basal ABA regulates local growth including hyponastic growth, skotomorphogenesis and lateral root growth. At the cellular level, basal ABA is essential for proper chloroplast biogenesis, central metabolism, and expression of cell-cycle genes. Basal ABA also regulates epidermis development in the shoot, by inhibiting stomatal development, and deposition of hydrophobic polymers like a cuticular wax layer covering the leaf surface. In the root, basal ABA is involved in xylem differentiation and suberization of the endodermis. Hormone crosstalk plays key roles in growth and developmental processes regulated by ABA. Phenotypes of ABA-deficient and insensitive mutants indicate prominent functions of basal ABA in plant growth and development. Full article

(This article belongs to the Special Issue New Advances in Research on the Role of Abscisic Acid in Plant Development)

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13 pages, 296 KiB

Open AccessEditor’s ChoiceReview

Gene-Environment Interactions in Schizophrenia: A Literature Review

by Marah H. Wahbeh and Dimitrios Avramopoulos

Genes 2021, 12(12), 1850; https://doi.org/10.3390/genes12121850 - 23 Nov 2021

Cited by 50 | Viewed by 8937

Abstract

Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant [...] Read more.

Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup. Here, we provide a brief review of studies reporting evidence of such interactions, exploring genes and variants that moderate the effect of the environment to increase risk of developing psychosis. Discovering these interactions is crucial to our understanding of the pathogenesis of complex disorders. It can help in identifying individuals at high risk, in developing individualized treatments and prevention plans, and can influence clinical management. Full article

(This article belongs to the Special Issue The Relationship between Psychiatric Disorders and Genetics)

28 pages, 2323 KiB

Open AccessEditor’s ChoiceArticle

Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data

by Victor B. Pedrosa, Flavio S. Schenkel, Shi-Yi Chen, Hinayah R. Oliveira, Theresa M. Casey, Melkaye G. Melka and Luiz F. Brito

Genes 2021, 12(11), 1830; https://doi.org/10.3390/genes12111830 - 19 Nov 2021

Cited by 48 | Viewed by 4799

Abstract

Lactation persistency and milk production are among the most economically important traits in the dairy industry. In this study, we explored the association of over 6.1 million imputed whole-genome sequence variants with lactation persistency (LP), milk yield (MILK), fat yield (FAT), fat percentage [...] Read more.

Lactation persistency and milk production are among the most economically important traits in the dairy industry. In this study, we explored the association of over 6.1 million imputed whole-genome sequence variants with lactation persistency (LP), milk yield (MILK), fat yield (FAT), fat percentage (FAT%), protein yield (PROT), and protein percentage (PROT%) in North American Holstein cattle. We identified 49, 3991, 2607, 4459, 805, and 5519 SNPs significantly associated with LP, MILK, FAT, FAT%, PROT, and PROT%, respectively. Various known associations were confirmed while several novel candidate genes were also revealed, including ARHGAP35, NPAS1, TMEM160, ZC3H4, SAE1, ZMIZ1, PPIF, LDB2, ABI3, SERPINB6, and SERPINB9 for LP; NIM1K, ZNF131, GABRG1, GABRA2, DCHS1, and SPIDR for MILK; NR6A1, OLFML2A, EXT2, POLD1, GOT1, and ETV6 for FAT; DPP6, LRRC26, and the KCN gene family for FAT%; CDC14A, RTCA, HSTN, and ODAM for PROT; and HERC3, HERC5, LALBA, CCL28, and NEURL1 for PROT%. Most of these genes are involved in relevant gene ontology (GO) terms such as fatty acid homeostasis, transporter regulator activity, response to progesterone and estradiol, response to steroid hormones, and lactation. The significant genomic regions found contribute to a better understanding of the molecular mechanisms related to LP and milk production in North American Holstein cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

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32 pages, 780 KiB

Open AccessEditor’s ChoiceReview

On the Identification of Body Fluids and Tissues: A Crucial Link in the Investigation and Solution of Crime

by Titia Sijen and SallyAnn Harbison

Genes 2021, 12(11), 1728; https://doi.org/10.3390/genes12111728 - 28 Oct 2021

Cited by 45 | Viewed by 11099

Abstract

Body fluid and body tissue identification are important in forensic science as they can provide key evidence in a criminal investigation and may assist the court in reaching conclusions. Establishing a link between identifying the fluid or tissue and the DNA profile adds [...] Read more.

Body fluid and body tissue identification are important in forensic science as they can provide key evidence in a criminal investigation and may assist the court in reaching conclusions. Establishing a link between identifying the fluid or tissue and the DNA profile adds further weight to this evidence. Many forensic laboratories retain techniques for the identification of biological fluids that have been widely used for some time. More recently, many different biomarkers and technologies have been proposed for identification of body fluids and tissues of forensic relevance some of which are now used in forensic casework. Here, we summarize the role of body fluid/ tissue identification in the evaluation of forensic evidence, describe how such evidence is detected at the crime scene and in the laboratory, elaborate different technologies available to do this, and reflect real life experiences. We explain how, by including this information, crucial links can be made to aid in the investigation and solution of crime. Full article

(This article belongs to the Special Issue Advances in Forensic Genetics)

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16 pages, 4772 KiB

Open AccessEditor’s ChoiceArticle

Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis

by Shuo Yu, Min Wang, Hang Zhang, Xingjun Guo and Renyi Qin

Genes 2021, 12(11), 1701; https://doi.org/10.3390/genes12111701 - 26 Oct 2021

Cited by 36 | Viewed by 2235

Abstract

Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to [...] Read more.

Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial–mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients. Full article

(This article belongs to the Special Issue MicroRNAs as Biomarkers and Therapeutic Targets in Disease)

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16 pages, 1950 KiB

Open AccessEditor’s ChoiceReview

Breeding for Resistance to Fusarium Wilt of Tomato: A Review

by Jessica Chitwood-Brown, Gary E. Vallad, Tong Geon Lee and Samuel F. Hutton

Genes 2021, 12(11), 1673; https://doi.org/10.3390/genes12111673 - 23 Oct 2021

Cited by 45 | Viewed by 8634

Abstract

For over a century, breeders have worked to develop tomato (Solanum lycopersicum) cultivars with resistance to Fusarium wilt (Fol) caused by the soilborne fungus Fusarium oxysporum f. sp. lycopersici. Host resistance is the most effective strategy for the [...] Read more.

For over a century, breeders have worked to develop tomato (Solanum lycopersicum) cultivars with resistance to Fusarium wilt (Fol) caused by the soilborne fungus Fusarium oxysporum f. sp. lycopersici. Host resistance is the most effective strategy for the management of this disease. For each of the three Fol races, resistance has been introgressed from wild tomato species, predominately in the form of R genes. The I, I-2, I-3, and I-7 R genes have each been identified, as well as the corresponding Avr effectors in the fungus with the exception of Avr7. The mechanisms by which the R gene protein products recognize these effectors, however, has not been elucidated. Extensive genetic mapping, gene cloning, and genome sequencing efforts support the development of tightly-linked molecular markers, which greatly expedite tomato breeding and the development of elite, Fol resistant cultivars. These resources also provide important tools for pyramiding resistance genes and should support the durability of host resistance. Full article

(This article belongs to the Special Issue Tomato Genetics)

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20 pages, 1474 KiB

Open AccessEditor’s ChoiceReview

ABA and Bud Dormancy in Perennials: Current Knowledge and Future Perspective

by Wenqiang Pan, Jiahui Liang, Juanjuan Sui, Jingru Li, Chang Liu, Yin Xin, Yanmin Zhang, Shaokun Wang, Yajie Zhao, Jie Zhang, Mingfang Yi, Sonia Gazzarrini and Jian Wu

Genes 2021, 12(10), 1635; https://doi.org/10.3390/genes12101635 - 18 Oct 2021

Cited by 43 | Viewed by 6097

Abstract

Bud dormancy is an evolved trait that confers adaptation to harsh environments, and affects flower differentiation, crop yield and vegetative growth in perennials. ABA is a stress hormone and a major regulator of dormancy. Although the physiology of bud dormancy is complex, several [...] Read more.

Bud dormancy is an evolved trait that confers adaptation to harsh environments, and affects flower differentiation, crop yield and vegetative growth in perennials. ABA is a stress hormone and a major regulator of dormancy. Although the physiology of bud dormancy is complex, several advancements have been achieved in this field recently by using genetics, omics and bioinformatics methods. Here, we review the current knowledge on the role of ABA and environmental signals, as well as the interplay of other hormones and sucrose, in the regulation of this process. We also discuss emerging potential mechanisms in this physiological process, including epigenetic regulation. Full article

(This article belongs to the Special Issue New Advances in Research on the Role of Abscisic Acid in Plant Development)

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29 pages, 8312 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Profiling of Maize (Zea mays L.) Leaves Reveals Key Cold-Responsive Genes, Transcription Factors, and Metabolic Pathways Regulating Cold Stress Tolerance at the Seedling Stage

by Joram Kiriga Waititu, Quan Cai, Ying Sun, Yinglu Sun, Congcong Li, Chunyi Zhang, Jun Liu and Huan Wang

Genes 2021, 12(10), 1638; https://doi.org/10.3390/genes12101638 - 18 Oct 2021

Cited by 24 | Viewed by 4034

Abstract

Cold tolerance is a complex trait that requires a critical perspective to understand its underpinning mechanism. To unravel the molecular framework underlying maize (Zea mays L.) cold stress tolerance, we conducted a comparative transcriptome profiling of 24 cold-tolerant and 22 cold-sensitive inbred [...] Read more.

Cold tolerance is a complex trait that requires a critical perspective to understand its underpinning mechanism. To unravel the molecular framework underlying maize (Zea mays L.) cold stress tolerance, we conducted a comparative transcriptome profiling of 24 cold-tolerant and 22 cold-sensitive inbred lines affected by cold stress at the seedling stage. Using the RNA-seq method, we identified 2237 differentially expressed genes (DEGs), namely 1656 and 581 annotated and unannotated DEGs, respectively. Further analysis of the 1656 annotated DEGs mined out two critical sets of cold-responsive DEGs, namely 779 and 877 DEGs, which were significantly enhanced in the tolerant and sensitive lines, respectively. Functional analysis of the 1656 DEGs highlighted the enrichment of signaling, carotenoid, lipid metabolism, transcription factors (TFs), peroxisome, and amino acid metabolism. A total of 147 TFs belonging to 32 families, including MYB, ERF, NAC, WRKY, bHLH, MIKC MADS, and C₂H₂, were strongly altered by cold stress. Moreover, the tolerant lines’ 779 enhanced DEGs were predominantly associated with carotenoid, ABC transporter, glutathione, lipid metabolism, and amino acid metabolism. In comparison, the cold-sensitive lines’ 877 enhanced DEGs were significantly enriched for MAPK signaling, peroxisome, ribosome, and carbon metabolism pathways. The biggest proportion of the unannotated DEGs was implicated in the roles of long non-coding RNAs (lncRNAs). Taken together, this study provides valuable insights that offer a deeper understanding of the molecular mechanisms underlying maize response to cold stress at the seedling stage, thus opening up possibilities for a breeding program of maize tolerance to cold stress. Full article

(This article belongs to the Special Issue Genetics and Evolution of Abiotic Stress Tolerance in Plants)

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22 pages, 825 KiB

Open AccessEditor’s ChoiceReview

The Expanding Constellation of Histone Post-Translational Modifications in the Epigenetic Landscape

by Vincenzo Cavalieri

Genes 2021, 12(10), 1596; https://doi.org/10.3390/genes12101596 - 10 Oct 2021

Cited by 48 | Viewed by 5459

Abstract

The emergence of a nucleosome-based chromatin structure accompanied the evolutionary transition from prokaryotes to eukaryotes. In this scenario, histones became the heart of the complex and precisely timed coordination between chromatin architecture and functions during adaptive responses to environmental influence by means of [...] Read more.

The emergence of a nucleosome-based chromatin structure accompanied the evolutionary transition from prokaryotes to eukaryotes. In this scenario, histones became the heart of the complex and precisely timed coordination between chromatin architecture and functions during adaptive responses to environmental influence by means of epigenetic mechanisms. Notably, such an epigenetic machinery involves an overwhelming number of post-translational modifications at multiple residues of core and linker histones. This review aims to comprehensively describe old and recent evidence in this exciting field of research. In particular, histone post-translational modification establishing/removal mechanisms, their genomic locations and implication in nucleosome dynamics and chromatin-based processes, as well as their harmonious combination and interdependence will be discussed. Full article

(This article belongs to the Special Issue Epigenetic Control of Chromatin Organization and Plasticity)

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13 pages, 3390 KiB

Open AccessEditor’s ChoiceReview

Renal Cell Carcinoma in Tuberous Sclerosis Complex

by Elizabeth P. Henske, Kristine M. Cornejo and Chin-Lee Wu

Genes 2021, 12(10), 1585; https://doi.org/10.3390/genes12101585 - 8 Oct 2021

Cited by 35 | Viewed by 4654

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent. There are three major renal lesions in TSC: angiomyolipomas, cysts, and renal cell carcinoma (RCC). Major recent advances have revolutionized our understanding of TSC-associated RCC, including two series [...] Read more.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent. There are three major renal lesions in TSC: angiomyolipomas, cysts, and renal cell carcinoma (RCC). Major recent advances have revolutionized our understanding of TSC-associated RCC, including two series that together include more than 100 TSC-RCC cases, demonstrating a mean age at onset of about 36 years, tumors in children as young as 7, and a striking 2:1 female predominance. These series also provide the first detailed understanding of the pathologic features of these distinctive tumors, which include chromophobe-like features and eosinophilia, with some of the tumors unclassified. This pathologic heterogeneity is distinctive and reminiscent of the pathologic heterogeneity in Birt–Hogg–Dube-associated RCC, which also includes chromophobe-like tumors. Additional advances include the identification of sporadic counterpart tumors that carry somatic TSC1/TSC2/mTOR mutations. These include unclassified eosinophilic tumors, eosinophilic solid cystic RCC (ESC-RCC), and RCC with leiomyomatous stroma (RCCLMS). A variety of epithelial renal neoplasms have been identified both in patients with tuberous sclerosis complex (TSC) and in the nonsyndromic setting associated with somatic mutations in the TSC1 and TSC2 genes. Interestingly, whether tumors are related to a germline or somatic TSC1/2 mutation, these tumors often display similar morphologic and immunophenotypic features. Finally, recent work has identified molecular links between TSC and BHD-associated tumors, involving the TFEB/TFE3 transcription factors. Full article

(This article belongs to the Special Issue Genetics of Inherited Kidney Cancer)

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18 pages, 978 KiB

Open AccessEditor’s ChoiceReview

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

by Naoki Yamamoto, Nao Nishida, Rain Yamamoto, Takashi Gojobori, Kunitada Shimotohno, Masashi Mizokami and Yasuo Ariumi

Genes 2021, 12(10), 1572; https://doi.org/10.3390/genes12101572 - 1 Oct 2021

Cited by 27 | Viewed by 4282

Abstract

The renin–angiotensin–aldosterone system (RAAS) appears to play an important role in SARS-CoV-2 infection. Polymorphisms within the genes that control this enzymatic system are candidates for elucidating the pathogenesis of COVID-19, since COVID-19 is not only a pulmonary disease but also affects many organs [...] Read more.

The renin–angiotensin–aldosterone system (RAAS) appears to play an important role in SARS-CoV-2 infection. Polymorphisms within the genes that control this enzymatic system are candidates for elucidating the pathogenesis of COVID-19, since COVID-19 is not only a pulmonary disease but also affects many organs and systems throughout the body in multiple ways. Most striking is the fact that ACE2, one of the major components of the RAAS, is a prerequisite for SARS-COV-2 infection. Recently, we and other groups reported an association between a polymorphism of the ACE1 gene (a homolog of ACE2) and the phenotypic expression of COVID-19, particularly in its severity. The ethnic difference in ACE1 insertion (I)/deletion (D) polymorphism seems to explain the apparent difference in mortality between the West and East Asia. The purpose of this review was to further evaluate the evidence linking ACE1 polymorphisms to COVID-19. We searched the Medline database (2019–2021) for reference citations of relevant articles and selected studies on the clinical outcome of COVID-19 related to ACE1 I/D polymorphism. Although the numbers of patients are not large enough yet, most available evidence supports the notion that the DD genotype adversely influences COVID-19 symptoms. Surprisingly, small studies conducted in several countries yielded opposite results, suggesting that the ACE1 II genotype is a risk factor. This contradictory result may be the case in certain geographic areas, especially in subgroups of patients. It may also be due to interactions with other genes or to yet unexplained biochemical mechanisms. According to our hypothesis, such candidates are genes that are functionally involved in the pathophysiology of COVID-19, can act in concert with the ACE1 DD genotype, and that show differences in their frequency between the West and East Asia. For this, we conducted research focusing on Alu-related genes. The current study on the ACE1 genotype will provide potentially new clues to the pathogenesis, treatment, and diagnosis of SARS-CoV-2 infections. Full article

(This article belongs to the Collection Genotype-Phenotype Study in Disease)

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40 pages, 2967 KiB

Open AccessEditor’s ChoiceReview

A Review of Probabilistic Genotyping Systems: EuroForMix, DNAStatistX and STRmix™

by Peter Gill, Corina Benschop, John Buckleton, Øyvind Bleka and Duncan Taylor

Genes 2021, 12(10), 1559; https://doi.org/10.3390/genes12101559 - 30 Sep 2021

Cited by 34 | Viewed by 5847

Abstract

Probabilistic genotyping has become widespread. EuroForMix and DNAStatistX are both based upon maximum likelihood estimation using a γ model, whereas STRmix™ is a Bayesian approach that specifies prior distributions on the unknown model parameters. A general overview is provided of the historical development [...] Read more.

Probabilistic genotyping has become widespread. EuroForMix and DNAStatistX are both based upon maximum likelihood estimation using a γ model, whereas STRmix™ is a Bayesian approach that specifies prior distributions on the unknown model parameters. A general overview is provided of the historical development of probabilistic genotyping. Some general principles of interpretation are described, including: the application to investigative vs. evaluative reporting; detection of contamination events; inter and intra laboratory studies; numbers of contributors; proposition setting and validation of software and its performance. This is followed by details of the evolution, utility, practice and adoption of the software discussed. Full article

(This article belongs to the Special Issue Advances in Forensic Genetics)

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12 pages, 1073 KiB

Open AccessEditor’s ChoiceReview

DEAD-Box RNA Helicases and Genome Stability

by Michael Cargill, Rasika Venkataraman and Stanley Lee

Genes 2021, 12(10), 1471; https://doi.org/10.3390/genes12101471 - 23 Sep 2021

Cited by 49 | Viewed by 8254

Abstract

DEAD-box RNA helicases are important regulators of RNA metabolism and have been implicated in the development of cancer. Interestingly, these helicases constitute a major recurring family of RNA-binding proteins important for protecting the genome. Current studies have provided insight into the connection between [...] Read more.

DEAD-box RNA helicases are important regulators of RNA metabolism and have been implicated in the development of cancer. Interestingly, these helicases constitute a major recurring family of RNA-binding proteins important for protecting the genome. Current studies have provided insight into the connection between genomic stability and several DEAD-box RNA helicase family proteins including DDX1, DDX3X, DDX5, DDX19, DDX21, DDX39B, and DDX41. For each helicase, we have reviewed evidence supporting their role in protecting the genome and their suggested mechanisms. Such helicases regulate the expression of factors promoting genomic stability, prevent DNA damage, and can participate directly in the response and repair of DNA damage. Finally, we summarized the pathological and therapeutic relationship between DEAD-box RNA helicases and cancer with respect to their novel role in genome stability. Full article

(This article belongs to the Special Issue Reciprocal Links between RNA Metabolism and DNA Damage)

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15 pages, 12451 KiB

Open AccessEditor’s ChoiceArticle

CpBBX19, a B-Box Transcription Factor Gene of Chimonanthus praecox, Improves Salt and Drought Tolerance in Arabidopsis

by Huafeng Wu, Xia Wang, Yinzhu Cao, Haiyuan Zhang, Run Hua, Huamin Liu and Shunzhao Sui

Genes 2021, 12(9), 1456; https://doi.org/10.3390/genes12091456 - 21 Sep 2021

Cited by 23 | Viewed by 2842

Abstract

Zinc-finger proteins are important transcription factors in plants, responding to adversity and regulating the growth and development of plants. However, the roles of the BBX gene family of zinc-finger proteins in wintersweet (Chimonanthus praecox) have yet to be elucidated. In this [...] Read more.

Zinc-finger proteins are important transcription factors in plants, responding to adversity and regulating the growth and development of plants. However, the roles of the BBX gene family of zinc-finger proteins in wintersweet (Chimonanthus praecox) have yet to be elucidated. In this study, a group IV subfamily BBX gene, CpBBX19, was identified and isolated from wintersweet. Quantitative real-time PCR (qRT-PCR) analyses revealed that CpBBX19 was expressed in all tissues and that expression was highest in cotyledons and inner petals. CpBBX19 was also expressed in all flower development stages, with the highest expression detected in early initiating bloom, followed by late initiating bloom and bloom. In addition, the expression of CpBBX19 was induced by different abiotic stress (cold, heat, NaCl, and drought) and hormone (ABA and MeJA) treatments. Heterologous expression of CpBBX19 in Arabidopsis thaliana (Arabidopsis) enhanced the tolerance of this plant to salt and drought stress as electrolyte leakage and malondialdehyde (MDA) concentrations in transgenic Arabidopsis after stress treatments were significantly lower than those in wild-type (WT) plants. In conclusion, this research demonstrated that CpBBX19 plays a role in the abiotic stress tolerance of wintersweet. These findings lay a foundation for future studies on the BBX gene family of wintersweet and enrich understanding of the molecular mechanism of stress resistance in wintersweet. Full article

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

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13 pages, 1352 KiB

Open AccessEditor’s ChoiceReview

Histone Acetylation Changes in Plant Response to Drought Stress

by Shuang Li, Xu He, Yuan Gao, Chenguang Zhou, Vincent L. Chiang and Wei Li

Genes 2021, 12(9), 1409; https://doi.org/10.3390/genes12091409 - 13 Sep 2021

Cited by 33 | Viewed by 4060

Abstract

Drought stress causes recurrent damage to a healthy ecosystem because it has major adverse effects on the growth and productivity of plants. However, plants have developed drought avoidance and resilience for survival through many strategies, such as increasing water absorption and conduction, reducing [...] Read more.

Drought stress causes recurrent damage to a healthy ecosystem because it has major adverse effects on the growth and productivity of plants. However, plants have developed drought avoidance and resilience for survival through many strategies, such as increasing water absorption and conduction, reducing water loss and conversing growth stages. Understanding how plants respond and regulate drought stress would be important for creating and breeding better plants to help maintain a sound ecosystem. Epigenetic marks are a group of regulators affecting drought response and resilience in plants through modification of chromatin structure to control the transcription of pertinent genes. Histone acetylation is an ubiquitous epigenetic mark. The level of histone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), determines whether the chromatin is open or closed, thereby controlling access of DNA-binding proteins for transcriptional activation. In this review, we summarize histone acetylation changes in plant response to drought stress, and review the functions of HATs and HDACs in drought response and resistance. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Changes in Plant Response to Abiotic Stress)

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13 pages, 269 KiB

Open AccessEditor’s ChoiceReview

Pharmacogenomics: An Update on Biologics and Small-Molecule Drugs in the Treatment of Psoriasis

by Valerio Caputo, Claudia Strafella, Terenzio Cosio, Caterina Lanna, Elena Campione, Giuseppe Novelli, Emiliano Giardina and Raffaella Cascella

Genes 2021, 12(9), 1398; https://doi.org/10.3390/genes12091398 - 10 Sep 2021

Cited by 29 | Viewed by 4014

Abstract

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able [...] Read more.

Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice. Full article

(This article belongs to the Special Issue Pharmacogenomics: Precision Medicine and Drug Response)

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