Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.2
2.8
Journals
Genes
Editor’s Choice
share announcement

Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
22 pages, 1790 KiB  
Review
Machine Learning-Assisted Approaches in Modernized Plant Breeding Programs
by Mohsen Yoosefzadeh Najafabadi, Mohsen Hesami and Milad Eskandari
Genes 2023, 14(4), 777; https://doi.org/10.3390/genes14040777 - 23 Mar 2023
Cited by 31 | Viewed by 7532
Abstract
In the face of a growing global population, plant breeding is being used as a sustainable tool for increasing food security. A wide range of high-throughput omics technologies have been developed and used in plant breeding to accelerate crop improvement and develop new [...] Read more.
In the face of a growing global population, plant breeding is being used as a sustainable tool for increasing food security. A wide range of high-throughput omics technologies have been developed and used in plant breeding to accelerate crop improvement and develop new varieties with higher yield performance and greater resilience to climate changes, pests, and diseases. With the use of these new advanced technologies, large amounts of data have been generated on the genetic architecture of plants, which can be exploited for manipulating the key characteristics of plants that are important for crop improvement. Therefore, plant breeders have relied on high-performance computing, bioinformatics tools, and artificial intelligence (AI), such as machine-learning (ML) methods, to efficiently analyze this vast amount of complex data. The use of bigdata coupled with ML in plant breeding has the potential to revolutionize the field and increase food security. In this review, some of the challenges of this method along with some of the opportunities it can create will be discussed. In particular, we provide information about the basis of bigdata, AI, ML, and their related sub-groups. In addition, the bases and functions of some learning algorithms that are commonly used in plant breeding, three common data integration strategies for the better integration of different breeding datasets using appropriate learning algorithms, and future prospects for the application of novel algorithms in plant breeding will be discussed. The use of ML algorithms in plant breeding will equip breeders with efficient and effective tools to accelerate the development of new plant varieties and improve the efficiency of the breeding process, which are important for tackling some of the challenges facing agriculture in the era of climate change. Full article
(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)
►▼ Show Figures

Figure 1

22 pages, 1064 KiB  
Review
Satellite DNAs—From Localized to Highly Dispersed Genome Components
by Eva Šatović-Vukšić and Miroslav Plohl
Genes 2023, 14(3), 742; https://doi.org/10.3390/genes14030742 - 17 Mar 2023
Cited by 30 | Viewed by 3676
Abstract
According to the established classical view, satellite DNAs are defined as abundant non-coding DNA sequences repeated in tandem that build long arrays located in heterochromatin. Advances in sequencing methodologies and development of specialized bioinformatics tools enabled defining a collection of all repetitive DNAs [...] Read more.
According to the established classical view, satellite DNAs are defined as abundant non-coding DNA sequences repeated in tandem that build long arrays located in heterochromatin. Advances in sequencing methodologies and development of specialized bioinformatics tools enabled defining a collection of all repetitive DNAs and satellite DNAs in a genome, the repeatome and the satellitome, respectively, as well as their reliable annotation on sequenced genomes. Supported by various non-model species included in recent studies, the patterns of satellite DNAs and satellitomes as a whole showed much more diversity and complexity than initially thought. Differences are not only in number and abundance of satellite DNAs but also in their distribution across the genome, array length, interspersion patterns, association with transposable elements, localization in heterochromatin and/or in euchromatin. In this review, we compare characteristic organizational features of satellite DNAs and satellitomes across different animal and plant species in order to summarize organizational forms and evolutionary processes that may lead to satellitomes’ diversity and revisit some basic notions regarding repetitive DNA landscapes in genomes. Full article
(This article belongs to the Special Issue Satellite DNA Genomics)
►▼ Show Figures

Figure 1

14 pages, 1406 KiB  
Article
Mutational Spectrum of the ABCA12 Gene and Genotype–Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis
by Alrun Hotz, Julia Kopp, Emmanuelle Bourrat, Vinzenz Oji, Kira Süßmuth, Katalin Komlosi, Bakar Bouadjar, Iliana Tantcheva-Poór, Maritta Hellström Pigg, Regina C. Betz, Kathrin Giehl, Fiona Schedel, Lisa Weibel, Solveig Schulz, Dora V. Stölzl, Gianluca Tadini, Emine Demiral, Karin Berggard, Andreas D. Zimmer, Svenja Alter and Judith Fischeradd Show full author list remove Hide full author list
Genes 2023, 14(3), 717; https://doi.org/10.3390/genes14030717 - 15 Mar 2023
Cited by 8 | Viewed by 5120
Abstract
Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, [...] Read more.
Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI. Full article
(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2023)
►▼ Show Figures

Figure 1

14 pages, 6061 KiB  
Article
SESN2 Could Be a Potential Marker for Diagnosis and Prognosis in Glioma
by Lingdan Xu, Zelin Liu, Huihui Wang, Jiyuan Lu, Jia Xu, Yucheng Meng, Ke Huang and Bin Liu
Genes 2023, 14(3), 701; https://doi.org/10.3390/genes14030701 - 12 Mar 2023
Cited by 6 | Viewed by 2252
Abstract
(1) Background: Glioma is among the most common brain tumors, and is difficult to eradicate with current therapeutic strategies due to its highly invasive and aggressive characteristics. Sestrin2 (SESN2) is an autophagy inducer. The effect of SESN2 on glioma is controversial [...] Read more.
(1) Background: Glioma is among the most common brain tumors, and is difficult to eradicate with current therapeutic strategies due to its highly invasive and aggressive characteristics. Sestrin2 (SESN2) is an autophagy inducer. The effect of SESN2 on glioma is controversial and unclear. (2) Methods: We downloaded related RNA-seq data from the TCGA and GTEx databases. Bioinformatic analyses including differential gene expression analysis, KM survival curve analysis, univariate and multivariate Cox regression analyses, nomogram analysis, ROC curve analysis, gene function enrichment analysis, and immune cell infiltration analysis were conducted. In addition, data from the Human Protein Atlas (HPA) database were collected to validate SESN2 expression in glioma. (3) Results: In comparison with normal tissue, expression of SESN2 in glioma tissue was higher, and those with higher expressions had significantly lower overall survival rates. The results of univariate Cox regression analyses showed that SESN2 can be a disadvantageous factor in poor glioma prognosis. Both nomograms and ROC curves confirmed these findings. Meanwhile, according to gene function analysis, SESN2 may be involved in immune responses and the tumor microenvironment (TME). Based on the HPA database results, SESN2 is localized in the cytosol and shows high expression in glioma. (4) Conclusions: The expression of SESN2 in gliomas was positively relevant to a poorer prognosis, suggesting that SESN2 could be used as a prognostic gene. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

18 pages, 6196 KiB  
Article
Codon Usage Analyses Reveal the Evolutionary Patterns among Plastid Genes of Saxifragales at a Larger-Sampling Scale
by De Bi, Shiyun Han, Jun Zhou, Maojin Zhao, Sijia Zhang and Xianzhao Kan
Genes 2023, 14(3), 694; https://doi.org/10.3390/genes14030694 - 11 Mar 2023
Cited by 6 | Viewed by 1763
Abstract
Saxifragales is a 15-family order of early-divergent Eudicots with a rich morphological diversity and an ancient rapid radiation. Codon usage bias (CUB) analyses have emerged as an essential tool for understanding the evolutionary dynamics in genes. Thus far, the codon utilization patterns had [...] Read more.
Saxifragales is a 15-family order of early-divergent Eudicots with a rich morphological diversity and an ancient rapid radiation. Codon usage bias (CUB) analyses have emerged as an essential tool for understanding the evolutionary dynamics in genes. Thus far, the codon utilization patterns had only been reported in four separate genera within Saxifragales. This study provides a comprehensive assessment of the codon manipulation based on 50 plastid genes, covering 11 constituent families at a larger sampling scale. Our results first showed a high preference for AT bases and AT-ending codons. We then used effective number of codons (ENC) to assess a range of codon bias levels in the plastid genes. We also detected high-informative intrafamilial differences of ENC in three families. Subsequently, parity rule 2 (PR2) plot analyses revealed both family-unique and order-shared bias patterns. Most importantly, the ENC plots and neutrality analyses collectively supported the dominant roles of selection in the CUB of Saxifragales plastid genes. Notably, the phylogenetic affinities inferred by both ML and BI methods were consistent with each other, and they all comprised two primary clades and four subclades. These findings significantly enhance our understanding of the evolutionary processes of the Saxifrage order, and could potentially inspire more CUB analyses at higher taxonomic levels. Full article
(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome)
►▼ Show Figures

Figure 1

13 pages, 2723 KiB  
Article
Genetic and Clinical Characterization of Danish Achromatopsia Patients
by Mette Kjøbæk Gundestrup Andersen, Mette Bertelsen, Karen Grønskov, Susanne Kohl and Line Kessel
Genes 2023, 14(3), 690; https://doi.org/10.3390/genes14030690 - 10 Mar 2023
Cited by 6 | Viewed by 2287
Abstract
Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This [...] Read more.
Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945–2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: CNGA3; CNGB3; GNAT2; PDE6C and PDE6H; and novel variants were identified in CNGB3 and PDE6C. Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in CNGB3 and PDE6C. The results indicate that myopia could be more frequently occurring with variants in GNAT2, PDE6C and PDE6H and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes. Full article
(This article belongs to the Special Issue Genetics in Retinal Diseases)
►▼ Show Figures

Figure 1

21 pages, 758 KiB  
Review
The Autism Spectrum: Behavioral, Psychiatric and Genetic Associations
by Ann Genovese and Merlin G. Butler
Genes 2023, 14(3), 677; https://doi.org/10.3390/genes14030677 - 9 Mar 2023
Cited by 42 | Viewed by 17141
Abstract
Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication skills and stereotypic, rigid or repetitive behaviors. We review common behavioral, psychiatric and genetic associations related to ASD. Autism affects about 2% of [...] Read more.
Autism spectrum disorder (ASD) consists of a group of heterogeneous genetic neurobehavioral disorders associated with developmental impairments in social communication skills and stereotypic, rigid or repetitive behaviors. We review common behavioral, psychiatric and genetic associations related to ASD. Autism affects about 2% of children with 4:1 male-to-female ratio and a heritability estimate between 70 and 90%. The etiology of ASD involves a complex interplay between inheritance and environmental factors influenced by epigenetics. Over 800 genes and dozens of genetic syndromes are associated with ASD. Novel gene–protein interactions with pathway and molecular function analyses have identified at least three functional pathways including chromatin modeling, Wnt, Notch and other signaling pathways and metabolic disturbances involving neuronal growth and dendritic spine profiles. An estimated 50% of individuals with ASD are diagnosed with chromosome deletions or duplications (e.g., 15q11.2, BP1-BP2, 16p11.2 and 15q13.3), identified syndromes (e.g., Williams, Phelan-McDermid and Shprintzen velocardiofacial) or single gene disorders. Behavioral and psychiatric conditions in autism impacted by genetics influence clinical evaluations, counseling, diagnoses, therapeutic interventions and treatment approaches. Pharmacogenetics testing is now possible to help guide the selection of psychotropic medications to treat challenging behaviors or co-occurring psychiatric conditions commonly seen in ASD. In this review of the autism spectrum disorder, behavioral, psychiatric and genetic observations and associations relevant to the evaluation and treatment of individuals with ASD are discussed. Full article
(This article belongs to the Special Issue Genes, Phenotypes and Molecular Mechanisms for Personalized Medicine in Autism)
►▼ Show Figures

Figure 1

33 pages, 2450 KiB  
Review
Personalized Systemic Therapies in Hereditary Cancer Syndromes
by Luciana Mastrodomenico, Claudia Piombino, Beatrice Riccò, Elena Barbieri, Marta Venturelli, Federico Piacentini, Massimo Dominici, Laura Cortesi and Angela Toss
Genes 2023, 14(3), 684; https://doi.org/10.3390/genes14030684 - 9 Mar 2023
Cited by 9 | Viewed by 2938
Abstract
Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth [...] Read more.
Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients. The present review aims to describe and discuss the personalized systemic therapies for inherited cancer syndromes that have been developed and investigated in clinical trials in recent decades. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

15 pages, 1846 KiB  
Article
Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL
by Lisa-Marie Vieler, Verena Nilius-Eliliwi, Roland Schroers, Deepak Ben Vangala, Huu Phuc Nguyen and Wanda Maria Gerding
Genes 2023, 14(3), 686; https://doi.org/10.3390/genes14030686 - 9 Mar 2023
Cited by 11 | Viewed by 2684
Abstract
(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to the genetic heterogeneity of mutations in adult patients, only a small proportion of aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up [...] Read more.
(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to the genetic heterogeneity of mutations in adult patients, only a small proportion of aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up new possibilities for the characterization of structural variants on a genome-wide level, thus enabling simultaneous analysis for a broad spectrum of genetic aberrations. (2) Methods: 11 adult ALL patients were examined using OGM. (3) Results: Genetic results obtained by karyotyping and FISH were confirmed by OGM for all patients. Karyotype was redefined, and additional genetic information was obtained in 82% (9/11) of samples by OGM, previously not diagnosed by standard of care. Besides gross-structural chromosome rearrangements, e.g., ring chromosome 9 and putative isodicentric chromosome 8q, deletions in CDKN2A/2B were detected in 7/11 patients, defining an approx. 20 kb minimum region of overlap, including an alternative exon 1 of the CDKN2A gene. The results further confirm recurrent ALL aberrations (e.g., PAX5, ETV6, VPREB1, IKZF1). (4) Conclusions: Genome-wide OGM analysis enables a broad genetic characterization in adult ALL patients in one single workup compared to standard clinical testing, facilitating a detailed genetic diagnosis, risk-stratification, and target-directed treatment strategies. Full article
(This article belongs to the Special Issue Commemorating the Launch of the Section "Cytogenomics")
►▼ Show Figures

Figure 1

11 pages, 1299 KiB  
Article
Exome-Wide Association Study of Competitive Performance in Elite Athletes
by Celal Bulgay, Anıl Kasakolu, Hasan Hüseyin Kazan, Raluca Mijaica, Erdal Zorba, Onur Akman, Isık Bayraktar, Rıdvan Ekmekci, Seyrani Koncagul, Korkut Ulucan, Ekaterina A. Semenova, Andrey K. Larin, Nikolay A. Kulemin, Edward V. Generozov, Lorand Balint, Georgian Badicu, Ildus I. Ahmetov and Mehmet Ali Ergun
Genes 2023, 14(3), 660; https://doi.org/10.3390/genes14030660 - 6 Mar 2023
Cited by 11 | Viewed by 3773
Abstract
The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies [...] Read more.
The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10−7) in genotype–phenotype and case–control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes. Full article
(This article belongs to the Special Issue Genetics, Sports and Training)
►▼ Show Figures

Figure 1

13 pages, 779 KiB  
Article
Genome-Wide Associations and Confirmatory Meta-Analyses in Diabetic Retinopathy
by Xinting Yu and Shisong Rong
Genes 2023, 14(3), 653; https://doi.org/10.3390/genes14030653 - 5 Mar 2023
Cited by 10 | Viewed by 6005
Abstract
The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list [...] Read more.
The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis. Full article
(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

12 pages, 2204 KiB  
Article
Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study
by Je Hyun Seo and Young Lee
Genes 2023, 14(3), 642; https://doi.org/10.3390/genes14030642 - 3 Mar 2023
Cited by 6 | Viewed by 2823
Abstract
Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association [...] Read more.
Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR–Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 × 10−8) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 × 10−8) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 × 10−8) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

18 pages, 2025 KiB  
Article
Winners and Losers of Atlantification: The Degree of Ocean Warming Affects the Structure of Arctic Microbial Communities
by Antonia Ahme, Anabel Von Jackowski, Rebecca A. McPherson, Klara K. E. Wolf, Mario Hoppmann, Stefan Neuhaus and Uwe John
Genes 2023, 14(3), 623; https://doi.org/10.3390/genes14030623 - 1 Mar 2023
Cited by 8 | Viewed by 2740
Abstract
Arctic microbial communities (i.e., protists and bacteria) are increasingly subjected to an intrusion of new species via Atlantification and an uncertain degree of ocean warming. As species differ in adaptive traits, these oceanic conditions may lead to compositional changes with functional implications for [...] Read more.
Arctic microbial communities (i.e., protists and bacteria) are increasingly subjected to an intrusion of new species via Atlantification and an uncertain degree of ocean warming. As species differ in adaptive traits, these oceanic conditions may lead to compositional changes with functional implications for the ecosystem. In June 2021, we incubated water from the western Fram Strait at three temperatures (2 °C, 6 °C, and 9 °C), mimicking the current and potential future properties of the Arctic Ocean. Our results show that increasing the temperature to 6 °C only minorly affects the community, while an increase to 9 °C significantly lowers the diversity and shifts the composition. A higher relative abundance of large hetero- and mixotrophic protists was observed at 2 °C and 6 °C compared to a higher abundance of intermediate-sized temperate diatoms at 9 °C. The compositional differences at 9 °C led to a higher chlorophyll a:POC ratio, but the C:N ratio remained similar. Our results contradict the common assumption that smaller organisms and heterotrophs are favored under warming and strongly indicate a thermal limit between 6 °C and 9 °C for many Arctic species. Consequently, the magnitude of temperature increase is a crucial factor for microbial community reorganization and the ensuing ecological consequences in the future Arctic Ocean. Full article
(This article belongs to the Special Issue Polar Genomics)
►▼ Show Figures

Figure 1

18 pages, 1711 KiB  
Review
TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae
by Bechara Zeinoun, Maria Teresa Teixeira and Aurélia Barascu
Genes 2023, 14(3), 618; https://doi.org/10.3390/genes14030618 - 28 Feb 2023
Cited by 8 | Viewed by 3868
Abstract
Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally [...] Read more.
Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA’s expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae. Full article
(This article belongs to the Special Issue DNA Damage and Repair at the Crossroad with Telomeres)
►▼ Show Figures

Figure 1

24 pages, 7083 KiB  
Article
Improving Agrobacterium tumefaciens−Mediated Genetic Transformation for Gene Function Studies and Mutagenesis in Cucumber (Cucumis sativus L.)
by Hanqiang Liu, Jianyu Zhao, Feifan Chen, Zhiming Wu, Junyi Tan, Nhien Hao Nguyen, Zhihui Cheng and Yiqun Weng
Genes 2023, 14(3), 601; https://doi.org/10.3390/genes14030601 - 27 Feb 2023
Cited by 8 | Viewed by 3981
Abstract
In the post−genomics era, Agrobacterium tumefaciens−mediated genetic transformation is becoming an increasingly indispensable tool for characterization of gene functions and crop improvement in cucumber (Cucumis sativus L.). However, cucumber transformation efficiency is still low. In this study, we evaluated the effects [...] Read more.
In the post−genomics era, Agrobacterium tumefaciens−mediated genetic transformation is becoming an increasingly indispensable tool for characterization of gene functions and crop improvement in cucumber (Cucumis sativus L.). However, cucumber transformation efficiency is still low. In this study, we evaluated the effects of several key factors affecting the shoot−regeneration rate and overall transformation efficiency in cucumber including genotypes, the age and sources of explants, Agrobacterium strains, infection/co−cultivation conditions, and selective agents. We showed that in general, North China cucumbers exhibited higher shoot−regeneration rate than US pickling or slicing cucumbers. The subapical ground meristematic regions from cotyledons or the hypocotyl had a similar shoot−regeneration efficiency that was also affected by the age of the explants. Transformation with the Agrobacterium strain AGL1 yielded a higher frequency of positive transformants than with GV3101. The antibiotic kanamycin was effective in selection against non−transformants or chimeras. Optimization of various factors was exemplified with the development of transgenic plants overexpressing the LittleLeaf (LL) gene or RNAi of the APRR2 gene in three cucumber lines. The streamlined protocol was also tested in transgenic studies in three additional genes. The overall transformation efficiency defined by the number of verified transgenic plants out of the number of seeds across multiple experiments was 0.2–1.7%. Screening among T1 OE transgenic plants identified novel, inheritable mutants for leaf or fruit color or size/shape, suggesting T−DNA insertion as a potential source of mutagenesis. The Agrobacterium−mediated transformation protocol from this study could be used as the baseline for further improvements in cucumber transformation. Full article
(This article belongs to the Special Issue Cucumber Genetics and Breeding - a Themed Issue in Memory of Academician Feng Hou (1928 - 2020))
►▼ Show Figures

Figure 1

24 pages, 1183 KiB  
Review
The Molecular and Cellular Basis of Hutchinson–Gilford Progeria Syndrome and Potential Treatments
by Noelle J. Batista, Sanket G. Desai, Alexis M. Perez, Alexa Finkelstein, Rachel Radigan, Manrose Singh, Aaron Landman, Brian Drittel, Daniella Abramov, Mina Ahsan, Samantha Cornwell and Dong Zhang
Genes 2023, 14(3), 602; https://doi.org/10.3390/genes14030602 - 27 Feb 2023
Cited by 10 | Viewed by 6350
Abstract
Hutchinson–Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome. HGPS is most often derived from a de novo point mutation in the LMNA gene, which results in an alternative splicing defect and the generation of the mutant protein, progerin. [...] Read more.
Hutchinson–Gilford progeria syndrome (HGPS) is a rare, autosomal-dominant, and fatal premature aging syndrome. HGPS is most often derived from a de novo point mutation in the LMNA gene, which results in an alternative splicing defect and the generation of the mutant protein, progerin. Progerin behaves in a dominant-negative fashion, leading to a variety of cellular and molecular changes, including nuclear abnormalities, defective DNA damage response (DDR) and DNA repair, and accelerated telomere attrition. Intriguingly, many of the manifestations of the HGPS cells are shared with normal aging cells. However, at a clinical level, HGPS does not fully match normal aging because of the accelerated nature of the phenotypes and its primary effects on connective tissues. Furthermore, the epigenetic changes in HGPS patients are of great interest and may play a crucial role in the pathogenesis of HGPS. Finally, various treatments for the HGPS patients have been developed in recent years with important effects at a cellular level, which translate to symptomatic improvement and increased lifespan. Full article
(This article belongs to the Special Issue DNA Replication/Repair, and the DNA Damage Response in Human Disease)
►▼ Show Figures

Figure 1

13 pages, 474 KiB  
Article
Efficient Selection of Gaussian Kernel SVM Parameters for Imbalanced Data
by Chen-An Tsai and Yu-Jing Chang
Genes 2023, 14(3), 583; https://doi.org/10.3390/genes14030583 - 25 Feb 2023
Cited by 7 | Viewed by 2097
Abstract
For medical data mining, the development of a class prediction model has been widely used to deal with various kinds of data classification problems. Classification models especially for high-dimensional gene expression datasets have attracted many researchers in order to identify marker genes for [...] Read more.
For medical data mining, the development of a class prediction model has been widely used to deal with various kinds of data classification problems. Classification models especially for high-dimensional gene expression datasets have attracted many researchers in order to identify marker genes for distinguishing any type of cancer cells from their corresponding normal cells. However, skewed class distributions often occur in the medical datasets in which at least one of the classes has a relatively small number of observations. A classifier induced by such an imbalanced dataset typically has a high accuracy for the majority class and poor prediction for the minority class. In this study, we focus on an SVM classifier with a Gaussian radial basis kernel for a binary classification problem. In order to take advantage of an SVM and to achieve the best generalization ability for improving the classification performance, we will address two important problems: the class imbalance and parameter selection during SVM parameter optimization. First of all, we proposed a novel adjustment method called b-SVM, for adjusting the cutoff threshold of the SVM. Second, we proposed a fast and simple approach, called the Min-max gamma selection, to optimize the model parameters of SVMs without carrying out an extensive k-fold cross validation. An extensive comparison with a standard SVM and well-known existing methods are carried out to evaluate the performance of our proposed algorithms using simulated and real datasets. The experimental results show that our proposed algorithms outperform the over-sampling techniques and existing SVM-based solutions. This study also shows that the proposed Min-max gamma selection is at least 10 times faster than the cross-validation selection based on the average running time on six real datasets. Full article
(This article belongs to the Special Issue Machine Learning Supervised Algorithms in Bioinformatics)
►▼ Show Figures

Graphical abstract

13 pages, 1063 KiB  
Review
Immunoepigenetic Regulation of Inflammatory Bowel Disease: Current Insights into Novel Epigenetic Modulations of the Systemic Immune Response
by Guillermo Bastida, Alejandro Mínguez, Pilar Nos and Inés Moret-Tatay
Genes 2023, 14(3), 554; https://doi.org/10.3390/genes14030554 - 23 Feb 2023
Cited by 7 | Viewed by 2373
Abstract
The immune system and environmental factors are involved in various diseases, such as inflammatory bowel disease (IBD), through their effect on genetics, which modulates immune cells. IBD encompasses two main phenotypes, Crohn’s disease, and ulcerative colitis, which are manifested as chronic and systemic [...] Read more.
The immune system and environmental factors are involved in various diseases, such as inflammatory bowel disease (IBD), through their effect on genetics, which modulates immune cells. IBD encompasses two main phenotypes, Crohn’s disease, and ulcerative colitis, which are manifested as chronic and systemic relapse-remitting gastrointestinal tract disorders with rising global incidence and prevalence. The pathophysiology of IBD is complex and not fully understood. Epigenetic research has resulted in valuable information for unraveling the etiology of this immune-mediated disease. Thus, the main objective of the present review is to summarize the current findings on the role of epigenetic mechanisms in IBD to shed light on their potential clinical relevance. This review focuses on the latest evidence regarding peripheral blood mononuclear cells and epigenetic changes in histone modification, DNA methylation, and telomere shortening in IBD. The various identified epigenetic DNA profiles with clinical value in IBD could be used as biomarkers for more accurately predicting disease development, treatment response, and therapy-related adverse events. Ultimately, the information presented here could be of potential relevance for future clinical practice in developing more efficient and precise medicine to improve the quality of life for patients with IBD. Full article
(This article belongs to the Special Issue Immunoepigenetics)
►▼ Show Figures

Figure 1

16 pages, 4091 KiB  
Article
Production and Characterization of K562 Cellular Clones Hyper-Expressing the Gene Encoding α-Globin: Preliminary Analysis of Biomarkers Associated with Autophagy
by Matteo Zurlo, Jessica Gasparello, Lucia Carmela Cosenza, Giulia Breveglieri, Chiara Papi, Cristina Zuccato, Roberto Gambari and Alessia Finotti
Genes 2023, 14(3), 556; https://doi.org/10.3390/genes14030556 - 23 Feb 2023
Cited by 6 | Viewed by 2021
Abstract
One of the most relevant pathophysiological hallmarks of β-thalassemia is the accumulation of toxic α-globin chains inside erythroid cells, which is responsible for their premature death (hemolysis). In this context, the availability of an experimental model system mimicking the excess in α-globin chain [...] Read more.
One of the most relevant pathophysiological hallmarks of β-thalassemia is the accumulation of toxic α-globin chains inside erythroid cells, which is responsible for their premature death (hemolysis). In this context, the availability of an experimental model system mimicking the excess in α-globin chain production is still lacking. The objective of the present study was to produce and characterize K562 cellular clones forced to produce high amounts of α-globin, in order to develop an experimental model system suitable for studies aimed at the reduction of the accumulation of toxic α-globin aggregates. In the present study, we produced and characterized K562 cellular clones that, unlike the original K562 cell line, stably produced high levels of α-globin protein. As expected, the obtained clones had a tendency to undergo apoptosis that was proportional to the accumulation of α-globin, confirming the pivotal role of α-globin accumulation in damaging erythroid cells. Interestingly, the obtained clones seemed to trigger autophagy spontaneously, probably to overcome the accumulation/toxicity of the α-globin. We propose this new model system for the screening of pharmacological agents able to activate the full program of autophagy to reduce α-globin accumulation, but the model may be also suitable for new therapeutical approaches targeted at the reduction of the expression of the α-globin gene. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

12 pages, 1267 KiB  
Article
Heterochiasmy and Sex Chromosome Evolution in Silene
by Dmitry A. Filatov
Genes 2023, 14(3), 543; https://doi.org/10.3390/genes14030543 - 22 Feb 2023
Cited by 7 | Viewed by 2423
Abstract
The evolution of a non-recombining sex-specific region is a key step in sex chromosome evolution. Suppression of recombination between the (proto-) X- and Y-chromosomes in male meiosis creates a non-recombining Y-linked region (NRY), while the X-chromosome continues to recombine in females. Lack of [...] Read more.
The evolution of a non-recombining sex-specific region is a key step in sex chromosome evolution. Suppression of recombination between the (proto-) X- and Y-chromosomes in male meiosis creates a non-recombining Y-linked region (NRY), while the X-chromosome continues to recombine in females. Lack of recombination in the NRY defines its main properties—genetic degeneration and accumulation of repetitive DNA, making X and Y chromosomes very different from each other. How and why recombination suppression on sex chromosomes evolves remains controversial. A strong difference in recombination rates between the sexes (heterochiasmy) can facilitate or even cause recombination suppression. In the extreme case—complete lack of recombination in the heterogametic sex (achiasmy)—the entire sex-specific chromosome is automatically non-recombining. In this study, I analyse sex-specific recombination rates in a dioecious plant Silene latifolia (Caryophyllaceae), which evolved separate sexes and sex chromosomes ~11 million years ago. I reconstruct high-density RNAseq-based genetic maps including over five thousand genic markers for the two sexes separately. The comparison of the male and female maps reveals only modest heterochiasmy across the genome, with the exception of the sex chromosomes, where recombination is suppressed in males. This indicates that heterochiasmy likely played only a minor, if any, role in NRY evolution in S. latifolia, as recombination suppression is specific to NRY rather than to the entire genome in males. Other mechanisms such as structural rearrangements and/or epigenetic modifications were likely involved, and comparative genome analysis and genetic mapping in multiple Silene species will help to shed light on the mechanism(s) of recombination suppression that led to the evolution of sex chromosomes. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
►▼ Show Figures

Figure 1

20 pages, 684 KiB  
Review
Enamel Phenotypes: Genetic and Environmental Determinants
by John Timothy Wright
Genes 2023, 14(3), 545; https://doi.org/10.3390/genes14030545 - 22 Feb 2023
Cited by 17 | Viewed by 6774
Abstract
Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its [...] Read more.
Dental enamel is a specialized tissue that has adapted over millions of years of evolution to enhance the survival of a variety of species. In humans, enamel evolved to form the exterior protective layer for the crown of the exposed tooth crown. Its unique composition, structure, physical properties and attachment to the underlying dentin tissue allow it to be a resilient, although not self-repairing, tissue. The process of enamel formation, known as amelogenesis, involves epithelial-derived cells called ameloblasts that secrete a unique extracellular matrix that influences the structure of the mineralizing enamel crystallites. There are over 115 known genetic conditions affecting amelogenesis that are associated with enamel phenotypes characterized by either a reduction of enamel amount and or mineralization. Amelogenesis involves many processes that are sensitive to perturbation and can be altered by numerous environmental stressors. Genetics, epigenetics, and environment factors can influence enamel formation and play a role in resistance/risk for developmental defects and the complex disease, dental caries. Understanding why and how enamel is affected and the enamel phenotypes seen clinically support diagnostics, prognosis prediction, and the selection of treatment approaches that are appropriate for the specific tissue defects (e.g., deficient amount, decreased mineral, reduced insulation and hypersensitivity). The current level of knowledge regarding the heritable enamel defects is sufficient to develop a new classification system and consensus nosology that effectively communicate the mode of inheritance, molecular defect/pathway, and the functional aberration and resulting enamel phenotype. Full article
(This article belongs to the Special Issue Genetic, Epigenetic and Environmental Factors in Dental Development and Pathologies: Genes, Interactions and Dental Development)
►▼ Show Figures

Figure 1

12 pages, 1273 KiB  
Article
Role of the Vitamin D Receptor (VDR) in the Pathogenesis of Osteoporosis: A Genetic, Epigenetic and Molecular Pilot Study
by Beatrice Gasperini, Virginia Veronica Visconti, Cinzia Ciccacci, Angela Falvino, Elena Gasbarra, Riccardo Iundusi, Maria Luisa Brandi, Annalisa Botta and Umberto Tarantino
Genes 2023, 14(3), 542; https://doi.org/10.3390/genes14030542 - 21 Feb 2023
Cited by 8 | Viewed by 2337
Abstract
The vitamin D receptor (VDR) regulates bone development and calcium homeostasis, suggesting a central role in musculoskeletal diseases such as osteoporosis (OP). Several studies have examined the contribution of VDR polymorphisms and epigenetic signatures in bone metabolism and OP risk, with sometimes inconclusive [...] Read more.
The vitamin D receptor (VDR) regulates bone development and calcium homeostasis, suggesting a central role in musculoskeletal diseases such as osteoporosis (OP). Several studies have examined the contribution of VDR polymorphisms and epigenetic signatures in bone metabolism and OP risk, with sometimes inconclusive results. Our study aimed to explore the association between genetic variability, expression and the methylation pattern of VDR with the risk of OP in a cohort of Caucasian patients. Genomic DNA from 139 OP, 54 osteopenic (Ope) and 73 healthy (CTR) subjects were used for genotyping the rs731236 (TaqI), rs2228570 (FokI) and rs11568820 (Cdx2) polymorphisms of the VDR gene by an allelic discrimination assay. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of VDR expression levels and pyrosequencing analysis of a VDR promoter CpG island were carried out in a subcohort (25 OP and 25 CTR) of subjects. Data obtained showed a significantly higher OP risk for rs11568820 G/A and A/A genotypes (p = 0.05). qRT-PCR revealed lower VDR gene expression levels in the OP group compared to CTR subjects (p = 0.0009), also associated with both the rs11568820 A/A genotype (p = 0.03) and femoral fragility fractures (p = 0.05). No association was found between the methylation pattern of the region analyzed of the VDR promoter and its expression levels. Our results identify a significative association between Cdx2 rs11568820 polymorphism and OP risk. In addition, the VDR transcriptomic profile suggests a putative interconnection with OP progression, providing a useful tool to stratify OP phenotype and fragility fracture risk. Full article
(This article belongs to the Special Issue Key Genetic Determinants of Osteoporosis: From Bench to Bedside)
►▼ Show Figures

Figure 1

15 pages, 4375 KiB  
Article
The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw
by Lorenzo Innocenti, Valerio Ortenzi, Rosa Scarpitta, Nicola Montemurro, Francesco Pasqualetti, Roberta Asseri, Stefano Lazzi, Anna Szumera-Cieckiewicz, Katia De Ieso, Paolo Perrini, Antonio Giuseppe Naccarato, Cristian Scatena and Giuseppe Nicolò Fanelli
Genes 2023, 14(2), 501; https://doi.org/10.3390/genes14020501 - 15 Feb 2023
Cited by 6 | Viewed by 1770
Abstract
Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series [...] Read more.
Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (p < 0.0001 and p = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (rs = 0.417—p = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, p = 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, p = 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, p = 0.006). Adjuvant treatment, methylguanine methyltransferase (MGMT) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM. Full article
(This article belongs to the Special Issue The Genomics of Glioblastoma)
►▼ Show Figures

Figure 1

17 pages, 1322 KiB  
Review
Phase Separation: Direct and Indirect Driving Force for High-Order Chromatin Organization
by Xiaoli Li, Ziyang An, Wenqing Zhang and Feifei Li
Genes 2023, 14(2), 499; https://doi.org/10.3390/genes14020499 - 15 Feb 2023
Cited by 7 | Viewed by 4195
Abstract
The multi-level spatial chromatin organization in the nucleus is closely related to chromatin activity. The mechanism of chromatin organization and remodeling attract much attention. Phase separation describes the biomolecular condensation which is the basis for membraneless compartments in cells. Recent research shows that [...] Read more.
The multi-level spatial chromatin organization in the nucleus is closely related to chromatin activity. The mechanism of chromatin organization and remodeling attract much attention. Phase separation describes the biomolecular condensation which is the basis for membraneless compartments in cells. Recent research shows that phase separation is a key aspect to drive high-order chromatin structure and remodeling. In addition, chromatin functional compartmentalization in the nucleus which is formed by phase separation also plays an important role in overall chromatin structure. In this review, we summarized the latest work about the role of phase separation in spatial chromatin organization, focusing on direct and indirect effects of phase separation on 3D chromatin organization and its impact on transcription regulation. Full article
(This article belongs to the Special Issue Dynamics of 3D Genome Organization)
►▼ Show Figures

Figure 1

16 pages, 1043 KiB  
Review
Exploiting Autophagy-Dependent Neoantigen Presentation in Tumor Microenvironment
by Evangelos Koustas, Eleni-Myrto Trifylli, Panagiotis Sarantis, Nikolaos Papadopoulos, Konstantinos Papanikolopoulos, Georgios Aloizos, Christos Damaskos, Nikolaos Garmpis, Anna Garmpi, Dimitris Matthaios and Michalis V. Karamouzis
Genes 2023, 14(2), 474; https://doi.org/10.3390/genes14020474 - 13 Feb 2023
Cited by 9 | Viewed by 2441
Abstract
Autophagy constitutes a well-known homeostatic and catabolic process that is responsible for degradation and recycling of cellular components. It is a key regulatory mechanism for several cellular functions, whereas its dysregulation is associated with tumorigenesis, tumor–stroma interactions and resistance to cancer therapy. A [...] Read more.
Autophagy constitutes a well-known homeostatic and catabolic process that is responsible for degradation and recycling of cellular components. It is a key regulatory mechanism for several cellular functions, whereas its dysregulation is associated with tumorigenesis, tumor–stroma interactions and resistance to cancer therapy. A growing body of evidence has proven that autophagy affects the tumor microenvironment, while it is also considered a key factor for function of several immune cells, such as APCs, T-cells, and macrophages. Moreover, it is implicated in presentation of neo-antigens of tumor cells in both MHC-I and MHC-II in dendritic cells (DCs) in functional activity of immune cells by creating T-cell memory, as well as in cross-presentation of neo-antigens for MHC-I presentation and the internalization process. Currently, autophagy has a crucial role in immunotherapy. Emergence of cancer immunotherapy has already shown some remarkable results, having changed therapeutic strategy in clinical practice for several cancer types. Despite these promising long-term responses, several patients seem to lack the ability to respond to immune checkpoint inhibitors. Thus, autophagy through neo-antigen presentation is a potential target in order to strengthen or attenuate the effects of immunotherapy against different types of cancer. This review will shed light on the recent advances and future directions of autophagy-dependent neo-antigen presentation and consequently its role in immunotherapy for malignant tumors. Full article
(This article belongs to the Special Issue Cell Signalling and Inflammation in Cancer)
►▼ Show Figures

Figure 1

17 pages, 2172 KiB  
Article
Impacts of Eccentric Resistance Exercise on DNA Methylation of Candidate Genes for Inflammatory Cytokines in Skeletal Muscle and Leukocytes of Healthy Males
by David John Hunter, Lynsey S. James, Bethan Hussey, Richard A. Ferguson, Martin R. Lindley and Sarabjit S. Mastana
Genes 2023, 14(2), 478; https://doi.org/10.3390/genes14020478 - 13 Feb 2023
Cited by 7 | Viewed by 2365
Abstract
Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose [...] Read more.
Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose of our study was to investigate the impacts of eccentric resistance exercise and fatty acid supplementation on DNA methylation and mRNA expression of TNF and IL6 in skeletal muscle and leukocytes. Eight non-resistance exercise-trained males completed three bouts of isokinetic eccentric contractions of the knee extensors. The first bout occurred at baseline, the second occurred following a three-week supplementation of either omega-3 polyunsaturated fatty acid or extra virgin olive oil and the final bout occurred after eight-weeks of eccentric resistance training and supplementation. Acute exercise decreased skeletal muscle TNF DNA methylation by 5% (p = 0.031), whereas IL6 DNA methylation increased by 3% (p = 0.01). Leukocyte DNA methylation was unchanged following exercise (p > 0.05); however, three hours post-exercise the TNF DNA methylation decreased by 2% (p = 0.004). In skeletal muscle, increased TNF and IL6 mRNA expression levels were identified immediately post-exercise (p < 0.027); however, the leukocyte mRNA expression was unchanged. Associations between DNA methylation and markers of exercise performance, inflammation and muscle damage were identified (p < 0.05). Acute eccentric resistance exercise is sufficient to induce tissue-specific DNA methylation modifications to TNF and IL6; however, neither eccentric training nor supplementation was sufficient to further modify the DNA methylation. Full article
(This article belongs to the Special Issue Genetics, Sports and Training)
►▼ Show Figures

Figure 1

11 pages, 3376 KiB  
Communication
Effects of Elexacaftor/Tezacaftor/Ivacaftor on Cardiorespiratory Polygraphy Parameters and Respiratory Muscle Strength in Cystic Fibrosis Patients with Severe Lung Disease
by Alessandro Giallongo, Giuseppe Fabio Parisi, Maria Papale, Sara Manti, Enza Mulé, Donatella Aloisio, Vito Terlizzi, Novella Rotolo and Salvatore Leonardi
Genes 2023, 14(2), 449; https://doi.org/10.3390/genes14020449 - 9 Feb 2023
Cited by 10 | Viewed by 1787
Abstract
Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA [...] Read more.
Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators represent targeted therapies directly acting on the CFTR channel. The triple therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) has been demonstrated to improve lung function and quality of life in cystic fibrosis (CF) patients. However, the effects of ELX/TEZ/IVA on sleep-disordered breathing (SDB) and respiratory muscle strength are poorly studied. The aim of this study was to assess the effects of ELX/TEZ/IVA in patients with CF and severe lung disease on cardiorespiratory polygraphy parameters, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) measures. Methods: patients with CF aged ≥ 12 who started treatment in a compassionate use program were retrospectively studied through the evaluation of nocturnal cardiorespiratory polygraphy parameters, MIP and MEP; and six-minute walk test (6MWT) at baseline and at months 3, 6, and 12 of treatment. Results: Nine patients (mean age 30.3 ± 6.5 years) with severe CF (mean baseline ppFEV1 34.6 ± 5.1%) were evaluated. A significant improvement in nocturnal oxygenation measured by mean SpO2 (92.4 vs. 96.4%, p < 0.05), time spent with SpO2 ≤ 90% (−12.6, −14.6, −15.2 min from baseline at months 3, 6, and 12, respectively, p < 0.05), and respiratory rate (RR) was shown, at month 12 and across the time points compared with baseline, as well as in respiratory muscle strength, although only the change in MEP was significant. Conclusions: We provide further evidence on the efficacy of the CFTR modulators ELX/TEZ/IVA, adding information about their effect on the respiratory muscles’ performance and cardiorespiratory polygraphy parameters in CF patients with severe lung disease. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

12 pages, 2717 KiB  
Article
The Satellite DNAs Populating the Genome of Trigona hyalinata and the Sharing of a Highly Abundant satDNA in Trigona Genus
by Jaqueline A. Pereira, Diogo C. Cabral-de-Mello and Denilce M. Lopes
Genes 2023, 14(2), 418; https://doi.org/10.3390/genes14020418 - 6 Feb 2023
Cited by 6 | Viewed by 1845
Abstract
Among Meliponini species, c-heterochromatin can occupy large portions of chromosomes. This characteristic could be useful for understanding evolutionary patterns of satellite DNAs (satDNAs), although few sequences have been characterized in these bees. In Trigona, phylogenetically represented by clades A and B, [...] Read more.
Among Meliponini species, c-heterochromatin can occupy large portions of chromosomes. This characteristic could be useful for understanding evolutionary patterns of satellite DNAs (satDNAs), although few sequences have been characterized in these bees. In Trigona, phylogenetically represented by clades A and B, the c-heterochromatin is mostly located in one chromosome arm. Here we used different techniques, including restriction endonucleases and genome sequencing followed by chromosomal analysis, to identify satDNAs that may be contributing to the evolution of c-heterochromatin in Trigona. Our results revealed a highly abundant ThyaSat01-301 satDNA, corresponding to about 13.77% of the Trigona hyalinata genome. Another seven satDNAs were identified, one corresponding to 2.24%, and the other six corresponding to 0.545% of the genome. The satDNA ThyaSat01-301 was shown to be one of the main constituents of the c-heterochromatin of this species, as well as of other species belonging to clade B of Trigona. However, this satDNA was not observed on the chromosomes of species from clade A, demonstrating that the c-heterochromatin is evolving divergently between species of clade A and B, as a consequence of the evolution of repetitive DNA sequences. Finally, our data suggest the molecular diversification of the karyotypes, despite a conservated macrochromosomal structure on the genus. Full article
(This article belongs to the Special Issue State-of-the-Art in Insect Cytogenetics)
►▼ Show Figures

Figure 1

17 pages, 1161 KiB  
Review
Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic
by Luis Daniel González-Vázquez and Miguel Arenas
Genes 2023, 14(2), 407; https://doi.org/10.3390/genes14020407 - 4 Feb 2023
Cited by 14 | Viewed by 4239
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10−3–10−4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments. Full article
(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)
►▼ Show Figures

Figure 1

20 pages, 13468 KiB  
Article
Making the Genome Huge: The Case of Triatoma delpontei, a Triatominae Species with More than 50% of Its Genome Full of Satellite DNA
by Pablo Mora, Sebastián Pita, Eugenia E. Montiel, José M. Rico-Porras, Teresa Palomeque, Francisco Panzera and Pedro Lorite
Genes 2023, 14(2), 371; https://doi.org/10.3390/genes14020371 - 31 Jan 2023
Cited by 12 | Viewed by 2162
Abstract
The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug [...] Read more.
The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug 1834, in order to shed light on the karyotypic and genomic evolution of these species. The T. delpontei repeatome analysis showed that the most abundant component in its genome is satellite DNA, which makes up more than half of the genome. The T. delpontei satellitome includes 160 satellite DNA families, most of them also present in T. infestans. In both species, only a few satellite DNA families are overrepresented on the genome. These families are the building blocks of the C-heterochromatic regions. Two of these satellite DNA families that form the heterochromatin are the same in both species. However, there are satellite DNA families highly amplified in the heterochromatin of one species that in the other species are in low abundance and located in the euchromatin. Therefore, the present results depicted the great impact of the satellite DNA sequences in the evolution of Triatominae genomes. Within this scenario, satellitome determination and analysis led to a hypothesis that explains how satDNA sequences have grown on T. delpontei to reach its huge genome size within true bugs. Full article
(This article belongs to the Special Issue State-of-the-Art in Insect Cytogenetics)
►▼ Show Figures

Figure 1

14 pages, 10577 KiB  
Review
GDP-Mannose Pyrophosphorylase B (GMPPB)-Related Disorders
by Pitcha Chompoopong and Margherita Milone
Genes 2023, 14(2), 372; https://doi.org/10.3390/genes14020372 - 31 Jan 2023
Cited by 6 | Viewed by 3237
Abstract
GDP-mannose pyrophosphorylase B (GMPPB) is a cytoplasmic protein that catalyzes the formation of GDP-mannose. Impaired GMPPB function reduces the amount of GDP-mannose available for the O-mannosylation of α-dystroglycan (α-DG) and ultimately leads to disruptions of the link between α-DG and extracellular proteins, hence [...] Read more.
GDP-mannose pyrophosphorylase B (GMPPB) is a cytoplasmic protein that catalyzes the formation of GDP-mannose. Impaired GMPPB function reduces the amount of GDP-mannose available for the O-mannosylation of α-dystroglycan (α-DG) and ultimately leads to disruptions of the link between α-DG and extracellular proteins, hence dystroglycanopathy. GMPPB-related disorders are inherited in an autosomal recessive manner and caused by mutations in either a homozygous or compound heterozygous state. The clinical spectrum of GMPPB-related disorders spans from severe congenital muscular dystrophy (CMD) with brain and eye abnormalities to mild forms of limb-girdle muscular dystrophy (LGMD) to recurrent rhabdomyolysis without overt muscle weakness. GMPPB mutations can also lead to the defect of neuromuscular transmission and congenital myasthenic syndrome due to altered glycosylation of the acetylcholine receptor subunits and other synaptic proteins. Such impairment of neuromuscular transmission is a unique feature of GMPPB-related disorders among dystroglycanopathies. LGMD is the most common phenotypic presentation, characterized by predominant proximal weakness involving lower more than upper limbs. Facial, ocular, bulbar, and respiratory muscles are largely spared. Some patients demonstrate fluctuating fatigable weakness suggesting neuromuscular junction involvement. Patients with CMD phenotype often also have structural brain defects, intellectual disability, epilepsy, and ophthalmic abnormalities. Creatine kinase levels are typically elevated, ranging from 2 to >50 times the upper limit of normal. Involvement of the neuromuscular junction is demonstrated by the decrement in the compound muscle action potential amplitude on low-frequency (2–3 Hz) repetitive nerve stimulation in proximal muscles but not in facial muscles. Muscle biopsies typically show myopathic changes with variable degrees of reduced α-DG expression. Higher mobility of β-DG on Western blotting represents a specific feature of GMPPB-related disorders, distinguishing it from other α-dystroglycanopathies. Patients with clinical and electrophysiologic features of neuromuscular transmission defect can respond to acetylcholinesterase inhibitors alone or combined with 3,4 diaminopyridine or salbutamol. Full article
(This article belongs to the Special Issue Genetics of Muscular Dystrophies from Pathogenesis to Gene Therapy)
►▼ Show Figures

Figure 1

19 pages, 2999 KiB  
Review
Nonsense-Mediated mRNA Decay as a Mediator of Tumorigenesis
by Preeti Nagar, Md Rafikul Islam and Mohammad Alinoor Rahman
Genes 2023, 14(2), 357; https://doi.org/10.3390/genes14020357 - 30 Jan 2023
Cited by 11 | Viewed by 5230
Abstract
Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved and well-characterized biological mechanism that ensures the fidelity and regulation of gene expression. Initially, NMD was described as a cellular surveillance or quality control process to promote selective recognition and rapid degradation of erroneous transcripts [...] Read more.
Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved and well-characterized biological mechanism that ensures the fidelity and regulation of gene expression. Initially, NMD was described as a cellular surveillance or quality control process to promote selective recognition and rapid degradation of erroneous transcripts harboring a premature translation-termination codon (PTC). As estimated, one-third of mutated and disease-causing mRNAs were reported to be targeted and degraded by NMD, suggesting the significance of this intricate mechanism in maintaining cellular integrity. It was later revealed that NMD also elicits down-regulation of many endogenous mRNAs without mutations (~10% of the human transcriptome). Therefore, NMD modulates gene expression to evade the generation of aberrant truncated proteins with detrimental functions, compromised activities, or dominant-negative effects, as well as by controlling the abundance of endogenous mRNAs. By regulating gene expression, NMD promotes diverse biological functions during development and differentiation, and facilitates cellular responses to adaptation, physiological changes, stresses, environmental insults, etc. Mutations or alterations (such as abnormal expression, degradation, post-translational modification, etc.) that impair the function or expression of proteins associated with the NMD pathway can be deleterious to cells and may cause pathological consequences, as implicated in developmental and intellectual disabilities, genetic defects, and cancer. Growing evidence in past decades has highlighted NMD as a critical driver of tumorigenesis. Advances in sequencing technologies provided the opportunity to identify many NMD substrate mRNAs in tumor samples compared to matched normal tissues. Interestingly, many of these changes are tumor-specific and are often fine-tuned in a tumor-specific manner, suggesting the complex regulation of NMD in cancer. Tumor cells differentially exploit NMD for survival benefits. Some tumors promote NMD to degrade a subset of mRNAs, such as those encoding tumor suppressors, stress response proteins, signaling proteins, RNA binding proteins, splicing factors, and immunogenic neoantigens. In contrast, some tumors suppress NMD to facilitate the expression of oncoproteins or other proteins beneficial for tumor growth and progression. In this review, we discuss how NMD is regulated as a critical mediator of oncogenesis to promote the development and progression of tumor cells. Understanding how NMD affects tumorigenesis differentially will pave the way for the development of more effective and less toxic, targeted therapeutic opportunities in the era of personalized medicine. Full article
(This article belongs to the Special Issue RNA Splicing in Cancer and Targeted Therapies)
►▼ Show Figures

Figure 1

17 pages, 602 KiB  
Review
The Genetic Side of the Mood: A Scientometric Review of the Genetic Basis of Mood Disorders
by Giovanni Bonacina, Alessandro Carollo and Gianluca Esposito
Genes 2023, 14(2), 352; https://doi.org/10.3390/genes14020352 - 30 Jan 2023
Cited by 7 | Viewed by 3399
Abstract
Mood disorders are highly heritable psychiatric disorders. Over the years, many genetic polymorphisms have been identified to pose a higher risk for the development of mood disorders. To overview the literature on the genetics of mood disorders, a scientometric analysis was performed on [...] Read more.
Mood disorders are highly heritable psychiatric disorders. Over the years, many genetic polymorphisms have been identified to pose a higher risk for the development of mood disorders. To overview the literature on the genetics of mood disorders, a scientometric analysis was performed on a sample of 5342 documents downloaded from Scopus. The most active countries and the most impactful documents in the field were identified. Furthermore, a total of 13 main thematic clusters emerged in the literature. From the qualitative inspection of clusters, it emerged that the research interest moved from a monogenic to a polygenic risk framework. Researchers have moved from the study of single genes in the early 1990s to conducting genome-wide association studies around 2015. In this way, genetic overlaps between mood disorders and other psychiatric conditions emerged too. Furthermore, around the 2010s, the interaction between genes and environmental factors emerged as pivotal in understanding the risk for mood disorders. The inspection of thematic clusters provides a valuable insight into the past and recent trends of research in the genetics of mood disorders and sheds light onto future lines of research. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Factors and Their Interactions in the Susceptibility to Multifactorial Diseases)
►▼ Show Figures

Figure 1

18 pages, 1254 KiB  
Review
Histone Modifications in Alzheimer’s Disease
by Dalileia Aparecida Santana, Marilia de Arruda Cardoso Smith and Elizabeth Suchi Chen
Genes 2023, 14(2), 347; https://doi.org/10.3390/genes14020347 - 29 Jan 2023
Cited by 32 | Viewed by 4343
Abstract
Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications [...] Read more.
Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease’s onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer’s disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

21 pages, 12528 KiB  
Article
Genome-Wide Identification, Evolutionary and Functional Analyses of WRKY Family Members in Ginkgo biloba
by Weixing Li, Nan Xiao, Yawen Wang, Ximeng Liu, Zhaoyu Chen, Xiaoyin Gu and Yadi Chen
Genes 2023, 14(2), 343; https://doi.org/10.3390/genes14020343 - 28 Jan 2023
Cited by 8 | Viewed by 2038
Abstract
WRKY transcription factors (TFs) are one of the largest families in plants which play essential roles in plant growth and stress response. Ginkgo biloba is a living fossil that has remained essentially unchanged for more than 200 million years, and now has become [...] Read more.
WRKY transcription factors (TFs) are one of the largest families in plants which play essential roles in plant growth and stress response. Ginkgo biloba is a living fossil that has remained essentially unchanged for more than 200 million years, and now has become widespread worldwide due to the medicinal active ingredients in its leaves. Here, 37 WRKY genes were identified, which were distributed randomly in nine chromosomes of G. biloba. Results of the phylogenetic analysis indicated that the GbWRKY could be divided into three groups. Furthermore, the expression patterns of GbWRKY genes were analyzed. Gene expression profiling and qRT−PCR revealed that different members of GbWRKY have different spatiotemporal expression patterns in different abiotic stresses. Most of the GbWRKY genes can respond to UV-B radiation, drought, high temperature and salt treatment. Meanwhile, all GbWRKY members performed phylogenetic tree analyses with the WRKY proteins of other species which were known to be associated with abiotic stress. The result suggested that GbWRKY may play a crucial role in regulating multiple stress tolerances. Additionally, GbWRKY13 and GbWRKY37 were all located in the nucleus, while GbWRKY15 was located in the nucleus and cytomembrane. Full article
(This article belongs to the Section Plant Genetics and Genomics)
►▼ Show Figures

Figure 1

23 pages, 651 KiB  
Review
Extracellular Vesicles as Potential Biomarkers in Amyotrophic Lateral Sclerosis
by Maruša Barbo and Metka Ravnik-Glavač
Genes 2023, 14(2), 325; https://doi.org/10.3390/genes14020325 - 27 Jan 2023
Cited by 15 | Viewed by 2807
Abstract
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, [...] Read more.
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, which is often accompanied by other neurological comorbidities, its diagnosis remains challenging. Perturbations in vesicle-mediated transport and autophagy as well as cell-autonomous disease initiation in glutamatergic neurons have been revealed in ALS. The use of extracellular vesicles (EVs) may be key in accessing pathologically relevant tissues for ALS, as EVs can cross the blood–brain barrier and be isolated from the blood. The number and content of EVs may provide indications of the disease pathogenesis, its stage, and prognosis. In this review, we collected a recent study aiming at the identification of EVs as a biomarker of ALS with respect to the size, quantity, and content of EVs in the biological fluids of patients compared to controls. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

14 pages, 2715 KiB  
Brief Report
Phenotypic Assessment of Pathogenic Variants in GNAO1 and Response to Caffeine in C. elegans Models of the Disease
by Martina Di Rocco, Serena Galosi, Francesca C. Follo, Enrico Lanza, Viola Folli, Alberto Martire, Vincenzo Leuzzi and Simone Martinelli
Genes 2023, 14(2), 319; https://doi.org/10.3390/genes14020319 - 26 Jan 2023
Cited by 6 | Viewed by 2130
Abstract
De novo mutations affecting the G protein α o subunit (Gαo)-encoding gene (GNAO1) cause childhood-onset developmental delay, hyperkinetic movement disorders, and epilepsy. Recently, we established Caenorhabditis elegans as an informative experimental model for deciphering pathogenic mechanisms associated with GNAO1 defects and [...] Read more.
De novo mutations affecting the G protein α o subunit (Gαo)-encoding gene (GNAO1) cause childhood-onset developmental delay, hyperkinetic movement disorders, and epilepsy. Recently, we established Caenorhabditis elegans as an informative experimental model for deciphering pathogenic mechanisms associated with GNAO1 defects and identifying new therapies. In this study, we generated two additional gene-edited strains that harbor pathogenic variants which affect residues Glu246 and Arg209—two mutational hotspots in Gαo. In line with previous findings, biallelic changes displayed a variable hypomorphic effect on Gαo-mediated signaling that led to the excessive release of neurotransmitters by different classes of neurons, which, in turn, caused hyperactive egg laying and locomotion. Of note, heterozygous variants showed a cell-specific dominant-negative behavior, which was strictly dependent on the affected residue. As with previously generated mutants (S47G and A221D), caffeine was effective in attenuating the hyperkinetic behavior of R209H and E246K animals, indicating that its efficacy is mutation-independent. Conversely, istradefylline, a selective adenosine A2A receptor antagonist, was effective in R209H animals but not in E246K worms, suggesting that caffeine acts through both adenosine receptor-dependent and receptor-independent mechanisms. Overall, our findings provide new insights into disease mechanisms and further support the potential efficacy of caffeine in controlling dyskinesia associated with pathogenic GNAO1 mutations. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

17 pages, 4116 KiB  
Article
The Adaptive Evolution in the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) Revealed by the Diversity of Larval Gut Bacteria
by Yan-Ping Wang, Xu Liu, Chun-Yan Yi, Xing-Yu Chen, Chang-Hua Liu, Cui-Cui Zhang, Qing-Dong Chen, Song Chen, Hong-Ling Liu and De-Qiang Pu
Genes 2023, 14(2), 321; https://doi.org/10.3390/genes14020321 - 26 Jan 2023
Cited by 9 | Viewed by 2077
Abstract
Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest’s gut bacteria remain to be [...] Read more.
Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest’s gut bacteria remain to be investigated to better understand their coevolution. In this study, differences in the gut bacterial communities were examined for the fifth and sixth instar larvae of S. frugiperda fed on leaves of different host plants (corn, sorghum, highland barley, and citrus). The 16S rDNA full-length amplification and sequencing method was used to determine the abundance and diversity of gut bacteria in larval intestines. The highest richness and diversity of gut bacteria were in corn-fed fifth instar larvae, whereas in sixth instar larvae, the richness and diversity were higher when larvae were fed by other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of fifth and sixth instar larvae. According to the LDA Effect Size (LEfSe) analysis, the host plants had important effects on the structure of gut bacterial communities in S. frugiperda. In the PICRUSt2 analysis, most predicted functional categories were associated with metabolism. Thus, the host plant species attacked by S. frugiperda larvae can affect their gut bacterial communities, and such changes are likely important in the adaptive evolution of S. frugiperda to host plants. Full article
(This article belongs to the Special Issue Genetics, Phylogeny, and Evolution of Insects)
►▼ Show Figures

Figure 1

14 pages, 834 KiB  
Review
miRNAs: The Road from Bench to Bedside
by Giuseppe Iacomino
Genes 2023, 14(2), 314; https://doi.org/10.3390/genes14020314 - 25 Jan 2023
Cited by 28 | Viewed by 6452
Abstract
miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids [...] Read more.
miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids has underscored their potential in the field of biomarker research. In addition, the therapeutic potential of miRNAs is receiving increasing attention in numerous conditions. On the other hand, many operative problems including stability, delivery systems, and bioavailability, still need to be solved. In this dynamic field, biopharmaceutical companies are increasingly engaged, and ongoing clinical trials point to anti-miR and miR-mimic molecules as an innovative class of molecules for upcoming therapeutic applications. This article aims to provide a comprehensive overview of current knowledge on several pending issues and new opportunities offered by miRNAs in the treatment of diseases and as early diagnostic tools in next-generation medicine. Full article
(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)
►▼ Show Figures

Figure 1

15 pages, 3272 KiB  
Article
Stage-Specific Transcriptomes of the Mussel Mytilus coruscus Reveals the Developmental Program for the Planktonic to Benthic Transition
by Yu-Qing Wang, Qi Liu, Yan Zhou, Lizhi Chen, Yue-Ming Yang, Xue Shi, Deborah M. Power and Yi-Feng Li
Genes 2023, 14(2), 287; https://doi.org/10.3390/genes14020287 - 21 Jan 2023
Cited by 6 | Viewed by 2201
Abstract
Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic—benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. [...] Read more.
Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic—benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. Analysis of highly upregulated differentially expressed genes (DEGs) at the pediveliger stage revealed enrichment of immune-related genes. The results may indicate that larvae co-opt molecules of the immune system to sense and respond to external chemical cues and neuroendocrine signaling pathways forecast and trigger the response. The upregulation of adhesive protein genes linked to byssal thread secretion indicates the anchoring capacity required for larval settlement arises prior to metamorphosis. The results of gene expression support a role for the immune and neuroendocrine systems in mussel metamorphosis and provide the basis for future studies to disentangle gene networks and the biology of this important lifecycle transformation. Full article
(This article belongs to the Special Issue Genetic Breeding and Genomics of Marine Shellfish)
►▼ Show Figures

Figure 1

13 pages, 2515 KiB  
Review
Genetic Improvement and Application Practices of Synthetic Hexaploid Wheat
by Hongshen Wan, Fan Yang, Jun Li, Qin Wang, Zehou Liu, Yonglu Tang and Wuyun Yang
Genes 2023, 14(2), 283; https://doi.org/10.3390/genes14020283 - 21 Jan 2023
Cited by 9 | Viewed by 2790
Abstract
Synthetic hexaploid wheat (SHW) is a useful genetic resource that can be used to improve the performance of common wheat by transferring favorable genes from a wide range of tetraploid or diploid donors. From the perspectives of physiology, cultivation, and molecular genetics, the [...] Read more.
Synthetic hexaploid wheat (SHW) is a useful genetic resource that can be used to improve the performance of common wheat by transferring favorable genes from a wide range of tetraploid or diploid donors. From the perspectives of physiology, cultivation, and molecular genetics, the use of SHW has the potential to increase wheat yield. Moreover, genomic variation and recombination were enhanced in newly formed SHW, which could generate more genovariation or new gene combinations compared to ancestral genomes. Accordingly, we presented a breeding strategy for the application of SHW—the ‘large population with limited backcrossing method’—and we pyramided stripe rust resistance and big-spike-related QTLs/genes from SHW into new high-yield cultivars, which represents an important genetic basis of big-spike wheat in southwestern China. For further breeding applications of SHW-derived cultivars, we used the ‘recombinant inbred line-based breeding method’ that combines both phenotypic and genotypic evaluations to pyramid multi-spike and pre-harvest sprouting resistance QTLs/genes from other germplasms to SHW-derived cultivars; consequently, we created record-breaking high-yield wheat in southwestern China. To meet upcoming environmental challenges and continuous global demand for wheat production, SHW with broad genetic resources from wild donor species will play a major role in wheat breeding. Full article
(This article belongs to the Special Issue Genetics Studies on Wheat)
►▼ Show Figures

Graphical abstract

18 pages, 1597 KiB  
Review
Novel Insights into Mitochondrial DNA: Mitochondrial Microproteins and mtDNA Variants Modulate Athletic Performance and Age-Related Diseases
by Hiroshi Kumagai, Brendan Miller, Su-Jeong Kim, Naphada Leelaprachakul, Naoki Kikuchi, Kelvin Yen and Pinchas Cohen
Genes 2023, 14(2), 286; https://doi.org/10.3390/genes14020286 - 21 Jan 2023
Cited by 15 | Viewed by 3662
Abstract
Sports genetics research began in the late 1990s and over 200 variants have been reported as athletic performance- and sports injuries-related genetic polymorphisms. Genetic polymorphisms in the α-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are well-established for athletic performance, while collagen-, inflammation-, and [...] Read more.
Sports genetics research began in the late 1990s and over 200 variants have been reported as athletic performance- and sports injuries-related genetic polymorphisms. Genetic polymorphisms in the α-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are well-established for athletic performance, while collagen-, inflammation-, and estrogen-related genetic polymorphisms are reported as genetic markers for sports injuries. Although the Human Genome Project was completed in the early 2000s, recent studies have discovered previously unannotated microproteins encoded in small open reading frames. Mitochondrial microproteins (also called mitochondrial-derived peptides) are encoded in the mtDNA, and ten mitochondrial microproteins, such as humanin, MOTS-c (mitochondrial ORF of the 12S rRNA type-c), SHLPs 1–6 (small humanin-like peptides 1 to 6), SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), and Gau (gene antisense ubiquitous in mtDNAs) have been identified to date. Some of those microproteins have crucial roles in human biology by regulating mitochondrial function, and those, including those to be discovered in the future, could contribute to a better understanding of human biology. This review describes a basic concept of mitochondrial microproteins and discusses recent findings about the potential roles of mitochondrial microproteins in athletic performance as well as age-related diseases. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Graphical abstract

20 pages, 1341 KiB  
Review
Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components
by Guangzhao Guan, Richard D. Cannon, Dawn E. Coates and Li Mei
Genes 2023, 14(2), 272; https://doi.org/10.3390/genes14020272 - 20 Jan 2023
Cited by 28 | Viewed by 6127
Abstract
The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate [...] Read more.
The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

23 pages, 1729 KiB  
Review
Adaptive Evolution of Rhizobial Symbiosis beyond Horizontal Gene Transfer: From Genome Innovation to Regulation Reconstruction
by Sheng Liu, Jian Jiao and Chang-Fu Tian
Genes 2023, 14(2), 274; https://doi.org/10.3390/genes14020274 - 20 Jan 2023
Cited by 9 | Viewed by 4489
Abstract
There are ubiquitous variations in symbiotic performance of different rhizobial strains associated with the same legume host in agricultural practices. This is due to polymorphisms of symbiosis genes and/or largely unexplored variations in integration efficiency of symbiotic function. Here, we reviewed cumulative evidence [...] Read more.
There are ubiquitous variations in symbiotic performance of different rhizobial strains associated with the same legume host in agricultural practices. This is due to polymorphisms of symbiosis genes and/or largely unexplored variations in integration efficiency of symbiotic function. Here, we reviewed cumulative evidence on integration mechanisms of symbiosis genes. Experimental evolution, in concert with reverse genetic studies based on pangenomics, suggests that gain of the same circuit of key symbiosis genes through horizontal gene transfer is necessary but sometimes insufficient for bacteria to establish an effective symbiosis with legumes. An intact genomic background of the recipient may not support the proper expression or functioning of newly acquired key symbiosis genes. Further adaptive evolution, through genome innovation and reconstruction of regulation networks, may confer the recipient of nascent nodulation and nitrogen fixation ability. Other accessory genes, either co-transferred with key symbiosis genes or stochastically transferred, may provide the recipient with additional adaptability in ever-fluctuating host and soil niches. Successful integrations of these accessory genes with the rewired core network, regarding both symbiotic and edaphic fitness, can optimize symbiotic efficiency in various natural and agricultural ecosystems. This progress also sheds light on the development of elite rhizobial inoculants using synthetic biology procedures. Full article
(This article belongs to the Special Issue Evolution of Root Nodule Symbioses)
►▼ Show Figures

Figure 1

14 pages, 1866 KiB  
Article
Construction of Fusion Protein for Enhanced Small RNA Loading to Extracellular Vesicles
by Masoumeh Es-Haghi, Olga Neustroeva, Iftekhar Chowdhury, Pia Laitinen, Mari-Anna Väänänen, Nea Korvenlaita, Tarja Malm, Mikko P. Turunen and Tiia A. Turunen
Genes 2023, 14(2), 261; https://doi.org/10.3390/genes14020261 - 19 Jan 2023
Cited by 7 | Viewed by 2656
Abstract
Extracellular vesicles (EVs) naturally carry cargo from producer cells, such as RNA and protein, and can transfer these messengers to other cells and tissue. This ability provides an interesting opportunity for using EVs as delivery vehicles for therapeutic agents, such as for gene [...] Read more.
Extracellular vesicles (EVs) naturally carry cargo from producer cells, such as RNA and protein, and can transfer these messengers to other cells and tissue. This ability provides an interesting opportunity for using EVs as delivery vehicles for therapeutic agents, such as for gene therapy. However, endogenous loading of cargo, such as microRNAs (miRNAs), is not very efficient as the copy number of miRNAs per EV is quite low. Therefore, new methods and tools to enhance the loading of small RNAs is required. In the current study, we developed fusion protein of EV membrane protein CD9 and RNA-binding protein AGO2 (hCD9.hAGO2). We show that the EVs engineered with hCD9.hAGO2 contain significantly higher levels of miRNA or shRNA (miR-466c or shRNA-451, respectively) compared to EVs that are isolated from cells that only overexpress the desired miRNA or shRNA. These hCD9.hAGO2 engineered EVs also transfer their RNA cargo to recipient cells more efficiently. We were not able to detect changes in gene expression levels in recipient cells after the EV treatments, but we show that the cell viability of HUVECs was increased after hCD9.hAGO2 EV treatments. This technical study characterizes the hCD9.hAGO2 fusion protein for the future development of enhanced RNA loading to EVs. Full article
(This article belongs to the Section RNA)
►▼ Show Figures

Figure 1

16 pages, 1521 KiB  
Article
Omics Data Preprocessing for Machine Learning: A Case Study in Childhood Obesity
by Álvaro Torres-Martos, Mireia Bustos-Aibar, Alberto Ramírez-Mena, Sofía Cámara-Sánchez, Augusto Anguita-Ruiz, Rafael Alcalá, Concepción M. Aguilera and Jesús Alcalá-Fdez
Genes 2023, 14(2), 248; https://doi.org/10.3390/genes14020248 - 18 Jan 2023
Cited by 6 | Viewed by 4176
Abstract
The use of machine learning techniques for the construction of predictive models of disease outcomes (based on omics and other types of molecular data) has gained enormous relevance in the last few years in the biomedical field. Nonetheless, the virtuosity of omics studies [...] Read more.
The use of machine learning techniques for the construction of predictive models of disease outcomes (based on omics and other types of molecular data) has gained enormous relevance in the last few years in the biomedical field. Nonetheless, the virtuosity of omics studies and machine learning tools are subject to the proper application of algorithms as well as the appropriate pre-processing and management of input omics and molecular data. Currently, many of the available approaches that use machine learning on omics data for predictive purposes make mistakes in several of the following key steps: experimental design, feature selection, data pre-processing, and algorithm selection. For this reason, we propose the current work as a guideline on how to confront the main challenges inherent to multi-omics human data. As such, a series of best practices and recommendations are also presented for each of the steps defined. In particular, the main particularities of each omics data layer, the most suitable preprocessing approaches for each source, and a compilation of best practices and tips for the study of disease development prediction using machine learning are described. Using examples of real data, we show how to address the key problems mentioned in multi-omics research (e.g., biological heterogeneity, technical noise, high dimensionality, presence of missing values, and class imbalance). Finally, we define the proposals for model improvement based on the results found, which serve as the bases for future work. Full article
(This article belongs to the Special Issue Selected Papers from the 9th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2022))
►▼ Show Figures

Figure 1

14 pages, 3116 KiB  
Article
Metatranscriptomic Analyses Reveal Important Roles of the Gut Microbiome in Primate Dietary Adaptation
by Mingyi Zhang, Xiaochen Wang, Ziming Wang, Shuxin Mao, Jiali Zhang, Ming Li and Huijuan Pan
Genes 2023, 14(1), 228; https://doi.org/10.3390/genes14010228 - 15 Jan 2023
Cited by 9 | Viewed by 3078
Abstract
The gut microbiome plays a vital role in host ecological adaptation, especially dietary adaptations. Primates have evolved a variety of dietary and gut physiological structures that are useful to explore the role of the gut microbiome in host dietary adaptations. Here, we characterize [...] Read more.
The gut microbiome plays a vital role in host ecological adaptation, especially dietary adaptations. Primates have evolved a variety of dietary and gut physiological structures that are useful to explore the role of the gut microbiome in host dietary adaptations. Here, we characterize gut microbiome transcriptional activity in ten fecal samples from primates with three different diets and compare the results to their previously reported metagenomic profile. Bacteria related to cellulose degradation, like Bacteroidaceae and Alcaligenaceae, were enriched and actively expressed in the gut microbiome of folivorous primates, and functional analysis revealed that the glycan biosynthesis and metabolic pathways were significantly active. In omnivorous primates, Helicobacteraceae, which promote lipid metabolism, were significantly enriched in expression, and activity and xenobiotic biodegradation and metabolism as well as lipid metabolism pathways were significantly active. In frugivorous primates, the abundance and activity of Elusimicrobiaceae, Neisseriaceae, and Succinivibrionaceae, which are associated with digestion of pectin and fructose, were significantly elevated, and the functional pathways involved in the endocrine system were significantly enriched. In conclusion, the gut microbiome contributes to host dietary adaptation by helping hosts digest the inaccessible nutrients in their specific diets. Full article
(This article belongs to the Special Issue Primate Phylogeny and Genetics)
►▼ Show Figures

Figure 1

18 pages, 2558 KiB  
Article
Spectrum of Genetic Variants in the Dystrophin Gene: A Single Centre Retrospective Analysis of 750 Duchenne and Becker Patients from Southern Italy
by Emanuela Viggiano, Esther Picillo, Luigia Passamano, Maria Elena Onore, Giulio Piluso, Marianna Scutifero, Annalaura Torella, Vincenzo Nigro and Luisa Politano
Genes 2023, 14(1), 214; https://doi.org/10.3390/genes14010214 - 14 Jan 2023
Cited by 12 | Viewed by 3410
Abstract
Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are [...] Read more.
Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are available. We report a large single-centre study on the spectrum of DMD gene variants observed in 750 patients analyzed for suspected Duchenne (DMD) or Becker (BMD) muscular dystrophy, over the past 30 years, at the Cardiomyology and Medical Genetics of the University of Campania. We found 534 (71.21%) large deletions, 73 (9.73%) large duplications, and 112 (14.93%) point mutations, of which 44 (5.9%) were small ins/del causing frame-shifts, 57 (7.6%) nonsense mutations, 8 (1.1%) splice site and 3 (0.4%) intronic mutations, and 31 (4.13%) non mutations. Moreover, we report the prevalence of the different types of mutations in patients with DMD and BMD according to their decade of birth, from 1930 to 2020, and correlate the data to the different techniques used over the years. In the most recent decades, we observed an apparent increase in the prevalence of point mutations, probably due to the use of Next-Generation Sequencing (NGS). In conclusion, in southern Italy, deletions are the most frequent variation observed in DMD and BMD patients followed by point mutations and duplications, as elsewhere in the world. NGS was useful to identify point mutations in cases of strong suspicion of DMD/BMD negative on deletions/duplications analyses. In the era of personalized medicine and availability of new causative therapies, a collective effort is necessary to enable DMD and BMD patients to have timely genetic diagnoses and avoid late implementation of standard of care and late initiation of appropriate treatment. Full article
(This article belongs to the Special Issue Genetics of Muscular Dystrophies from Pathogenesis to Gene Therapy)
►▼ Show Figures

Figure 1

12 pages, 2388 KiB  
Article
Genome-Wide Identification of DUF668 Gene Family and Expression Analysis under Drought and Salt Stresses in Sweet Potato [Ipomoea batatas (L.) Lam]
by Enliang Liu, Zhiqiang Li, Zhengqian Luo, Linli Xu, Ping Jin, Shun Ji, Guohui Zhou, Zhenyang Wang, Zhilin Zhou and Hua Zhang
Genes 2023, 14(1), 217; https://doi.org/10.3390/genes14010217 - 14 Jan 2023
Cited by 10 | Viewed by 2587
Abstract
The domain of unknown function 668 (DUF668) is a gene family that plays a vital role in responses to adversity coercion stresses in plant. However, the function of the DUF668 gene family is not fully understood in sweet potato. In this study, bioinformatics [...] Read more.
The domain of unknown function 668 (DUF668) is a gene family that plays a vital role in responses to adversity coercion stresses in plant. However, the function of the DUF668 gene family is not fully understood in sweet potato. In this study, bioinformatics methods were used to analyze the number, physicochemical properties, evolution, structure, and promoter cis-acting elements of the IbDUF668 family genes, and RNA-seq and qRT–PCR were performed to detect gene expression and their regulation under hormonal and abiotic stress. A total of 14 IbDUF668 proteins were identified in sweet potato, distributed on nine chromosomes. By phylogenetic analysis, IbDUF668 proteins can be divided into two subfamilies. Transcriptome expression profiling revealed that many genes from DUF668 in sweet potato showed specificity and differential expression under cold, heat, drought, salt and hormones (ABA, GA3 and IAA). Four genes (IbDUF668-6, 7, 11 and 13) of sweet potato were significantly upregulated by qRT-PCR under ABA, drought and NaCl stress. Results suggest that the DUF668 gene family is involved in drought and salt tolerance in sweet potato, and it will further provide the basic information of DUF668 gene mechanisms in plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
►▼ Show Figures

Figure 1

20 pages, 2181 KiB  
Review
Parvalbumin: A Major Fish Allergen and a Forensically Relevant Marker
by Subham Mukherjee, Petra Horka, Kamila Zdenkova and Eliska Cermakova
Genes 2023, 14(1), 223; https://doi.org/10.3390/genes14010223 - 14 Jan 2023
Cited by 16 | Viewed by 7556
Abstract
Parvalbumins (PVALBs) are low molecular weight calcium-binding proteins. In addition to their role in many biological processes, PVALBs play an important role in regulating Ca2+ switching in muscles with fast-twitch fibres in addition to their role in many biological processes. The PVALB gene [...] Read more.
Parvalbumins (PVALBs) are low molecular weight calcium-binding proteins. In addition to their role in many biological processes, PVALBs play an important role in regulating Ca2+ switching in muscles with fast-twitch fibres in addition to their role in many biological processes. The PVALB gene family is divided into two gene types, alpha (α) and beta (β), with the β gene further divided into two gene types, beta1 (β1) and beta2 (β2), carrying traces of whole genome duplication. A large variety of commonly consumed fish species contain PVALB proteins which are known to cause fish allergies. More than 95% of all fish-induced food allergies are caused by PVALB proteins. The authentication of fish species has become increasingly important as the seafood industry continues to grow and the growth brings with it many cases of food fraud. Since the PVALB gene plays an important role in the initiation of allergic reactions, it has been used for decades to develop alternate assays for fish identification. A brief review of the significance of the fish PVALB genes is presented in this article, which covers evolutionary diversity, allergic properties, and potential use as a forensic marker. Full article
(This article belongs to the Special Issue Genomics in Aquaculture and Fisheries)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 51-100 on page 2 of 14.

Go to page    chevron_left 1 2 3 4 5 chevron_right last_page
Back to TopTop