Genes

18 pages, 1098 KiB

Open AccessEditor’s ChoiceReview

miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer

by Atonu Chakrabortty, Daniel J. Patton, Bruce F. Smith and Payal Agarwal

Genes 2023, 14(7), 1375; https://doi.org/10.3390/genes14071375 - 29 Jun 2023

Cited by 21 | Viewed by 6956

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown [...] Read more.

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target. Full article

(This article belongs to the Special Issue MicroRNA in Cancers)

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14 pages, 973 KiB

Open AccessEditor’s ChoiceSystematic Review

Spinal Muscular Atrophy Treatment in Patients Identified by Newborn Screening—A Systematic Review

by Karolina Aragon-Gawinska, Charlotte Mouraux, Tamara Dangouloff and Laurent Servais

Genes 2023, 14(7), 1377; https://doi.org/10.3390/genes14071377 - 29 Jun 2023

Cited by 18 | Viewed by 3429

Abstract

Background: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials [...] Read more.

Background: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials conducted in presymptomatic individuals, as in some cases disease presents very early. Methods: we conducted a systematic review of articles published up to January 2023. Results: Among 35 patients with three SMN2 copies treated before 42 days of age and followed-up for at least 18 months, all but one achieved autonomous ambulation. Of 41 patients with two SMN2 copies, who were non-symptomatic at treatment initiation, all achieved a sitting position independently and 31 were able to walk. Of 16 patients with two SMN2 copies followed-up for at least 18 months who presented with symptoms at treatment onset, 3 achieved the walking milestone and all but one were able to sit without support. Conclusions: evaluation of data from 18 publications indicates that the results of early treatment depend on the number of SMN2 copies and the initial neurological status of the patient. Full article

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

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32 pages, 1104 KiB

Open AccessEditor’s ChoiceReview

Genes and Athletic Performance: The 2023 Update

by Ekaterina A. Semenova, Elliott C. R. Hall and Ildus I. Ahmetov

Genes 2023, 14(6), 1235; https://doi.org/10.3390/genes14061235 - 8 Jun 2023

Cited by 15 | Viewed by 13460

Abstract

Phenotypes of athletic performance and exercise capacity are complex traits influenced by both genetic and environmental factors. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status summarises recent advances in sports genomics research, including findings from candidate gene [...] Read more.

Phenotypes of athletic performance and exercise capacity are complex traits influenced by both genetic and environmental factors. This update on the panel of genetic markers (DNA polymorphisms) associated with athlete status summarises recent advances in sports genomics research, including findings from candidate gene and genome-wide association (GWAS) studies, meta-analyses, and findings involving larger-scale initiatives such as the UK Biobank. As of the end of May 2023, a total of 251 DNA polymorphisms have been associated with athlete status, of which 128 genetic markers were positively associated with athlete status in at least two studies (41 endurance-related, 45 power-related, and 42 strength-related). The most promising genetic markers include the AMPD1 rs17602729 C, CDKN1A rs236448 A, HFE rs1799945 G, MYBPC3 rs1052373 G, NFIA-AS2 rs1572312 C, PPARA rs4253778 G, and PPARGC1A rs8192678 G alleles for endurance; ACTN3 rs1815739 C, AMPD1 rs17602729 C, CDKN1A rs236448 C, CPNE5 rs3213537 G, GALNTL6 rs558129 T, IGF2 rs680 G, IGSF3 rs699785 A, NOS3 rs2070744 T, and TRHR rs7832552 T alleles for power; and ACTN3 rs1815739 C, AR ≥21 CAG repeats, LRPPRC rs10186876 A, MMS22L rs9320823 T, PHACTR1 rs6905419 C, and PPARG rs1801282 G alleles for strength. It should be appreciated, however, that elite performance still cannot be predicted well using only genetic testing. Full article

(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)

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31 pages, 416 KiB

Open AccessEditor’s ChoiceReview

Hereditary Cancer Syndromes: A Comprehensive Review with a Visual Tool

by Mattia Garutti, Lorenzo Foffano, Roberta Mazzeo, Anna Michelotti, Lucia Da Ros, Alessandra Viel, Gianmaria Miolo, Alberto Zambelli and Fabio Puglisi

Genes 2023, 14(5), 1025; https://doi.org/10.3390/genes14051025 - 30 Apr 2023

Cited by 14 | Viewed by 5315

Abstract

Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could [...] Read more.

Hereditary cancer syndromes account for nearly 10% of cancers even though they are often underdiagnosed. Finding a pathogenic gene variant could have dramatic implications in terms of pharmacologic treatments, tailored preventive programs, and familiar cascade testing. However, diagnosing a hereditary cancer syndrome could be challenging because of a lack of validated testing criteria or because of their suboptimal performance. In addition, many clinicians are not sufficiently well trained to identify and select patients that could benefit from a genetic test. Herein, we searched the available literature to comprehensively review and categorize hereditary cancer syndromes affecting adults with the aim of helping clinicians in their daily clinical practice through a visual tool. Full article

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

42 pages, 3406 KiB

Open AccessEditor’s ChoiceReview

The Hexosamine Biosynthesis Pathway: Regulation and Function

by Alysta Paneque, Harvey Fortus, Julia Zheng, Guy Werlen and Estela Jacinto

Genes 2023, 14(4), 933; https://doi.org/10.3390/genes14040933 - 18 Apr 2023

Cited by 31 | Viewed by 7227

Abstract

The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate-N-acetyl glucosamine, UDP-GlcNAc, which is a key metabolite that is used for N- or O-linked glycosylation, a co- or post-translational modification, respectively, that modulates protein activity and expression. The production of hexosamines [...] Read more.

The hexosamine biosynthesis pathway (HBP) produces uridine diphosphate-N-acetyl glucosamine, UDP-GlcNAc, which is a key metabolite that is used for N- or O-linked glycosylation, a co- or post-translational modification, respectively, that modulates protein activity and expression. The production of hexosamines can occur via de novo or salvage mechanisms that are catalyzed by metabolic enzymes. Nutrients including glutamine, glucose, acetyl-CoA, and UTP are utilized by the HBP. Together with availability of these nutrients, signaling molecules that respond to environmental signals, such as mTOR, AMPK, and stress-regulated transcription factors, modulate the HBP. This review discusses the regulation of GFAT, the key enzyme of the de novo HBP, as well as other metabolic enzymes that catalyze the reactions to produce UDP-GlcNAc. We also examine the contribution of the salvage mechanisms in the HBP and how dietary supplementation of the salvage metabolites glucosamine and N-acetylglucosamine could reprogram metabolism and have therapeutic potential. We elaborate on how UDP-GlcNAc is utilized for N-glycosylation of membrane and secretory proteins and how the HBP is reprogrammed during nutrient fluctuations to maintain proteostasis. We also consider how O-GlcNAcylation is coupled to nutrient availability and how this modification modulates cell signaling. We summarize how deregulation of protein N-glycosylation and O-GlcNAcylation can lead to diseases including cancer, diabetes, immunodeficiencies, and congenital disorders of glycosylation. We review the current pharmacological strategies to inhibit GFAT and other enzymes involved in the HBP or glycosylation and how engineered prodrugs could have better therapeutic efficacy for the treatment of diseases related to HBP deregulation. Full article

(This article belongs to the Special Issue Signaling and Gene Regulation in Metabolism)

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22 pages, 1790 KiB

Open AccessEditor’s ChoiceReview

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 22 | Viewed by 5715

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)

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22 pages, 1064 KiB

Open AccessEditor’s ChoiceReview

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 23 | Viewed by 2951

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)

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21 pages, 758 KiB

Open AccessEditor’s ChoiceReview

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 32 | Viewed by 12101

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)

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17 pages, 1161 KiB

Open AccessEditor’s ChoiceReview

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 12 | Viewed by 3466

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)

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18 pages, 1254 KiB

Open AccessEditor’s ChoiceReview

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 24 | Viewed by 3268

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)

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14 pages, 834 KiB

Open AccessEditor’s ChoiceReview

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 18 | Viewed by 4477

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)

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20 pages, 1341 KiB

Open AccessEditor’s ChoiceReview

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 20 | Viewed by 4770

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)

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20 pages, 2181 KiB

Open AccessEditor’s ChoiceReview

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 12 | Viewed by 6296

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)

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20 pages, 980 KiB

Open AccessEditor’s ChoiceReview

Genetic Diversity, Conservation, and Utilization of Plant Genetic Resources

by Romesh Kumar Salgotra and Bhagirath Singh Chauhan

Genes 2023, 14(1), 174; https://doi.org/10.3390/genes14010174 - 9 Jan 2023

Cited by 71 | Viewed by 20161

Abstract

Plant genetic resources (PGRs) are the total hereditary material, which includes all the alleles of various genes, present in a crop species and its wild relatives. They are a major resource that humans depend on to increase farming resilience and profit. Hence, the [...] Read more.

Plant genetic resources (PGRs) are the total hereditary material, which includes all the alleles of various genes, present in a crop species and its wild relatives. They are a major resource that humans depend on to increase farming resilience and profit. Hence, the demand for genetic resources will increase as the world population increases. There is a need to conserve and maintain the genetic diversity of these valuable resources for sustainable food security. Due to environmental changes and genetic erosion, some valuable genetic resources have already become extinct. The landraces, wild relatives, wild species, genetic stock, advanced breeding material, and modern varieties are some of the important plant genetic resources. These diverse resources have contributed to maintaining sustainable biodiversity. New crop varieties with desirable traits have been developed using these resources. Novel genes/alleles linked to the trait of interest are transferred into the commercially cultivated varieties using biotechnological tools. Diversity should be maintained as a genetic resource for the sustainable development of new crop varieties. Additionally, advances in biotechnological tools, such as next-generation sequencing, molecular markers, in vitro culture technology, cryopreservation, and gene banks, help in the precise characterization and conservation of rare and endangered species. Genomic tools help in the identification of quantitative trait loci (QTLs) and novel genes in plants that can be transferred through marker-assisted selection and marker-assisted backcrossing breeding approaches. This article focuses on the recent development in maintaining the diversity of genetic resources, their conservation, and their sustainable utilization to secure global food security. Full article

(This article belongs to the Special Issue Genetic Diversity, Conservation and Utilization of Plant Genetic Resources)

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12 pages, 304 KiB

Open AccessEditor’s ChoiceReview

Interaction between Boron and Other Elements in Plants

by Ying Long and Jiashi Peng

Genes 2023, 14(1), 130; https://doi.org/10.3390/genes14010130 - 3 Jan 2023

Cited by 16 | Viewed by 4705

Abstract

Boron (B) is an essential mineral nutrient for growth of plants, and B deficiency is now a worldwide problem that limits production of B deficiency-sensitive crops, such as rape and cotton. Agronomic practice has told that balanced B and other mineral nutrient fertilizer [...] Read more.

Boron (B) is an essential mineral nutrient for growth of plants, and B deficiency is now a worldwide problem that limits production of B deficiency-sensitive crops, such as rape and cotton. Agronomic practice has told that balanced B and other mineral nutrient fertilizer applications is helpful to promote crop yield. In recent years, much research has reported that applying B can also reduce the accumulation of toxic elements such as cadmium and aluminum in plants and alleviate their toxicity symptoms. Therefore, the relation between B and other elements has become an interesting issue for plant nutritionists. Here we summarize the research progress of the interaction between B and macronutrients such as nitrogen, phosphorus, calcium, potassium, magnesium, and sulfur, essential micronutrients such as iron, manganese, zinc, copper, and molybdenum, and beneficial elements such as sodium, selenium, and silicon. Moreover, the interaction between B and toxic elements such as cadmium and aluminum, which pose a serious threat to agriculture, is also discussed in this paper. Finally, the possible physiological mechanisms of the interaction between B and other elements in plants is reviewed. We propose that the cell wall is an important intermediary between interaction of B and other elements, and competitive inhibition of elements and related signal transduction pathways also play a role. Currently, research on the physiological role of B in plants mainly focuses on its involvement in the structure and function of cell walls, and our understanding of the details for interactions between B and other elements also tend to relate to the cell wall. However, we know little about the metabolic process of B inside cells, including its interactions with other elements. More research is needed to address the aforementioned research questions in future. Full article

(This article belongs to the Special Issue Signal Transduction Pathway in Plants)

21 pages, 6313 KiB

Open AccessEditor’s ChoiceArticle

An Aggrephagy-Related LncRNA Signature for the Prognosis of Pancreatic Adenocarcinoma

by Xueyuan Huang, Hao Chi, Siqi Gou, Xiyuan Guo, Lin Li, Gaoge Peng, Jinhao Zhang, Jiayu Xu, Siji Nian and Qing Yuan

Genes 2023, 14(1), 124; https://doi.org/10.3390/genes14010124 - 2 Jan 2023

Cited by 15 | Viewed by 2286

Abstract

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a [...] Read more.

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50). Full article

(This article belongs to the Special Issue Bioinformatics and Genetics of Human Diseases)

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21 pages, 364 KiB

Open AccessEditor’s ChoiceArticle

Polymorphisms in ACE1, TMPRSS2, IFIH1, IFNAR2, and TYK2 Genes Are Associated with Worse Clinical Outcomes in COVID-19

by Cristine Dieter, Leticia de Almeida Brondani, Natália Emerim Lemos, Ariell Freires Schaeffer, Caroline Zanotto, Denise Taurino Ramos, Eliandra Girardi, Felipe Mateus Pellenz, Joiza Lins Camargo, Karla Suzana Moresco, Lucas Lima da Silva, Mariana Rauback Aubin, Mayara Souza de Oliveira, Tatiana Helena Rech, Luís Henrique Canani, Fernando Gerchman, Cristiane Bauermann Leitão and Daisy Crispim

Genes 2023, 14(1), 29; https://doi.org/10.3390/genes14010029 - 22 Dec 2022

Cited by 16 | Viewed by 2236

Abstract

Although advanced age, male sex, and some comorbidities impact the clinical course of COVID-19, these factors only partially explain the inter-individual variability in disease severity. Some studies have shown that genetic polymorphisms contribute to COVID-19 severity; however, the results are inconclusive. Thus, we [...] Read more.

Although advanced age, male sex, and some comorbidities impact the clinical course of COVID-19, these factors only partially explain the inter-individual variability in disease severity. Some studies have shown that genetic polymorphisms contribute to COVID-19 severity; however, the results are inconclusive. Thus, we investigated the association between polymorphisms in ACE1, ACE2, DPP9, IFIH1, IFNAR2, IFNL4, TLR3, TMPRSS2, and TYK2 and the clinical course of COVID-19. A total of 694 patients with COVID-19 were categorized as: (1) ward inpatients (moderate symptoms) or patients admitted at the intensive care unit (ICU; severe symptoms); and (2) survivors or non-survivors. In females, the rs1990760/IFIH1 T/T genotype was associated with risk of ICU admission and death. Moreover, the rs1799752/ACE1 Ins and rs12329760/TMPRSS2 T alleles were associated with risk of ICU admission. In non-white patients, the rs2236757/IFNAR2 A/A genotype was associated with risk of ICU admission, while the rs1799752/ACE1 Ins/Ins genotype, rs2236757/IFNAR2 A/A genotype, and rs12329760/TMPRSS2 T allele were associated with risk of death. Moreover, some of the analyzed polymorphisms interact in the risk of worse COVID-19 outcomes. In conclusion, this study shows an association of rs1799752/ACE1, rs1990760/IFIH1, rs2236757/IFNAR2, rs12329760/TMPRSS2, and rs2304256/TYK2 polymorphisms with worse COVID-19 outcomes, especially among female and non-white patients. Full article

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

21 pages, 2452 KiB

Open AccessEditor’s ChoiceReview

53BP1: Keeping It under Control, Even at a Distance from DNA Damage

by Emilie Rass, Simon Willaume and Pascale Bertrand

Genes 2022, 13(12), 2390; https://doi.org/10.3390/genes13122390 - 16 Dec 2022

Cited by 12 | Viewed by 6333

Abstract

Double-strand breaks (DSBs) are toxic lesions that can be generated by exposure to genotoxic agents or during physiological processes, such as during V(D)J recombination. The repair of these DSBs is crucial to prevent genomic instability and to maintain cellular homeostasis. Two main pathways [...] Read more.

Double-strand breaks (DSBs) are toxic lesions that can be generated by exposure to genotoxic agents or during physiological processes, such as during V(D)J recombination. The repair of these DSBs is crucial to prevent genomic instability and to maintain cellular homeostasis. Two main pathways participate in repairing DSBs, namely, non-homologous end joining (NHEJ) and homologous recombination (HR). The P53-binding protein 1 (53BP1) plays a pivotal role in the choice of DSB repair mechanism, promotes checkpoint activation and preserves genome stability upon DSBs. By preventing DSB end resection, 53BP1 promotes NHEJ over HR. Nonetheless, the balance between DSB repair pathways remains crucial, as unscheduled NHEJ or HR events at different phases of the cell cycle may lead to genomic instability. Therefore, the recruitment of 53BP1 to chromatin is tightly regulated and has been widely studied. However, less is known about the mechanism regulating 53BP1 recruitment at a distance from the DNA damage. The present review focuses on the mechanism of 53BP1 recruitment to damage and on recent studies describing novel mechanisms keeping 53BP1 at a distance from DSBs. Full article

(This article belongs to the Special Issue Dynamics of DNA Double Strand Breaks)

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14 pages, 1816 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity Analysis and Core Germplasm Collection Construction of Camellia oleifera Based on Fruit Phenotype and SSR Data

by Yunzheng Zhu, Deyang Liang, Zejun Song, Yi Tan, Xiaolan Guo and Delu Wang

Genes 2022, 13(12), 2351; https://doi.org/10.3390/genes13122351 - 13 Dec 2022

Cited by 15 | Viewed by 2009

Abstract

Many Camellia oleifera germplasm resources were collected from Guizhou Province, but the fruit morphological variation and genetic diversity of C. oleifera germplasm resources remain unclear. The genetic diversity of C. oleifera germplasms resources in Guizhou was studied based on fruit traits and simple [...] Read more.

Many Camellia oleifera germplasm resources were collected from Guizhou Province, but the fruit morphological variation and genetic diversity of C. oleifera germplasm resources remain unclear. The genetic diversity of C. oleifera germplasms resources in Guizhou was studied based on fruit traits and simple sequence repeat (SSR) molecular markers to build a core collection. This paper aims to provide a scientific basis for the collection, management, development, and utilization of C. oleifera resources in Guizhou province. The variation coefficients among and within varieties of seven fruit phenotypic traits of C. oleifera ranged from 11.79% to 61.76% and from 8.15% to 42.31%, respectively, showing rich phenotypic variation. Furthermore, 12 SSR markers were used to analyze the genetic diversity. These primers generated 214 polymorphic bands, and the average number was 17.833. The average number of effective alleles (Ne), Shannon’s information index (I), observed heterozygosity (Ho), expected heterozygosity (He), polymorphic information content (PIC), and major allele frequency (MAF) were 8.999, 2.301, 0.965, 0.50, 0.836, and 0.238, respectively. The results showed that 12 SSR markers had high polymorphism, and the genetic diversity of 167 C. oleifera germplasm resources was high. Based on SSR molecular marker information and fruit traits clustering, 167 C. oleifera germplasm resources were divided into three groups. When constructing core collections based on fruit traits and molecular marker information, the PowerCore-25 of core collections greatly preserves fruit traits and improves genetic diversity. This paper can provide a reference for the genetic diversity and fruit traits variation of C. camellia germplasm resources in Guizhou Province. It is significant for establishing a core collection, thus promoting germplasm innovation and the development of the oil tea industry in Guizhou. Full article

(This article belongs to the Special Issue Genetic Diversity, Conservation and Utilization of Plant Genetic Resources)

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15 pages, 1017 KiB

Open AccessEditor’s ChoiceArticle

Molecular Pathway-Based Classification of Ectodermal Dysplasias: First Five-Yearly Update

by Nicolai Peschel, John T. Wright, Maranke I. Koster, Angus J. Clarke, Gianluca Tadini, Mary Fete, Smail Hadj-Rabia, Virginia P. Sybert, Johanna Norderyd, Sigrun Maier-Wohlfart, Timothy J. Fete, Nina Pagnan, Atila F. Visinoni and Holm Schneider

Genes 2022, 13(12), 2327; https://doi.org/10.3390/genes13122327 - 10 Dec 2022

Cited by 12 | Viewed by 5456

Abstract

To keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we [...] Read more.

To keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we searched the databases PubMed and OMIM for the term “ectodermal dysplasia”, referring mainly to changes in the last 5 years. We also tried to obtain information about those diseases on which the last scientific report appeared more than 15 years ago by contacting the authors of the most recent publication. A group of experts, composed of researchers who attended the 8th International Conference on Ectodermal Dysplasias and additional members of the previous classification panel, reviewed the proposed amendments and agreed on a final table listing all 49 currently known ectodermal dysplasias for which the molecular genetic basis has been clarified, including 15 new entities. A newly reported ectodermal dysplasia, linked to the gene LRP6, is described here in more detail. These ectodermal dysplasias, in the strict sense, should be distinguished from syndromes with features of ectodermal dysplasia that are related to genes extraneous to the currently known pathways involved in ectodermal development. The latter group consists of 34 syndromes which had been placed on the previous list of ectodermal dysplasias, but most if not all of them could actually be classified elsewhere. This update should streamline the classification of ectodermal dysplasias, provide guidance to the correct diagnosis of rare disease entities, and facilitate the identification of individuals who could benefit from novel treatment options. Full article

(This article belongs to the Special Issue Molecular Biology and Treatment of Genodermatoses)

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34 pages, 7541 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Metagenomics and Metatranscriptomics Tools: A Guide to Making the Right Choice

by Laura C. Terrón-Camero, Fernando Gordillo-González, Eduardo Salas-Espejo and Eduardo Andrés-León

Genes 2022, 13(12), 2280; https://doi.org/10.3390/genes13122280 - 3 Dec 2022

Cited by 12 | Viewed by 9505

Abstract

The study of microorganisms is a field of great interest due to their environmental (e.g., soil contamination) and biomedical (e.g., parasitic diseases, autism) importance. The advent of revolutionary next-generation sequencing techniques, and their application to the hypervariable regions of the 16S, 18S or [...] Read more.

The study of microorganisms is a field of great interest due to their environmental (e.g., soil contamination) and biomedical (e.g., parasitic diseases, autism) importance. The advent of revolutionary next-generation sequencing techniques, and their application to the hypervariable regions of the 16S, 18S or 23S ribosomal subunits, have allowed the research of a large variety of organisms more in-depth, including bacteria, archaea, eukaryotes and fungi. Additionally, together with the development of analysis software, the creation of specific databases (e.g., SILVA or RDP) has boosted the enormous growth of these studies. As the cost of sequencing per sample has continuously decreased, new protocols have also emerged, such as shotgun sequencing, which allows the profiling of all taxonomic domains in a sample. The sequencing of hypervariable regions and shotgun sequencing are technologies that enable the taxonomic classification of microorganisms from the DNA present in microbial communities. However, they are not capable of measuring what is actively expressed. Conversely, we advocate that metatranscriptomics is a “new” technology that makes the identification of the mRNAs of a microbial community possible, quantifying gene expression levels and active biological pathways. Furthermore, it can be also used to characterise symbiotic interactions between the host and its microbiome. In this manuscript, we examine the three technologies above, and discuss the implementation of different software and databases, which greatly impact the obtaining of reliable results. Finally, we have developed two easy-to-use pipelines leveraging Nextflow technology. These aim to provide everything required for an average user to perform a metagenomic analysis of marker genes with QIMME2 and a metatranscriptomic study using Kraken2/Bracken. Full article

(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)

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22 pages, 1237 KiB

Open AccessEditor’s ChoiceReview

Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer

by Mariana K. Najjar, Sara G. Manore, Angelina T. Regua and Hui-Wen Lo

Genes 2022, 13(11), 2065; https://doi.org/10.3390/genes13112065 - 8 Nov 2022

Cited by 24 | Viewed by 6549

Abstract

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of [...] Read more.

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted monoclonal antibodies with the potent cytotoxic effects of various small molecules, such as tubulin inhibitors and topoisomerase inhibitors. To date, two HER2-targeting ADCs have been approved by the FDA for the treatment of HER2-positive breast cancer: Ado-trastuzumab emtansine (T-DM1; Kadcyla^®) and fam-trastuzumab deruxtecan-nxki (T-Dxd; Enhertu^®). Kadcyla and Enhertu are approved for use as a second-line treatment after trastuzumab-taxane-based therapy in patients with HER2-positive breast cancer. The success of ADCs in the treatment of HER2-positive breast cancer provides novel therapeutic advancements in the management of the disease. In this review, we discuss the basic biology of HER2, its downstream signaling pathways, currently available anti-HER2 therapeutic modalities and their mechanisms of action, and the latest clinical and safety characteristics of ADCs used for the treatment of HER2-positive breast cancer. Full article

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

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12 pages, 291 KiB

Open AccessEditor’s ChoiceArticle

Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors

by César Fernández-de-las-Peñas, Lars Arendt-Nielsen, Gema Díaz-Gil, Francisco Gómez-Esquer, Antonio Gil-Crujera, Stella M. Gómez-Sánchez, Silvia Ambite-Quesada, María A. Palomar-Gallego, Oscar J. Pellicer-Valero and Rocco Giordano

Genes 2022, 13(11), 1935; https://doi.org/10.3390/genes13111935 - 24 Oct 2022

Cited by 17 | Viewed by 2068

Abstract

The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 [...] Read more.

The aim of the study was to identify the association between four selected COVID-19 polymorphisms of ACE2 and TMPRSS2 receptors genes with the presence of long-COVID symptomatology in COVID-19 survivors. These genes were selected as they associate with the entry of the SARS-CoV-2 virus into the cells, so polymorphisms could be important for the prognoses of long-COVID symptoms. Two hundred and ninety-three (n = 293, 49.5% female, mean age: 55.6 ± 12.9 years) individuals who had been previously hospitalized due to COVID-19 were included. Three potential genotypes of the following single nucleotide polymorphisms (SNPs) were obtained from non-stimulated saliva samples of participants: ACE2 (rs2285666), ACE2 (rs2074192), TMPRSS2 (rs12329760), TMPRSS2 (rs2070788). Participants were asked to self-report the presence of any post-COVID defined as a symptom that started no later than one month after SARS-CoV-2 acute infection and whether the symptom persisted at the time of the study. At the time of the study (mean: 17.8, SD: 5.2 months after hospital discharge), 87.7% patients reported at least one symptom. Fatigue (62.8%), pain (39.9%) or memory loss (32.1%) were the most prevalent post-COVID symptoms. Overall, no differences in long-COVID symptoms were dependent on ACE2 rs2285666, ACE2 rs2074192, TMPRSS2 rs12329760, or TMPRSS2 rs2070788 genotypes. The four SNPs assessed, albeit previously associated with COVID-19 severity, do not predispose for developing long-COVID symptoms in people who were previously hospitalized due to COVID-19 during the first wave of the pandemic. Full article

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

34 pages, 2433 KiB

Open AccessEditor’s ChoiceReview

Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management

by Nipith Charoenngam, Aryan Nasr, Arash Shirvani and Michael F. Holick

Genes 2022, 13(10), 1880; https://doi.org/10.3390/genes13101880 - 17 Oct 2022

Cited by 16 | Viewed by 6330

Abstract

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent [...] Read more.

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases. Full article

(This article belongs to the Special Issue Genetics and Genomics of Inherited Metabolic Disorders)

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16 pages, 626 KiB

Open AccessEditor’s ChoiceReview

Obesity and Adipose Tissue Dysfunction: From Pediatrics to Adults

by Ana Menendez, Heather Wanczyk, Joanne Walker, Beiyan Zhou, Melissa Santos and Christine Finck

Genes 2022, 13(10), 1866; https://doi.org/10.3390/genes13101866 - 15 Oct 2022

Cited by 12 | Viewed by 4824

Abstract

Obesity is a growing health problem that affects both children and adults. The increasing prevalence of childhood obesity is associated with comorbidities such as cardiovascular disease, type 2 diabetes and metabolic syndrome due to chronic low-grade inflammation present at early stages of the [...] Read more.

Obesity is a growing health problem that affects both children and adults. The increasing prevalence of childhood obesity is associated with comorbidities such as cardiovascular disease, type 2 diabetes and metabolic syndrome due to chronic low-grade inflammation present at early stages of the disease. In pediatric patients suffering from obesity, the role of epigenetics, the gut microbiome and intrauterine environment have emerged as causative factors Interestingly, pediatric obesity is strongly associated with low birth weight. Accelerated weight gain oftentimes occurs in these individuals during the post-natal period, which can lead to increased risk of adiposity and metabolic disease. The pathophysiology of obesity is complex and involves biological and physiological factors compounded by societal factors such as family and community. On a cellular level, adipocytes contained within adipose tissue become dysregulated and further contribute to development of comorbidities similar to those present in adults with obesity. This review provides an overview of the current understanding of adipose tissue immune, inflammatory and metabolic adaptation of the adipose tissue in obesity. Early cellular changes as well as the role of immune cells and inflammation on the progression of disease in pivotal pediatric clinical trials, adult studies and mouse models are emphasized. Understanding the initial molecular and cellular changes that occur during obesity can facilitate new and improved treatments aimed at early intervention and subsequent prevention of adulthood comorbidities. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Immune Cell Function in Obesity and Related Diseases)

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28 pages, 1975 KiB

Open AccessEditor’s ChoiceReview

The Genetic Factors of the Airway Epithelium Associated with the Pathology of Asthma

by Maral Ranjbar, Christiane E. Whetstone, Hafsa Omer, Lucy Power, Ruth P. Cusack and Gail M. Gauvreau

Genes 2022, 13(10), 1870; https://doi.org/10.3390/genes13101870 - 15 Oct 2022

Cited by 14 | Viewed by 4416

Abstract

Asthma is a chronic disease of the airways characterized by inflammation, tightened muscles, and thickened airway walls leading to symptoms such as shortness of breath, chest tightness, and cough in patients. The increased risk of asthma in children of asthmatics parents supports the [...] Read more.

Asthma is a chronic disease of the airways characterized by inflammation, tightened muscles, and thickened airway walls leading to symptoms such as shortness of breath, chest tightness, and cough in patients. The increased risk of asthma in children of asthmatics parents supports the existence of genetic factors involved in the pathogenesis of this disease. Genome-wide association studies have discovered several single nucleotide polymorphisms associated with asthma. These polymorphisms occur within several genes and can contribute to different asthma phenotypes, affect disease severity, and clinical response to different therapies. The complexity in the etiology of asthma also results from interactions between environmental and genetic factors. Environmental exposures have been shown to increase the prevalence of asthma in individuals who are genetically susceptible. This review summarizes what is currently known about the genetics of asthma in relation to risk, response to common treatments, and gene-environmental interactions. Full article

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

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11 pages, 1258 KiB

Open AccessEditor’s ChoiceArticle

Runs of Homozygosity Revealed Reproductive Traits of Hu Sheep

by Yuzhe Li, Zitao Chen, Yifei Fang, Caiyun Cao, Zhe Zhang, Yuchun Pan and Qishan Wang

Genes 2022, 13(10), 1848; https://doi.org/10.3390/genes13101848 - 13 Oct 2022

Cited by 14 | Viewed by 2558

Abstract

Hu sheep, a famous breed in the Taihu Basin, has the advantages of non-seasonal estrus, multiple fetuses, coarse feeding tolerance, and suitability for house feeding. Runs of homozygosity (ROHs) were found to be an effective tool to detect the animal population structure and [...] Read more.

Hu sheep, a famous breed in the Taihu Basin, has the advantages of non-seasonal estrus, multiple fetuses, coarse feeding tolerance, and suitability for house feeding. Runs of homozygosity (ROHs) were found to be an effective tool to detect the animal population structure and economic traits. The detection of ROHs is beneficial for reducing the incidence of inbreeding as well as identifying harmful variants in the genome. However, there is a lack of systemic reports on ruminants in previous studies of ROHs. Here, we sequenced 108 Hu sheep, detected ROHs in Hu sheep to calculate their inbreeding coefficient, and selected genes of Hu sheep breeds within the ROH islands which are relevant to agricultural economic characteristics. Then, we compared the characteristics of the occurrences of SNPs between Hu sheep and other sheep breeds, and also investigated the distribution of the frequencies of SNPs within specific gene regions of Hu sheep breeds to select their breed-specific genes. Furthermore, we performed a comparative genome and transcriptome analysis in human and sheep breeds to identify important reproduction-related genes. In this way, we found some significant SNPs, and mapped these with a set of interesting candidate genes which are related to the productive value of livestock (FGF9, BMPR1B, EFNB3, MICU2, GFRA3), healthy characteristics (LGSN, EPHA5, ALOX15B), and breed specificity (FGF9, SAP18, MICU2). These results in our study describe various production traits of Hu sheep from a genetic perspective, and provide insights into the genetic management and complementary understanding of Hu sheep. Full article

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

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25 pages, 454 KiB

Open AccessEditor’s ChoiceReview

Risk Factors for Thoracic Aortic Dissection

by Zhen Zhou, Alana C. Cecchi, Siddharth K. Prakash and Dianna M. Milewicz

Genes 2022, 13(10), 1814; https://doi.org/10.3390/genes13101814 - 7 Oct 2022

Cited by 23 | Viewed by 4451

Abstract

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above [...] Read more.

Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase the risk for thoracic aortic aneurysms and dissections (TAD). In this review, we discuss the predominant TAD-associated risk factors, focusing primarily on the non-genetic factors, and discuss the underlying mechanisms leading to TAD. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Vascular Disease)

18 pages, 803 KiB

Open AccessFeature PaperEditor’s ChoiceReview

From Genotype to Phenotype—A Review of Kabuki Syndrome

by Kelly K. Barry, Michaelangelo Tsaparlis, Deborah Hoffman, Deborah Hartman, Margaret P. Adam, Christina Hung and Olaf A. Bodamer

Genes 2022, 13(10), 1761; https://doi.org/10.3390/genes13101761 - 29 Sep 2022

Cited by 18 | Viewed by 8149

Abstract

Kabuki syndrome (KS) is a rare neuro-developmental disorder caused by variants in genes of histone modification, including KMT2D and KDM6A. This review assesses our current understanding of KS, which was originally named Niikawa–Kuroki syndrome, and aims to guide surveillance and medical care [...] Read more.

Kabuki syndrome (KS) is a rare neuro-developmental disorder caused by variants in genes of histone modification, including KMT2D and KDM6A. This review assesses our current understanding of KS, which was originally named Niikawa–Kuroki syndrome, and aims to guide surveillance and medical care of affected individuals as well as identify gaps in knowledge and unmet patient needs. Ovid MEDLINE and EMBASE databases were searched from 1981 to 2021 to identify reports related to genotype and systems-based phenotype characterization of KS. A total of 2418 articles were retrieved, and 152 were included in this review, representing a total of 1369 individuals with KS. Genotype, phenotype, and the developmental and behavioral profile of KS are reviewed. There is a continuous clinical phenotype spectrum associated with KS with notable variability between affected individuals and an emerging genotype–phenotype correlation. The observed clinical variability may be attributable to differences in genotypes and/or unknown genetic and epigenetic factors. Clinical management is symptom oriented, fragmented, and lacks established clinical care standards. Additional research should focus on enhancing understanding of the burden of illness, the impact on quality of life, the adult phenotype, life expectancy and development of standard-of-care guidelines. Full article

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

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17 pages, 14250 KiB

Open AccessEditor’s ChoiceReview

Melatonin Function and Crosstalk with Other Phytohormones under Normal and Stressful Conditions

by Murtaza Khan, Sajid Ali, Hakim Manghwar, Saddam Saqib, Fazal Ullah, Asma Ayaz and Wajid Zaman

Genes 2022, 13(10), 1699; https://doi.org/10.3390/genes13101699 - 22 Sep 2022

Cited by 44 | Viewed by 3876

Abstract

Melatonin was discovered in plants in the late nineties, but its role, signaling, and crosstalk with other phytohormones remain unknown. Research on melatonin in plants has risen dramatically in recent years and the role of this putative plant hormone under biotic and abiotic [...] Read more.

Melatonin was discovered in plants in the late nineties, but its role, signaling, and crosstalk with other phytohormones remain unknown. Research on melatonin in plants has risen dramatically in recent years and the role of this putative plant hormone under biotic and abiotic stress conditions has been reported. In the present review, we discuss the main functions of melatonin in the growth and development of plants, its role under abiotic stresses, such as water stress (waterlogging and drought), extreme temperature (low and high), salinity, heavy metal, and light-induced stress. Similarly, we also discuss the role of melatonin under biotic stresses (antiviral, antibacterial, and antifungal effects). Moreover, the present review meticulously discusses the crosstalk of melatonin with other phytohormones such as auxins, gibberellic acids, cytokinins, ethylene, and salicylic acid under normal and stressful conditions and reports melatonin receptors and signaling in plants. All these aspects of melatonin suggest that phytomelatonin is a key player in crop improvement and biotic and abiotic stress regulation. Full article

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

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22 pages, 798 KiB

Open AccessEditor’s ChoiceReview

Recent Developments in Autism Genetic Research: A Scientometric Review from 2018 to 2022

by Mengyu Lim, Alessandro Carollo, Dagmara Dimitriou and Gianluca Esposito

Genes 2022, 13(9), 1646; https://doi.org/10.3390/genes13091646 - 14 Sep 2022

Cited by 14 | Viewed by 4927

Abstract

Genetic research in Autism Spectrum Disorder (ASD) has progressed tremendously in recent decades. Dozens of genetic loci and hundreds of alterations in the genetic sequence, expression, epigenetic transformation, and interactions with other physiological and environmental systems have been found to increase the likelihood [...] Read more.

Genetic research in Autism Spectrum Disorder (ASD) has progressed tremendously in recent decades. Dozens of genetic loci and hundreds of alterations in the genetic sequence, expression, epigenetic transformation, and interactions with other physiological and environmental systems have been found to increase the likelihood of developing ASD. There is therefore a need to represent this wide-ranging yet voluminous body of literature in a systematic manner so that this information can be synthesised and understood at a macro level. Therefore, this study made use of scientometric methods, particularly document co-citation analysis (DCA), to systematically review literature on ASD genetic research from 2018 to 2022. A total of 14,818 articles were extracted from Scopus and analyzed with CiteSpace. An optimized DCA analysis revealed that recent literature on ASD genetic research can be broadly organised into 12 major clusters representing various sub-topics. These clusters are briefly described in the manuscript and potential applications of this study are discussed. Full article

(This article belongs to the Special Issue Genetic and Epigenetic Factors and Their Interactions in the Susceptibility to Multifactorial Diseases)

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27 pages, 990 KiB

Open AccessEditor’s ChoiceReview

Interleukin-17 Family Cytokines in Metabolic Disorders and Cancer

by Eileen Victoria Meehan and Kepeng Wang

Genes 2022, 13(9), 1643; https://doi.org/10.3390/genes13091643 - 13 Sep 2022

Cited by 19 | Viewed by 6570

Abstract

Interleukin-17 (IL-17) family cytokines are potent drivers of inflammatory responses. Although IL-17 was originally identified as a cytokine that induces protective effects against bacterial and fungal infections, IL-17 can also promote chronic inflammation in a number of autoimmune diseases. Research in the last [...] Read more.

Interleukin-17 (IL-17) family cytokines are potent drivers of inflammatory responses. Although IL-17 was originally identified as a cytokine that induces protective effects against bacterial and fungal infections, IL-17 can also promote chronic inflammation in a number of autoimmune diseases. Research in the last decade has also elucidated critical roles of IL-17 during cancer development and treatment. Intriguingly, IL-17 seems to play a role in the risk of cancers that are associated with metabolic disorders. In this review, we summarize our current knowledge on the biochemical basis of IL-17 signaling, IL-17′s involvement in cancers and metabolic disorders, and postulate how IL-17 family cytokines may serve as a bridge between these two types of diseases. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Immune Cell Function in Obesity and Related Diseases)

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37 pages, 4519 KiB

Open AccessEditor’s ChoiceArticle

The Gain and Loss of Cryptochrome/Photolyase Family Members during Evolution

by Peter Deppisch, Charlotte Helfrich-Förster and Pingkalai R. Senthilan

Genes 2022, 13(9), 1613; https://doi.org/10.3390/genes13091613 - 8 Sep 2022

Cited by 13 | Viewed by 3981

Abstract

The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. In this study, we took advantage of the large number of already sequenced and annotated genes available [...] Read more.

The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. In this study, we took advantage of the large number of already sequenced and annotated genes available in databases and systematically searched for the protein sequences of CRY/PL family members in all taxonomic groups primarily focusing on metazoans and limiting the number of species per taxonomic order to five. Using BLASTP searches and subsequent phylogenetic tree and motif analyses, we identified five distinct photolyases (CPDI, CPDII, CPDIII, 6-4 photolyase, and the plant photolyase PPL) and six cryptochrome subfamilies (DASH-CRY, mammalian-type MCRY, Drosophila-type DCRY, cnidarian-specific ACRY, plant-specific PCRY, and the putative magnetoreceptor CRY4. Manually assigning the CRY/PL subfamilies to the species studied, we have noted that over evolutionary history, an initial increase of various CRY/PL subfamilies was followed by a decrease and specialization. Thus, in more primitive organisms (e.g., bacteria, archaea, simple eukaryotes, and in basal metazoans), we find relatively few CRY/PL members. As species become more evolved (e.g., cnidarians, mollusks, echinoderms, etc.), the CRY/PL repertoire also increases, whereas it appears to decrease again in more recent organisms (humans, fruit flies, etc.). Moreover, our study indicates that all cryptochromes, although largely active in the circadian clock, arose independently from different photolyases, explaining their different modes of action. Full article

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

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20 pages, 1320 KiB

Open AccessEditor’s ChoiceReview

Crosstalk between Hypoxia and Extracellular Matrix in the Tumor Microenvironment in Breast Cancer

by Yasmin Dekker, Sylvia E. Le Dévédec, Erik H. J. Danen and Qiuyu Liu

Genes 2022, 13(9), 1585; https://doi.org/10.3390/genes13091585 - 3 Sep 2022

Cited by 22 | Viewed by 3739

Abstract

Even though breast cancer is the most diagnosed cancer among women, treatments are not always successful in preventing its progression. Recent studies suggest that hypoxia and the extracellular matrix (ECM) are important in altering cell metabolism and tumor metastasis. Therefore, the aim of [...] Read more.

Even though breast cancer is the most diagnosed cancer among women, treatments are not always successful in preventing its progression. Recent studies suggest that hypoxia and the extracellular matrix (ECM) are important in altering cell metabolism and tumor metastasis. Therefore, the aim of this review is to study the crosstalk between hypoxia and the ECM and to assess their impact on breast cancer progression. The findings indicate that hypoxic signaling engages multiple mechanisms that directly contribute to ECM remodeling, ultimately increasing breast cancer aggressiveness. Second, hypoxia and the ECM cooperate to alter different aspects of cell metabolism. They mutually enhance aerobic glycolysis through upregulation of glucose transport, glycolytic enzymes, and by regulating intracellular pH. Both alter lipid and amino acid metabolism by stimulating lipid and amino acid uptake and synthesis, thereby providing the tumor with additional energy for growth and metastasis. Third, YAP/TAZ signaling is not merely regulated by the tumor microenvironment and cell metabolism, but it also regulates it primarily through its target c-Myc. Taken together, this review provides a better understanding of the crosstalk between hypoxia and the ECM in breast cancer. Additionally, it points to a role for the YAP/TAZ mechanotransduction pathway as an important link between hypoxia and the ECM in the tumor microenvironment, driving breast cancer progression. Full article

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

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13 pages, 1583 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer’s Disease

by Valeria D’Argenio, Iolanda Veneruso, Chunmei Gong, Valentina Cecarini, Laura Bonfili and Anna Maria Eleuteri

Genes 2022, 13(9), 1564; https://doi.org/10.3390/genes13091564 - 31 Aug 2022

Cited by 16 | Viewed by 2831

Abstract

Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible [...] Read more.

Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the Coprococcus and an increased abundance of Escherichia_Shigella and Barnesiella genera in the AD mice compatible with a pro-inflammatory status and the development of AD-related pathogenetic features. Moreover, the fungal Dipodascaceae family was significantly increased, thus suggesting a possible contribution to the metabolic alterations found in AD. Our data point out the strict connection between bacterial dysbiosis and AD and, even if further studies are required to clarify the underlining mechanisms, it clearly indicates the need for extensive metagenomic studies over the bacterial counterpart. Full article

(This article belongs to the Special Issue Human Microbiota: Current Updates on Pathogenetic Mechanisms and Methodological Advances)

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24 pages, 1345 KiB

Open AccessEditor’s ChoiceReview

Next Generation and Other Sequencing Technologies in Diagnostic Microbiology and Infectious Diseases

by Evann E. Hilt and Patricia Ferrieri

Genes 2022, 13(9), 1566; https://doi.org/10.3390/genes13091566 - 31 Aug 2022

Cited by 39 | Viewed by 11754

Abstract

Next-generation sequencing (NGS) technologies have become increasingly available for use in the clinical microbiology diagnostic environment. There are three main applications of these technologies in the clinical microbiology laboratory: whole genome sequencing (WGS), targeted metagenomics sequencing and shotgun metagenomics sequencing. These applications are [...] Read more.

Next-generation sequencing (NGS) technologies have become increasingly available for use in the clinical microbiology diagnostic environment. There are three main applications of these technologies in the clinical microbiology laboratory: whole genome sequencing (WGS), targeted metagenomics sequencing and shotgun metagenomics sequencing. These applications are being utilized for initial identification of pathogenic organisms, the detection of antimicrobial resistance mechanisms and for epidemiologic tracking of organisms within and outside hospital systems. In this review, we analyze these three applications and provide a comprehensive summary of how these applications are currently being used in public health, basic research, and clinical microbiology laboratory environments. In the public health arena, WGS is being used to identify and epidemiologically track food borne outbreaks and disease surveillance. In clinical hospital systems, WGS is used to identify multi-drug-resistant nosocomial infections and track the transmission of these organisms. In addition, we examine how metagenomics sequencing approaches (targeted and shotgun) are being used to circumvent the traditional and biased microbiology culture methods to identify potential pathogens directly from specimens. We also expand on the important factors to consider when implementing these technologies, and what is possible for these technologies in infectious disease diagnosis in the next 5 years. Full article

(This article belongs to the Special Issue Next Generation Sequencing in Clinical Diagnostics)

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18 pages, 4670 KiB

Open AccessEditor’s ChoiceArticle

Comparative Analysis of Complete Chloroplast Genomes of Nine Species of Litsea (Lauraceae): Hypervariable Regions, Positive Selection, and Phylogenetic Relationships

by Weicai Song, Zimeng Chen, Wenbo Shi, Weiqi Han, Qi Feng, Chao Shi, Michael S. Engel and Shuo Wang

Genes 2022, 13(9), 1550; https://doi.org/10.3390/genes13091550 - 28 Aug 2022

Cited by 17 | Viewed by 2292

Abstract

Litsea is a group of evergreen trees or shrubs in the laurel family, Lauraceae. Species of the genus are widely used for a wide range of medicinal and industrial aspects. At present, most studies related to the gene resources of Litsea are restricted [...] Read more.

Litsea is a group of evergreen trees or shrubs in the laurel family, Lauraceae. Species of the genus are widely used for a wide range of medicinal and industrial aspects. At present, most studies related to the gene resources of Litsea are restricted to morphological analyses or features of individual genomes, and currently available studies of select molecular markers are insufficient. In this study, we assembled and annotated the complete chloroplast genomes of nine species in Litsea, carried out a series of comparative analyses, and reconstructed phylogenetic relationships within the genus. The genome length ranged from 152,051 to 152,747 bp and a total of 128 genes were identified. High consistency patterns of codon bias, repeats, divergent analysis, single nucleotide polymorphisms (SNP) and insertions and deletions (InDels) were discovered across the genus. Variations in gene length and the presence of the pseudogene ycf1^Ψ, resulting from IR contraction and expansion, are reported. The hyper-variable gene rpl16 was identified for its exceptionally high Ka/Ks and Pi values, implying that those frequent mutations occurred as a result of positive selection. Phylogenetic relationships were recovered for the genus based on analyses of full chloroplast genomes and protein-coding genes. Overall, both genome sequences and potential molecular markers provided in this study enrich the available genomic resources for species of Litsea. Valuable genomic resources and divergent analysis are also provided for further research of the evolutionary patterns, molecular markers, and deeper phylogenetic relationships of Litsea. Full article

(This article belongs to the Special Issue Advances in Evolution of Plant Organelle Genome)

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9 pages, 936 KiB

Open AccessEditor’s ChoiceArticle

TwoStepCisMR: A Novel Method and R Package for Attenuating Bias in cis-Mendelian Randomization Analyses

by Benjamin Woolf, Loukas Zagkos and Dipender Gill

Genes 2022, 13(9), 1541; https://doi.org/10.3390/genes13091541 - 26 Aug 2022

Cited by 12 | Viewed by 3823

Abstract

Mendelian randomisation (MR) is an increasingly popular method for strengthening causal inference in epidemiological studies. cis-MR in particular uses genetic variants in the gene region of a drug target protein as an instrumental variable to provide quasi-experimental evidence for on-target drug effects. [...] Read more.

Mendelian randomisation (MR) is an increasingly popular method for strengthening causal inference in epidemiological studies. cis-MR in particular uses genetic variants in the gene region of a drug target protein as an instrumental variable to provide quasi-experimental evidence for on-target drug effects. A limitation of this framework is when the genetic variant is correlated to another variant that also effects the outcome of interest (confounding through linkage disequilibrium). Methods for correcting this bias, such as multivariable MR, struggle in a cis setting because of the high correlation among genetic variants. Here, through simulation experiments and an applied example considering the effect of interleukin 6 receptor signaling on coronary artery disease risk, we present an alternative method for attenuating bias that does not suffer from this problem. As our method uses both MR and the product and difference method for mediation analysis, our proposal inherits all assumptions of these methods. We have additionally developed an R package, TwoStepCisMR, to facilitate the implementation of the method. Full article

(This article belongs to the Special Issue Mendelian Randomization Studies in Cardiometabolic Diseases)

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14 pages, 508 KiB

Open AccessEditor’s ChoiceReview

Next Generation Sequencing after Invasive Prenatal Testing in Fetuses with Congenital Malformations: Prenatal or Neonatal Investigation

by Alexandra Emms, James Castleman, Stephanie Allen, Denise Williams, Esther Kinning and Mark Kilby

Genes 2022, 13(9), 1517; https://doi.org/10.3390/genes13091517 - 24 Aug 2022

Cited by 12 | Viewed by 2963

Abstract

Congenital malformations diagnosed by ultrasound screening complicate 3–5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however [...] Read more.

Congenital malformations diagnosed by ultrasound screening complicate 3–5% of pregnancies and many of these have an underlying genetic cause. Approximately 40% of prenatally diagnosed fetal malformations are associated with aneuploidy or copy number variants, detected by conventional karyotyping, QF-PCR and microarray techniques, however monogenic disorders are not diagnosed by these tests. Next generation sequencing as a secondary prenatal genetic test offers additional diagnostic yield for congenital abnormalities deemed to be potentially associated with an underlying genetic aetiology, as demonstrated by two large cohorts: the ‘Prenatal assessment of genomes and exomes’ (PAGE) study and ‘Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study’ performed at Columbia University in the US. These were large and prospective studies but relatively ‘unselected’ congenital malformations, with little Clinical Genetics input to the pre-test selection process. This review focuses on the incremental yield of next generation sequencing in single system congenital malformations, using evidence from the PAGE, Columbia and subsequent cohorts, with particularly high yields in those fetuses with cardiac and neurological anomalies, large nuchal translucency and non-immune fetal hydrops (of unknown aetiology). The total additional yield gained by exome sequencing in congenital heart disease was 12.7%, for neurological malformations 13.8%, 13.1% in increased nuchal translucency and 29% in non-immune fetal hydrops. This demonstrates significant incremental yield with exome sequencing in single-system anomalies and supports next generation sequencing as a secondary genetic test in routine clinical care of fetuses with congenital abnormalities. Full article

(This article belongs to the Special Issue Novel Insights into Prenatal Genetic Testing)

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8 pages, 1189 KiB

Open AccessEditor’s ChoiceArticle

When a Synonymous Variant Is Nonsynonymous

by Mauno Vihinen

Genes 2022, 13(8), 1485; https://doi.org/10.3390/genes13081485 - 19 Aug 2022

Cited by 17 | Viewed by 2907

Abstract

Term synonymous variation is widely used, but frequently in a wrong or misleading meaning and context. Twenty three point eight % of possible nucleotide substitution types in the universal genetic code are for synonymous amino acid changes, but when these variants have a [...] Read more.

Term synonymous variation is widely used, but frequently in a wrong or misleading meaning and context. Twenty three point eight % of possible nucleotide substitution types in the universal genetic code are for synonymous amino acid changes, but when these variants have a phenotype and functional effect, they are very seldom synonymous. Such variants may manifest changes at DNA, RNA and/or protein levels. Large numbers of variations are erroneously annotated as synonymous, which causes problems e.g., in clinical genetics and diagnosis of diseases. To facilitate precise communication, novel systematics and nomenclature are introduced for variants that when looking only at the genetic code seem like synonymous, but which have phenotypes. A new term, unsense variant is defined as a substitution in the mRNA coding region that affects gene expression and protein production without introducing a stop codon in the variation site. Such variants are common and need to be correctly annotated. Proper naming and annotation are important also to increase awareness of these variants and their consequences. Full article

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

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20 pages, 4337 KiB

Open AccessEditor’s ChoiceArticle

IbMYB308, a Sweet Potato R2R3-MYB Gene, Improves Salt Stress Tolerance in Transgenic Tobacco

by Chong Wang, Lianjun Wang, Jian Lei, Shasha Chai, Xiaojie Jin, Yuyan Zou, Xiaoqiong Sun, Yuqin Mei, Xianliang Cheng, Xinsun Yang, Chunhai Jiao and Xiaohai Tian

Genes 2022, 13(8), 1476; https://doi.org/10.3390/genes13081476 - 18 Aug 2022

Cited by 14 | Viewed by 2235

Abstract

The MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factor family plays an important role in plant growth, development, and response to biotic and abiotic stresses. However, the gene functions of MYB transcription factors in sweet potato (Ipomoea batatas (L.) Lam) have [...] Read more.

The MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factor family plays an important role in plant growth, development, and response to biotic and abiotic stresses. However, the gene functions of MYB transcription factors in sweet potato (Ipomoea batatas (L.) Lam) have not been elucidated. In this study, an MYB transcription factor gene, IbMYB308, was identified and isolated from sweet potato. Multiple sequence alignment showed that IbMYB308 is a typical R2R3-MYB transcription factor. Further, quantitative real-time PCR (qRT-PCR) analysis revealed that IbMYB308 was expressed in root, stem, and, especially, leaf tissues. Moreover, it showed that IbMYB308 had a tissue-specific profile. The experiment also showed that the expression of IbMYB308 was induced by different abiotic stresses (20% PEG-6000, 200 mM NaCl, and 20% H₂O₂). After a 200 mM NaCl treatment, the expression of several stress-related genes (SOD, POD, APX, and P5CS) was upregulation in transgenic plants, and the CAT activity, POD activity, proline content, and protein content in transgenic tobacco had increased, while MDA content had decreased. In conclusion, this study demonstrated that IbMYB308 could improve salt stress tolerance in transgenic tobacco. These findings lay a foundation for future studies on the R2R3-MYB gene family of sweet potato and suggest that IbMYB308 could potentially be used as an important positive factor in transgenic plant breeding to improve salt stress tolerance in sweet potato plants. Full article

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

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19 pages, 1644 KiB

Open AccessEditor’s ChoiceReview

Molecular Factors and Mechanisms Driving Multidrug Resistance in Uropathogenic Escherichia coli—An Update

by Marcin Rozwadowski and Damian Gawel

Genes 2022, 13(8), 1397; https://doi.org/10.3390/genes13081397 - 6 Aug 2022

Cited by 23 | Viewed by 5799

Abstract

The rapid emergence of multidrug-resistant (MDR) bacteria indisputably constitutes a major global health problem. Pathogenic Escherichia coli are listed among the most critical group of bacteria that require fast development of new antibiotics and innovative treatment strategies. Among harmful extraintestinal Enterobacteriaceae strains, uropathogenic [...] Read more.

The rapid emergence of multidrug-resistant (MDR) bacteria indisputably constitutes a major global health problem. Pathogenic Escherichia coli are listed among the most critical group of bacteria that require fast development of new antibiotics and innovative treatment strategies. Among harmful extraintestinal Enterobacteriaceae strains, uropathogenic E. coli (UPEC) pose a significant health threat. UPEC are considered the major causative factor of urinary tract infection (UTI), the second-most commonly diagnosed infectious disease in humans worldwide. UTI treatment places a substantial financial burden on healthcare systems. Most importantly, the misuse of antibiotics during treatment has caused selection of strains with the ability to acquire MDR via miscellaneous mechanisms resulting in gaining resistance against many commonly prescribed antibiotics like ampicillin, gentamicin, cotrimoxazole and quinolones. Mobile genetic elements (MGEs) such as transposons, integrons and conjugative plasmids are the major drivers in spreading resistance genes in UPEC. The co-occurrence of various bacterial evasion strategies involving MGEs and the SOS stress response system requires further research and can potentially lead to the discovery of new, much-awaited therapeutic targets. Here, we analyzed and summarized recent discoveries regarding the role, mechanisms, and perspectives of MDR in the pathogenicity of UPEC. Full article

(This article belongs to the Special Issue Genetics and Genomics of Antimicrobial Resistance)

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16 pages, 2904 KiB

Open AccessEditor’s ChoiceReview

Bridging Disciplines to Form a New One: The Emergence of Forensic Genetic Genealogy

by Claire L. Glynn

Genes 2022, 13(8), 1381; https://doi.org/10.3390/genes13081381 - 1 Aug 2022

Cited by 15 | Viewed by 9922

Abstract

Forensic Genetic Genealogy (FGG) has fast become a popular tool in criminal investigations since it first emerged in 2018. FGG is a novel investigatory tool that has been applied to hundreds of unresolved cold cases in the United States to generate investigative leads [...] Read more.

Forensic Genetic Genealogy (FGG) has fast become a popular tool in criminal investigations since it first emerged in 2018. FGG is a novel investigatory tool that has been applied to hundreds of unresolved cold cases in the United States to generate investigative leads and identify unknown individuals. Consumer DNA testing and the public’s increased curiosity about their own DNA and genetic ancestry, have greatly contributed to the availability of human genetic data. Genetic genealogy has been a field of study/interest for many years as both amateur and professional genetic genealogists use consumer DNA data to explore genetic connections in family trees. FGG encompasses this knowledge by applying advanced sequencing technologies to forensic DNA evidence samples and by performing genetic genealogy methods and genealogical research, to produce possible identities of unknown perpetrators of violent crimes and unidentified human remains. This combination of forensic genetics, genetic genealogy, and genealogical research has formed a new subdiscipline within the forensic sciences. This paper will summarize the individual disciplines that led to the emergence of FGG, its practice in forensic investigations, and current/future considerations for its use. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics)

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26 pages, 3158 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genomic Analysis of Antarctic Pseudomonas Isolates with 2,4,6-Trinitrotoluene Transformation Capabilities Reveals Their Unique Features for Xenobiotics Degradation

by Ma. Ángeles Cabrera, Sebastián L. Márquez and José M. Pérez-Donoso

Genes 2022, 13(8), 1354; https://doi.org/10.3390/genes13081354 - 28 Jul 2022

Cited by 15 | Viewed by 2187

Abstract

The nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) is a highly toxic and persistent environmental pollutant. Since physicochemical methods for remediation are poorly effective, the use of microorganisms has gained interest as an alternative to restore TNT-contaminated sites. We previously demonstrated the high TNT-transforming capability of [...] Read more.

The nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) is a highly toxic and persistent environmental pollutant. Since physicochemical methods for remediation are poorly effective, the use of microorganisms has gained interest as an alternative to restore TNT-contaminated sites. We previously demonstrated the high TNT-transforming capability of three novel Pseudomonas spp. isolated from Deception Island, Antarctica, which exceeded that of the well-characterized TNT-degrading bacterium Pseudomonas putida KT2440. In this study, a comparative genomic analysis was performed to search for the metabolic functions encoded in the genomes of these isolates that might explain their TNT-transforming phenotype, and also to look for differences with 21 other selected pseudomonads, including xenobiotics-degrading species. Comparative analysis of xenobiotic degradation pathways revealed that our isolates have the highest abundance of key enzymes related to the degradation of fluorobenzoate, TNT, and bisphenol A. Further comparisons considering only TNT-transforming pseudomonads revealed the presence of unique genes in these isolates that would likely participate directly in TNT-transformation, and others involved in the β-ketoadipate pathway for aromatic compound degradation. Lastly, the phylogenomic analysis suggested that these Antarctic isolates likely represent novel species of the genus Pseudomonas, which emphasizes their relevance as potential agents for the bioremediation of TNT and other xenobiotics. Full article

(This article belongs to the Special Issue Microbial Genetics of Extreme Environments)

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18 pages, 7512 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Analysis Identifies Key Metabolic Changes in the Brain of Takifugu rubripes in Response to Chronic Hypoxia

by Fengqin Shang, Yun Lu, Yan Li, Bing Han, Renjie Wei, Shengmei Liu, Ying Liu, Yang Liu and Xiuli Wang

Genes 2022, 13(8), 1347; https://doi.org/10.3390/genes13081347 - 27 Jul 2022

Cited by 12 | Viewed by 2109

Abstract

The brain is considered to be an extremely sensitive tissue to hypoxia, and the brain of fish plays an important role in regulating growth and adapting to environmental changes. As an important aquatic organism in northern China, the economic yield of Takifugu rubripes [...] Read more.

The brain is considered to be an extremely sensitive tissue to hypoxia, and the brain of fish plays an important role in regulating growth and adapting to environmental changes. As an important aquatic organism in northern China, the economic yield of Takifugu rubripes is deeply influenced by the oxygen content of seawater. In this regard, we performed RNA-seq analysis of T. rubripes brains under hypoxia and normoxia to reveal the expression patterns of genes involved in the hypoxic response and their enrichment of metabolic pathways. Studies have shown that carbohydrate, lipid and amino acid metabolism are significant pathways for the enrichment of differentially expressed genes (DEGs) and that DEGs are significantly upregulated in those pathways. In addition, some biological processes such as the immune system and signal transduction, where enrichment is not significant but important, are also discussed. Interestingly, the DEGs associated with those pathways were significantly downregulated or inhibited. The present study reveals the mechanism of hypoxia tolerance in T. rubripes at the transcriptional level and provides a useful resource for studying the energy metabolism mechanism of hypoxia response in this species. Full article

(This article belongs to the Special Issue Advances of Brain Transcriptomics)

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30 pages, 4002 KiB

Open AccessEditor’s ChoiceArticle

Nrf2/HO-1 Signaling Stimulation through Acetyl-11-Keto-Beta-Boswellic Acid (AKBA) Provides Neuroprotection in Ethidium Bromide-Induced Experimental Model of Multiple Sclerosis

by Shubham Upadhayay, Sidharth Mehan, Aradhana Prajapati, Pranshul Sethi, Manisha Suri, Ayat Zawawi, Majed N. Almashjary and Shams Tabrez

Genes 2022, 13(8), 1324; https://doi.org/10.3390/genes13081324 - 25 Jul 2022

Cited by 19 | Viewed by 3030

Abstract

Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white [...] Read more.

Multiple sclerosis (MS) is a severe immune-mediated neurological disease characterized by neuroinflammation, demyelination, and axonal degeneration in the central nervous system (CNS). This is frequently linked to motor abnormalities and cognitive impairments. The pathophysiological hallmarks of MS include inflammatory demyelination, axonal injury, white matter degeneration, and the development of CNS lesions that result in severe neuronal degeneration. Several studies suggested downregulation of nuclear factor erythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling is a causative factor for MS pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active pentacyclictriterpenoid obtained from Boswellia serrata, possessing antioxidant and anti-inflammatory properties. The present study explores the protective potential of AKBA on behavioral, molecular, neurochemical, and gross pathological abnormalitiesandhistopathological alterations by H&E and LFB staining techniques in an experimental model of multiple sclerosis, emphasizing the increase inNrf2/HO-1 levels in the brain. Moreover, we also examine the effect of AKBA on the intensity of myelin basic protein (MBP) in CSF and rat brain homogenate. Specific apoptotic markers (Bcl-2, Bax, andcaspase-3) were also estimated in rat brain homogenate. Neuro behavioralabnormalities in rats were examined using an actophotometer, rotarod test, beam crossing task (BCT),and Morris water maze (MWM). AKBA 50 mg/kg and 100 mg/kg were given orally from day 8 to 35 to alleviate MS symptoms in the EB-injected rats. Furthermore, cellular, molecular, neurotransmitter, neuroinflammatory cytokine, and oxidative stress markers in rat whole brain homogenate, blood plasma, and cerebral spinal fluid were investigated. This study shows that AKBA upregulates the level of antioxidant proteins such as Nrf2 and HO-1 in the rat brain. AKBA restores altered neurochemical levels, potentially preventing gross pathological abnormalities during MS progression. Full article

(This article belongs to the Special Issue Genetic and Molecular Mechanisms in Multiple Sclerosis)

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10 pages, 2834 KiB

Open AccessEditor’s ChoiceArticle

State of the Art for Microhaplotypes

by Kenneth K. Kidd and Andrew J. Pakstis

Genes 2022, 13(8), 1322; https://doi.org/10.3390/genes13081322 - 24 Jul 2022

Cited by 15 | Viewed by 2714

Abstract

In recent years, the number of publications on microhaplotypes has averaged more than a dozen papers annually. Many have contributed to a significant increase in the number of highly polymorphic microhaplotype loci. This increase allows microhaplotypes to be very informative in four main [...] Read more.

In recent years, the number of publications on microhaplotypes has averaged more than a dozen papers annually. Many have contributed to a significant increase in the number of highly polymorphic microhaplotype loci. This increase allows microhaplotypes to be very informative in four main areas of forensic uses of DNA: individualization, ancestry inference, kinship analysis, and mixture deconvolution. The random match Probability (RMP) can be as small as 10⁻¹⁰⁰ for a large panel of microhaplotypes. It is possible to measure the heterozygosity of an MH as the effective number of alleles (A_e). A_e > 7.5 exists for African populations and >4.5 exists for Native American populations for a smaller panel of two dozen selected microhaplotypes. Using STRUCTURE, at least 10 different ancestral clusters can be defined by microhaplotypes. The A_e for a locus is also identical to the Paternity Index (PI), the measure of how informative a locus will be in parentage testing. High A_e loci can also be useful in missing persons cases. Finally, high A_e microhaplotypes allow the near certainty of seeing multiple additional alleles in a mixture of two or more individuals in a DNA sample. In summary, a panel of higher A_e microhaplotypes can outperform the standard CODIS markers. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics)

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24 pages, 1338 KiB

Open AccessEditor’s ChoiceReview

Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer’s Disease

by Chiara Villa and Andrea Stoccoro

Genes 2022, 13(8), 1308; https://doi.org/10.3390/genes13081308 - 22 Jul 2022

Cited by 14 | Viewed by 3395

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation [...] Read more.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation of protein tau in neurofibrillary tangles. These pathological modifications start many years prior to clinical manifestations of disease and the spectrum of AD progresses along a continuum from preclinical to clinical phases. Therefore, identifying specific biomarkers for detecting AD at early stages greatly improves clinical management. However, stable and non-invasive biomarkers are not currently available for the early detection of the disease. In the search for more reliable biomarkers, epigenetic mechanisms, able to mediate the interaction between the genome and the environment, are emerging as important players in AD pathogenesis. Herein, we discuss altered epigenetic signatures in blood as potential peripheral biomarkers for the early detection of AD in order to help diagnosis and improve therapy. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease)

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11 pages, 3136 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Analysis Identifies Candidate Genes Encoding Feather Color in Ducks

by Qixin Guo, Yong Jiang, Zhixiu Wang, Yulin Bi, Guohong Chen, Hao Bai and Guobin Chang

Genes 2022, 13(7), 1249; https://doi.org/10.3390/genes13071249 - 14 Jul 2022

Cited by 14 | Viewed by 2335

Abstract

Comparative population genomics and genome-wide association studies (GWAS) offer opportunities to discover human-driven detectable signatures within the genome. From the point of view of evolutionary biology, the identification of genes associated with the domestication of traits is of interest for the elucidation of [...] Read more.

Comparative population genomics and genome-wide association studies (GWAS) offer opportunities to discover human-driven detectable signatures within the genome. From the point of view of evolutionary biology, the identification of genes associated with the domestication of traits is of interest for the elucidation of the selection of these traits. To this end, an F₂ population of ducks, consisting of 275 ducks, was genotyped using a whole genome re-sequence containing 12.6 Mb single nucleotide polymorphisms (SNPs) and four plumage colors. GWAS was used to identify the candidate and potential SNPs of four plumage colors in ducks (white, spot, grey, and black plumage). In addition, FST and genetic diversity (π ratio) were used to screen signals of the selective sweep, which relate to the four plumage colors. Major genomic regions associated with white, spotted, and black feathers overlapped with their candidate selection regions, whereas no such overlap was observed with grey plumage. In addition, MITF and EDNRB2 are functional candidate genes that contribute to white and black plumage due to their indirect involvement in the melanogenesis pathway. This study provides new insights into the genetic factors that may influence the diversity of plumage color. Full article

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

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19 pages, 3386 KiB

Open AccessEditor’s ChoiceArticle

Identification of Novel Circular RNAs of the Human Protein Arginine Methyltransferase 1 (PRMT1) Gene, Expressed in Breast Cancer Cells

by Maria Papatsirou, Marios A. Diamantopoulos, Katerina Katsaraki, Dimitris Kletsas, Christos K. Kontos and Andreas Scorilas

Genes 2022, 13(7), 1133; https://doi.org/10.3390/genes13071133 - 24 Jun 2022

Cited by 12 | Viewed by 2276

Abstract

Circular RNAs (circRNAs) constitute a type of RNA formed through back-splicing. In breast cancer, circRNAs are implicated in tumor onset and progression. Although histone methylation by PRMT1 is largely involved in breast cancer development and metastasis, the effect of circular transcripts deriving from [...] Read more.

Circular RNAs (circRNAs) constitute a type of RNA formed through back-splicing. In breast cancer, circRNAs are implicated in tumor onset and progression. Although histone methylation by PRMT1 is largely involved in breast cancer development and metastasis, the effect of circular transcripts deriving from this gene has not been examined. In this study, total RNA was extracted from four breast cancer cell lines and reversely transcribed using random hexamer primers. Next, first- and second-round PCRs were performed using gene-specific divergent primers. Sanger sequencing followed for the determination of the sequence of each novel PRMT1 circRNA. Lastly, bioinformatics analysis was conducted to predict the functions of the novel circRNAs. In total, nine novel circRNAs were identified, comprising both complete and truncated exons of the PRMT1 gene. Interestingly, we demonstrated that the back-splice junctions consist of novel splice sites of the PRMT1 exons. Moreover, the circRNA expression pattern differed among these four breast cancer cell lines. All the novel circRNAs are predicted to act as miRNA and/or protein sponges, while five circRNAs also possess an open reading frame. In summary, we described the complete sequence of nine novel circRNAs of the PRMT1 gene, comprising distinct back-splice junctions and probably having different molecular properties. Full article

(This article belongs to the Special Issue Alternative Splicing in Human Physiology and Disease)

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