Genes

21 pages, 3129 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 16 | Viewed by 8695

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

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

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

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15 pages, 2210 KiB

Open AccessEditor’s ChoiceArticle

Evaluation and Genetic Analysis of Parthenocarpic Germplasms in Cucumber

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

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

Cited by 10 | Viewed by 3591

Abstract

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

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

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

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15 pages, 1946 KiB

Open AccessEditor’s ChoiceReview

Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes

by Takeshi Sakuno and Yasushi Hiraoka

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

Cited by 12 | Viewed by 5839

Abstract

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

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

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

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16 pages, 4221 KiB

Open AccessEditor’s ChoiceArticle

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

by Xiaomei Luo, Juncheng Liu and Zhoujian He

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

Cited by 9 | Viewed by 2705

Abstract

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

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

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

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9 pages, 3104 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Different Cleaning Strategies for Removal of Contaminating DNA Molecules

by Martina Nilsson, Hanne De Maeyer and Marie Allen

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

Cited by 16 | Viewed by 6441

Abstract

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

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

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

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18 pages, 1900 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

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

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

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

Cited by 15 | Viewed by 2950

Abstract

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

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

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

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Graphical abstract

13 pages, 2058 KiB

Open AccessEditor’s ChoiceReview

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

by Peace Mabeta, Rodney Hull and Zodwa Dlamini

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

Cited by 16 | Viewed by 2548

Abstract

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

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

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

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28 pages, 5592 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 23 | Viewed by 3310

Abstract

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

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

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

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17 pages, 4295 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 17 | Viewed by 2636

Abstract

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

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

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

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19 pages, 3098 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 22 | Viewed by 6792

Abstract

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

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

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

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19 pages, 402 KiB

Open AccessEditor’s ChoiceReview

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

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

Genes 2022, 13(1), 117; https://doi.org/10.3390/genes13010117 - 09 Jan 2022

Cited by 9 | Viewed by 3028

Abstract

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

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

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

14 pages, 2034 KiB

Open AccessEditor’s ChoiceArticle

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

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

Genes 2022, 13(1), 113; https://doi.org/10.3390/genes13010113 - 07 Jan 2022

Cited by 9 | Viewed by 3229

Abstract

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

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

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

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18 pages, 499 KiB

Open AccessEditor’s ChoicePerspective

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

by Julie Heng and Henry H. Heng

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

Cited by 25 | Viewed by 4427

Abstract

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

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

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

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15 pages, 300 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 26 | Viewed by 7704

Abstract

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

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

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

17 pages, 959 KiB

Open AccessEditor’s ChoiceReview

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

by Lisa Bleul, Patrice Francois and Christiane Wolz

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

Cited by 27 | Viewed by 5897

Abstract

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

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

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

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13 pages, 9753 KiB

Open AccessEditor’s ChoiceArticle

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

by Ernesto Picardi, Luigi Mansi and Graziano Pesole

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

Cited by 24 | Viewed by 3268

Abstract

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

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

(This article belongs to the Section Bioinformatics)

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23 pages, 815 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 27 | Viewed by 9474

Abstract

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

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

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

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18 pages, 1243 KiB

Open AccessEditor’s ChoiceReview

Genetics and Epigenetics in Allergic Rhinitis

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

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

Cited by 32 | Viewed by 7478

Abstract

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

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

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

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22 pages, 1337 KiB

Open AccessEditor’s ChoiceReview

Role of Basal ABA in Plant Growth and Development

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

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

Cited by 67 | Viewed by 7630

Abstract

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

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

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

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13 pages, 296 KiB

Open AccessEditor’s ChoiceReview

Gene-Environment Interactions in Schizophrenia: A Literature Review

by Marah H. Wahbeh and Dimitrios Avramopoulos

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

Cited by 42 | Viewed by 7658

Abstract

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

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

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

28 pages, 2323 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 38 | Viewed by 4169

Abstract

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

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

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

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32 pages, 780 KiB

Open AccessEditor’s ChoiceReview

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

by Titia Sijen and SallyAnn Harbison

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

Cited by 36 | Viewed by 9953

Abstract

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

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

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

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16 pages, 4772 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 30 | Viewed by 1981

Abstract

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

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

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

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16 pages, 1950 KiB

Open AccessEditor’s ChoiceReview

Breeding for Resistance to Fusarium Wilt of Tomato: A Review

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

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

Cited by 39 | Viewed by 7529

Abstract

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

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

(This article belongs to the Special Issue Tomato Genetics)

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20 pages, 1474 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 34 | Viewed by 5381

Abstract

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

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

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

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29 pages, 8312 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 22 | Viewed by 3534

Abstract

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

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

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

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22 pages, 825 KiB

Open AccessEditor’s ChoiceReview

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

by Vincenzo Cavalieri

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

Cited by 43 | Viewed by 4877

Abstract

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

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

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

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13 pages, 3390 KiB

Open AccessEditor’s ChoiceReview

Renal Cell Carcinoma in Tuberous Sclerosis Complex

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

Genes 2021, 12(10), 1585; https://doi.org/10.3390/genes12101585 - 08 Oct 2021

Cited by 31 | Viewed by 4096

Abstract

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

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

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

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18 pages, 978 KiB

Open AccessEditor’s ChoiceReview

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

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

Genes 2021, 12(10), 1572; https://doi.org/10.3390/genes12101572 - 01 Oct 2021

Cited by 27 | Viewed by 3899

Abstract

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

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

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

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40 pages, 2967 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 25 | Viewed by 5159

Abstract

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

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

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

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12 pages, 1073 KiB

Open AccessEditor’s ChoiceReview

DEAD-Box RNA Helicases and Genome Stability

by Michael Cargill, Rasika Venkataraman and Stanley Lee

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

Cited by 40 | Viewed by 7348

Abstract

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

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

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

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15 pages, 12451 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 18 | Viewed by 2506

Abstract

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

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

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

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13 pages, 1352 KiB

Open AccessEditor’s ChoiceReview

Histone Acetylation Changes in Plant Response to Drought Stress

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

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

Cited by 24 | Viewed by 3635

Abstract

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

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

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

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13 pages, 269 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 27 | Viewed by 3675

Abstract

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

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

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

13 pages, 2015 KiB

Open AccessEditor’s ChoiceReview

ATM’s Role in the Repair of DNA Double-Strand Breaks

by Atsushi Shibata and Penny A. Jeggo

Genes 2021, 12(9), 1370; https://doi.org/10.3390/genes12091370 - 31 Aug 2021

Cited by 36 | Viewed by 4577

Abstract

Ataxia telangiectasia mutated (ATM) is a central kinase that activates an extensive network of responses to cellular stress via a signaling role. ATM is activated by DNA double strand breaks (DSBs) and by oxidative stress, subsequently phosphorylating a plethora of target proteins. In [...] Read more.

Ataxia telangiectasia mutated (ATM) is a central kinase that activates an extensive network of responses to cellular stress via a signaling role. ATM is activated by DNA double strand breaks (DSBs) and by oxidative stress, subsequently phosphorylating a plethora of target proteins. In the last several decades, newly developed molecular biological techniques have uncovered multiple roles of ATM in response to DNA damage—e.g., DSB repair, cell cycle checkpoint arrest, apoptosis, and transcription arrest. Combinational dysfunction of these stress responses impairs the accuracy of repair, consequently leading to dramatic sensitivity to ionizing radiation (IR) in ataxia telangiectasia (A-T) cells. In this review, we summarize the roles of ATM that focus on DSB repair. Full article

(This article belongs to the Special Issue Role of ATM and MRE11 in Genomic Stability and Oxidative Stress Responses)

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13 pages, 1065 KiB

Open AccessEditor’s ChoiceReview

Bardet–Biedl Syndrome—Multiple Kaleidoscope Images: Insight into Mechanisms of Genotype–Phenotype Correlations

by Laura Florea, Lavinia Caba and Eusebiu Vlad Gorduza

Genes 2021, 12(9), 1353; https://doi.org/10.3390/genes12091353 - 29 Aug 2021

Cited by 30 | Viewed by 5096

Abstract

Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It [...] Read more.

Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet–Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management. Full article

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

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13 pages, 571 KiB

Open AccessEditor’s ChoiceReview

MiRNAs and Cancer: Key Link in Diagnosis and Therapy

by Yu Shi, Zihao Liu, Qun Lin, Qing Luo, Yinghuan Cen, Juanmei Li, Xiaolin Fang and Chang Gong

Genes 2021, 12(8), 1289; https://doi.org/10.3390/genes12081289 - 23 Aug 2021

Cited by 51 | Viewed by 4304

Abstract

Since the discovery of the first microRNA (miRNA), the exploration of miRNA biology has come to a new era in recent decades. Monumental studies have proven that miRNAs can be dysregulated in different types of cancers and the roles of miRNAs turn out [...] Read more.

Since the discovery of the first microRNA (miRNA), the exploration of miRNA biology has come to a new era in recent decades. Monumental studies have proven that miRNAs can be dysregulated in different types of cancers and the roles of miRNAs turn out to function to either tumor promoters or tumor suppressors. The interplay between miRNAs and the development of cancers has grabbed attention of miRNAs as novel tools and targets for therapeutic attempts. Moreover, the development of miRNA delivery system accelerates miRNA preclinical implications. In this review, we depict recent advances of miRNAs in cancer and discuss the potential diagnostic or therapeutic approaches of miRNAs. Full article

(This article belongs to the Special Issue The Role of MicroRNA in Cancer)

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19 pages, 2561 KiB

Open AccessEditor’s ChoiceArticle

Development and Evaluation of the Ancestry Informative Marker Panel of the VISAGE Basic Tool

by María de la Puente, Jorge Ruiz-Ramírez, Adrián Ambroa-Conde, Catarina Xavier, Jacobo Pardo-Seco, Jose Álvarez-Dios, Ana Freire-Aradas, Ana Mosquera-Miguel, Theresa E. Gross, Elaine Y. Y. Cheung, Wojciech Branicki, Michael Nothnagel, Walther Parson, Peter M. Schneider, Manfred Kayser, Ángel Carracedo, Maria Victoria Lareu, Christopher Phillips and on behalf of the VISAGE Consortium

Genes 2021, 12(8), 1284; https://doi.org/10.3390/genes12081284 - 22 Aug 2021

Cited by 19 | Viewed by 4669

Abstract

We detail the development of the ancestry informative single nucleotide polymorphisms (SNPs) panel forming part of the VISAGE Basic Tool (BT), which combines 41 appearance predictive SNPs and 112 ancestry predictive SNPs (three SNPs shared between sets) in one massively parallel sequencing (MPS) [...] Read more.

We detail the development of the ancestry informative single nucleotide polymorphisms (SNPs) panel forming part of the VISAGE Basic Tool (BT), which combines 41 appearance predictive SNPs and 112 ancestry predictive SNPs (three SNPs shared between sets) in one massively parallel sequencing (MPS) multiplex, whereas blood-based age analysis using methylation markers is run in a parallel MPS analysis pipeline. The selection of SNPs for the BT ancestry panel focused on established forensic markers that already have a proven track record of good sequencing performance in MPS, and the overall SNP multiplex scale closely matched that of existing forensic MPS assays. SNPs were chosen to differentiate individuals from the five main continental population groups of Africa, Europe, East Asia, America, and Oceania, extended to include differentiation of individuals from South Asia. From analysis of 1000 Genomes and HGDP-CEPH samples from these six population groups, the BT ancestry panel was shown to have no classification error using the Bayes likelihood calculators of the Snipper online analysis portal. The differentiation power of the component ancestry SNPs of BT was balanced as far as possible to avoid bias in the estimation of co-ancestry proportions in individuals with admixed backgrounds. The balancing process led to very similar cumulative population-specific divergence values for Africa, Europe, America, and Oceania, with East Asia being slightly below average, and South Asia an outlier from the other groups. Comparisons were made of the African, European, and Native American estimated co-ancestry proportions in the six admixed 1000 Genomes populations, using the BT ancestry panel SNPs and 572,000 Affymetrix Human Origins array SNPs. Very similar co-ancestry proportions were observed down to a minimum value of 10%, below which, low-level co-ancestry was not always reliably detected by BT SNPs. The Snipper analysis portal provides a comprehensive population dataset for the BT ancestry panel SNPs, comprising a 520-sample standardised reference dataset; 3445 additional samples from 1000 Genomes, HGDP-CEPH, Simons Foundation and Estonian Biocentre genome diversity projects; and 167 samples of six populations from in-house genotyping of individuals from Middle East, North and East African regions complementing those of the sampling regimes of the other diversity projects. Full article

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

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22 pages, 1184 KiB

Open AccessEditor’s ChoiceReview

HD-ZIP Gene Family: Potential Roles in Improving Plant Growth and Regulating Stress-Responsive Mechanisms in Plants

by Rahat Sharif, Ali Raza, Peng Chen, Yuhong Li, Enas M. El-Ballat, Abdur Rauf, Christophe Hano and Mohamed A. El-Esawi

Genes 2021, 12(8), 1256; https://doi.org/10.3390/genes12081256 - 17 Aug 2021

Cited by 68 | Viewed by 6990

Abstract

Exploring the molecular foundation of the gene-regulatory systems underlying agronomic parameters or/and plant responses to both abiotic and biotic stresses is crucial for crop improvement. Thus, transcription factors, which alone or in combination directly regulated the targeted gene expression levels, are appropriate players [...] Read more.

Exploring the molecular foundation of the gene-regulatory systems underlying agronomic parameters or/and plant responses to both abiotic and biotic stresses is crucial for crop improvement. Thus, transcription factors, which alone or in combination directly regulated the targeted gene expression levels, are appropriate players for enlightening agronomic parameters through genetic engineering. In this regard, homeodomain leucine zipper (HD-ZIP) genes family concerned with enlightening plant growth and tolerance to environmental stresses are considered key players for crop improvement. This gene family containing HD and LZ domain belongs to the homeobox superfamily. It is further classified into four subfamilies, namely HD-ZIP I, HD-ZIP II, HD-ZIP III, and HD-ZIP IV. The first HD domain-containing gene was discovered in maize cells almost three decades ago. Since then, with advanced technologies, these genes were functionally characterized for their distinct roles in overall plant growth and development under adverse environmental conditions. This review summarized the different functions of HD-ZIP genes in plant growth and physiological-related activities from germination to fruit development. Additionally, the HD-ZIP genes also respond to various abiotic and biotic environmental stimuli by regulating defense response of plants. This review, therefore, highlighted the various significant aspects of this important gene family based on the recent findings. The practical application of HD-ZIP biomolecules in developing bioengineered plants will not only mitigate the negative effects of environmental stresses but also increase the overall production of crop plants. Full article

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

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20 pages, 1106 KiB

Open AccessEditor’s ChoiceReview

Genetic Resources and Vulnerabilities of Major Cucurbit Crops

by Rebecca Grumet, James D. McCreight, Cecilia McGregor, Yiqun Weng, Michael Mazourek, Kathleen Reitsma, Joanne Labate, Angela Davis and Zhangjun Fei

Genes 2021, 12(8), 1222; https://doi.org/10.3390/genes12081222 - 07 Aug 2021

Cited by 31 | Viewed by 6521

Abstract

The Cucurbitaceae family provides numerous important crops including watermelons (Citrullus lanatus), melons (Cucumis melo), cucumbers (Cucumis sativus), and pumpkins and squashes (Cucurbita spp.). Centers of domestication in Africa, Asia, and the Americas were followed by distribution [...] Read more.

The Cucurbitaceae family provides numerous important crops including watermelons (Citrullus lanatus), melons (Cucumis melo), cucumbers (Cucumis sativus), and pumpkins and squashes (Cucurbita spp.). Centers of domestication in Africa, Asia, and the Americas were followed by distribution throughout the world and the evolution of secondary centers of diversity. Each of these crops is challenged by multiple fungal, oomycete, bacterial, and viral diseases and insects that vector disease and cause feeding damage. Cultivated varieties are constrained by market demands, the necessity for climatic adaptations, domestication bottlenecks, and in most cases, limited capacity for interspecific hybridization, creating narrow genetic bases for crop improvement. This analysis of crop vulnerabilities examines the four major cucurbit crops, their uses, challenges, and genetic resources. ex situ germplasm banks, the primary strategy to preserve genetic diversity, have been extensively utilized by cucurbit breeders, especially for resistances to biotic and abiotic stresses. Recent genomic efforts have documented genetic diversity, population structure, and genetic relationships among accessions within collections. Collection size and accessibility are impacted by historical collections, current ability to collect, and ability to store and maintain collections. The biology of cucurbits, with insect-pollinated, outcrossing plants, and large, spreading vines, pose additional challenges for regeneration and maintenance. Our ability to address ongoing and future cucurbit crop vulnerabilities will require a combination of investment, agricultural, and conservation policies, and technological advances to facilitate collection, preservation, and access to critical Cucurbitaceae diversity. Full article

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

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21 pages, 1276 KiB

Open AccessEditor’s ChoiceSystematic Review

A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

by Mahdi Abdoli Shadbad, Sahar Safaei, Oronzo Brunetti, Afshin Derakhshani, Parisa Lotfinejad, Ahad Mokhtarzadeh, Nima Hemmat, Vito Racanelli, Antonio Giovanni Solimando, Antonella Argentiero, Nicola Silvestris and Behzad Baradaran

Genes 2021, 12(8), 1206; https://doi.org/10.3390/genes12081206 - 04 Aug 2021

Cited by 30 | Viewed by 3873

Abstract

The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, [...] Read more.

The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC. Therefore, we conducted the current systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to provide a comprehensive and unbiased synthesis of currently available evidence regarding the effect of PD-L1-inhibiting miRs restoration on TNBC development and tumor microenvironment. For this purpose, we systematically searched the Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid, and IranDoc databases to obtain the relevant peer-reviewed studies published before 25 May 2021. Based on the current evidence, the restoration of miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, and miR-497-5p can inhibit tumoral PD-L1 expression, transform immunosuppressive tumor microenvironment into the pro-inflammatory tumor microenvironment, inhibit tumor proliferation, suppress tumor migration, enhance chemosensitivity of tumoral cells, stimulate tumor apoptosis, arrest cell cycle, repress the clonogenicity of tumoral cells, and regulate various oncogenic signaling pathways in TNBC cells. Concerning the biocompatibility of biomimetic carriers and the valuable insights provided by the single-cell sequencing technologies, single-cell sequencing-guided biomimetic delivery of these PD-L1-inhibiting miRs can decrease the toxicity of traditional approaches, increase the specificity of miR-delivery, enhance the efficacy of miR delivery, and provide the affected patients with personalized cancer therapy. Full article

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

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17 pages, 695 KiB

Open AccessEditor’s ChoiceReview

Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World

by Ashay D. Bhatwadekar, Aumer Shughoury, Ameya Belamkar and Thomas A. Ciulla

Genes 2021, 12(8), 1200; https://doi.org/10.3390/genes12081200 - 31 Jul 2021

Cited by 25 | Viewed by 5304

Abstract

Diabetic retinopathy (DR) is a chronic complication of diabetes and a leading cause of blindness in the industrialized world. Traditional risk factors, such as glycemic control and duration of diabetes, are unable to explain why some individuals remain protected while others progress to [...] Read more.

Diabetic retinopathy (DR) is a chronic complication of diabetes and a leading cause of blindness in the industrialized world. Traditional risk factors, such as glycemic control and duration of diabetes, are unable to explain why some individuals remain protected while others progress to a more severe form of the disease. Differences are also observed in DR heritability as well as the response to anti-vascular endothelial growth factor (VEGF) treatment. This review discusses various aspects of genetics in DR to shed light on DR pathogenesis and treatment. First, we discuss the global burden of DR followed by a discussion on disease pathogenesis as well as the role genetics plays in the prevalence and progression of DR. Subsequently, we provide a review of studies related to DR’s genetic contribution, such as candidate gene studies, linkage studies, and genome-wide association studies (GWAS) as well as other clinical and meta-analysis studies that have identified putative candidate genes. With the advent of newer cutting-edge technologies, identifying the genetic components in DR has played an important role in understanding DR incidence, progression, and response to treatment, thereby developing newer therapeutic targets and therapies. Full article

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

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17 pages, 7428 KiB

Open AccessEditor’s ChoiceArticle

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

by Emel Rothzerg, Xuan Dung Ho, Jiake Xu, David Wood, Aare Märtson and Sulev Kõks

Genes 2021, 12(8), 1132; https://doi.org/10.3390/genes12081132 - 26 Jul 2021

Cited by 27 | Viewed by 3494

Abstract

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as [...] Read more.

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma. Full article

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

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20 pages, 2600 KiB

Open AccessEditor’s ChoiceReview

T-Cell Acute Lymphoblastic Leukemia: Biomarkers and Their Clinical Usefulness

by Valentina Bardelli, Silvia Arniani, Valentina Pierini, Danika Di Giacomo, Tiziana Pierini, Paolo Gorello, Cristina Mecucci and Roberta La Starza

Genes 2021, 12(8), 1118; https://doi.org/10.3390/genes12081118 - 23 Jul 2021

Cited by 37 | Viewed by 7202

Abstract

T-cell acute lymphoblastic leukemias (T-ALL) are immature lymphoid tumors localizing in the bone marrow, mediastinum, central nervous system, and lymphoid organs. They account for 10–15% of pediatric and about 25% of adult acute lymphoblastic leukemia (ALL) cases. It is a widely heterogeneous disease [...] Read more.

T-cell acute lymphoblastic leukemias (T-ALL) are immature lymphoid tumors localizing in the bone marrow, mediastinum, central nervous system, and lymphoid organs. They account for 10–15% of pediatric and about 25% of adult acute lymphoblastic leukemia (ALL) cases. It is a widely heterogeneous disease that is caused by the co-occurrence of multiple genetic abnormalities, which are acquired over time, and once accumulated, lead to full-blown leukemia. Recurrently affected genes deregulate pivotal cell processes, such as cycling (CDKN1B, RB1, TP53), signaling transduction (RAS pathway, IL7R/JAK/STAT, PI3K/AKT), epigenetics (PRC2 members, PHF6), and protein translation (RPL10, CNOT3). A remarkable role is played by NOTCH1 and CDKN2A, as they are altered in more than half of the cases. The activation of the NOTCH1 signaling affects thymocyte specification and development, while CDKN2A haploinsufficiency/inactivation, promotes cell cycle progression. Among recurrently involved oncogenes, a major role is exerted by T-cell-specific transcription factors, whose deregulated expression interferes with normal thymocyte development and causes a stage-specific differentiation arrest. Hence, TAL and/or LMO deregulation is typical of T-ALL with a mature phenotype (sCD3 positive) that of TLX1, NKX2-1, or TLX3, of cortical T-ALL (CD1a positive); HOXA and MEF2C are instead over-expressed in subsets of Early T-cell Precursor (ETP; immature phenotype) and early T-ALL. Among immature T-ALL, genomic alterations, that cause BCL11B transcriptional deregulation, identify a specific genetic subgroup. Although comprehensive cytogenetic and molecular studies have shed light on the genetic background of T-ALL, biomarkers are not currently adopted in the diagnostic workup of T-ALL, and only a limited number of studies have assessed their clinical implications. In this review, we will focus on recurrent T-ALL abnormalities that define specific leukemogenic pathways and on oncogenes/oncosuppressors that can serve as diagnostic biomarkers. Moreover, we will discuss how the complex genomic profile of T-ALL can be used to address and test innovative/targeted therapeutic options. Full article

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

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17 pages, 341 KiB

Open AccessEditor’s ChoiceReview

Plants’ Epigenetic Mechanisms and Abiotic Stress

by Matin Miryeganeh

Genes 2021, 12(8), 1106; https://doi.org/10.3390/genes12081106 - 21 Jul 2021

Cited by 58 | Viewed by 7609

Abstract

Plants are sessile organisms that need to adapt to constantly changing environmental conditions. Unpredictable climate change places plants under a variety of abiotic stresses. Studying the regulation of stress-responsive genes can help to understand plants’ ability to adapt to fluctuating environmental conditions. Changes [...] Read more.

Plants are sessile organisms that need to adapt to constantly changing environmental conditions. Unpredictable climate change places plants under a variety of abiotic stresses. Studying the regulation of stress-responsive genes can help to understand plants’ ability to adapt to fluctuating environmental conditions. Changes in epigenetic marks such as histone modifications and DNA methylation are known to regulate gene expression by their dynamic variation in response to stimuli. This can then affect their phenotypic plasticity, which helps with the adaptation of plants to adverse conditions. Epigenetic marks may also provide a mechanistic basis for stress memory, which enables plants to respond more effectively and efficiently to recurring stress and prepare offspring for potential future stresses. Studying epigenetic changes in addition to genetic factors is important to better understand the molecular mechanisms underlying plant stress responses. This review summarizes the epigenetic mechanisms behind plant responses to some main abiotic stresses. Full article

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

18 pages, 4054 KiB

Open AccessEditor’s ChoiceReview

Hydroxyurea—The Good, the Bad and the Ugly

by Marcelina W. Musiałek and Dorota Rybaczek

Genes 2021, 12(7), 1096; https://doi.org/10.3390/genes12071096 - 19 Jul 2021

Cited by 43 | Viewed by 10323

Abstract

Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one [...] Read more.

Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one which has proved to be effective in treating chronic myeloproliferative disorders and which is considered a staple agent in sickle anemia therapy and—recently—a promising factor in preventing cognitive decline in Alzheimer’s disease. The reversibility of HU-induced replication inhibition also makes it a common laboratory ingredient used to synchronize cell cycles. On the other hand, prolonged treatment or higher dosage of hydroxyurea causes cell death due to accumulation of DNA damage and oxidative stress. Hydroxyurea treatments are also still far from perfect and it has been suggested that it facilitates skin cancer progression. Also, recent studies have shown that hydroxyurea may affect a larger number of enzymes due to its less specific interaction mechanism, which may contribute to further as-yet unspecified factors affecting cell response. In this review, we examine the actual state of knowledge about hydroxyurea and the mechanisms behind its cytotoxic effects. The practical applications of the recent findings may prove to enhance the already existing use of the drug in new and promising ways. Full article

(This article belongs to the Special Issue Mechanisms of DNA Damage, Repair and Mutagenesis)

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13 pages, 834 KiB

Open AccessEditor’s ChoiceReview

Cornelia de Lange Syndrome: From a Disease to a Broader Spectrum

by Angelo Selicorni, Milena Mariani, Antonella Lettieri and Valentina Massa

Genes 2021, 12(7), 1075; https://doi.org/10.3390/genes12071075 - 15 Jul 2021

Cited by 22 | Viewed by 11936

Abstract

Cornelia de Lange syndrome (CdLS) is a genetic disease that exemplifies the evolution of knowledge in the field of rare genetic disorders. Originally described as a unique pattern of major and minor anomalies, over time this syndrome has been shown to be characterized [...] Read more.

Cornelia de Lange syndrome (CdLS) is a genetic disease that exemplifies the evolution of knowledge in the field of rare genetic disorders. Originally described as a unique pattern of major and minor anomalies, over time this syndrome has been shown to be characterized by a significant variability of clinical expression. By increasing the number of patients described, knowledge of the natural history of the condition has been enriched with the demonstration of the relative frequency of various potential comorbidities. Since 2006, the discovery of CdLS’s molecular basis has shown an equally vast genetic heterogeneity linked to the presence of variants in genes encoding for the cohesin complex pathway. The most recent clinical-genetic data led to the classification of the “original syndrome” into a “clinical spectrum” that foresees the presence of classic patients, of non-classic forms, and of conditions that show a modest phenotypic overlapping with the original disease. Finally, the knowledge of the molecular basis of the disease has allowed the development of basic research projects that could lay the foundations for the development of possible innovative pharmacological treatments. Full article

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

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27 pages, 2970 KiB

Open AccessEditor’s ChoiceReview

Role and Evolution of the Extracellular Matrix in the Acquisition of Complex Multicellularity in Eukaryotes: A Macroalgal Perspective

by Bernard Kloareg, Yacine Badis, J. Mark Cock and Gurvan Michel

Genes 2021, 12(7), 1059; https://doi.org/10.3390/genes12071059 - 10 Jul 2021

Cited by 30 | Viewed by 7165

Abstract

Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular [...] Read more.

Multicellular eukaryotes are characterized by an expanded extracellular matrix (ECM) with a diversified composition. The ECM is involved in determining tissue texture, screening cells from the outside medium, development, and innate immunity, all of which are essential features in the biology of multicellular eukaryotes. This review addresses the origin and evolution of the ECM, with a focus on multicellular marine algae. We show that in these lineages the expansion of extracellular matrix played a major role in the acquisition of complex multicellularity through its capacity to connect, position, shield, and defend the cells. Multiple innovations were necessary during these evolutionary processes, leading to striking convergences in the structures and functions of the ECMs of algae, animals, and plants. Full article

(This article belongs to the Special Issue Evolution of Multicellularity)

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19 pages, 1261 KiB

Open AccessEditor’s ChoiceReview

Epilepsy Syndromes in the First Year of Life and Usefulness of Genetic Testing for Precision Therapy

by Allan Bayat, Michael Bayat, Guido Rubboli and Rikke S. Møller

Genes 2021, 12(7), 1051; https://doi.org/10.3390/genes12071051 - 08 Jul 2021

Cited by 36 | Viewed by 11377

Abstract

The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and [...] Read more.

The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrumental in providing insights into the pathophysiology of both early-onset benign and self-limited syndromes and devastating developmental and epileptic encephalopathies (DEEs). Genetic heterogeneity is seen in many epilepsy syndromes such as West syndrome and epilepsy of infancy with migrating focal seizures (EIMFS), indicating that two or more genetic loci produce the same or similar phenotypes. At the same time, some genes such as SCN2A can be associated with a wide range of epilepsy syndromes ranging from self-limited familial neonatal epilepsy at the mild end to Ohtahara syndrome, EIFMS, West syndrome, Lennox–Gastaut syndrome, or unclassifiable DEEs at the severe end of the spectrum. The aim of this study was to review the clinical and genetic heterogeneity associated with epilepsy syndromes starting in the first year of life including: Self-limited familial neonatal, neonatal-infantile or infantile epilepsies, genetic epilepsy with febrile seizures plus spectrum, myoclonic epilepsy in infancy, Ohtahara syndrome, early myoclonic encephalopathy, West syndrome, Dravet syndrome, EIMFS, and unclassifiable DEEs. We also elaborate on the advantages and pitfalls of genetic testing in such conditions. Finally, we describe how a genetic diagnosis can potentially enable precision therapy in monogenic epilepsies and emphasize that early genetic testing is a cornerstone for such therapeutic strategies. Full article

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

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22 pages, 1150 KiB

Open AccessEditor’s ChoiceReview

Roles of ncRNAs as ceRNAs in Gastric Cancer

by Junhong Ye, Jifu Li and Ping Zhao

Genes 2021, 12(7), 1036; https://doi.org/10.3390/genes12071036 - 02 Jul 2021

Cited by 32 | Viewed by 4229

Abstract

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs [...] Read more.

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC’s mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC’s ceRNA network. Full article

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

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