Genes

16 pages, 3521 KiB

Open AccessArticle

Identification of Potential Risk Genes and the Immune Landscape of Idiopathic Pulmonary Arterial Hypertension via Microarray Gene Expression Dataset Reanalysis

by Jing Xu, Yicheng Yang, Yuejin Yang and Changming Xiong

Genes 2021, 12(1), 125; https://doi.org/10.3390/genes12010125 - 19 Jan 2021

Cited by 7 | Viewed by 3953

Abstract

Gene dysfunction and immune cell infiltration play an essential role in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). We aimed to investigate the immune landscape and novel differentially expressed genes (DEGs) of IPAH. In addition, potential druggable molecular targets for IPAH were [...] Read more.

Gene dysfunction and immune cell infiltration play an essential role in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). We aimed to investigate the immune landscape and novel differentially expressed genes (DEGs) of IPAH. In addition, potential druggable molecular targets for IPAH were also explored. In this study, the GSE117261 dataset was reanalyzed to explore the immune landscape and hub DEGs of IPAH. Lasso Cox regression analysis and receiver operating characteristic curve analysis were performed to detect the predictive value of IPAH. Additionally, the underlying drug targets for IPAH treatment were determined by drug–gene analysis. IPAH was significantly associated with the transforming growth factor-β (TGF-β) signaling pathway and Wnt signaling pathway as well as energetic metabolism dysfunction. We identified 31 upregulated and 39 downregulated DEGs in IPAH patients. Six hub genes, namely, SAA1, CCL5, CXCR1, CXCR2, CCR1, and ADORA3, were related to IPAH pathogenesis regardless of sex differences. Prediction model analysis showed that the area under the curve values of the hub DEGs except CXCR2 were all above 0.9 for distinguishing IPAH patients. In addition, the relative proportions of 5 subtypes of immune cells, namely, CD₈⁺ T cells, CD₄⁺ memory resting T cells, γ delta T cells, M1 macrophages, and resting mast cells, were significantly upregulated in the IPAH samples, while 6 subtypes of immune cells, namely, CD₄⁺ naive T cells, resting NK cells, monocytes, M0 macrophages, activated mast cells, and neutrophils, were downregulated. Additionally, a total of 17 intersecting drugs targeting 5 genes, CCL5, CXCR1, CXCR2, CCR1, and ADORA3, were generated as potential druggable molecular targets for IPAH. Our study revealed the underlying correlations between genes and immune cells in IPAH and demonstrated for the first time that SAA1, CCL5, CXCR1, CCR1, and ADORA3 may be novel genetic targets for IPAH. Full article

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

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13 pages, 560 KiB

Open AccessReview

Bridging the Gap between Vertebrate Cytogenetics and Genomics with Single-Chromosome Sequencing (ChromSeq)

by Alessio Iannucci, Alexey I. Makunin, Artem P. Lisachov, Claudio Ciofi, Roscoe Stanyon, Marta Svartman and Vladimir A. Trifonov

Genes 2021, 12(1), 124; https://doi.org/10.3390/genes12010124 - 19 Jan 2021

Cited by 12 | Viewed by 4708

Abstract

The study of vertebrate genome evolution is currently facing a revolution, brought about by next generation sequencing technologies that allow researchers to produce nearly complete and error-free genome assemblies. Novel approaches however do not always provide a direct link with information on vertebrate [...] Read more.

The study of vertebrate genome evolution is currently facing a revolution, brought about by next generation sequencing technologies that allow researchers to produce nearly complete and error-free genome assemblies. Novel approaches however do not always provide a direct link with information on vertebrate genome evolution gained from cytogenetic approaches. It is useful to preserve and link cytogenetic data with novel genomic discoveries. Sequencing of DNA from single isolated chromosomes (ChromSeq) is an elegant approach to determine the chromosome content and assign genome assemblies to chromosomes, thus bridging the gap between cytogenetics and genomics. The aim of this paper is to describe how ChromSeq can support the study of vertebrate genome evolution and how it can help link cytogenetic and genomic data. We show key examples of ChromSeq application in the refinement of vertebrate genome assemblies and in the study of vertebrate chromosome and karyotype evolution. We also provide a general overview of the approach and a concrete example of genome refinement using this method in the species Anolis carolinensis. Full article

(This article belongs to the Special Issue Chromosome-Centric View of the Genome Organization and Evolution)

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17 pages, 2779 KiB

Open AccessArticle

Satellite DNA in Neotropical Deer Species

by Miluse Vozdova, Svatava Kubickova, Natália Martínková, David Javier Galindo, Agda Maria Bernegossi, Halina Cernohorska, Dita Kadlcikova, Petra Musilová, Jose Mauricio Duarte and Jiri Rubes

Genes 2021, 12(1), 123; https://doi.org/10.3390/genes12010123 - 19 Jan 2021

Cited by 11 | Viewed by 3788

Abstract

The taxonomy and phylogenetics of Neotropical deer have been mostly based on morphological criteria and needs a critical revision on the basis of new molecular and cytogenetic markers. In this study, we used the variation in the sequence, copy number, and chromosome localization [...] Read more.

The taxonomy and phylogenetics of Neotropical deer have been mostly based on morphological criteria and needs a critical revision on the basis of new molecular and cytogenetic markers. In this study, we used the variation in the sequence, copy number, and chromosome localization of satellite I-IV DNA to evaluate evolutionary relationships among eight Neotropical deer species. Using FISH with satI-IV probes derived from Mazama gouazoubira, we proved the presence of satellite DNA blocks in peri/centromeric regions of all analyzed deer. Satellite DNA was also detected in the interstitial chromosome regions of species of the genus Mazama with highly reduced chromosome numbers. In contrast to Blastocerus dichotomus, Ozotoceros bezoarticus, and Odocoileus virginianus, Mazama species showed high abundance of satIV DNA by FISH. The phylogenetic analysis of the satellite DNA showed close relationships between O. bezoarticus and B. dichotomus. Furthermore, the Neotropical and Nearctic populations of O. virginianus formed a single clade. However, the satellite DNA phylogeny did not allow resolving the relationships within the genus Mazama. The high abundance of the satellite DNA in centromeres probably contributes to the formation of chromosomal rearrangements, thus leading to a fast and ongoing speciation in this genus, which has not yet been reflected in the satellite DNA sequence diversification. Full article

(This article belongs to the Special Issue Satellite DNAs: From Cellular Functions to Diseases)

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18 pages, 1933 KiB

Open AccessArticle

A Novel Carboxylesterase Derived from a Compost Metagenome Exhibiting High Stability and Activity towards High Salinity

by Mingji Lu and Rolf Daniel

Genes 2021, 12(1), 122; https://doi.org/10.3390/genes12010122 - 19 Jan 2021

Cited by 13 | Viewed by 2903

Abstract

Halotolerant lipolytic enzymes have gained growing interest, due to potential applications under harsh conditions, such as hypersalinity and presence of organic solvents. In this study, a lipolytic gene, est56, encoding 287 amino acids was identified by functional screening of a compost metagenome. [...] Read more.

Halotolerant lipolytic enzymes have gained growing interest, due to potential applications under harsh conditions, such as hypersalinity and presence of organic solvents. In this study, a lipolytic gene, est56, encoding 287 amino acids was identified by functional screening of a compost metagenome. Subsequently, the gene was heterologously expressed, and the recombinant protein (Est56) was purified and characterized. Est56 is a mesophilic (T_opt 50 °C) and moderate alkaliphilic (pH_opt 8) enzyme, showing high thermostability at 30 and 40 °C. Strikingly, Est56 is halotolerant as it exhibited high activity and stability in the presence of up to 4 M NaCl or KCl. Est56 also displayed enhanced stability against high temperatures (50 and 60 °C) and urea (2, 4, and 6 M) in the presence of NaCl. In addition, the recently reported halotolerant lipolytic enzymes were summarized. Phylogenetic analysis grouped these enzymes into 13 lipolytic protein families. The majority (45%) including Est56 belonged to family IV. To explore the haloadaptation of halotolerant enzymes, the amino acid composition between halotolerant and halophilic enzymes was statistically compared. The most distinctive feature of halophilic from non-halophilic enzymes are the higher content of acidic residues (Asp and Glu), and a lower content of lysine, aliphatic hydrophobic (Leu, Met and Ile) and polar (Asn) residues. The amino acid composition and 3-D structure analysis suggested that the high content of acidic residues (Asp and Glu, 12.2%) and low content of lysine residues (0.7%), as well as the excess of surface-exposed acidic residues might be responsible for the haloadaptation of Est56. Full article

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

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13 pages, 1877 KiB

Open AccessArticle

The Desmin (DES) Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy

by Olga Kulikova, Andreas Brodehl, Anna Kiseleva, Roman Myasnikov, Alexey Meshkov, Caroline Stanasiuk, Anna Gärtner, Mikhail Divashuk, Evgeniia Sotnikova, Sergey Koretskiy, Maria Kharlap, Viktoria Kozlova, Elena Mershina, Polina Pilus, Valentin Sinitsyn, Hendrik Milting, Sergey Boytsov and Oxana Drapkina

Genes 2021, 12(1), 121; https://doi.org/10.3390/genes12010121 - 19 Jan 2021

Cited by 28 | Viewed by 4499

Abstract

Here, we present a small Russian family, where the index patient received a diagnosis of left-ventricular non-compaction cardiomyopathy (LVNC) in combination with a skeletal myopathy. Clinical follow-up analysis revealed a LVNC phenotype also in her son. Therefore, we applied a broad next-generation sequencing [...] Read more.

Here, we present a small Russian family, where the index patient received a diagnosis of left-ventricular non-compaction cardiomyopathy (LVNC) in combination with a skeletal myopathy. Clinical follow-up analysis revealed a LVNC phenotype also in her son. Therefore, we applied a broad next-generation sequencing gene panel approach for the identification of the underlying mutation. Interestingly, DES-p.A337P was identified in the genomes of both patients, whereas only the index patient carried DSP-p.L1348X. DES encodes the muscle-specific intermediate filament protein desmin and DSP encodes desmoplakin, which is a cytolinker protein connecting desmosomes with the intermediate filaments. Because the majority of DES mutations cause severe filament assembly defects and because this mutation was found in both affected patients, we analyzed this DES mutation in vitro by cell transfection experiments in combination with confocal microscopy. Of note, desmin-p.A337P forms cytoplasmic aggregates in transfected SW-13 cells and in cardiomyocytes derived from induced pluripotent stem cells underlining its pathogenicity. In conclusion, we suggest including the DES gene in the genetic analysis for LVNC patients in the future, especially if clinical involvement of the skeletal muscle is present. Full article

(This article belongs to the Special Issue Cardiovascular Genetics)

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15 pages, 3672 KiB

Open AccessArticle

HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas

by Yiyun Sun, Dandan Xu, Chundong Zhang, Yitao Wang, Lian Zhang, Deqian Qiao, Youquan Bu and Ying Zhang

Genes 2021, 12(1), 120; https://doi.org/10.3390/genes12010120 - 19 Jan 2021

Cited by 7 | Viewed by 3183

Abstract

We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading [...] Read more.

We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remains obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from The Cancer Genome Atlas (TCGA) database using the correlation analysis of gene expression and gene set enrichment analysis (GSEA), which revealed that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited the Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected using RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2, and BUB1, was involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with the shorter overall survival of LSCC patients. Taken together, our results indicate that GLI1/2 mediates the expression of the PRR11-SKA2-centric gene set that serves as an unfavorable prognostic indicator for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC. Full article

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

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17 pages, 2947 KiB

Open AccessArticle

Overexpression of Activated AMPK in the Anopheles stephensi Midgut Impacts Mosquito Metabolism, Reproduction and Plasmodium Resistance

by Chioma Oringanje, Lillian R. Delacruz, Yunan Han, Shirley Luckhart and Michael A. Riehle

Genes 2021, 12(1), 119; https://doi.org/10.3390/genes12010119 - 19 Jan 2021

Cited by 9 | Viewed by 3970

Abstract

Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly [...] Read more.

Mitochondrial integrity and homeostasis in the midgut are key factors controlling mosquito fitness and anti-pathogen resistance. Targeting genes that regulate mitochondrial dynamics represents a potential strategy for limiting mosquito-borne diseases. AMP-activated protein kinase (AMPK) is a key cellular energy sensor found in nearly all eukaryotic cells. When activated, AMPK inhibits anabolic pathways that consume ATP and activates catabolic processes that synthesize ATP. In this study, we overexpressed a truncated and constitutively active α-subunit of AMPK under the control of the midgut-specific carboxypeptidase promotor in the midgut of female Anopheles stephensi. As expected, AMPK overexpression in homozygous transgenic mosquitoes was associated with changes in nutrient storage and metabolism, decreasing glycogen levels at 24 h post-blood feeding when transgene expression was maximal, and concurrently increasing circulating trehalose at the same time point. When transgenic lines were challenged with Plasmodium falciparum, we observed a significant decrease in the prevalence and intensity of infection relative to wild type controls. Surprisingly, we did not observe a significant difference in the survival of adult mosquitoes fed either sugar only or both sugar and bloodmeals throughout adult life. This may be due to the limited period that the transgene was activated before homeostasis was restored. However, we did observe a significant decrease in egg production, suggesting that manipulation of AMPK activity in the mosquito midgut resulted in the re-allocation of resources away from egg production. In summary, this work identifies midgut AMPK activity as an important regulator of metabolism, reproduction, and innate immunity in An. stephensi, a highly invasive and important malaria vector species. Full article

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

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3 pages, 191 KiB

Open AccessEditorial

Embryo Genetics

by Carmen Rubio and Carlos Simón

Genes 2021, 12(1), 118; https://doi.org/10.3390/genes12010118 - 19 Jan 2021

Cited by 5 | Viewed by 3285

Abstract

Advances in embryo and reproductive genetics have influenced clinical approaches to overcome infertility. Since the 1990s, many attempts have been made to decipher the genetic causes of infertility and to understand the role of chromosome aneuploidies in embryo potential. At the embryo stage, [...] Read more.

Advances in embryo and reproductive genetics have influenced clinical approaches to overcome infertility. Since the 1990s, many attempts have been made to decipher the genetic causes of infertility and to understand the role of chromosome aneuploidies in embryo potential. At the embryo stage, preimplantation genetic testing for chromosomal abnormalities and genetic disorders has offered many couples the opportunity to have healthy offspring. Recently, the application of new technologies has resulted in more comprehensive and accurate diagnoses of chromosomal abnormalities and genetic conditions to improve clinical outcome. In this Special Issue, we include a collection of reviews and original articles covering many aspects of embryo diagnosis, genome editing, and maternal–embryo cross-communication during the implantation process. Full article

(This article belongs to the Special Issue EmbryoGenetics)

15 pages, 2357 KiB

Open AccessArticle

Weighted Single-Step GWAS Identified Candidate Genes Associated with Growth Traits in a Duroc Pig Population

by Donglin Ruan, Zhanwei Zhuang, Rongrong Ding, Yibin Qiu, Shenping Zhou, Jie Wu, Cineng Xu, Linjun Hong, Sixiu Huang, Enqin Zheng, Gengyuan Cai, Zhenfang Wu and Jie Yang

Genes 2021, 12(1), 117; https://doi.org/10.3390/genes12010117 - 19 Jan 2021

Cited by 33 | Viewed by 4414

Abstract

Growth traits are important economic traits of pigs that are controlled by several major genes and multiple minor genes. To better understand the genetic architecture of growth traits, we performed a weighted single-step genome-wide association study (wssGWAS) to identify genomic regions and candidate [...] Read more.

Growth traits are important economic traits of pigs that are controlled by several major genes and multiple minor genes. To better understand the genetic architecture of growth traits, we performed a weighted single-step genome-wide association study (wssGWAS) to identify genomic regions and candidate genes that are associated with days to 100 kg (AGE), average daily gain (ADG), backfat thickness (BF) and lean meat percentage (LMP) in a Duroc pig population. In this study, 3945 individuals with phenotypic and genealogical information, of which 2084 pigs were genotyped with a 50 K single-nucleotide polymorphism (SNP) array, were used for association analyses. We found that the most significant regions explained 2.56–3.07% of genetic variance for four traits, and the detected significant regions (>1%) explained 17.07%, 18.59%, 23.87% and 21.94% for four traits. Finally, 21 genes that have been reported to be associated with metabolism, bone growth, and fat deposition were treated as candidate genes for growth traits in pigs. Moreover, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses implied that the identified genes took part in bone formation, the immune system, and digestion. In conclusion, such full use of phenotypic, genotypic, and genealogical information will accelerate the genetic improvement of growth traits in pigs. Full article

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

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11 pages, 1411 KiB

Open AccessArticle

Sex Chromosome Turnover in Bent-Toed Geckos (Cyrtodactylus)

by Shannon E. Keating, Madison Blumer, L. Lee Grismer, Aung Lin, Stuart V. Nielsen, Myint Kyaw Thura, Perry L. Wood, Jr., Evan S. H. Quah and Tony Gamble

Genes 2021, 12(1), 116; https://doi.org/10.3390/genes12010116 - 19 Jan 2021

Cited by 20 | Viewed by 4058

Abstract

Lizards and snakes (squamates) are known for their varied sex determining systems, and gecko lizards are especially diverse, having evolved sex chromosomes independently multiple times. While sex chromosomes frequently turnover among gecko genera, intrageneric turnovers are known only from Gekko and Hemidactylus. [...] Read more.

Lizards and snakes (squamates) are known for their varied sex determining systems, and gecko lizards are especially diverse, having evolved sex chromosomes independently multiple times. While sex chromosomes frequently turnover among gecko genera, intrageneric turnovers are known only from Gekko and Hemidactylus. Here, we used RADseq to identify sex-specific markers in two species of Burmese bent-toed geckos. We uncovered XX/XY sex chromosomes in Cyrtodactylus chaunghanakwaensis and ZZ/ZW sex chromosomes in Cyrtodactylus pharbaungensis. This is the third instance of intrageneric turnover of sex chromosomes in geckos. Additionally, Cyrtodactylus are closely related to another genus with intrageneric turnover, Hemidactylus. Together, these data suggest that sex chromosome turnover may be common in this clade, setting them apart as exceptionally diverse in a group already known for diverse sex determination systems. Full article

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

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14 pages, 1769 KiB

Open AccessArticle

Whole Genome Analysis of Environmental Pseudomonas mendocina Strains: Virulence Mechanisms and Phylogeny

by Lidia Ruiz-Roldán, María de Toro and Yolanda Sáenz

Genes 2021, 12(1), 115; https://doi.org/10.3390/genes12010115 - 19 Jan 2021

Cited by 3 | Viewed by 3386

Abstract

Pseudomonas mendocina is an environmental bacterium, rarely isolated in clinical specimens, although it has been described as producing endocarditis and sepsis. Little is known about its genome. Whole genome sequencing can be used to learn about the phylogeny, evolution, or pathogenicity of these [...] Read more.

Pseudomonas mendocina is an environmental bacterium, rarely isolated in clinical specimens, although it has been described as producing endocarditis and sepsis. Little is known about its genome. Whole genome sequencing can be used to learn about the phylogeny, evolution, or pathogenicity of these isolates. Thus, the aim of this study was to analyze the resistome, virulome, and phylogenetic relationship of two P. mendocina strains, Ps542 and Ps799, isolated from a healthy Anas platyrhynchos fecal sample and a lettuce, respectively. Among all of the small number of P.mendocina genomes available in the National Center for Biotechnology Information (NCBI) repository, both strains were placed within one of two well-defined phylogenetic clusters. Both P. mendocina strains lacked antimicrobial resistance genes, but the Ps799 genome showed a MOB_P3 family relaxase. Nevertheless, this study revealed that P. mendocina possesses an important number of virulence factors, including a leukotoxin, flagella, pili, and the Type 2 and Type 6 Secretion Systems, that could be responsible for their pathogenesis. More phenotypical and in vivo studies are needed to deepen the association with human infections and the potential P. mendocina pathogenicity. Full article

(This article belongs to the Special Issue Microbial Genomics and Evolution)

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14 pages, 4011 KiB

Open AccessArticle

Merging Genomics and Transcriptomics for Predicting Fusarium Head Blight Resistance in Wheat

by Sebastian Michel, Christian Wagner, Tetyana Nosenko, Barbara Steiner, Mina Samad-Zamini, Maria Buerstmayr, Klaus Mayer and Hermann Buerstmayr

Genes 2021, 12(1), 114; https://doi.org/10.3390/genes12010114 - 19 Jan 2021

Cited by 10 | Viewed by 4579

Abstract

Genomic selection with genome-wide distributed molecular markers has evolved into a well-implemented tool in many breeding programs during the last decade. The resistance against Fusarium head blight (FHB) in wheat is probably one of the most thoroughly studied systems within this framework. Aside [...] Read more.

Genomic selection with genome-wide distributed molecular markers has evolved into a well-implemented tool in many breeding programs during the last decade. The resistance against Fusarium head blight (FHB) in wheat is probably one of the most thoroughly studied systems within this framework. Aside from the genome, other biological strata like the transcriptome have likewise shown some potential in predictive breeding strategies but have not yet been investigated for the FHB-wheat pathosystem. The aims of this study were thus to compare the potential of genomic with transcriptomic prediction, and to assess the merit of blending incomplete transcriptomic with complete genomic data by the single-step method. A substantial advantage of gene expression data over molecular markers has been observed for the prediction of FHB resistance in the studied diversity panel of breeding lines and released cultivars. An increase in prediction ability was likewise found for the single-step predictions, although this can mostly be attributed to an increased accuracy among the RNA-sequenced genotypes. The usage of transcriptomics can thus be seen as a complement to already established predictive breeding pipelines with pedigree and genomic data, particularly when more cost-efficient multiplexing techniques for RNA-sequencing will become more accessible in the future. Full article

(This article belongs to the Special Issue Quantitative Genetics and Genomics to Accelerate Plant Breeding Research)

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12 pages, 1203 KiB

Open AccessArticle

Morphological Abnormalities and Gene Expression Changes Caused by High Incubation Temperatures in Zebrafish Xenografts with Human Cancer Cells

by Pablo Cabezas-Sainz, Carlos Coppel, Alba Pensado-López, Pedro Fernandez, Laura Muinelo-Romay, Rafael López-López, Juan A. Rubiolo and Laura Sánchez

Genes 2021, 12(1), 113; https://doi.org/10.3390/genes12010113 - 19 Jan 2021

Cited by 6 | Viewed by 2995

Abstract

Published studies show that most of the human cancer xenograft studies in zebrafish embryos have used incubation temperatures in the range of 32–34 °C for 3–6 days post-injection, trying to find a compromise temperature between the zebrafish embryos (28 °C) and the human [...] Read more.

Published studies show that most of the human cancer xenograft studies in zebrafish embryos have used incubation temperatures in the range of 32–34 °C for 3–6 days post-injection, trying to find a compromise temperature between the zebrafish embryos (28 °C) and the human injected cells (37 °C). While this experimental setup is widely used, a question remains: is possible to overcome the drawbacks caused by a suboptimal temperature for the injected cells? To clarify the effect of temperature and injected cells on the host, in this study, we analyzed the development and health of the last in response to different temperatures in the presence or absence of injected human cancer cells. Comparing different incubation temperatures (28, 34 and 36 °C), we determined morphological abnormalities and developmental effects in injected and non-injected embryos at different time points. Besides this, the expression of selected genes was determined by qPCR to determine temperature affected metabolic processes in the embryos. The results indicate that an incubation temperature of 36 °C during a period of 48 h is suitable for xenotransplantation without morphological or metabolic changes that could be affecting the host or the injected cells, allowing them to proliferate near their optimal temperature. Full article

(This article belongs to the Special Issue Zebrafish Animal Models)

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21 pages, 1078 KiB

Open AccessReview

Hereditary Optic Neuropathies: Induced Pluripotent Stem Cell-Based 2D/3D Approaches

by Marta García-López, Joaquín Arenas and M. Esther Gallardo

Genes 2021, 12(1), 112; https://doi.org/10.3390/genes12010112 - 18 Jan 2021

Cited by 6 | Viewed by 3924

Abstract

Inherited optic neuropathies share visual impairment due to the degeneration of retinal ganglion cells (RGCs) as the hallmark of the disease. This group of genetic disorders are caused by mutations in nuclear genes or in the mitochondrial DNA (mtDNA). An impaired mitochondrial function [...] Read more.

Inherited optic neuropathies share visual impairment due to the degeneration of retinal ganglion cells (RGCs) as the hallmark of the disease. This group of genetic disorders are caused by mutations in nuclear genes or in the mitochondrial DNA (mtDNA). An impaired mitochondrial function is the underlying mechanism of these diseases. Currently, optic neuropathies lack an effective treatment, and the implementation of induced pluripotent stem cell (iPSC) technology would entail a huge step forward. The generation of iPSC-derived RGCs would allow faithfully modeling these disorders, and these RGCs would represent an appealing platform for drug screening as well, paving the way for a proper therapy. Here, we review the ongoing two-dimensional (2D) and three-dimensional (3D) approaches based on iPSCs and their applications, taking into account the more innovative technologies, which include tissue engineering or microfluidics. Full article

(This article belongs to the Special Issue Application Status and Development Prospects of Stem Cells)

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26 pages, 10369 KiB

Open AccessArticle

Defining the Rhizobium leguminosarum Species Complex

by J. Peter W. Young, Sara Moeskjær, Alexey Afonin, Praveen Rahi, Marta Maluk, Euan K. James, Maria Izabel A. Cavassim, M. Harun-or Rashid, Aregu Amsalu Aserse, Benjamin J. Perry, En Tao Wang, Encarna Velázquez, Evgeny E. Andronov, Anastasia Tampakaki, José David Flores Félix, Raúl Rivas González, Sameh H. Youseif, Marc Lepetit, Stéphane Boivin, Beatriz Jorrin, Gregory J. Kenicer, Álvaro Peix, Michael F. Hynes, Martha Helena Ramírez-Bahena, Arvind Gulati and Chang-Fu Tian Show full author list Hide full author list

Genes 2021, 12(1), 111; https://doi.org/10.3390/genes12010111 - 18 Jan 2021

Cited by 57 | Viewed by 10474

Abstract

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show [...] Read more.

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show that the Rlc is a distinct entity, well separated from other species in the genus. Its sister taxon is R. anhuiense. We constructed a phylogeny based on concatenated sequences of 120 universal (core) genes, and calculated pairwise average nucleotide identity (ANI) between all genomes. From these analyses, we concluded that the Rlc includes 18 distinct genospecies, plus 7 unique strains that are not placed in these genospecies. Each genospecies is separated by a distinct gap in ANI values, usually at approximately 96% ANI, implying that it is a ‘natural’ unit. Five of the genospecies include the type strains of named species: R. laguerreae, R. sophorae, R. ruizarguesonis, “R. indicum” and R. leguminosarum itself. The 16S ribosomal RNA sequence is remarkably diverse within the Rlc, but does not distinguish the genospecies. Partial sequences of housekeeping genes, which have frequently been used to characterize isolate collections, can mostly be assigned unambiguously to a genospecies, but alleles within a genospecies do not always form a clade, so single genes are not a reliable guide to the true phylogeny of the strains. We conclude that access to a large number of genome sequences is a powerful tool for characterizing the diversity of bacteria, and that taxonomic conclusions should be based on all available genome sequences, not just those of type strains. Full article

(This article belongs to the Special Issue Genes at Ten)

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28 pages, 3643 KiB

Open AccessArticle

Dissecting the Polygenic Basis of Cold Adaptation Using Genome-Wide Association of Traits and Environmental Data in Douglas-fir

by Amanda R. De La Torre, Benjamin Wilhite, Daniela Puiu, John Bradley St. Clair, Marc W. Crepeau, Steven L. Salzberg, Charles H. Langley, Brian Allen and David B. Neale

Genes 2021, 12(1), 110; https://doi.org/10.3390/genes12010110 - 18 Jan 2021

Cited by 19 | Viewed by 5849

Abstract

Understanding the genomic and environmental basis of cold adaptation is key to understand how plants survive and adapt to different environmental conditions across their natural range. Univariate and multivariate genome-wide association (GWAS) and genotype-environment association (GEA) analyses were used to test associations among [...] Read more.

Understanding the genomic and environmental basis of cold adaptation is key to understand how plants survive and adapt to different environmental conditions across their natural range. Univariate and multivariate genome-wide association (GWAS) and genotype-environment association (GEA) analyses were used to test associations among genome-wide SNPs obtained from whole-genome resequencing, measures of growth, phenology, emergence, cold hardiness, and range-wide environmental variation in coastal Douglas-fir (Pseudotsuga menziesii). Results suggest a complex genomic architecture of cold adaptation, in which traits are either highly polygenic or controlled by both large and small effect genes. Newly discovered associations for cold adaptation in Douglas-fir included 130 genes involved in many important biological functions such as primary and secondary metabolism, growth and reproductive development, transcription regulation, stress and signaling, and DNA processes. These genes were related to growth, phenology and cold hardiness and strongly depend on variation in environmental variables such degree days below 0c, precipitation, elevation and distance from the coast. This study is a step forward in our understanding of the complex interconnection between environment and genomics and their role in cold-associated trait variation in boreal tree species, providing a baseline for the species’ predictions under climate change. Full article

(This article belongs to the Special Issue Genome Diversity of Adaptation and Speciation)

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11 pages, 2243 KiB

Open AccessArticle

Litter Size of Sheep (Ovis aries): Inbreeding Depression and Homozygous Regions

by Lin Tao, Xiaoyun He, Xiangyu Wang, Ran Di and Mingxing Chu

Genes 2021, 12(1), 109; https://doi.org/10.3390/genes12010109 - 18 Jan 2021

Cited by 10 | Viewed by 3912

Abstract

Ovine litter size (LS) is an important trait showing variability within breeds. It remains largely unknown whether inbreeding depression on LS exists based on genomic homozygous regions, and whether the homozygous regions resulted from inbreeding are significantly associated with LS in sheep. We [...] Read more.

Ovine litter size (LS) is an important trait showing variability within breeds. It remains largely unknown whether inbreeding depression on LS exists based on genomic homozygous regions, and whether the homozygous regions resulted from inbreeding are significantly associated with LS in sheep. We here reanalyze a set of single nucleotide polymorphism (SNP) chip of six breeds to characterize the patterns of runs of homozygosity (ROH), to evaluate inbreeding levels and inbreeding depressions on LS, and to identify candidate homozygous regions responsible for LS. Consequently, unique ROH patterns were observed among six sheep populations. Inbreeding depression on LS was only found in Hu sheep, where a significant reduction of 0.016, 0.02, and 0.02 per 1% elevated inbreeding F_ROH4–8, F_ROH_>₈ and the total inbreeding measure was observed, respectively. Nine significantly homozygous regions were found for LS in Hu sheep, where some promising genes for LS possibly via regulation of the development of oocytes (NGF, AKT1, and SYCP1), fertilization (SPAG17, MORC1, TDRD9, ZFYVE21, ADGRB3, and CKB), embryo implantation (PPP1R13B, INF2, and VANGL1) and development (DPPA2, DPPA4, CDCA4, CSDE1, and ADSSL1), and reproductive health (NRG3, BAG5, CKB, and XRCC3) were identified. These results from the present study would provide insights into the genetic management and complementary understandings of LS in sheep. Full article

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

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21 pages, 1724 KiB

Open AccessReview

Suprabasin—A Review

by Miroslav Pribyl, Zdenek Hodny and Iva Kubikova

Genes 2021, 12(1), 108; https://doi.org/10.3390/genes12010108 - 18 Jan 2021

Cited by 19 | Viewed by 3439

Abstract

Among the ~22,000 human genes, very few remain that have unknown functions. One such example is suprabasin (SBSN). Originally described as a component of the cornified envelope, the function of stratified epithelia-expressed SBSN is unknown. Both the lack of knowledge about [...] Read more.

Among the ~22,000 human genes, very few remain that have unknown functions. One such example is suprabasin (SBSN). Originally described as a component of the cornified envelope, the function of stratified epithelia-expressed SBSN is unknown. Both the lack of knowledge about the gene role under physiological conditions and the emerging link of SBSN to various human diseases, including cancer, attract research interest. The association of SBSN expression with poor prognosis of patients suffering from oesophageal carcinoma, glioblastoma multiforme, and myelodysplastic syndromes suggests that SBSN may play a role in human tumourigenesis. Three SBSN isoforms code for the secreted proteins with putative function as signalling molecules, yet with poorly described effects. In this first review about SBSN, we summarised the current knowledge accumulated since its original description, and we discuss the potential mechanisms and roles of SBSN in both physiology and pathology. Full article

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

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18 pages, 1559 KiB

Open AccessArticle

Patterns of Epigenetic Diversity in Two Sympatric Fish Species: Genetic vs. Environmental Determinants

by Laura Fargeot, Géraldine Loot, Jérôme G. Prunier, Olivier Rey, Charlotte Veyssière and Simon Blanchet

Genes 2021, 12(1), 107; https://doi.org/10.3390/genes12010107 - 16 Jan 2021

Cited by 10 | Viewed by 4255

Abstract

Epigenetic components are hypothesized to be sensitive to the environment, which should permit species to adapt to environmental changes. In wild populations, epigenetic variation should therefore be mainly driven by environmental variation. Here, we tested whether epigenetic variation (DNA methylation) observed in wild [...] Read more.

Epigenetic components are hypothesized to be sensitive to the environment, which should permit species to adapt to environmental changes. In wild populations, epigenetic variation should therefore be mainly driven by environmental variation. Here, we tested whether epigenetic variation (DNA methylation) observed in wild populations is related to their genetic background, and/or to the local environment. Focusing on two sympatric freshwater fish species (Gobio occitaniae and Phoxinus phoxinus), we tested the relationships between epigenetic differentiation, genetic differentiation (using microsatellite and single nucleotide polymorphism (SNP) markers), and environmental distances between sites. We identify positive relationships between pairwise genetic and epigenetic distances in both species. Moreover, epigenetic marks better discriminated populations than genetic markers, especially in G. occitaniae. In G. occitaniae, both pairwise epigenetic and genetic distances were significantly associated to environmental distances between sites. Nonetheless, when controlling for genetic differentiation, the link between epigenetic differentiation and environmental distances was not significant anymore, indicating a noncausal relationship. Our results suggest that fish epigenetic variation is mainly genetically determined and that the environment weakly contributed to epigenetic variation. We advocate the need to control for the genetic background of populations when inferring causal links between epigenetic variation and environmental heterogeneity in wild populations. Full article

(This article belongs to the Special Issue Evolutionary Dynamics of Wild Populations)

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18 pages, 1902 KiB

Open AccessArticle

Real-Time Culture-Independent Microbial Profiling Onboard the International Space Station Using Nanopore Sequencing

by Sarah Stahl-Rommel, Miten Jain, Hang N. Nguyen, Richard R. Arnold, Serena M. Aunon-Chancellor, Gretta Marie Sharp, Christian L. Castro, Kristen K. John, Sissel Juul, Daniel J. Turner, David Stoddart, Benedict Paten, Mark Akeson, Aaron S. Burton and Sarah L. Castro-Wallace

Genes 2021, 12(1), 106; https://doi.org/10.3390/genes12010106 - 16 Jan 2021

Cited by 45 | Viewed by 10862

Abstract

For the past two decades, microbial monitoring of the International Space Station (ISS) has relied on culture-dependent methods that require return to Earth for analysis. This has a number of limitations, with the most significant being bias towards the detection of culturable organisms [...] Read more.

For the past two decades, microbial monitoring of the International Space Station (ISS) has relied on culture-dependent methods that require return to Earth for analysis. This has a number of limitations, with the most significant being bias towards the detection of culturable organisms and the inherent delay between sample collection and ground-based analysis. In recent years, portable and easy-to-use molecular-based tools, such as Oxford Nanopore Technologies’ MinION™ sequencer and miniPCR bio’s miniPCR™ thermal cycler, have been validated onboard the ISS. Here, we report on the development, validation, and implementation of a swab-to-sequencer method that provides a culture-independent solution to real-time microbial profiling onboard the ISS. Method development focused on analysis of swabs collected in a low-biomass environment with limited facility resources and stringent controls on allowed processes and reagents. ISS-optimized procedures included enzymatic DNA extraction from a swab tip, bead-based purifications, altered buffers, and the use of miniPCR and the MinION. Validation was conducted through extensive ground-based assessments comparing current standard culture-dependent and newly developed culture-independent methods. Similar microbial distributions were observed between the two methods; however, as expected, the culture-independent data revealed microbial profiles with greater diversity. Protocol optimization and verification was established during NASA Extreme Environment Mission Operations (NEEMO) analog missions 21 and 22, respectively. Unique microbial profiles obtained from analog testing validated the swab-to-sequencer method in an extreme environment. Finally, four independent swab-to-sequencer experiments were conducted onboard the ISS by two crewmembers. Microorganisms identified from ISS swabs were consistent with historical culture-based data, and primarily consisted of commonly observed human-associated microbes. This simplified method has been streamlined for high ease-of-use for a non-trained crew to complete in an extreme environment, thereby enabling environmental and human health diagnostics in real-time as future missions take us beyond low-Earth orbit. Full article

(This article belongs to the Special Issue MetaGenomics Sequencing In Situ)

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21 pages, 3149 KiB

Open AccessArticle

An 8.22 Mb Assembly and Annotation of the Alpaca (Vicugna pacos) Y Chromosome

by Matthew J. Jevit, Brian W. Davis, Caitlin Castaneda, Andrew Hillhouse, Rytis Juras, Vladimir A. Trifonov, Ahmed Tibary, Jorge C. Pereira, Malcolm A. Ferguson-Smith and Terje Raudsepp

Genes 2021, 12(1), 105; https://doi.org/10.3390/genes12010105 - 16 Jan 2021

Cited by 3 | Viewed by 4221

Abstract

The unique evolutionary dynamics and complex structure make the Y chromosome the most diverse and least understood region in the mammalian genome, despite its undisputable role in sex determination, development, and male fertility. Here we present the first contig-level annotated draft assembly for [...] Read more.

The unique evolutionary dynamics and complex structure make the Y chromosome the most diverse and least understood region in the mammalian genome, despite its undisputable role in sex determination, development, and male fertility. Here we present the first contig-level annotated draft assembly for the alpaca (Vicugna pacos) Y chromosome based on hybrid assembly of short- and long-read sequence data of flow-sorted Y. The latter was also used for cDNA selection providing Y-enriched testis transcriptome for annotation. The final assembly of 8.22 Mb comprised 4.5 Mb of male specific Y (MSY) and 3.7 Mb of the pseudoautosomal region. In MSY, we annotated 15 X-degenerate genes and two novel transcripts, but no transposed sequences. Two MSY genes, HSFY and RBMY, are multicopy. The pseudoautosomal boundary is located between SHROOM2 and HSFY. Comparative analysis shows that the small and cytogenetically distinct alpaca Y shares most of MSY sequences with the larger dromedary and Bactrian camel Y chromosomes. Most of alpaca X-degenerate genes are also shared with other mammalian MSYs, though WWC3Y is Y-specific only in alpaca/camels and the horse. The partial alpaca Y assembly is a starting point for further expansion and will have applications in the study of camelid populations and male biology. Full article

(This article belongs to the Special Issue Camelid Genomics)

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15 pages, 1767 KiB

Open AccessArticle

Genetic Admixture in the Population of Wild Apple (Malus sieversii) from the Tien Shan Mountains, Kazakhstan

by Young-Ho Ha, Seung-Hwan Oh and Soo-Rang Lee

Genes 2021, 12(1), 104; https://doi.org/10.3390/genes12010104 - 15 Jan 2021

Cited by 17 | Viewed by 3713

Abstract

There is growing attention given to gene flow between crops and the wild relatives as global landscapes have been rapidly converted into agricultural farm fields over the past century. Crop-to-wild introgression may advance the extinction risks of rare plants through demographic swamping and/or [...] Read more.

There is growing attention given to gene flow between crops and the wild relatives as global landscapes have been rapidly converted into agricultural farm fields over the past century. Crop-to-wild introgression may advance the extinction risks of rare plants through demographic swamping and/or genetic swamping. Malus sieversii, the progenitor of the apple, is exclusively distributed along the Tien Shan mountains. Habitat fragmentation and hybridization between M. sieversii and the cultivated apples have been proposed to be the causal mechanism of the accelerated extinction risk. We examined the genetic diversity pattern of eleven wild and domesticated apple populations and assessed the gene flow between M. sieversii and the cultivated apples in Kazakhstan using thirteen nuclear microsatellite loci. On average, apple populations harbored fairly high within-population diversity, whereas population divergences were very low suggesting likely influence of human-mediated dispersal. Assignment results showed a split pattern between the cultivated and wild apples and frequent admixture among the apple populations. Coupled with the inflated contemporary migration rates, the admixture pattern might be the signature of increased human intervention within the recent past. Our study highlighted the prevalent crop to wild gene flow of apples occurring in Kazakhstan, proposing an accelerated risk of genetic swamping. Full article

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

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14 pages, 1700 KiB

Open AccessReview

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

by Timothy F. Spracklen, Graham Chakafana, Peter J. Schwartz, Maria-Christina Kotta, Gasnat Shaboodien, Ntobeko A. B. Ntusi and Karen Sliwa

Genes 2021, 12(1), 103; https://doi.org/10.3390/genes12010103 - 15 Jan 2021

Cited by 20 | Viewed by 6276

Abstract

Peripartum cardiomyopathy (PPCM) is a condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. Over the last decade, genetic advances in heritable cardiomyopathy have provided new insights into the role of genetics in PPCM. In [...] Read more.

Peripartum cardiomyopathy (PPCM) is a condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. Over the last decade, genetic advances in heritable cardiomyopathy have provided new insights into the role of genetics in PPCM. In this review, we summarise current knowledge of the genetics of PPCM and potential avenues for further research, including the role of molecular chaperone mutations in PPCM. Evidence supporting a genetic basis for PPCM has emanated from observations of familial disease, overlap with familial dilated cardiomyopathy, and sequencing studies of PPCM cohorts. Approximately 20% of PPCM patients screened for cardiomyopathy genes have an identified pathogenic mutation, with TTN truncations most commonly implicated. As a stress-associated condition, PPCM may be modulated by molecular chaperones such as heat shock proteins (Hsps). Recent studies have led to the identification of Hsp mutations in a PPCM model, suggesting that variation in these stress-response genes may contribute to PPCM pathogenesis. Although some Hsp genes have been implicated in dilated cardiomyopathy, their roles in PPCM remain to be determined. Additional areas of future investigation may include the delineation of genotype-phenotype correlations and the screening of newly-identified cardiomyopathy genes for their roles in PPCM. Nevertheless, these findings suggest that the construction of a family history may be advised in the management of PPCM and that genetic testing should be considered. A better understanding of the genetics of PPCM holds the potential to improve treatment, prognosis, and family management. Full article

(This article belongs to the Special Issue Cardiovascular Genetics)

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11 pages, 2682 KiB

Open AccessArticle

Overexpression of a Pak Choi Gene, BcAS2, Causes Leaf Curvature in Arabidopsis thaliana

by Ye Lin, Hualan Hou, Yuhang Zhang and Xilin Hou

Genes 2021, 12(1), 102; https://doi.org/10.3390/genes12010102 - 15 Jan 2021

Cited by 8 | Viewed by 2833

Abstract

The LBD (Lateral Organ Boundaries Domain) family are a new group of plant-specific genes, which encode a class of transcription factors containing conserved Lateral Organization Boundary (LOB) domains, and play an important role in regulating the adaxial–abaxial polarity of plant leaves. In Arabidopsis [...] Read more.

The LBD (Lateral Organ Boundaries Domain) family are a new group of plant-specific genes, which encode a class of transcription factors containing conserved Lateral Organization Boundary (LOB) domains, and play an important role in regulating the adaxial–abaxial polarity of plant leaves. In Arabidopsis thaliana, ASYMMETRIC LEAVES 2 (AS2) has a typical LOB domain and is involved in determining the adaxial cell fate. In this study, we isolated the BcAS2 gene from the pak choi cultivar “NHCC001”, and analyzed its expression pattern. The results showed that the BcAS2 encoded a protein made up of 202 amino acid residues which were located in the nucleus and cytomembrane. The Yeast two-hybrid system (Y2H) assay indicated that BcAS2 interacts with BcAS1-1 and BcAS1-2 (the homologous genes of AS1 gene in pak choi). In the transgenic Arabidopsis thaliana that overexpressed BcAS2 gene, it presented an abnormal phenotype with a curly shape. Taken together, our findings not only validate the function of BcAS2 in leaf development in Arabidopsis thaliana, but also contribute in unravelling the molecular regulatory mechanism of BcAS2, which fulfills a special role by forming complexes with BcAS1-1/2 in the establishment of the adaxial–abaxial polarity of the lateral organs in pak choi. Full article

(This article belongs to the Special Issue Genetic Research and Plant Breeding)

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14 pages, 2317 KiB

Open AccessArticle

WNT-FRIZZLED-LRP5/6 Signaling Mediates Posterior Fate and Proliferation during Planarian Regeneration

by Eudald Pascual-Carreras, Miquel Sureda-Gómez, Ramon Barrull-Mascaró, Natàlia Jordà, Maria Gelabert, Pablo Coronel-Córdoba, Emili Saló and Teresa Adell

Genes 2021, 12(1), 101; https://doi.org/10.3390/genes12010101 - 15 Jan 2021

Cited by 8 | Viewed by 4167

Abstract

An organizer is defined as a group of cells that secrete extracellular proteins that specify the fate of surrounding cells according to their concentration. Their function during embryogenesis is key in patterning new growing tissues. Although organizers should also participate in adult development [...] Read more.

An organizer is defined as a group of cells that secrete extracellular proteins that specify the fate of surrounding cells according to their concentration. Their function during embryogenesis is key in patterning new growing tissues. Although organizers should also participate in adult development when new structures are regenerated, their presence in adults has only been identified in a few species with striking regenerative abilities, such as planarians. Planarians provide a unique model to understand the function of adult organizers, since the presence of adult pluripotent stem cells provides them with the ability to regenerate any body part. Previous studies have shown that the differential activation of the WNT/β-catenin signal in each wound is fundamental to establish an anterior or a posterior organizer in the corresponding wound. Here, we identify the receptors that mediate the WNT/β-catenin signal in posterior-facing wounds. We found that Wnt1-Fzd1-LRP5/6 signaling is evolutionarily conserved in executing a WNT/β-catenin signal to specify cell fate and to trigger a proliferative response. Our data allow a better understanding of the mechanism through which organizers signal to a “competent” field of cells and integrate the patterning and growth required during de novo formation of organs and tissues. Full article

(This article belongs to the Special Issue The Evolution of Invertebrate Animals)

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11 pages, 2374 KiB

Open AccessArticle

Systematic Identification and Analysis of Circular RNAs of Japanese Flounder (Paralichthys olivaceus) in Response to Vibrio anguillarum Infection

by Xianhui Ning and Li Sun

Genes 2021, 12(1), 100; https://doi.org/10.3390/genes12010100 - 15 Jan 2021

Cited by 9 | Viewed by 2227

Abstract

Circular RNA (circRNA) is a new class of non-coding RNA that is structured into a closed loop without polyadenylation. Recent studies showed that circRNAs are involved in the host immune response to pathogen infection. Japanese flounder (Paralichthys olivaceus), an important economical [...] Read more.

Circular RNA (circRNA) is a new class of non-coding RNA that is structured into a closed loop without polyadenylation. Recent studies showed that circRNAs are involved in the host immune response to pathogen infection. Japanese flounder (Paralichthys olivaceus), an important economical marine fish cultured in north Asia, is affected by Vibrio anguillarum, a pathogenic bacterium that can infect a large number of fish. In this study, we systematically explored the circRNAs in the spleen of V. anguillarum-infected flounder at different infection time points. A total of 6581 circRNAs were identified, 148 of which showed differential expression patterns after V. anguillarum infection and were named DEcirs. Most of the DEcirs were strongly time-specific. The parental genes of the DEcirs were identified and functionally classified into diverse pathways, including immune-related pathways. Among the immune-related DEcirs, seven were predicted to sponge 18 targeted miRNAs that were differentially expressed during V. anguillarum infection (named DETmiRs). Further analysis showed that the DEcirs and their corresponding DETmiRs intertwined into complicated immune related networks. These results indicate that in flounder, circRNAs are regulated by V. anguillarum and form interactive networks with mRNAs and miRNAs that likely play important roles in the immune defense against pathogen infection. Full article

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

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13 pages, 6726 KiB

Open AccessArticle

Inhibition of the Lipid Droplet–Peroxisome Proliferator-Activated Receptor α Axis Suppresses Cancer Stem Cell Properties

by Kenta Kuramoto, Masahiro Yamamoto, Shuhei Suzuki, Keita Togashi, Tomomi Sanomachi, Chifumi Kitanaka and Masashi Okada

Genes 2021, 12(1), 99; https://doi.org/10.3390/genes12010099 - 14 Jan 2021

Cited by 28 | Viewed by 3676

Abstract

Cancer stem cells (CSCs), having both self-renewal and tumorigenic capacity, utilize an energy metabolism system different from that of non-CSCs. Lipid droplets (LDs) are organelles that store neutral lipids, including triacylglycerol. Previous studies demonstrated that LDs are formed and store lipids as an [...] Read more.

Cancer stem cells (CSCs), having both self-renewal and tumorigenic capacity, utilize an energy metabolism system different from that of non-CSCs. Lipid droplets (LDs) are organelles that store neutral lipids, including triacylglycerol. Previous studies demonstrated that LDs are formed and store lipids as an energy source in some CSCs. LDs play central roles not only in lipid storage, but also as a source of endogenous lipid ligands, which are involved in numerous signaling pathways, including the peroxisome proliferator-activated receptor (PPAR) signaling pathway. However, it remains unclear whether LD-derived signal transduction is involved in the maintenance of the properties of CSCs. We investigated the roles of LDs in cancer stemness using pancreatic and colorectal CSCs and isogenic non-CSCs. PPARα was activated in CSCs in which LDs accumulated, but not in non-CSCs, and pharmacological and genetic inhibition of PPARα suppressed cancer stemness. In addition, inhibition of both re-esterification and lipolysis pathways suppressed cancer stemness. Our study suggested that LD metabolic turnover accompanying PPARα activation is a promising anti-CSC therapeutic target. Full article

(This article belongs to the Special Issue Molecular Oncology–Unmask the True Nature of Cancer)

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14 pages, 2181 KiB

Open AccessArticle

Metagenome Analysis of a Hydrocarbon-Degrading Bacterial Consortium Reveals the Specific Roles of BTEX Biodegraders

by Michael O. Eze

Genes 2021, 12(1), 98; https://doi.org/10.3390/genes12010098 - 14 Jan 2021

Cited by 25 | Viewed by 4634

Abstract

Environmental contamination by petroleum hydrocarbons is of concern due to the carcinogenicity and neurotoxicity of these compounds. Successful bioremediation of organic contaminants requires bacterial populations with degradative capacity for these contaminants. Through successive enrichment of microorganisms from a petroleum-contaminated soil using diesel fuel [...] Read more.

Environmental contamination by petroleum hydrocarbons is of concern due to the carcinogenicity and neurotoxicity of these compounds. Successful bioremediation of organic contaminants requires bacterial populations with degradative capacity for these contaminants. Through successive enrichment of microorganisms from a petroleum-contaminated soil using diesel fuel as the sole carbon and energy source, we successfully isolated a bacterial consortium that can degrade diesel fuel hydrocarbons. Metagenome analysis revealed the specific roles of different microbial populations involved in the degradation of benzene, toluene, ethylbenzene and xylene (BTEX), and the metabolic pathways involved in these reactions. One hundred and five putative coding DNA sequences were identified as responsible for both the activation of BTEX and central metabolism (ring-cleavage) of catechol and alkylcatechols during BTEX degradation. The majority of the Coding DNA sequences (CDSs) were affiliated to Acidocella, which was also the dominant bacterial genus in the consortium. The inoculation of diesel fuel contaminated soils with the consortium resulted in approximately 70% hydrocarbon biodegradation, indicating the potential of the consortium for environmental remediation of petroleum hydrocarbons. Full article

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10 pages, 1438 KiB

Open AccessArticle

Sequencing Red Fox Y Chromosome Fragments to Develop Phylogenetically Informative SNP Markers and Glimpse Male-Specific Trans-Pacific Phylogeography

by Benjamin N. Sacks, Zachary T. Lounsberry, Halie M. Rando, Kristopher Kluepfel, Steven R. Fain, Sarah K. Brown and Anna V. Kukekova

Genes 2021, 12(1), 97; https://doi.org/10.3390/genes12010097 - 14 Jan 2021

Cited by 3 | Viewed by 2770

Abstract

The red fox (Vulpes vulpes) has a wide global distribution with many ecotypes and has been bred in captivity for various traits, making it a useful evolutionary model system. The Y chromosome represents one of the most informative markers of phylogeography, [...] Read more.

The red fox (Vulpes vulpes) has a wide global distribution with many ecotypes and has been bred in captivity for various traits, making it a useful evolutionary model system. The Y chromosome represents one of the most informative markers of phylogeography, yet it has not been well-studied in the red fox due to a lack of the necessary genomic resources. We used a target capture approach to sequence a portion of the red fox Y chromosome in a geographically diverse red fox sample, along with other canid species, to develop single nucleotide polymorphism (SNP) markers, 13 of which we validated for use in subsequent studies. Phylogenetic analyses of the Y chromosome sequences, including calibration to outgroups, confirmed previous estimates of the timing of two intercontinental exchanges of red foxes, the initial colonization of North America from Eurasia approximately half a million years ago and a subsequent continental exchange before the last Pleistocene glaciation (~100,000 years ago). However, in contrast to mtDNA, which showed unidirectional transfer from Eurasia to North America prior to the last glaciation, the Y chromosome appears to have been transferred from North America to Eurasia during this period. Additional sampling is needed to confirm this pattern and to further clarify red fox Y chromosome phylogeography. Full article

(This article belongs to the Collection Tools for Population and Evolutionary Genetics)

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4 pages, 174 KiB

Open AccessEditorial

Emerging Trends in Deciphering the Pathogenesis of Human Diseases through Genetic Analysis

by David Q.-H. Wang

Genes 2021, 12(1), 96; https://doi.org/10.3390/genes12010096 - 13 Jan 2021

Cited by 2 | Viewed by 1934

Abstract

Any changes in gene expression or protein functions can cause abnormal anatomical, physiological, biochemical, and behavioral modifications in human beings, which can lead to disease [...] Full article

(This article belongs to the Special Issue Selected Papers From the Advanced Genetics Conference 2019)

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