Genes

18 pages, 4646 KiB

Open AccessArticle

BPA and BPS Affect Connexin 37 in Bovine Cumulus Cells

by Reem Sabry, Charlotte Apps, Jaqueline A. Reiter-Saunders, Angela C. Saleh, Sumetha Balachandran, Elizabeth J. St. John and Laura A. Favetta

Genes 2021, 12(2), 321; https://doi.org/10.3390/genes12020321 - 23 Feb 2021

Cited by 11 | Viewed by 2779

Abstract

Bisphenol S (BPS) is used as an alternative plasticizer to Bisphenol A (BPA), despite limited knowledge of potential adverse effects. BPA exhibits endocrine disrupting effects during development. This article focuses on the impact of bisphenols during oocyte maturation. Connexins (Cx) are gap junctional [...] Read more.

Bisphenol S (BPS) is used as an alternative plasticizer to Bisphenol A (BPA), despite limited knowledge of potential adverse effects. BPA exhibits endocrine disrupting effects during development. This article focuses on the impact of bisphenols during oocyte maturation. Connexins (Cx) are gap junctional proteins that may be affected by bisphenols, providing insight into their mechanism during development. Cxs 37 and 43 are crucial in facilitating cell communication between cumulus cells and oocytes. Cumulus-oocyte complexes (COCs), denuded oocytes, and cumulus cells were exposed to 0.05 mg/mL BPA or BPS for 24 h. Both compounds had no effect on Cx43. Cumulus cells exhibited a significant increase in Cx37 expression following BPA (p = 0.001) and BPS (p = 0.017) exposure. COCs treated with BPA had increased Cx37 protein expression, whilst BPS showed no effects, suggesting BPA and BPS act through different mechanisms. Experiments conducted in in vitro cultured cumulus cells, obtained by stripping germinal vesicle oocytes, showed significantly increased expression of Cx37 in BPA, but not the BPS, treated group. BPA significantly increased Cx37 protein expression, while BPS did not. Disrupted Cx37 following BPA exposure provides an indication of possible effects of bisphenols on connexins during the early stages of development. Full article

(This article belongs to the Special Issue Early Embryo Development in Livestock)

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10 pages, 1230 KiB

Open AccessBrief Report

Differential Expression of BARD1 Isoforms in Melanoma

by Lorissa I. McDougall, Ryan M. Powell, Magdalena Ratajska, Chi F. Lynch-Sutherland, Sultana Mehbuba Hossain, George A. R. Wiggins, Agnieszka Harazin-Lechowska, Bożena Cybulska-Stopa, Jyoti Motwani, Erin C. Macaulay, Glen Reid, Logan C. Walker, Janusz Ryś and Michael R. Eccles

Genes 2021, 12(2), 320; https://doi.org/10.3390/genes12020320 - 23 Feb 2021

Cited by 2 | Viewed by 2851

Abstract

Melanoma comprises <5% of cutaneous malignancies, yet it causes a significant proportion of skin cancer-related deaths worldwide. While new therapies for melanoma have been developed, not all patients respond well. Thus, further research is required to better predict patient outcomes. Using long-range nanopore [...] Read more.

Melanoma comprises <5% of cutaneous malignancies, yet it causes a significant proportion of skin cancer-related deaths worldwide. While new therapies for melanoma have been developed, not all patients respond well. Thus, further research is required to better predict patient outcomes. Using long-range nanopore sequencing, RT-qPCR, and RNA sequencing analyses, we examined the transcription of BARD1 splice isoforms in melanoma cell lines and patient tissue samples. Seventy-six BARD1 mRNA variants were identified in total, with several previously characterised isoforms (γ, φ, δ, ε, and η) contributing to a large proportion of the expressed transcripts. In addition, we identified four novel splice events, namely, Δ(E3_E9), ▼(i8), IVS10+131▼46, and IVS10▼176, occurring in various combinations in multiple transcripts. We found that short-read RNA-Seq analyses were limited in their ability to predict isoforms containing multiple non-contiguous splicing events, as compared to long-range nanopore sequencing. These studies suggest that further investigations into the functional significance of the identified BARD1 splice variants in melanoma are warranted. Full article

(This article belongs to the Special Issue BARD1 in Cancer)

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13 pages, 1732 KiB

Open AccessArticle

Meta-Analysis of Gene Popularity: Less Than Half of Gene Citations Stem from Gene Regulatory Networks

by Ionut Sebastian Mihai, Debojyoti Das, Gabija Maršalkaite and Johan Henriksson

Genes 2021, 12(2), 319; https://doi.org/10.3390/genes12020319 - 23 Feb 2021

Cited by 2 | Viewed by 2666

Abstract

The reasons for selecting a gene for further study might vary from historical momentum to funding availability, thus leading to unequal attention distribution among all genes. However, certain biological features tend to be overlooked in evaluating a gene’s popularity. Here we present a [...] Read more.

The reasons for selecting a gene for further study might vary from historical momentum to funding availability, thus leading to unequal attention distribution among all genes. However, certain biological features tend to be overlooked in evaluating a gene’s popularity. Here we present a meta-analysis of the reasons why different genes have been studied and to what extent, with a focus on the gene-specific biological features. From unbiased datasets we can define biological properties of genes that reasonably may affect their perceived importance. We make use of both linear and nonlinear computational approaches for estimating gene popularity to then compare their relative importance. We find that roughly 25% of the studies are the result of a historical positive feedback, which we may think of as social reinforcement. Of the remaining features, gene family membership is the most indicative followed by disease relevance and finally regulatory pathway association. Disease relevance has been an important driver until the 1990s, after which the focus shifted to exploring every single gene. We also present a resource that allows one to study the impact of reinforcement, which may guide our research toward genes that have not yet received proportional attention. Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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21 pages, 5691 KiB

Open AccessReview

Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor

by Hao Li, Peter Hohenstein and Satu Kuure

Genes 2021, 12(2), 318; https://doi.org/10.3390/genes12020318 - 23 Feb 2021

Cited by 21 | Viewed by 5382

Abstract

The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells [...] Read more.

The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor. Full article

(This article belongs to the Special Issue Molecular Roadblocks for Cellular Differentiation, Transdifferentiation or Conversion)

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13 pages, 633 KiB

Open AccessArticle

Investigating the Adoption of Clinical Genomics in Australia. An Implementation Science Case Study

by Stephanie Best, Janet C. Long, Clara Gaff, Jeffrey Braithwaite and Natalie Taylor

Genes 2021, 12(2), 317; https://doi.org/10.3390/genes12020317 - 23 Feb 2021

Cited by 9 | Viewed by 3357

Abstract

Despite the overwhelming interest in clinical genomics, uptake has been slow. Implementation science offers a systematic approach to reveal pathways to adoption and a theory informed approach to addressing barriers presented. Using case study methodology, we undertook 16 in-depth interviews with nongenetic medical [...] Read more.

Despite the overwhelming interest in clinical genomics, uptake has been slow. Implementation science offers a systematic approach to reveal pathways to adoption and a theory informed approach to addressing barriers presented. Using case study methodology, we undertook 16 in-depth interviews with nongenetic medical specialists to identify barriers and enablers to the uptake of clinical genomics. Data collection and analysis was guided by two evidence-based behaviour change models: the Theoretical Domains Framework (TDF), and the Capability, Opportunity Motivation Behaviour model (COM-B). Our findings revealed the use of implementation science not only provided a theoretical structure to frame the study but also facilitated uncovering of traditionally difficult to access responses from participants, e.g., “safety in feeling vulnerable” (TDF code emotion/COM-B code motivation). The most challenging phase for participants was ensuring appropriate patients were offered genomic testing. There were several consistent TDF codes: professional identity, social influences, and environmental context and resources and COM-B codes opportunity and motivation, with others varying along the patient journey. We conclude that implementation science methods can maximise the value created by the exploration of factors affecting the uptake of clinical genomics to ensure future interventions are designed to meet the needs of novice nongenetic medical specialists. Full article

(This article belongs to the Special Issue Applied Genomics: Bridging the Gap between R&D and Practical Implementations within Clinical and Public Health Settings)

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Graphical abstract

17 pages, 2795 KiB

Open AccessArticle

Genomic Regions Associated with Variation in Pigmentation Loss in Saddle Tan Beagles

by Mia E. Nord and Per Jensen

Genes 2021, 12(2), 316; https://doi.org/10.3390/genes12020316 - 23 Feb 2021

Cited by 2 | Viewed by 2765

Abstract

Loss of pigmentation is a hallmark of domestication, and dogs offer a unique model for understanding the genetics of fur coloration. The aim of this study was to use dense genetic mapping to map loci underlying variations in color and whiteness in a [...] Read more.

Loss of pigmentation is a hallmark of domestication, and dogs offer a unique model for understanding the genetics of fur coloration. The aim of this study was to use dense genetic mapping to map loci underlying variations in color and whiteness in a population of laboratory beagles. A total of 190 beagles with well-defined pedigrees were phenotyped for the amount of white color in six different body parts, including the saddle. All individuals were genotyped on 85,172 informative and valid SNP-markers and the genome-wide associations for the amount of white in each body part were determined. There was a large variation in the amount of white on different parts of the body, and the whiteness was highly correlated within individuals, except for saddle color which was only moderately correlated with overall whiteness. The GWAS showed significant associations with two loci, one on chromosome 5, containing the MC1R gene, and one on chromosome 20, containing the MITF gene. Our results suggest that the variation in loss of pigmentation is largely a function of regulatory variation related to these genes. Full article

(This article belongs to the Special Issue Canine Genetics 2)

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11 pages, 1412 KiB

Open AccessReview

The Sex Determination Cascade in the Silkworm

by Xu Yang, Kai Chen, Yaohui Wang, Dehong Yang and Yongping Huang

Genes 2021, 12(2), 315; https://doi.org/10.3390/genes12020315 - 23 Feb 2021

Cited by 13 | Viewed by 4199

Abstract

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect [...] Read more.

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm. Full article

(This article belongs to the Special Issue The Evolution of Sexual Development in Arthropods)

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9 pages, 2488 KiB

Open AccessArticle

Expression Pattern of Nitric Oxide Synthase during Development of the Marine Gastropod Mollusc, Crepidula fornicata

by Marta Truchado-Garcia, Filomena Caccavale, Cristina Grande and Salvatore D’Aniello

Genes 2021, 12(2), 314; https://doi.org/10.3390/genes12020314 - 22 Feb 2021

Cited by 7 | Viewed by 2210

Abstract

Nitric Oxide (NO) plays a key role in the induction of larval metamorphosis in several invertebrate phyla. The inhibition of the NO synthase in Crepidula fornicata, a molluscan model for evolutionary, developmental, and ecological research, has been demonstrated to block the initiation [...] Read more.

Nitric Oxide (NO) plays a key role in the induction of larval metamorphosis in several invertebrate phyla. The inhibition of the NO synthase in Crepidula fornicata, a molluscan model for evolutionary, developmental, and ecological research, has been demonstrated to block the initiation of metamorphosis highlighting that endogenous NO is crucial in the control of this developmental and morphological process. Nitric Oxide Synthase contributes to the development of shell gland, digestive gland and kidney, being expressed in cells that presumably correspond to FMRF-amide, serotoninergic and catecolaminergic neurons. Here we identified a single Nos gene in embryonic and larval transcriptomes of C. fornicata and studied its localization during development, through whole-mount in situ hybridization, in order to compare its expression pattern with that of other marine invertebrate animal models. Full article

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

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8 pages, 1384 KiB

Open AccessCase Report

A Novel ATM Pathogenic Variant in an Italian Woman with Gallbladder Cancer

by Elisa De Paolis, Andrea Urbani, Lisa Salvatore, Laura Foca, Giampaolo Tortora, Angelo Minucci and Paola Concolino

Genes 2021, 12(2), 313; https://doi.org/10.3390/genes12020313 - 22 Feb 2021

Cited by 2 | Viewed by 2523

Abstract

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving [...] Read more.

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (ATM) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline ATM large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with ATM-deficient cancers. Full article

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

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16 pages, 1301 KiB

Open AccessArticle

Quantitative Approach to Fish Cytogenetics in the Context of Vertebrate Genome Evolution

by Veronika Borůvková, W. Mike Howell, Dominik Matoulek and Radka Symonová

Genes 2021, 12(2), 312; https://doi.org/10.3390/genes12020312 - 22 Feb 2021

Cited by 7 | Viewed by 2604

Abstract

Our novel Python-based tool EVANGELIST allows the visualization of GC and repeats percentages along chromosomes in sequenced genomes and has enabled us to perform quantitative large-scale analyses on the chromosome level in fish and other vertebrates. This is a different approach from the [...] Read more.

Our novel Python-based tool EVANGELIST allows the visualization of GC and repeats percentages along chromosomes in sequenced genomes and has enabled us to perform quantitative large-scale analyses on the chromosome level in fish and other vertebrates. This is a different approach from the prevailing analyses, i.e., analyses of GC% in the coding sequences that make up not more than 2% in human. We identified GC content (GC%) elevations in microchromosomes in ancient fish lineages similar to avian microchromosomes and a large variability in the relationship between the chromosome size and their GC% across fish lineages. This raises the question as to what extent does the chromosome size drive GC% as posited by the currently accepted explanation based on the recombination rate. We ascribe the differences found across fishes to varying GC% of repetitive sequences. Generally, our results suggest that the GC% of repeats and proportion of repeats are independent of the chromosome size. This leaves an open space for another mechanism driving the GC evolution in vertebrates. Full article

(This article belongs to the Special Issue Fish Cytogenetics: Present and Future)

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12 pages, 1810 KiB

Open AccessArticle

Clustering Single-Cell RNA-Seq Data with Regularized Gaussian Graphical Model

by Zhenqiu Liu

Genes 2021, 12(2), 311; https://doi.org/10.3390/genes12020311 - 22 Feb 2021

Cited by 11 | Viewed by 3002

Abstract

Single-cell RNA-seq (scRNA-seq) is a powerful tool to measure the expression patterns of individual cells and discover heterogeneity and functional diversity among cell populations. Due to variability, it is challenging to analyze such data efficiently. Many clustering methods have been developed using at [...] Read more.

Single-cell RNA-seq (scRNA-seq) is a powerful tool to measure the expression patterns of individual cells and discover heterogeneity and functional diversity among cell populations. Due to variability, it is challenging to analyze such data efficiently. Many clustering methods have been developed using at least one free parameter. Different choices for free parameters may lead to substantially different visualizations and clusters. Tuning free parameters is also time consuming. Thus there is need for a simple, robust, and efficient clustering method. In this paper, we propose a new regularized Gaussian graphical clustering (RGGC) method for scRNA-seq data. RGGC is based on high-order (partial) correlations and subspace learning, and is robust over a wide-range of a regularized parameter

λ

. Therefore, we can simply set

λ = 2

or

λ = log (p)

for AIC (Akaike information criterion) or BIC (Bayesian information criterion) without cross-validation. Cell subpopulations are discovered by the Louvain community detection algorithm that determines the number of clusters automatically. There is no free parameter to be tuned with RGGC. When evaluated with simulated and benchmark scRNA-seq data sets against widely used methods, RGGC is computationally efficient and one of the top performers. It can detect inter-sample cell heterogeneity, when applied to glioblastoma scRNA-seq data. Full article

(This article belongs to the Special Issue Computational Methods for the Analysis of Genomic Data and Biological Processes (II))

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14 pages, 6364 KiB

Open AccessArticle

Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry

by Yichuan Liu, Xiao Chang, Hui-Qi Qu, Lifeng Tian, Joseph Glessner, Jingchun Qu, Dong Li, Haijun Qiu, Patrick Sleiman and Hakon Hakonarson

Genes 2021, 12(2), 310; https://doi.org/10.3390/genes12020310 - 22 Feb 2021

Cited by 10 | Viewed by 2354

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated [...] Read more.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA. Multiple novel rare recurrent variants were identified in exonic regions, functionally classified as stop-gains and frameshifts for known ADHD genes. Deletion in introns of the protocadherins families and the ncRNA HGB8P were identified in two independent EA ADHD patients. A meta-analysis of the two ethnicities for differential ADHD recurrent variants compared to controls shows a small number of overlaps. These results suggest that rare recurrent variants in noncoding regions may be involved in the pathogenesis of ADHD in children of both AA and EA ancestry; thus, WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD. Full article

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

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15 pages, 1610 KiB

Open AccessArticle

The Postmedieval Latvian Oral Microbiome in the Context of Modern Dental Calculus and Modern Dental Plaque Microbial Profiles

by Alisa Kazarina, Elina Petersone-Gordina, Janis Kimsis, Jevgenija Kuzmicka, Pawel Zayakin, Žans Griškjans, Guntis Gerhards and Renate Ranka

Genes 2021, 12(2), 309; https://doi.org/10.3390/genes12020309 - 22 Feb 2021

Cited by 6 | Viewed by 2636

Abstract

Recent advantages in paleomicrobiology have provided an opportunity to investigate the composition of ancient microbial ecologies. Here, using metagenome analysis, we investigated the microbial profiles of historic dental calculus retrieved from archaeological human remains from postmedieval Latvia dated 16–17th century AD and examined [...] Read more.

Recent advantages in paleomicrobiology have provided an opportunity to investigate the composition of ancient microbial ecologies. Here, using metagenome analysis, we investigated the microbial profiles of historic dental calculus retrieved from archaeological human remains from postmedieval Latvia dated 16–17th century AD and examined the associations of oral taxa and microbial diversity with specific characteristics. We evaluated the preservation of human oral microbiome patterns in historic samples and compared the microbial composition of historic dental calculus, modern human dental plaque, modern human dental calculus samples and burial soil microbiota. Overall, the results showed that the majority of microbial DNA in historic dental calculus originated from the oral microbiome with little impact of the burial environment. Good preservation of ancient DNA in historical dental calculus samples has provided reliable insight into the composition of the oral microbiome of postmedieval Latvian individuals. The relative stability of the classifiable oral microbiome composition was observed. Significant differences between the microbiome profiles of dental calculus and dental plaque samples were identified, suggesting microbial adaptation to a specific human body environment. Full article

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

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28 pages, 950 KiB

Open AccessReview

The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review

by Maheen Khan and Devanand Sarkar

Genes 2021, 12(2), 308; https://doi.org/10.3390/genes12020308 - 22 Feb 2021

Cited by 14 | Viewed by 3036

Abstract

Since its initial cloning in 2002, a plethora of studies in a vast number of cancer indications, has strongly established AEG-1 as a bona fide oncogene. In all types of cancer cells, overexpression and knockdown studies have demonstrated that AEG-1 performs a seminal [...] Read more.

Since its initial cloning in 2002, a plethora of studies in a vast number of cancer indications, has strongly established AEG-1 as a bona fide oncogene. In all types of cancer cells, overexpression and knockdown studies have demonstrated that AEG-1 performs a seminal role in regulating proliferation, invasion, angiogenesis, metastasis and chemoresistance, the defining cancer hallmarks, by a variety of mechanisms, including protein-protein interactions activating diverse oncogenic pathways, RNA-binding promoting translation and regulation of inflammation, lipid metabolism and tumor microenvironment. These findings have been strongly buttressed by demonstration of increased tumorigenesis in tissue-specific AEG-1 transgenic mouse models, and profound resistance of multiple types of cancer development and progression in total and conditional AEG-1 knockout mouse models. Additionally, clinicopathologic correlations of AEG-1 expression in a diverse array of cancers establishing AEG-1 as an independent biomarker for highly aggressive, chemoresistance metastatic disease with poor prognosis have provided a solid foundation to the mechanistic and mouse model studies. In this review a comprehensive analysis of the current and up-to-date literature is provided to delineate the clinical significance of AEG-1 in cancer highlighting the commonality of the findings and the discrepancies and discussing the implications of these observations. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Solid Tumors)

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16 pages, 335 KiB

Open AccessArticle

Epigenetic Regulation of Processes Related to High Level of Fibroblast Growth Factor 21 in Obese Subjects

by Teresa Płatek, Anna Polus, Joanna Góralska, Urszula Raźny, Agnieszka Dziewońska, Agnieszka Micek, Aldona Dembińska-Kieć, Bogdan Solnica and Małgorzata Malczewska-Malec

Genes 2021, 12(2), 307; https://doi.org/10.3390/genes12020307 - 21 Feb 2021

Cited by 9 | Viewed by 2403

Abstract

We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants [...] Read more.

We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants with BMI 27–45 kg/m². Fasting FGF21, glucose, insulin, GIP, lipids, adipokines, miokines and cytokines were measured and compared in high serum FGF21 (n = 68) group to low FGF21 (n = 68) group. Human DNA Methylation Microarrays were analysed in leukocytes from each group (n = 16). Expression of miRNAs was evaluated using quantitative PCR-TLDA. The study identified differentially methylated genes in pathways related to glucose transport, insulin secretion and signalling, lipid transport and cellular metabolism, response to nutrient levels, thermogenesis, browning of adipose tissue and bone mineralisation. Additionally, it detected transcription factor genes regulating FGF21 and fibroblast growth factor receptor and vascular endothelial growth factor receptor pathways regulation. Increased expression of hsa-miR-875-5p and decreased expression of hsa-miR-133a-3p, hsa-miR-185-5p and hsa-miR-200c-3p were found in the group with high serum FGF21. These changes were associated with high FGF21, VEGF and low adiponectin serum levels. Our results point to a significant role of the epigenetic regulation of genes involved in metabolic pathways related to FGF21 action. Full article

(This article belongs to the Special Issue Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation)

11 pages, 1808 KiB

Open AccessArticle

BAF57/SMARCE1 Interacting with Splicing Factor SRSF1 Regulates Mechanical Stress-Induced Alternative Splicing of Cyclin D1

by Jianguo Feng, Xichao Xu, Xin Fan, Qian Yi and Liling Tang

Genes 2021, 12(2), 306; https://doi.org/10.3390/genes12020306 - 21 Feb 2021

Cited by 13 | Viewed by 2639

Abstract

Background: Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and cyclin D1 alternative splicing generates a cyclin D1b isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing processes are sensitive to mechanical stimuli, whether the alternative splicing [...] Read more.

Background: Cyclin D1 regulates cyclin-dependent protein kinase activity of the cell cycle, and cyclin D1 alternative splicing generates a cyclin D1b isoform, acting as a mediator of aberrant cellular proliferation. As alternative splicing processes are sensitive to mechanical stimuli, whether the alternative splicing of cyclin D1 is regulated by mechanical stress and what kinds of factors may act as the regulator of mechano-induced alternative splicing remain unknown. Methods: The alternative splicing of Cyclin D1 was examined using reverse transcription polymerase chain reaction (RT-PCR) in osteoblast cell lines and keratinocyte cells loaded by a cyclic stretch. The expression of splicing factors and switching defective/sucrose non-fermenting (SWI/SNF) complex subunits were detected in stretched cells using real-time quantitative PCR (RT-qPCR). The protein interaction was tested by co-immunoprecipitation assay (Co-IP). Results:Cyclin D1 expression decreased with its splice variant upregulated in stretched cells. Serine/arginine-rich splicing factor 1 (SRSF1) and SWI/SNF complex subunit Brahma-related gene-1-associated factor 57 (BAF57), also named SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 (SMARCE1), could respond to mechanical stimuli. Overexpression and knockdown experiments indicated the BAF57/SMARCE1 is probably a critical factor regulating the alternative splicing of cyclin D1. Co-IP showed an interaction between BAF57/SMARCE1 and SRSF1, implying a possible underlying mechanism of the regulator role of BAF57/SMARCE1 in the splicing process of cyclin D1. Conclusions: The splicing factor SRSF1 and BAF57/SMARCE1 are possibly responsible for the mechanical stress-induced alternative splicing of cyclin D1. Full article

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

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16 pages, 1550 KiB

Open AccessEditor’s ChoiceReview

Sex Determination and Differentiation in Decapod and Cladoceran Crustaceans: An Overview of Endocrine Regulation

by Kenji Toyota, Hitoshi Miyakawa, Chizue Hiruta, Tomomi Sato, Hidekazu Katayama, Tsuyoshi Ohira and Taisen Iguchi

Genes 2021, 12(2), 305; https://doi.org/10.3390/genes12020305 - 21 Feb 2021

Cited by 27 | Viewed by 5174

Abstract

Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are [...] Read more.

Mechanisms underlying sex determination and differentiation in animals are known to encompass a diverse array of molecular clues. Recent innovations in high-throughput sequencing and mass spectrometry technologies have been widely applied in non-model organisms without reference genomes. Crustaceans are no exception. They are particularly diverse among the Arthropoda and contain a wide variety of commercially important fishery species such as shrimps, lobsters and crabs (Order Decapoda), and keystone species of aquatic ecosystems such as water fleas (Order Branchiopoda). In terms of decapod sex determination and differentiation, previous approaches have attempted to elucidate their molecular components, to establish mono-sex breeding technology. Here, we overview reports describing the physiological functions of sex hormones regulating masculinization and feminization, and gene discovery by transcriptomics in decapod species. Moreover, this review summarizes the recent progresses of studies on the juvenile hormone-driven sex determination system of the branchiopod genus Daphnia, and then compares sex determination and endocrine systems between decapods and branchiopods. This review provides not only substantial insights for aquaculture research, but also the opportunity to re-organize the current and future trends of this field. Full article

(This article belongs to the Special Issue The Evolution of Sexual Development in Arthropods)

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14 pages, 1732 KiB

Open AccessArticle

A Deadly Cargo: Gene Repertoire of Cytotoxic Effector Proteins in the Camelidae

by Ján Futas, Jan Oppelt, Pamela Anna Burger and Petr Horin

Genes 2021, 12(2), 304; https://doi.org/10.3390/genes12020304 - 21 Feb 2021

Cited by 3 | Viewed by 2118

Abstract

Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to [...] Read more.

Cytotoxic T cells and natural killer cells can kill target cells based on their expression and release of perforin, granulysin, and granzymes. Genes encoding these molecules have been only poorly annotated in camelids. Based on bioinformatic analyses of genomic resources, sequences corresponding to perforin, granulysin, and granzymes were identified in genomes of camelids and related ungulate species, and annotation of the corresponding genes was performed. A phylogenetic tree was constructed to study evolutionary relationships between the species analyzed. Re-sequencing of all genes in a panel of 10 dromedaries and 10 domestic Bactrian camels allowed analyzing their individual genetic polymorphisms. The data showed that all extant Old World camelids possess functional genes for two pore-forming proteins (PRF1, GNLY) and six granzymes (GZMA, GZMB, GZMH, GZMK, GZMM, and GZMO). All these genes were represented as single copies in the genome except the GZMH gene exhibiting interspecific differences in the number of loci. High protein sequence similarities with other camelid and ungulate species were observed for GZMK and GZMM. The protein variability in dromedaries and Bactrian camels was rather low, except for GNLY and chymotrypsin-like granzymes (GZMB, GZMH). Full article

(This article belongs to the Special Issue Camelid Genomics)

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18 pages, 5423 KiB

Open AccessArticle

Waves Out of the Korean Peninsula and Inter- and Intra-Species Replacements in Freshwater Fishes in Japan

by Shoji Taniguchi, Johanna Bertl, Andreas Futschik, Hirohisa Kishino and Toshio Okazaki

Genes 2021, 12(2), 303; https://doi.org/10.3390/genes12020303 - 21 Feb 2021

Cited by 7 | Viewed by 4034

Abstract

The Japanese archipelago is located at the periphery of the continent of Asia. Rivers in the Japanese archipelago, separated from the continent of Asia by about 17 Ma, have experienced an intermittent exchange of freshwater fish taxa through a narrow land bridge generated [...] Read more.

The Japanese archipelago is located at the periphery of the continent of Asia. Rivers in the Japanese archipelago, separated from the continent of Asia by about 17 Ma, have experienced an intermittent exchange of freshwater fish taxa through a narrow land bridge generated by lowered sea level. As the Korean Peninsula and Japanese archipelago were not covered by an ice sheet during glacial periods, phylogeographical analyses in this region can trace the history of biota that were, for a long time, beyond the last glacial maximum. In this study, we analyzed the phylogeography of four freshwater fish taxa, Hemibarbus longirostris, dark chub Nipponocypris temminckii, Tanakia ssp. and Carassius ssp., whose distributions include both the Korean Peninsula and Western Japan. We found for each taxon that a small component of diverse Korean clades of freshwater fishes migrated in waves into the Japanese archipelago to form the current phylogeographic structure of biota. The replacements of indigenous populations by succeeding migrants may have also influenced the phylogeography. Full article

(This article belongs to the Special Issue Genetic Structure of World Animal Populations)

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23 pages, 6221 KiB

Open AccessArticle

Comprehensive Genome-Wide Exploration of C2H2 Zinc Finger Family in Grapevine (Vitis vinifera L.): Insights into the Roles in the Pollen Development Regulation

by Oscar Arrey-Salas, José Carlos Caris-Maldonado, Bairon Hernández-Rojas and Enrique Gonzalez

Genes 2021, 12(2), 302; https://doi.org/10.3390/genes12020302 - 20 Feb 2021

Cited by 21 | Viewed by 3112

Abstract

Some C2H2 zinc-finger proteins (ZFP) transcription factors are involved in the development of pollen in plants. In grapevine (Vitis vinifera L.), it has been suggested that abnormalities in pollen development lead to the phenomenon called parthenocarpy that occurs in some varieties of [...] Read more.

Some C2H2 zinc-finger proteins (ZFP) transcription factors are involved in the development of pollen in plants. In grapevine (Vitis vinifera L.), it has been suggested that abnormalities in pollen development lead to the phenomenon called parthenocarpy that occurs in some varieties of this cultivar. At present, a network involving several transcription factors types has been revealed and key roles have been assigned to members of the C2H2 zinc-finger proteins (ZFP) family in model plants. However, particularities of the regulatory mechanisms controlling pollen formation in grapevine remain unknown. In order to gain insight into the participation of ZFPs in grapevine gametophyte development, we performed a genome-wide identification and characterization of genes encoding ZFP (VviZFP family). A total of 98 genes were identified and renamed based on the gene distribution into grapevine genome. The analysis performed indicate significant changes throughout VviZFP genes evolution explained by high heterogeneity in sequence, length, number of ZF and presence of another conserved domains. Moreover, segmental duplication participated in the gene family expansion in grapevine. The VviZFPs were classified based on domain and phylogenetic analysis into three sets and different groups. Heat-map demonstrated differential and tissue-specific expression patterns of these genes and k-means clustering allowed to identify a group of putative orthologs to some ZFPs related to pollen development. In transgenic plants carrying the promVviZFP13::GUS and promVviZFP68::GUS constructs, GUS signals were detectable in the anther and mature pollen grains. Expression profiling of selected VviZFP genes showed differential expression pattern during flower development and provides a basis for deepening in the understanding of VviZFPs role on grapevine reproductive development. Full article

(This article belongs to the Special Issue New Insights into Plant Development and Signal Transduction)

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22 pages, 3428 KiB

Open AccessArticle

Understanding Rice-Magnaporthe Oryzae Interaction in Resistant and Susceptible Cultivars of Rice under Panicle Blast Infection Using a Time-Course Transcriptome Analysis

by Vishesh Kumar, Priyanka Jain, Sureshkumar Venkadesan, Suhas Gorakh Karkute, Jyotika Bhati, Malik Zainul Abdin, Amitha Mithra Sevanthi, Dwijesh Chandra Mishra, Krishna Kumar Chaturvedi, Anil Rai, Tilak Raj Sharma and Amolkumar U. Solanke

Genes 2021, 12(2), 301; https://doi.org/10.3390/genes12020301 - 20 Feb 2021

Cited by 17 | Viewed by 4711

Abstract

Rice blast is a global threat to food security with up to 50% yield losses. Panicle blast is a more severe form of rice blast and the response of rice plant to leaf and panicle blast is distinct in different genotypes. To understand [...] Read more.

Rice blast is a global threat to food security with up to 50% yield losses. Panicle blast is a more severe form of rice blast and the response of rice plant to leaf and panicle blast is distinct in different genotypes. To understand the specific response of rice in panicle blast, transcriptome analysis of blast resistant cultivar Tetep, and susceptible cultivar HP2216 was carried out using RNA-Seq approach after 48, 72 and 96 h of infection with Magnaporthe oryzae along with mock inoculation. Transcriptome data analysis of infected panicle tissues revealed that 3553 genes differentially expressed in HP2216 and 2491 genes in Tetep, which must be the responsible factor behind the differential disease response. The defense responsive genes are involved mainly in defense pathways namely, hormonal regulation, synthesis of reactive oxygen species, secondary metabolites and cell wall modification. The common differentially expressed genes in both the cultivars were defense responsive transcription factors, NBS-LRR genes, kinases, pathogenesis related genes and peroxidases. In Tetep, cell wall strengthening pathway represented by PMR5, dirigent, tubulin, cell wall proteins, chitinases, and proteases was found to be specifically enriched. Additionally, many novel genes having DOMON, VWF, and PCaP1 domains which are specific to cell membrane were highly expressed only in Tetep post infection, suggesting their role in panicle blast resistance. Thus, our study shows that panicle blast resistance is a complex phenomenon contributed by early defense response through ROS production and detoxification, MAPK and LRR signaling, accumulation of antimicrobial compounds and secondary metabolites, and cell wall strengthening to prevent the entry and spread of the fungi. The present investigation provided valuable candidate genes that can unravel the mechanisms of panicle blast resistance and help in the rice blast breeding program. Full article

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

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28 pages, 1151 KiB

Open AccessReview

The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases

by Camilla Ceccatelli Berti, Giulia di Punzio, Cristina Dallabona, Enrico Baruffini, Paola Goffrini, Tiziana Lodi and Claudia Donnini

Genes 2021, 12(2), 300; https://doi.org/10.3390/genes12020300 - 20 Feb 2021

Cited by 17 | Viewed by 2988

Abstract

The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) [...] Read more.

The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) and mitochondrial genome makes the yeast Saccharomyces cerevisiae an excellent model system for investigating the role of these new variants in mitochondrial-related conditions and dissecting the molecular mechanisms associated with these diseases. The aim of this review was to highlight the main advantages offered by this model for the study of mitochondrial diseases, from the validation and characterisation of novel mutations to the dissection of the role played by genes in mitochondrial functionality and the discovery of potential therapeutic molecules. The review also provides a summary of the main contributions to the understanding of mitochondrial diseases emerged from the study of this simple eukaryotic organism. Full article

(This article belongs to the Special Issue Yeast Applications in Gene Mutation)

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18 pages, 3143 KiB

Open AccessCommunication

Analysis of the Differential Gene and Protein Expression Profiles of Corneal Epithelial Cells Stimulated with Alternating Current Electric Fields

by Bhavani S. Kowtharapu, Jyoti Damaraju, Nitesh Kumar Singh, Josefin Ziebart, Rainer Bader, Dirk Koczan and Oliver Stachs

Genes 2021, 12(2), 299; https://doi.org/10.3390/genes12020299 - 20 Feb 2021

Cited by 6 | Viewed by 3340

Abstract

In cells, intrinsic endogenous direct current (DC) electric fields (EFs) serve as morphogenetic cues and are necessary for several important cellular responses including activation of multiple signaling pathways, cell migration, tissue regeneration and wound healing. Endogenous DC EFs, generated spontaneously following injury in [...] Read more.

In cells, intrinsic endogenous direct current (DC) electric fields (EFs) serve as morphogenetic cues and are necessary for several important cellular responses including activation of multiple signaling pathways, cell migration, tissue regeneration and wound healing. Endogenous DC EFs, generated spontaneously following injury in physiological conditions, directly correlate with wound healing rate, and different cell types respond to these EFs via directional orientation and migration. Application of external DC EFs results in electrode polarity and is known to activate intracellular signaling events in specific direction. In contrast, alternating current (AC) EFs are known to induce continuous bidirectional flow of charged particles without electrode polarity and also minimize electrode corrosion. In this context, the present study is designed to study effects of AC EFs on corneal epithelial cell gene and protein expression profiles in vitro. We performed gene and antibody arrays, analyzed the data to study specific influence of AC EFs, and report that AC EFs has no deleterious effect on epithelial cell function. Gene Ontology results, following gene and protein array data analysis, showed that AC EFs influence similar biological processes that are predominantly responsive to organic substance, chemical, or external stimuli. Both arrays activate cytokine–cytokine receptor interaction, MAPK and IL-17 signaling pathways. Further, in comparison to the gene array data, the protein array data show enrichment of diverse activated signaling pathways through several interconnecting networks. Full article

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

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15 pages, 2191 KiB

Open AccessBrief Report

Insights into the Transcriptional Regulation of Branching Hormonal Signaling Pathways Genes under Drought Stress in Arabidopsis

by Nkulu Kabange Rolly, Bong-Gyu Mun and Byung-Wook Yun

Genes 2021, 12(2), 298; https://doi.org/10.3390/genes12020298 - 20 Feb 2021

Cited by 6 | Viewed by 2953

Abstract

A large number of hormonal biosynthetic or signaling pathways genes controlling shoot branching are widely known for their roles in regulating plant growth and development, operating in synergetic or antagonistic manner. However, their involvement in abiotic stress response mechanism remains unexplored. Initially, we [...] Read more.

A large number of hormonal biosynthetic or signaling pathways genes controlling shoot branching are widely known for their roles in regulating plant growth and development, operating in synergetic or antagonistic manner. However, their involvement in abiotic stress response mechanism remains unexplored. Initially, we performed an in silico analysis to identify potential transcription binding sites for the basic leucine zipper 62 transcription factor (bZIP62 TF) in the target branching related genes. The results revealed the presence of cis-regulatory elements specific to two bZIP TFs, AtbZIP18 and AtbZIP69, rather than AtbZIP62. Interestingly, these bZIP TFs were previously proposed to be negatively regulated by the AtbZIP62 TF under salinity in Arabidopsis. Therefore, we investigated the transcriptional regulation of more axillary branching (MAX, strigolactone), PIN-FORMED (PINs, auxin carriers), gibberellic acid (GA)-biosynthetic genes as well as isopentenyltransferase (IPT, cytokinin biosynthesis pathway) genes in response to drought stress in Arabidopsis Col-0 wild type. In addition, in the perspective of exploring the transcriptional interplay of the selected genes with the AtbZIP62, we measured their expression by qPCR in the atbzip62 (lacking the AtbZIP62 gene) background under the same conditions. Our findings revealed that the expression of AtMAX2, AtMAX3, and AtMAX4 was differentially regulated by drought stress between the atbzip62 and Col-0 wild type, but not AtMAX1. Similarly, the transcripts accumulation of AtPIN3 and AtPIN7 (known as auxin efflux carriers), and that of the AtAXR1 showed similar regulation patterns in atbzip62. However, AtPIN1 expression was downregulated in Col-0, but no change was observed in atbzip62. Furthermore, AtIPT5 and AtIPT7 exhibited a differential transcripts accumulation pattern in atbzip62 and Col-0 wild type (WT). In the same way, the expression of the GA biosynthetic genes AtGA2ox1 and AtGA20ox2, and that of AtRGA1 were differentially regulated in atbzip62 compared to the Col-0. Meanwhile, AtGA2ox1 showed a similar expression pattern with Col-0. Therefore, all results suggest PIN, MAX, IPT, and GA-biosynthetic genes, which are differentially regulated by AtbZIP62 transcription factor, as emerging candidate genes that could be involved in drought stress response mechanism in Arabidopsis. Full article

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

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18 pages, 2958 KiB

Open AccessArticle

Functions of Forkhead Box O on Glucose Metabolism in Abalone Haliotis discus hannai and Its Responses to High Levels of Dietary Lipid

by Liu Wang, Yanlin Guo, Mingzhu Pan, Xinxin Li, Dong Huang, Yue Liu, Chenglong Wu, Wenbing Zhang and Kangsen Mai

Genes 2021, 12(2), 297; https://doi.org/10.3390/genes12020297 - 20 Feb 2021

Cited by 9 | Viewed by 2581

Abstract

The forkhead box O (FoxO) subfamily is a member of the forkhead transcription factor family. It has regulation functions in glucose metabolism in mammals and fish. In the present study, a gene of the foxo homolog in abalone Haliotis discus hannai was cloned. [...] Read more.

The forkhead box O (FoxO) subfamily is a member of the forkhead transcription factor family. It has regulation functions in glucose metabolism in mammals and fish. In the present study, a gene of the foxo homolog in abalone Haliotis discus hannai was cloned. A conservative forkhead (FH) domain and a transactivation (FoxO-TAD) domain were identified. Abalone foxo-specific siRNA (small interfering RNA) was injected to investigate the functions of foxo on glucose metabolism. Knockdown of foxo inhibited expression of phosphoenolpyruvate carboxykinase (pepck) and significantly increased expressions of hexokinase (hk) and pyruvate kinase (pk), but it failed to inhibit the relative mRNA level of glucose-6-phosphatase (g6pase). Then, a 100-day feeding trial was conducted to investigate the response of foxo and glucose metabolism in abalone fed with 1.57% (LFD, low-fat diet), 3.82% (MFD, middle-fat diet) and 6.72% (HFD, high-fat diet) of dietary lipid, respectively. The insulin-signaling pathway (AKT) was depressed and FoxO was activated by the HFD, but it did not inhibit glycolysis (hk) or improved gluconeogenesis significantly (pepck and g6pase). At the same time, impaired hepatopancreas glycogen storage raised hemolymph glucose levels. In conclusion, abalone foxo can be regulated by dietary lipid and can regulate gluconeogenesis or glycolysis in response to changes of dietary lipid levels, in which glycogen metabolism plays an important role. Full article

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

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10 pages, 405 KiB

Open AccessArticle

4mCPred-CNN—Prediction of DNA N4-Methylcytosine in the Mouse Genome Using a Convolutional Neural Network

by Zeeshan Abbas, Hilal Tayara and Kil To Chong

Genes 2021, 12(2), 296; https://doi.org/10.3390/genes12020296 - 20 Feb 2021

Cited by 19 | Viewed by 2625

Abstract

Among DNA modifications, N4-methylcytosine (4mC) is one of the most significant ones, and it is linked to the development of cell proliferation and gene expression. To know different its biological functions, the accurate detection of 4mC sites is required. Although we have several [...] Read more.

Among DNA modifications, N4-methylcytosine (4mC) is one of the most significant ones, and it is linked to the development of cell proliferation and gene expression. To know different its biological functions, the accurate detection of 4mC sites is required. Although we have several techniques for the prediction of 4mC sites in different genomes based on both machine learning (ML) and convolutional neural networks (CNNs), there is no CNN-based tool for the identification of 4mC sites in the mouse genome. In this article, a CNN-based model named 4mCPred-CNN was developed to classify 4mC locations in the mouse genome. Until now, we had only two ML-based models for this purpose; they utilized several feature encoding schemes, and thus still had a lot of space available to improve the prediction accuracy. Utilizing only a single feature encoding scheme—one-hot encoding—we outperformed both of the previous ML-based techniques. In a ten-fold validation test, the proposed model, 4mCPred-CNN, achieved an accuracy of 85.71% and Matthews correlation coefficient (MCC) of 0.717. On an independent dataset, the achieved accuracy was 87.50% with an MCC value of 0.750. The attained results exhibit that the proposed model can be of great use for researchers in the fields of biology and bioinformatics. Full article

(This article belongs to the Special Issue Computational Methods for the Analysis of Genomic Data and Biological Processes (II))

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17 pages, 4084 KiB

Open AccessArticle

Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins

by Eman Rabie, Khalda Amr, Suher Zada, Heba El-Sayed, Mohamad El Darouti and Ghada El-Kamah

Genes 2021, 12(2), 295; https://doi.org/10.3390/genes12020295 - 20 Feb 2021

Cited by 4 | Viewed by 2587

Abstract

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. [...] Read more.

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migration flows. Clinical and genetic profiling improves diagnosis, management, counselling, and implementation of future targeted therapies. Full article

(This article belongs to the Special Issue Genetic Disease in Mediterranean Region)

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13 pages, 1607 KiB

Open AccessArticle

Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum

by Abdulaziz Asiri, Deemah Alwadaani, Muhammad Umair, Kheloud M. Alhamoudi, Mohammed H. Almuhanna, Abdul Nasir, Bahauddeen M. Alrfaei, Abeer Al Tuwaijri, Tlili Barhoumi, Yusra Alyafee, Bader Almuzzaini, Mohammed Aldrees, Mariam Ballow, Latifah Alayyar, Abdulkareem Al Abdulrahman, Yazeid Alhaidan, Nahlah Al Ghasham, Sulaiman Al-Ajaji, Mohammad Alsalamah, Wafa Al Suwairi and Majid Alfadhel Show full author list Hide full author list

Genes 2021, 12(2), 294; https://doi.org/10.3390/genes12020294 - 20 Feb 2021

Cited by 10 | Viewed by 2680

Abstract

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology [...] Read more.

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response. Full article

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

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15 pages, 2267 KiB

Open AccessArticle

G2PMineR: A Genome to Phenome Literature Review Approach

by John M. A. Wojahn, Stephanie J. Galla, Anthony E. Melton and Sven Buerki

Genes 2021, 12(2), 293; https://doi.org/10.3390/genes12020293 - 20 Feb 2021

Cited by 2 | Viewed by 3547

Abstract

There is a gap in the conceptual framework linking genes to phenotypes (G2P) for non-model organisms, as most non-model organisms do not yet have genomic resources readily available. To address this, researchers often perform literature reviews to understand G2P linkages by curating a [...] Read more.

There is a gap in the conceptual framework linking genes to phenotypes (G2P) for non-model organisms, as most non-model organisms do not yet have genomic resources readily available. To address this, researchers often perform literature reviews to understand G2P linkages by curating a list of likely gene candidates, hinging upon other studies already conducted in closely related systems. Sifting through hundreds to thousands of articles is a cumbersome task that slows down the scientific process and may introduce bias into a study. To fill this gap, we created G2PMineR, a free and open source literature mining tool developed specifically for G2P research. This R package uses automation to make the G2P review process efficient and unbiased, while also generating hypothesized associations between genes and phenotypes within a taxonomical framework. We applied the package to a literature review for drought-tolerance in plants. The analysis provides biologically meaningful results within the known framework of drought tolerance in plants. Overall, the package is useful for conducting literature reviews for genome to phenome projects, and also has broad appeal to scientists investigating a wide range of study systems as it can conduct analyses under the auspices of three different kingdoms (Plantae, Animalia, and Fungi). Full article

(This article belongs to the Section Technologies and Resources for Genetics)

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19 pages, 2786 KiB

Open AccessArticle

Comparative Mitogenomics in Hyalella (Amphipoda: Crustacea)

by Francesco Zapelloni, José A. Jurado-Rivera, Damià Jaume, Carlos Juan and Joan Pons

Genes 2021, 12(2), 292; https://doi.org/10.3390/genes12020292 - 19 Feb 2021

Cited by 4 | Viewed by 2874

Abstract

We present the sequencing and comparative analysis of 17 mitochondrial genomes of Nearctic and Neotropical amphipods of the genus Hyalella, most from the Andean Altiplano. The mitogenomes obtained comprised the usual 37 gene-set of the metazoan mitochondrial genome showing a gene rearrangement [...] Read more.

We present the sequencing and comparative analysis of 17 mitochondrial genomes of Nearctic and Neotropical amphipods of the genus Hyalella, most from the Andean Altiplano. The mitogenomes obtained comprised the usual 37 gene-set of the metazoan mitochondrial genome showing a gene rearrangement (a reverse transposition and a reversal) between the North and South American Hyalella mitogenomes. Hyalella mitochondrial genomes show the typical AT-richness and strong nucleotide bias among codon sites and strands of pancrustaceans. Protein-coding sequences are biased towards AT-rich codons, with a preference for leucine and serine amino acids. Numerous base changes (539) were found in tRNA stems, with 103 classified as fully compensatory, 253 hemi-compensatory and the remaining base mismatches and indels. Most compensatory Watson–Crick switches were AU -> GC linked in the same haplotype, whereas most hemi-compensatory changes resulted in wobble GU and a few AC pairs. These results suggest a pairing fitness increase in tRNAs after crossing low fitness valleys. Branch-site level models detected positive selection for several amino acid positions in up to eight mitochondrial genes, with atp6 and nad5 as the genes displaying more sites under selection. Full article

(This article belongs to the Special Issue Molecular Evolution of the Mitochondrial DNA in Animals)

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