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Genes, Volume 11, Issue 7 (July 2020) – 61 articles

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Open AccessArticle
Mitochondrial PCK2 Missense Variant in Shetland Sheepdogs with Paroxysmal Exercise-Induced Dyskinesia (PED)
Genes 2020, 11(7), 774; https://doi.org/10.3390/genes11070774 (registering DOI) - 09 Jul 2020
Abstract
Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant [...] Read more.
Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant. Full article
(This article belongs to the Special Issue Molecular Basis of Inherited Diseases in Companion Animals)
Open AccessFeature PaperArticle
PRPH2-Related Retinal Diseases: Broadening the Clinical Spectrum and Describing a New Mutation
Genes 2020, 11(7), 773; https://doi.org/10.3390/genes11070773 (registering DOI) - 09 Jul 2020
Abstract
Over 175 pathogenic mutations in the Peripherin-2 (PRPH2) gene are linked to various retinal diseases. We report the phenotype and genotype of eight families (24 patients) with retinal diseases associated with seven distinct PRPH2 gene mutations. We identified a new mutation, c.824_828+3delinsCATTTGGGCTCCTCATTTGG, [...] Read more.
Over 175 pathogenic mutations in the Peripherin-2 (PRPH2) gene are linked to various retinal diseases. We report the phenotype and genotype of eight families (24 patients) with retinal diseases associated with seven distinct PRPH2 gene mutations. We identified a new mutation, c.824_828+3delinsCATTTGGGCTCCTCATTTGG, in a patient with adult-onset vitelliform macular dystrophy (AVMD). One family with the p.Arg46Ter mutation presented with the already described AVMD phenotype, but another family presented with the same mutation and two heterozygous pathogenic mutations (p.Leu2027Phe and p.Gly1977Ser) in the ATP Binding Cassette Subfamily A Member 4 (ABCA4) gene that cause extensive chorioretinal atrophy (ECA), which could be a blended phenotype. The p.Lys154del PRPH2 gene mutation associated with the p.Arg2030Glu mutation in the ABCA4 gene was found in a patient with multifocal pattern dystrophy simulating fundus flavimaculatus (PDsFF), for whom we considered ABCA4 as a possible modifying gene. The mutation p.Gly167Ser was already known to cause pattern dystrophy, but we also found ECA, PDsFF, and autosomal-dominant retinitis pigmentosa (ADRP) as possible phenotypes. Finally, we identified the mutation p.Arg195Leu in a large family with common ancestry, which previously was described to cause central areolar choroidal dystrophy (CACD), but we also found ADRP and observed that it caused ECA more frequently than CACD in this family. Full article
(This article belongs to the Special Issue Molecular Genetics of Retinal Dystrophies)
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Open AccessCommunication
Ectopic Expressions of the GhLETM1 Gene Reveal Sensitive Dose Effects on Precise Stamen Development and Male Fertility in Cotton
Genes 2020, 11(7), 772; https://doi.org/10.3390/genes11070772 (registering DOI) - 09 Jul 2020
Abstract
The homologous leucine zipper/EF-hand-containing transmembranes (LETMs) are highly conserved across a broad range of eukaryotic organisms. The LETM functional characteristics involved in biological process have been identified primarily in animals, but little is known about the LETM biological function mode in plants. Based [...] Read more.
The homologous leucine zipper/EF-hand-containing transmembranes (LETMs) are highly conserved across a broad range of eukaryotic organisms. The LETM functional characteristics involved in biological process have been identified primarily in animals, but little is known about the LETM biological function mode in plants. Based on the results of the current investigation, the GhLETM1 gene crucially affects filament elongation and anther dehiscence of the stamen in cotton. Both excessive and lower expression of the GhLETM1 gene lead to defective stamen development, resulting in shortened filaments and indehiscent anthers with pollen abortion. The results also showed that the phenotype of the shortened filaments was negatively correlated with anther defects in the seesaw model under the ectopic expression of GhLETM1. Moreover, our results notably indicated that the gene requires accurate expression and exhibits a sensitive dose effect for its proper function. This report has important fundamental and practical significance in crop science, and has crucial prospects for genetic engineering of new cytoplasmic male sterility lines and breeding of crop hybrid varieties. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Plant Reproduction)
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Open AccessArticle
Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration
Genes 2020, 11(7), 771; https://doi.org/10.3390/genes11070771 (registering DOI) - 09 Jul 2020
Abstract
Intervertebral disc (IVD) degeneration (IDD) is a multifactorial physiological process which is often associated with lower back pain. Previous studies have identified some molecular markers associated with disc degeneration, which despite their significant contributions, have provided limited insight into the etiology of IDD. [...] Read more.
Intervertebral disc (IVD) degeneration (IDD) is a multifactorial physiological process which is often associated with lower back pain. Previous studies have identified some molecular markers associated with disc degeneration, which despite their significant contributions, have provided limited insight into the etiology of IDD. In this study, we utilized a network medicine approach to uncover potential molecular mediators of IDD. Our systematic analyses of IDD associated with 284 genes included functional annotation clustering, interaction networks, network cluster analysis and Transcription factors (TFs)-target gene network analysis. The functional enrichment and protein–protein interaction network analysis highlighted the role of inflammatory genes and cytokine/chemokine signaling in IDD. Moreover, sub-network analysis identified significant clusters possessing organized networks of 24 cytokine and chemokine genes, which may be considered as key modulators for IDD. The expression of these genes was validated in independent microarray datasets. In addition, the regulatory network analysis identified the role of multiple transcription factors, with RUNX1 being a master regulator in the pathogenesis of IDD. Our analyses highlighted the role of cytokine genes and interacting pathways in IDD and further improved our understanding of the genetic mechanisms underlying IDD. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
Analyses of Hybrid Viability across a Hybrid Zone between Two Alnus Species Using Microsatellites and cpDNA Markers
Genes 2020, 11(7), 770; https://doi.org/10.3390/genes11070770 (registering DOI) - 09 Jul 2020
Abstract
Diploid Alnus glutinosa s. str. and autotetraploid A. rohlenae form a narrow hybrid zone in a study area in southern Serbia, which results in triploid hybrid formation. The vast majority of previous studies have been focused on studies of maternal plants, but the [...] Read more.
Diploid Alnus glutinosa s. str. and autotetraploid A. rohlenae form a narrow hybrid zone in a study area in southern Serbia, which results in triploid hybrid formation. The vast majority of previous studies have been focused on studies of maternal plants, but the offspring resulting from their crossing have not been much studied. Here, we use the variability of microsatellites and chloroplast DNA between these species and their putative hybrids to create an overall picture of the development of the hybrid zone and its predicted type. To elucidate the gene transfer within both species, the origins of individual ploidies and especially the role of triploid hybrids, a germination experiment was carried out linked with a flow cytometry study of the resulting seedlings. The tension zone model seems to offer the most adequate explanation of our observations, with selection against triploid hybrids and the spatial positioning of the hybrid zone. Despite selection against them, the triploid hybrids play an important role in the exchange of genes between the two species and therefore serve as a bridge for introgression. The presence of fertile triploids is essential for enriching the haplotype diversity between these species and for the development of new genetic lineages. Full article
(This article belongs to the Special Issue Research Progress and Application Prospects of Microsatellites)
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Open AccessArticle
Identification of Genes Encoding CENP-A and Heterochromatin Protein 1 of Lipomyces starkeyi and Functional Analysis Using Schizosaccharomyces pombe
Genes 2020, 11(7), 769; https://doi.org/10.3390/genes11070769 (registering DOI) - 08 Jul 2020
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Abstract
Centromeres function as a platform for the assembly of multiple kinetochore proteins and are essential for chromosome segregation. An active centromere is characterized by the presence of a centromere-specific histone H3 variant, CENP-A. Faithful centromeric localization of CENP-A is supported by heterochromatin in [...] Read more.
Centromeres function as a platform for the assembly of multiple kinetochore proteins and are essential for chromosome segregation. An active centromere is characterized by the presence of a centromere-specific histone H3 variant, CENP-A. Faithful centromeric localization of CENP-A is supported by heterochromatin in almost all eukaryotes; however, heterochromatin proteins have been lost in most Saccharomycotina. Here, identification of CENP-A (CENP-AL.s.) and heterochromatin protein 1 (Lsw1) in a Saccharomycotina species, the oleaginous yeast Lipomyces starkeyi, is reported. To determine if these proteins are functional, the proteins in S. pombe, a species widely used to study centromeres, were ectopically expressed. CENP-AL.s. localizes to centromeres and can be replaced with S. pombe CENP-A, indicating that CENP-AL.s. is a functional centromere-specific protein. Lsw1 binds at heterochromatin regions, and chromatin binding is dependent on methylation of histone H3 at lysine 9. In other species, self-interaction of heterochromatin protein 1 is thought to cause folding of chromatin, triggering transcription repression and heterochromatin formation. Consistent with this, it was found that Lsw1 can self-interact. L. starkeyi chromatin contains the methylation of histone H3 at lysine 9. These results indicated that L. starkeyi has a primitive heterochromatin structure and is an attractive model for analysis of centromere heterochromatin evolution. Full article
(This article belongs to the Special Issue Genetic Aspects of Yeast: Cell Biology, Ecology and Biotechnology)
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Open AccessCommunication
TLR4 Polymorphism, Nasopharyngeal Bacterial Colonization, and the Development of Childhood Asthma: A Prospective Birth-Cohort Study in Finnish Children
Genes 2020, 11(7), 768; https://doi.org/10.3390/genes11070768 (registering DOI) - 08 Jul 2020
Viewed by 75
Abstract
We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and [...] Read more.
We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. TLR4 polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between TLR4 genotype, bacterial colonization, and asthma were analyzed. Children with TLR4 AG or GG genotype were more often colonized with Moraxella catarrhalis at 2 months of age (p = 0.009) and Haemophilus influenzae at 13 months of age (p = 0.018). Children who were colonized with H. influenzae at 13 months of age had a significantly higher risk of later development of asthma (p = 0.004). M. catarrhalis or H. Influenzae colonization at 2 months of age or TLR4 genotype Asp299Gly were not associated with the development of childhood asthma. TLR4 Asp299Gly polymorphism was associated with an increased risk of colonization of M. catarrhalis and H. influenzae in children. The colonization with H. influenzae at 13 months of age was associated with a higher risk of later development of childhood asthma. Full article
(This article belongs to the Special Issue Host Genetics in Susceptibility to Infectious Diseases)
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Open AccessFeature PaperArticle
Identification of Loci and Pathways Associated with Heifer Conception Rate in U.S. Holsteins
Genes 2020, 11(7), 767; https://doi.org/10.3390/genes11070767 (registering DOI) - 08 Jul 2020
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Abstract
Heifer conception rate (HCR) is defined as the percentage of inseminated heifers that become pregnant at each service. The genome-wide association analyses in this study focused on identifying the loci associated with Holstein heifer (n = 2013) conception rate at first service [...] Read more.
Heifer conception rate (HCR) is defined as the percentage of inseminated heifers that become pregnant at each service. The genome-wide association analyses in this study focused on identifying the loci associated with Holstein heifer (n = 2013) conception rate at first service (HCR1) and the number of times bred (TBRD) to achieve a pregnancy. There were 348 unique loci associated (p < 5 × 10−8) with HCR1 and 615 unique loci associated (p < 5 × 10−8) with TBRD. The two phenotypes shared 302 loci, and 56 loci were validated in independent cattle populations. There were 52 transcription factor binding sites (TFBS) and 552 positional candidate genes identified in the HCR1- and TBRD-associated loci. The positional candidate genes and the TFBS associated with HCR1 and TBRD were used in the ingenuity pathway analysis (IPA). In the IPA, 11 pathways, 207 master regulators and 11 upstream regulators were associated (p < 1.23 × 10−5) with HCR1 and TBRD. The validated loci associated with both HCR1 and TBRD make good candidates for genomic selection and further investigations to elucidate the mechanisms associated with subfertility and infertility. Full article
(This article belongs to the Special Issue Genetics and Genomics Applied to Livestock Production)
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Open AccessArticle
Matrix Metalloproteinase Genes (MMP1, MMP10, MMP12) on Chromosome 11q22 and the Risk of Non-Contact Anterior Cruciate Ligament Ruptures
Genes 2020, 11(7), 766; https://doi.org/10.3390/genes11070766 (registering DOI) - 08 Jul 2020
Viewed by 74
Abstract
Background: Sequence variants within the matrix metalloproteinases genes remain plausible biological candidates for further investigation of anterior cruciate ligament (ACL) rupture risk. The aim of the present study was to establish whether variants within the MMP1 (rs1799750, ->G), MMP10 (rs486055, C > T) [...] Read more.
Background: Sequence variants within the matrix metalloproteinases genes remain plausible biological candidates for further investigation of anterior cruciate ligament (ACL) rupture risk. The aim of the present study was to establish whether variants within the MMP1 (rs1799750, ->G), MMP10 (rs486055, C > T) and MMP12 (rs2276109, T > C) genes were associated with non-contact ACL rupture in a Polish cohort. Methods: The unrelated, self-reported Polish Caucasian participants consisted of 228 (157 male) individuals with primary non-contact ACL rupture and 202 (117 male) participants without any history of ACL rupture. All samples were genotyped in duplicate using the Applied Biosystems TaqMan® methodology. The statistical analyses were involved in determining the distribution of genotype and allele frequencies for the investigated polymorphisms between the diagnostic groups. Furthermore, pseudo-haplotypes were constructed to assess possible gene–gene interactions. Results: All genotype frequencies in the ACL rupture and control groups conformed to Hardy Weinberg Equilibrium expectations. None of the polymorphisms were associated with risk of non-contact ACL rupture under the codominant, dominant, recessive and over-dominant genetic models. Likewise, no genotype–genotype combinations inferred as “haplotypes” as a proxy of gene–gene interactions were associated with the risk of non-contact ACL ruptures. Conclusions: Despite the fact that the current study did not support existing evidence suggesting that variants within the MMP1, MMP10, and MMP12 genes influence non-contact ACL rupture risk, future work should include high-throughput sequencing technologies to identify potential targeted polymorphisms to fully characterize the 11q22 region with susceptibility to non-contact ACL rupture susceptibility in a Polish cohort. Full article
(This article belongs to the Special Issue Genetic Influence in Exercise Performance)
Open AccessFeature PaperReview
Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies
Genes 2020, 11(7), 765; https://doi.org/10.3390/genes11070765 (registering DOI) - 08 Jul 2020
Viewed by 189
Abstract
Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive condition caused primarily by out-of-frame mutations in the dystrophin gene. In males, DMD presents with progressive body-wide muscle deterioration, culminating in death as a result of cardiac or respiratory failure. A milder form of [...] Read more.
Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive condition caused primarily by out-of-frame mutations in the dystrophin gene. In males, DMD presents with progressive body-wide muscle deterioration, culminating in death as a result of cardiac or respiratory failure. A milder form of DMD exists, called Becker muscular dystrophy (BMD), which is typically caused by in-frame dystrophin gene mutations. It should be emphasized that DMD and BMD are not exclusive to males, as some female dystrophin mutation carriers do present with similar symptoms, generally at reduced levels of severity. Cardiac involvement in particular is a pressing concern among manifesting females, as it may develop into serious heart failure or could predispose them to certain risks during pregnancy or daily life activities. It is known that about 8% of carriers present with dilated cardiomyopathy, though it may vary from 0% to 16.7%, depending on if the carrier is classified as having DMD or BMD. Understanding the genetic and molecular mechanisms underlying cardiac manifestations in dystrophin-deficient females is therefore of critical importance. In this article, we review available information from the literature on this subject, as well as discuss the implications of female carrier studies on the development of therapies aiming to increase dystrophin levels in the heart. Full article
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Open AccessArticle
Development of a Multilocus Sequence Typing Scheme for Giardia intestinalis
Genes 2020, 11(7), 764; https://doi.org/10.3390/genes11070764 (registering DOI) - 08 Jul 2020
Viewed by 154
Abstract
Giardia intestinalis is an intestinal protozoan most commonly found in humans. It has been grouped into 8 assemblages (A-H). Markers such as the glutamate dehydrogenase gene, triose phosphate isomerase and beta-giardin (β-giardin) have been widely used for genotyping. In addition, different genetic targets [...] Read more.
Giardia intestinalis is an intestinal protozoan most commonly found in humans. It has been grouped into 8 assemblages (A-H). Markers such as the glutamate dehydrogenase gene, triose phosphate isomerase and beta-giardin (β-giardin) have been widely used for genotyping. In addition, different genetic targets have been proposed as a valuable alternative to assess diversity and genetics of this microorganism. Thus, our objective was to evaluate new markers for the study of the diversity and intra-taxa genetic structure of G. intestinalis in silico and in DNA obtained from stool samples. We analysed nine constitutive genes in 80 complete genome sequences and in a group of 24 stool samples from Colombia. Allelic diversity was evaluated by locus and for the concatenated sequence of nine loci that could discriminate up to 53 alleles. Phylogenetic reconstructions allowed us to identify AI, AII and B assemblages. We found evidence of intra- and inter-assemblage recombination events. Population structure analysis showed genetic differentiation among the assemblages analysed. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle
Quantitative Proteomics of Urinary Bladder Cancer Cell Lines Identify UAP1 as a Potential Therapeutic Target
Genes 2020, 11(7), 763; https://doi.org/10.3390/genes11070763 (registering DOI) - 08 Jul 2020
Viewed by 162
Abstract
Bladder carcinoma (BC) incidence and mortality rates are increasing worldwide. The development of novel therapeutic strategies is required to improve clinical management of this cancer. Aberrant protein expression may lead to cancer initiation and progression. Therefore, the identification of these potential protein targets [...] Read more.
Bladder carcinoma (BC) incidence and mortality rates are increasing worldwide. The development of novel therapeutic strategies is required to improve clinical management of this cancer. Aberrant protein expression may lead to cancer initiation and progression. Therefore, the identification of these potential protein targets and limiting their expression levels would provide alternative treatment options. In this study, we utilized a liquid-chromatography tandem mass spectrometry-based global proteomics approach to identify differentially expressed proteins in bladder cancer cell lines. A total of 3913 proteins were identified in this study, of which 479 proteins were overexpressed and 141 proteins were downregulated in 4 out of 6 BC cell lines when compared with normal human urothelial cell line (TERT-NHUC). We evaluated the role of UDP-N-acetylhexosamine pyrophosphorylase (UAP1) in bladder cancer pathogenesis. The silencing of UAP1 led to reduction in proliferation, invasion, colony formation and migration capability of bladder cancer cell lines. Thus, our study reveals UAP1 as a promising therapeutic target for bladder cancer. Full article
(This article belongs to the Special Issue Genetic Complexity of Hormone Sensitive Cancers)
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Open AccessArticle
Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1
Genes 2020, 11(7), 762; https://doi.org/10.3390/genes11070762 (registering DOI) - 08 Jul 2020
Viewed by 316
Abstract
Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect [...] Read more.
Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect of mebendazole, alone or in combination with cyclooxygenase-2 (COX-2) inhibitors, on the prevention of NF1-related malignancies in a cis Nf1+/-;Tp53+/- (NPcis) mouse model of NF1. Our in vitro findings showed that mebendazole (MBZ) inhibits the growth of NF1-related malignant peripheral nerve sheath tumors (MPNSTs) through a reduction in activated guanosine triphosphate (GTP)-bound Ras. The daily MBZ treatment of NPcis mice dosed at 195 mg/kg daily, initiated 60 days after birth, substantially delayed the formation of solid malignancies and increased median survival (p < 0.0001). Compared to placebo-treated mice, phosphorylated extracellular signal-regulated kinase (pERK) levels were decreased in the malignancies of MBZ-treated mice. The combination of MBZ with COX-2 inhibitor celecoxib (CXB) further enhanced the chemopreventative effect in female mice beyond each drug alone. These findings demonstrate the feasibility of a prevention strategy for malignancy development in high-risk NF1 individuals. Full article
(This article belongs to the Special Issue Genomics and Models of Nerve Sheath Tumors)
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Open AccessArticle
Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts
Genes 2020, 11(7), 761; https://doi.org/10.3390/genes11070761 (registering DOI) - 07 Jul 2020
Viewed by 223
Abstract
The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We [...] Read more.
The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide. Full article
(This article belongs to the Special Issue Rapid Evolution)
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Open AccessFeature PaperArticle
Protein Coding and Long Noncoding RNA (lncRNA) Transcriptional Landscape in SARS-CoV-2 Infected Bronchial Epithelial Cells Highlight a Role for Interferon and Inflammatory Response
Genes 2020, 11(7), 760; https://doi.org/10.3390/genes11070760 - 07 Jul 2020
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Abstract
The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from [...] Read more.
The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated. Full article
(This article belongs to the Special Issue Genomics of Host-Pathogen Interactions)
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Open AccessArticle
A SNP-Based Genome-Wide Association Study to Mine Genetic Loci Associated to Salinity Tolerance in Mungbean (Vigna radiata L.)
Genes 2020, 11(7), 759; https://doi.org/10.3390/genes11070759 (registering DOI) - 07 Jul 2020
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Abstract
Mungbean (Vigna radiata (L.) R. Wilzeck var. radiata) is a protein-rich short-duration legume that fits well as a rotation crop into major cereal production systems of East and South-East Asia. Salinity stress in arid areas affects mungbean, being more of a [...] Read more.
Mungbean (Vigna radiata (L.) R. Wilzeck var. radiata) is a protein-rich short-duration legume that fits well as a rotation crop into major cereal production systems of East and South-East Asia. Salinity stress in arid areas affects mungbean, being more of a glycophyte than cereals. A significant portion of the global arable land is either salt or sodium affected. Thus, studies to understand and improve salt-stress tolerance are imminent. Here, we conducted a genome-wide association study (GWAS) to mine genomic loci underlying salt-stress tolerance during seed germination of mungbean. The World Vegetable Center (WorldVeg) mungbean minicore collection representing the diversity of mungbean germplasm was utilized as the study panel and variation for salt stress tolerance was found in this germplasm collection. The germplasm panel was classed into two agro-climatic groups and showed significant differences in their germination abilities under salt stress. A total of 5288 SNP markers obtained through genotyping-by-sequencing (GBS) were used to mine alleles associated with salt stress tolerance. Associated SNPs were identified on chromosomes 7 and 9. The associated region at chromosome 7 (position 2,696,072 to 2,809,200 bp) contains the gene Vradi07g01630, which was annotated as the ammonium transport protein (AMT). The associated region in chromosome 9 (position 19,390,227 bp to 20,321,817 bp) contained the genes Vradi09g09510 and Vradi09g09600, annotated as OsGrx_S16-glutaredoxin subgroup II and dnaJ domain proteins respectively. These proteins were reported to have functions related to salt-stress tolerance. Full article
(This article belongs to the Special Issue Food Legume Genomics)
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Open AccessFeature PaperArticle
Semen Modulates the Expression of NGF, ABHD2, VCAN, and CTEN in the Reproductive Tract of Female Rabbits
Genes 2020, 11(7), 758; https://doi.org/10.3390/genes11070758 - 07 Jul 2020
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Abstract
Semen changes the gene expression in endometrial and oviductal tissues modulating important processes for reproduction. We tested the hypothesis that mating and/or sperm-free seminal plasma deposition in the reproductive tract affect the expression of genes associated with sperm-lining epithelium interactions, ovulation, and pre-implantation [...] Read more.
Semen changes the gene expression in endometrial and oviductal tissues modulating important processes for reproduction. We tested the hypothesis that mating and/or sperm-free seminal plasma deposition in the reproductive tract affect the expression of genes associated with sperm-lining epithelium interactions, ovulation, and pre-implantation effects (nerve growth factor, NGF; α/β hydrolase domain-containing protein 2, ABHD2; C-terminal tensin-like protein, CTEN or TNS4; and versican, VCAN) in the period 10–72 h post-mating. In Experiment 1, does (n = 9) were treated with gonadotropin-releasing hormone (GnRH) (control), GnRH-stimulated, and vaginally infused with sperm-free seminal plasma (SP-AI), or GnRH-stimulated and naturally mated (NM). In Experiment 2, does (n = 15) were GnRH-stimulated and naturally mated. Samples were retrieved from the internal reproductive tracts (cervix-to-infundibulum) 20 h post-treatment (Experiment 1) or sequentially collected at 10, 24, 36, 68, or 72 h post-mating (Experiment 2, 3 does/period). All samples were processed for gene expression analysis by quantitative PCR. Data showed an upregulation of endometrial CTEN and NGF by NM, but not by SP-AI. The findings suggest that the NGF gene affects the reproductive tract of the doe during ovulation and beyond, influencing the maternal environment during early embryonic development. Full article
(This article belongs to the Special Issue Genetics and Genomics Applied to Livestock Production)
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Open AccessBrief Report
The Need for Establishing a Universal CTG Sizing Method in Myotonic Dystrophy Type 1
Genes 2020, 11(7), 757; https://doi.org/10.3390/genes11070757 - 07 Jul 2020
Viewed by 172
Abstract
The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset [...] Read more.
The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset and clinical severity. However, accurate determination of CTG expansion size is challenging due to its characteristic instability. We compared five different approaches (heat pulse extension polymerase chain reaction [PCR], long PCR-Southern blot [with three different primers sets—1, 2 and 3] and small pool [SP]-PCR) to estimate CTG expansion size in the progenitor allele as well as the most abundant CTG expansion size, in 15 patients with DM1. Our results indicated variability between the methods (although we found no overall differences between long PCR 1 and 2 and SP-PCR, respectively). While keeping in mind the limited sample size of our patient cohort, SP-PCR appeared as the most suitable technique, with an inverse significant correlation found between CTG expansion size of the progenitor allele, as determined by this method, and age of disease onset (r = −0.734, p = 0.016). Yet, in light of the variability of the results obtained with the different methods, we propose that an international agreement is needed to determine which is the most suitable method for assessing CTG expansion size in DM1. Full article
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Open AccessArticle
ShadowCaster: Compositional Methods under the Shadow of Phylogenetic Models to Detect Horizontal Gene Transfers in Prokaryotes
Genes 2020, 11(7), 756; https://doi.org/10.3390/genes11070756 - 07 Jul 2020
Viewed by 244
Abstract
Horizontal gene transfer (HGT) plays an important role for evolutionary innovations within prokaryotic communities and is a crucial event for their survival. Several computational approaches have arisen to identify HGT events in recipient genomes. However, this has been proven to be a complex [...] Read more.
Horizontal gene transfer (HGT) plays an important role for evolutionary innovations within prokaryotic communities and is a crucial event for their survival. Several computational approaches have arisen to identify HGT events in recipient genomes. However, this has been proven to be a complex task due to the generation of a great number of false positives and the prediction disagreement among the existing methods. Phylogenetic reconstruction methods turned out to be the most reliable ones, but they are not extensible to all genes/species and are computationally demanding when dealing with large datasets. In contrast, the so-called surrogate methods that use heuristic solutions either based on nucleotide composition patterns or phyletic distribution of BLAST hits can be applied easily to the genomic scale, but they fail in identifying common HGT events. Here, we present ShadowCaster, a hybrid approach that sequentially combines nucleotide composition-based predictions by support vector machines (SVMs) under the shadow of phylogenetic models independent of tree reconstruction, to improve the detection of HGT events in prokaryotes. ShadowCaster successfully predicted close and distant HGT events in both artificial and bacterial genomes. ShadowCaster detected HGT related to heavy metal resistance in the genome of Rhodanobacter denitrificans with higher accuracy than the most popular state-of-the-art computational approaches, encompassing most of the predicted cases made by other methods. ShadowCaster is released at the GitHub platform as an open-source software under the GPLv3 license. Full article
(This article belongs to the Special Issue Horizontal Gene Transfer in Bacteria)
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Open AccessReview
Actions of L-thyroxine (T4) and Tetraiodothyroacetic Acid (Tetrac) on Gene Expression in Thyroid Cancer Cells
Genes 2020, 11(7), 755; https://doi.org/10.3390/genes11070755 - 07 Jul 2020
Viewed by 149
Abstract
The clinical behavior of thyroid cancers is seen to reflect inherent transcriptional activities of mutated genes and trophic effects on tumors of circulating pituitary thyrotropin (TSH). The thyroid hormone, L-thyroxine (T4), has been shown to stimulate proliferation of a large number of different [...] Read more.
The clinical behavior of thyroid cancers is seen to reflect inherent transcriptional activities of mutated genes and trophic effects on tumors of circulating pituitary thyrotropin (TSH). The thyroid hormone, L-thyroxine (T4), has been shown to stimulate proliferation of a large number of different forms of cancer. This activity of T4 is mediated by a cell surface receptor on the extracellular domain of integrin αvβ3. In this brief review, we describe what is known about T4 as a circulating trophic factor for differentiated (papillary and follicular) thyroid cancers. Given T4′s cancer-stimulating activity in differentiated thyroid cancers, it was not surprising to find that genomic actions of T4 were anti-apoptotic. Transduction of the T4-generated signal at the integrin primarily involved mitogen-activated protein kinase (MAPK). In thyroid C cell-origin medullary carcinoma of the thyroid (MTC), effects of thyroid hormone analogues, such as tetraiodothyroacetic acid (tetrac), include pro-angiogenic and apoptosis-linked genes. Tetrac is an inhibitor of the actions of T4 at αvβ3, and it is assumed, but not yet proved, that the anti-angiogenic and pro-apoptotic actions of tetrac in MTC cells are matched by T4 effects that are pro-angiogenic and anti-apoptotic. We also note that papillary thyroid carcinoma cells may express the leptin receptor, and circulating leptin from adipocytes may stimulate tumor cell proliferation. Transcription was stimulated by leptin in anaplastic, papillary, and follicular carcinomas of genes involved in invasion, such as matrix metalloproteinases (MMPs). In summary, thyroid hormone analogues may act at their receptor on integrin αvβ3 in a variety of types of thyroid cancer to modulate transcription of genes relevant to tumor invasiveness, apoptosis, and angiogenesis. These effects are independent of TSH. Full article
(This article belongs to the Special Issue Genetic Perspectives in Thyroid Cancer)
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Open AccessLetter
Heat Diffusion Kernel Algorithm-Based Interpretation of the Disease Intervention Mechanism for DHA
Genes 2020, 11(7), 754; https://doi.org/10.3390/genes11070754 - 07 Jul 2020
Viewed by 206
Abstract
Docosahexaenoic acid (DHA) is effective in the prevention and treatment of cancer, congenital disorders, and various chronic diseases. According to the omnigenic hypothesis, these complex diseases are caused by disordered gene regulatory networks comprising dozens to hundreds of core genes and a mass [...] Read more.
Docosahexaenoic acid (DHA) is effective in the prevention and treatment of cancer, congenital disorders, and various chronic diseases. According to the omnigenic hypothesis, these complex diseases are caused by disordered gene regulatory networks comprising dozens to hundreds of core genes and a mass of peripheral genes. However, conventional research on the disease intervention mechanism of DHA only focused on specific types of genes or pathways instead of examining genes at the network level, resulting in conflicting conclusions. In this study, we used HotNet2, a heat diffusion kernel algorithm, to calculate the gene regulatory networks of connectivity map (cMap)-derived agents (including DHA) based on gene expression profiles, aiming to interpret the disease intervention mechanism of DHA at the network level. As a result, significant gene regulatory networks for DHA and 676 cMap-derived agents were identified respectively. The biological functions of the DHA-regulated gene network provide preliminary insights into the mechanism by which DHA intervenes in disease. In addition, we compared the gene regulatory networks of DHA with those of cMap-derived agents, which allowed us to predict the pharmacological effects and disease intervention mechanism of DHA by analogy with similar agents with clear indications and mechanisms. Some of our analysis results were supported by experimental observations. Therefore, this study makes a significant contribution to research on the disease intervention mechanism of DHA at the regulatory network level, demonstrating the potential application value of this methodology in clarifying the mechanisms about nutrients influencing health. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
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Open AccessArticle
Hybridization of Russian Sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeberg, 1833) and American Paddlefish (Polyodon spathula, Walbaum 1792) and Evaluation of Their Progeny
Genes 2020, 11(7), 753; https://doi.org/10.3390/genes11070753 - 06 Jul 2020
Viewed by 211
Abstract
Two species from the families Acipenseridae and Polyodontidae, Russian sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeberg, 1833; functional tetraploid) and American paddlefish (Polyodon spathula, Walbaum 1792, functional diploid) were hybridized. The hybridization was repeated using eggs from three sturgeon and [...] Read more.
Two species from the families Acipenseridae and Polyodontidae, Russian sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeberg, 1833; functional tetraploid) and American paddlefish (Polyodon spathula, Walbaum 1792, functional diploid) were hybridized. The hybridization was repeated using eggs from three sturgeon and sperm from four paddlefish individuals. Survival in all hybrid family groups ranged from 62% to 74% 30 days after hatching. This was the first successful hybridization between these two species and between members of the family Acipenseridae and Polyodontidae. Flow cytometry and chromosome analysis revealed two ploidy levels in hybrids. The chromosome numbers of the hybrids ranged between 156–184 and 300–310, in “functional” triploids and “functional” pentaploids, respectively. The hybrid origin and the ploidy levels were also confirmed by microsatellite analyses. In hybrids, the size and the number of dorsal and ventral scutes correlated with the ploidy levels as well as with the calculated ratio of the maternal and paternal chromosome sets. An extra haploid cell lineage was found in three hybrid individuals irrespective of the ploidy level, suggesting polyspermy. Although the growth performance showed high variance in hybrids (mean: 1.2 kg, SD: 0.55), many individuals reached a size of approximately 1 kg by the age of one year under intensive rearing conditions. Full article
(This article belongs to the Special Issue Fish Cytogenetics: Present and Future)
Open AccessFeature PaperArticle
The Importance of ATM and ATR in Physcomitrella patens DNA Damage Repair, Development, and Gene Targeting
Genes 2020, 11(7), 752; https://doi.org/10.3390/genes11070752 - 06 Jul 2020
Viewed by 194
Abstract
Coordinated by ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR), two highly conserved kinases, DNA damage repair ensures genome integrity and survival in all organisms. The Arabidopsis thaliana (A. thaliana) orthologues are well characterized and exhibit typical mammalian characteristics. We mutated the [...] Read more.
Coordinated by ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR), two highly conserved kinases, DNA damage repair ensures genome integrity and survival in all organisms. The Arabidopsis thaliana (A. thaliana) orthologues are well characterized and exhibit typical mammalian characteristics. We mutated the Physcomitrella patens (P. patens) PpATM and PpATR genes by deleting functionally important domains using gene targeting. Both mutants showed growth abnormalities, indicating that these genes, particularly PpATR, are important for normal vegetative development. ATR was also required for repair of both direct and replication-coupled double-strand breaks (DSBs) and dominated the transcriptional response to direct DSBs, whereas ATM was far less important, as shown by assays assessing resistance to DSB induction and SuperSAGE-based transcriptomics focused on DNA damage repair genes. These characteristics differed significantly from the A. thaliana genes but resembled those in yeast (Saccharomyces cerevisiae). PpATR was not important for gene targeting, pointing to differences in the regulation of gene targeting and direct DSB repair. Our analysis suggests that ATM and ATR functions can be substantially diverged between plants. The differences in ATM and ATR reflect the differences in DSB repair pathway choices between A. thaliana and P. patens, suggesting that they represent adaptations to different demands for the maintenance of genome stability. Full article
(This article belongs to the Special Issue DNA Damage Repair in Plants)
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Open AccessArticle
Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas
Genes 2020, 11(7), 751; https://doi.org/10.3390/genes11070751 - 06 Jul 2020
Viewed by 354
Abstract
TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC [...] Read more.
TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Solid Tumors)
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Open AccessArticle
Detection of Multiple Transgene Fragments in a Mouse Model of Gene Doping Based on Plasmid Vector Using TaqMan-qPCR Assay
Genes 2020, 11(7), 750; https://doi.org/10.3390/genes11070750 - 06 Jul 2020
Viewed by 154
Abstract
The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the augmentation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been [...] Read more.
The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the augmentation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. Firstly, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan- quantitative real-time PCR(qPCR) assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessReview
Genetic and Genomic Landscape of Secondary and Therapy-Related Acute Myeloid Leukemia
Genes 2020, 11(7), 749; https://doi.org/10.3390/genes11070749 - 06 Jul 2020
Viewed by 145
Abstract
A subset of acute myeloid leukemia (AML) arises either from an antecedent myeloid malignancy (secondary AML, sAML) or as a complication of DNA-damaging therapy for other cancers (therapy-related myeloid neoplasm, t-MN). These secondary leukemias have unique biological and clinical features that distinguish them [...] Read more.
A subset of acute myeloid leukemia (AML) arises either from an antecedent myeloid malignancy (secondary AML, sAML) or as a complication of DNA-damaging therapy for other cancers (therapy-related myeloid neoplasm, t-MN). These secondary leukemias have unique biological and clinical features that distinguish them from de novo AML. Over the last decade, molecular techniques have unraveled the complex subclonal architecture of sAML and t-MN. In this review, we compare and contrast biological and clinical features of de novo AML with sAML and t-MN. We discuss the role of genetic mutations, including those involved in RNA splicing, epigenetic modification, tumor suppression, transcription regulation, and cell signaling, in the pathogenesis of secondary leukemia. We also discuss clonal hematopoiesis in otherwise healthy individuals, as well as in the context of another malignancy, and how it challenges the conventional notion of sAML/t-MN. We conclude by summarizing the current and emerging treatment strategies, including allogenic transplant, in these complex scenarios. Full article
(This article belongs to the Special Issue Genetics and Genomics of Acute Myeloid Leukemia)
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Open AccessArticle
Spatial and Temporal Dynamics of Contact Zones Between Chromosomal Races of House Mice, Mus musculus domesticus, on Madeira Island
Genes 2020, 11(7), 748; https://doi.org/10.3390/genes11070748 - 06 Jul 2020
Viewed by 163
Abstract
Analysis of contact zones between parapatric chromosomal races can help our understanding of chromosomal divergence and its influence on the speciation process. Monitoring the position and any movement of contact zones can allow particular insights. This study investigates the present (2012–2014) and past [...] Read more.
Analysis of contact zones between parapatric chromosomal races can help our understanding of chromosomal divergence and its influence on the speciation process. Monitoring the position and any movement of contact zones can allow particular insights. This study investigates the present (2012–2014) and past (1998–2002) distribution of two parapatric house mouse chromosomal races—PEDC (Estreito da Calheta) and PADC (Achadas da Cruz)—on Madeira Island, aiming to identify changes in the location and width of their contact. We also extended the 1998–2002 sampling area into the range of another chromosomal race—PLDB (Lugar de Baixo). Clinal analysis indicates no major geographic alterations in the distribution and chromosomal characteristics of the PEDC and PADC races but exhibited a significant shift in position of the Rb (7.15) fusion, resulting in the narrowing of the contact zone over a 10+ year period. We discuss how this long-lasting contact zone highlights the role of landscape on mouse movements, in turn influencing the chromosomal characteristics of populations. The expansion of the sampling area revealed new chromosomal features in the north and a new contact zone in the southern range involving the PEDC and PLDB races. We discuss how different interacting mechanisms (landscape resistance, behaviour, chromosomal incompatibilities, meiotic drive) may help to explain the pattern of chromosomal variation at these contacts between chromosomal races. Full article
(This article belongs to the Special Issue Mechanisms of Driving Karyotype Evolution and Genomic Architecture)
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Open AccessFeature PaperReview
Precision and Personalized Medicine: How Genomic Approach Improves the Management of Cardiovascular and Neurodegenerative Disease
Genes 2020, 11(7), 747; https://doi.org/10.3390/genes11070747 - 06 Jul 2020
Viewed by 214
Abstract
Life expectancy has gradually grown over the last century. This has deeply affected healthcare costs, since the growth of an aging population is correlated to the increasing burden of chronic diseases. This represents the interesting challenge of how to manage patients with chronic [...] Read more.
Life expectancy has gradually grown over the last century. This has deeply affected healthcare costs, since the growth of an aging population is correlated to the increasing burden of chronic diseases. This represents the interesting challenge of how to manage patients with chronic diseases in order to improve health care budgets. Effective primary prevention could represent a promising route. To this end, precision, together with personalized medicine, are useful instruments in order to investigate pathological processes before the appearance of clinical symptoms and to guide physicians to choose a targeted therapy to manage the patient. Cardiovascular and neurodegenerative diseases represent suitable models for taking full advantage of precision medicine technologies applied to all stages of disease development. The availability of high technology incorporating artificial intelligence and advancement progress made in the field of biomedical research have been substantial to understand how genes, epigenetic modifications, aging, nutrition, drugs, microbiome and other environmental factors can impact health and chronic disorders. The aim of the present review is to address how precision and personalized medicine can bring greater clarity to the clinical and biological complexity of these types of disorders associated with high mortality, involving tremendous health care costs, by describing in detail the methods that can be applied. This might offer precious tools for preventive strategies and possible clues on the evolution of the disease and could help in predicting morbidity, mortality and detecting chronic disease indicators much earlier in the disease course. This, of course, will have a major effect on both improving the quality of care and quality of life of the patients and reducing time efforts and healthcare costs. Full article
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Open AccessArticle
Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment
Genes 2020, 11(7), 746; https://doi.org/10.3390/genes11070746 - 06 Jul 2020
Viewed by 178
Abstract
Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation [...] Read more.
Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. Methods: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. Results: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). Conclusion: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline. Full article
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Open AccessArticle
A New Intra-Specific and High-Resolution Genetic Map of Eggplant Based on a RIL Population, and Location of QTLs Related to Plant Anthocyanin Pigmentation and Seed Vigour
Genes 2020, 11(7), 745; https://doi.org/10.3390/genes11070745 (registering DOI) - 04 Jul 2020
Viewed by 357
Abstract
Eggplant is the second most important solanaceous berry-producing crop after tomato. Despite mapping studies based on bi-parental progenies and GWAS approaches having been performed, an eggplant intraspecific high-resolution map is still lacking. We developed a RIL population from the intraspecific cross ‘305E40’, (androgenetic [...] Read more.
Eggplant is the second most important solanaceous berry-producing crop after tomato. Despite mapping studies based on bi-parental progenies and GWAS approaches having been performed, an eggplant intraspecific high-resolution map is still lacking. We developed a RIL population from the intraspecific cross ‘305E40’, (androgenetic introgressed line carrying the locus Rfo-Sa1 conferring Fusarium resistance) x ‘67/3’ (breeding line whose genome sequence was recently released). One hundred and sixty-three RILs were genotyped by a genotype-by-sequencing (GBS) approach, which allowed us to identify 10,361 polymorphic sites. Overall, 267 Gb of sequencing data were generated and ~773 M Illumina paired end (PE) reads were mapped against the reference sequence. A new linkage map was developed, including 7249 SNPs assigned to the 12 chromosomes and spanning 2169.23 cM, with [email protected] average distance of 0.4 cM between adjacent markers. This was used to elucidate the genetic bases of seven traits related to anthocyanin content in different organs recorded in three locations as well as seed vigor. Overall, from 7 to 17 QTLs (at least one major QTL) were identified for each trait. These results demonstrate that our newly developed map supplies valuable information for QTL fine mapping, candidate gene identification, and the development of molecular markers for marker assisted selection (MAS) of favorable alleles. Full article
(This article belongs to the Special Issue Genetic Diversity Assessment and Marker-Assisted Selection in Crops)
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