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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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12 pages, 256 KiB  
Review
Advances in Ophthalmic Epigenetics and Implications for Epigenetic Therapies: A Review
by Spencer M. Moore and John B. Christoforidis
Genes 2023, 14(2), 417; https://doi.org/10.3390/genes14020417 - 5 Feb 2023
Cited by 4 | Viewed by 3752
Abstract
The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events [...] Read more.
The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events in retinal development, aging, and degeneration. Epigenetic signaling regulates retinal progenitor (RPC) cell cycle exit during retinal laminar development, giving rise to retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, photoreceptors, and Müller glia. Age-related epigenetic changes such as DNA methylation in the retina and optic nerve are accelerated in pathogenic conditions such as glaucoma and macular degeneration, but reversing these epigenetic marks may represent a novel therapeutic target. Epigenetic writers also integrate environmental signals such as hypoxia, inflammation, and hyperglycemia in complex retinal conditions such as diabetic retinopathy (DR) and choroidal neovascularization (CNV). Histone deacetylase (HDAC) inhibitors protect against apoptosis and photoreceptor degeneration in animal models of retinitis pigmentosa (RP). The epigenome represents an intriguing therapeutic target for age-, genetic-, and neovascular-related retinal diseases, though more work is needed before advancement to clinical trials. Full article
(This article belongs to the Special Issue Ophthalmic Genetics, Epigenetics, and Disease)
6 pages, 238 KiB  
Communication
Effect of Different Anticoagulant Agents on Immune-Related Genes in Leukocytes Isolated from the Whole-Blood of Holstein Cows
by Viviana Floridia, Marta Sfulcini, Enrico D’Alessandro, Luca Cattaneo, Matteo Mezzetti, Luigi Liotta, Erminio Trevisi, Vincenzo Lopreiato and Andrea Minuti
Genes 2023, 14(2), 406; https://doi.org/10.3390/genes14020406 - 4 Feb 2023
Cited by 1 | Viewed by 2509
Abstract
Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate (Na-citrate), or heparin are normally used in hematological clinical tests to prevent coagulation. Although anticoagulants are fundamental for the correct application of clinical tests, they produce adverse effects in different fields, such as those involving [...] Read more.
Anticoagulants, such as ethylenediaminetetraacetic acid (EDTA), sodium citrate (Na-citrate), or heparin are normally used in hematological clinical tests to prevent coagulation. Although anticoagulants are fundamental for the correct application of clinical tests, they produce adverse effects in different fields, such as those involving specific molecular techniques; for instance, quantitative real time polymerase chain reactions (qPCR) and gene expression evaluation. For this reason, the aim of this study was to evaluate the expression of 14 genes in leukocytes that were isolated from the blood of Holstein cows, and which were collected in Li-heparin, K-EDTA, or Na-citrate tubes; then, they were analyzed using qPCR. Only the SDHA gene showed a significant dependence (p ≤ 0.05) on the anticoagulant that was used with the lowest expression; this was observed in Na-Citrate after being compared with Li-heparin and K-EDTA (p < 0.05). Although a variation in transcript abundance with the three anticoagulants was observed in almost all the investigated genes, the relative abundance levels were not statistically significant. In conclusion, the qPCR results were not influenced by the presence of the anticoagulant; thus, we had the opportunity to choose the test tube that was used in the experiment without interfering effects impacting the gene expression levels caused by the anticoagulant. Full article
(This article belongs to the Section Animal Genetics and Genomics)
17 pages, 1161 KiB  
Review
Molecular Evolution of SARS-CoV-2 during the COVID-19 Pandemic
by Luis Daniel González-Vázquez and Miguel Arenas
Genes 2023, 14(2), 407; https://doi.org/10.3390/genes14020407 - 4 Feb 2023
Cited by 19 | Viewed by 5272
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10−3–10−4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments. Full article
(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)
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14 pages, 2165 KiB  
Article
An Iterative Unsupervised Method for Gene Expression Differentiation
by Olga Georgieva
Genes 2023, 14(2), 412; https://doi.org/10.3390/genes14020412 - 4 Feb 2023
Cited by 1 | Viewed by 1819
Abstract
For several decades, intensive research for understanding gene activity and its role in organism’s lives is the research focus of scientists in different areas. A part of these investigations is the analysis of gene expression data for selecting differentially expressed genes. Methods that [...] Read more.
For several decades, intensive research for understanding gene activity and its role in organism’s lives is the research focus of scientists in different areas. A part of these investigations is the analysis of gene expression data for selecting differentially expressed genes. Methods that identify the interested genes have been proposed on statistical data analysis. The problem is that there is no good agreement among them, as different results are produced by distinct methods. By taking the advantage of the unsupervised data analysis, an iterative clustering procedure that finds differentially expressed genes shows promising results. In the present paper, a comparative study of the clustering methods applied for gene expression analysis is presented to explicate the choice of the clustering algorithm implemented in the method. An investigation of different distance measures is provided to reveal those that increase the efficiency of the method in finding the real data structure. Further, the method is improved by incorporating an additional aggregation measure based on the standard deviation of the expression levels. Its usage increases the gene distinction as a new amount of differentially expressed genes is found. The method is summarized in a detailed procedure. The significance of the method is proved by an analysis of two mice strain data sets. The differentially expressed genes defined by the proposed method are compared with those selected by the well-known statistical methods applied to the same data set. Full article
(This article belongs to the Special Issue Selected Papers from the 9th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2022))
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8 pages, 1029 KiB  
Communication
Fusion Gene-Based Classification of Variant Cytogenetic Rearrangements in Acute Myeloid Leukemia
by Mary Gudipati, Melody Butler, Rima Koka, Maria R. Baer and Yi Ning
Genes 2023, 14(2), 396; https://doi.org/10.3390/genes14020396 - 3 Feb 2023
Cited by 1 | Viewed by 2587
Abstract
Acute myeloid leukemia (AML) represents a heterogeneous disease entity that is continuously moving to a more genetically defined classification. The classification of AML with recurrent chromosomal translocations, including those involving core binding factor subunits, plays a critical role in diagnosis, prognosis, treatment stratification, [...] Read more.
Acute myeloid leukemia (AML) represents a heterogeneous disease entity that is continuously moving to a more genetically defined classification. The classification of AML with recurrent chromosomal translocations, including those involving core binding factor subunits, plays a critical role in diagnosis, prognosis, treatment stratification, and residual disease evaluation. Accurate classification of variant cytogenetic rearrangements in AML contributes to effective clinical management. We report here the identification of four variant t(8;V;21) translocations in newly diagnosed AML patients. Two patients showed a t(8;14) and a t(8;10) variation, respectively, with a morphologically normal-appearing chromosome 21 in each initial karyotype. Subsequent fluorescence in situ hybridization (FISH) on metaphase cells revealed cryptic three-way translocations t(8;14;21) and t(8;10;21). Each resulted in RUNX1::RUNX1T1 fusion. The other two patients showed karyotypically visible three-way translocations t(8;16;21) and t(8;20;21), respectively. Each resulted in RUNX1::RUNX1T1 fusion. Our findings demonstrate the importance of recognizing variant forms of t(8;21) translocations and emphasize the value of applying RUNX1::RUNX1T1 FISH for the detection of cryptic and complex rearrangements when abnormalities involving chromosome band 8q22 are observed in patients with AML. Full article
(This article belongs to the Special Issue Advances in Clinical Cytogenetics)
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15 pages, 1815 KiB  
Article
Increased On-Target Rate and Risk of Concatemerization after CRISPR-Enhanced Targeting in ES Cells
by Valérie Erbs, Romain Lorentz, Benjamin Eisenman, Laurence Schaeffer, Laurence Luppi, Loic Lindner, Yann Hérault, Guillaume Pavlovic, Marie Wattenhofer-Donzé and Marie-Christine Birling
Genes 2023, 14(2), 401; https://doi.org/10.3390/genes14020401 - 3 Feb 2023
Cited by 5 | Viewed by 3021
Abstract
The French mouse clinic (Institut Clinique de la Souris; ICS) has produced more than 2000 targeting vectors for ‘à la carte’ mutagenesis in C57BL/6N mice. Although most of the vectors were used successfully for homologous recombination in murine embryonic stem cells (ESCs), a [...] Read more.
The French mouse clinic (Institut Clinique de la Souris; ICS) has produced more than 2000 targeting vectors for ‘à la carte’ mutagenesis in C57BL/6N mice. Although most of the vectors were used successfully for homologous recombination in murine embryonic stem cells (ESCs), a few have failed to target a specific locus after several attempts. We show here that co-electroporation of a CRISPR plasmid with the same targeting construct as the one that failed previously allows the systematic achievement of positive clones. A careful validation of these clones is, however, necessary as a significant number of clones (but not all) show a concatemerization of the targeting plasmid at the locus. A detailed Southern blot analysis permitted characterization of the nature of these events as standard long-range 5′ and 3′ PCRs were not able to distinguish between correct and incorrect alleles. We show that a simple and inexpensive PCR performed prior to ESC amplification allows detection and elimination of those clones with concatemers. Finally, although we only tested murine ESCs, our results highlight the risk of mis-validation of any genetically modified cell line (such as established lines, induced pluripotent stem cells or those used for ex vivo gene therapy) that combines the use of CRISPR/Cas9 and a circular double-stranded donor. We strongly advise the CRISPR community to perform a Southern blot with internal probes when using CRISPR to enhance homologous recombination in any cell type, including fertilized oocytes. Full article
(This article belongs to the Special Issue Transgenic Animal Models for Disease Research)
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17 pages, 5048 KiB  
Review
The Genetics of Primary Biliary Cholangitis: A GWAS and Post-GWAS Update
by Yuki Hitomi and Minoru Nakamura
Genes 2023, 14(2), 405; https://doi.org/10.3390/genes14020405 - 3 Feb 2023
Cited by 15 | Viewed by 3716
Abstract
Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which the small intrahepatic bile ducts are destroyed by autoimmune reactions. Among autoimmune diseases, which are polygenic complex traits caused by the combined contribution of genetic and environmental factors, PBC exhibits [...] Read more.
Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which the small intrahepatic bile ducts are destroyed by autoimmune reactions. Among autoimmune diseases, which are polygenic complex traits caused by the combined contribution of genetic and environmental factors, PBC exhibits the strongest involvement of genetic heritability in disease development. As at December 2022, genome-wide association studies (GWASs) and associated meta-analyses identified approximately 70 PBC susceptibility gene loci in various populations, including those of European and East Asian descent. However, the molecular mechanisms through which these susceptibility loci affect the pathogenesis of PBC are not fully understood. This study provides an overview of current data regarding the genetic factors of PBC as well as post-GWAS approaches to identifying primary functional variants and effector genes in disease-susceptibility loci. Possible mechanisms of these genetic factors in the development of PBC are also discussed, focusing on four major disease pathways identified by in silico gene set analyses, namely, (1) antigen presentation by human leukocyte antigens, (2) interleukin-12-related pathways, (3) cellular responses to tumor necrosis factor, and (4) B cell activation, maturation, and differentiation pathways. Full article
(This article belongs to the Special Issue Genetics of Autoimmune Diseases)
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11 pages, 1559 KiB  
Article
Detecting Melanocortin 1 Receptor Gene’s SNPs by CRISPR/enAsCas12a
by Wei Yang, Dagang Tao, Bingrong Xu, Yueting Zheng and Shuhong Zhao
Genes 2023, 14(2), 394; https://doi.org/10.3390/genes14020394 - 2 Feb 2023
Cited by 5 | Viewed by 2279
Abstract
Beyond its powerful genome-editing capabilities, the CRISPR/Cas system has opened up a new era of molecular diagnostics due to its highly specific base recognition and trans-cleavage activity. However, most CRISPR/Cas detection systems are mainly used to detect nucleic acids of bacteria or viruses, [...] Read more.
Beyond its powerful genome-editing capabilities, the CRISPR/Cas system has opened up a new era of molecular diagnostics due to its highly specific base recognition and trans-cleavage activity. However, most CRISPR/Cas detection systems are mainly used to detect nucleic acids of bacteria or viruses, while the application of single nucleotide polymorphism (SNP) detection is limited. The MC1R SNPs were investigated by CRISPR/enAsCas12a and are not limited to the protospacer adjacent motif (PAM) sequence in vitro. Specifically, we optimized the reaction conditions, which proved that the enAsCas12a has a preference for divalent magnesium ion (Mg2+) and can effectively distinguish the genes with a single base difference in the presence of Mg2+, and the Melanocortin l receptor (MC1R) gene with three kinds of SNP sites (T305C, T363C, and G727A) was quantitatively detected. Since the enAsCas12a is not limited by PAM sequence in vitro, the method shown here can extend this extraordinary CRISPR/enAsCas12a detection system to other SNP targets, thus providing a general SNP detection toolbox. Full article
(This article belongs to the Special Issue CRISPR-Based Nucleic Acid Detection and Genome Editing in Animals)
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25 pages, 2038 KiB  
Review
Morphological and Molecular Bases of Male Infertility: A Closer Look at Sperm Flagellum
by Rute Pereira and Mário Sousa
Genes 2023, 14(2), 383; https://doi.org/10.3390/genes14020383 - 1 Feb 2023
Cited by 16 | Viewed by 10452
Abstract
Infertility is a major health problem worldwide without an effective therapy or cure. It is estimated to affect 8–12% of couples in the reproductive age group, equally affecting both genders. There is no single cause of infertility, and its knowledge is still far [...] Read more.
Infertility is a major health problem worldwide without an effective therapy or cure. It is estimated to affect 8–12% of couples in the reproductive age group, equally affecting both genders. There is no single cause of infertility, and its knowledge is still far from complete, with about 30% of infertile couples having no cause identified (named idiopathic infertility). Among male causes of infertility, asthenozoospermia (i.e., reduced sperm motility) is one of the most observed, being estimated that more than 20% of infertile men have this condition. In recent years, many researchers have focused on possible factors leading to asthenozoospermia, revealing the existence of many cellular and molecular players. So far, more than 4000 genes are thought to be involved in sperm production and as regulators of different aspects of sperm development, maturation, and function, and all can potentially cause male infertility if mutated. In this review, we aim to give a brief overview of the typical sperm flagellum morphology and compile some of the most relevant information regarding the genetic factors involved in male infertility, with a focus on sperm immotility and on genes related to sperm flagellum development, structure, or function. Full article
(This article belongs to the Special Issue Genetic Causes of Human Infertility)
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21 pages, 1401 KiB  
Article
Assessing Outlier Probabilities in Transcriptomics Data When Evaluating a Classifier
by Magdalena Kircher, Josefin Säurich, Michael Selle and Klaus Jung
Genes 2023, 14(2), 387; https://doi.org/10.3390/genes14020387 - 1 Feb 2023
Viewed by 2887
Abstract
Outliers in the training or test set used to fit and evaluate a classifier on transcriptomics data can considerably change the estimated performance of the model. Hence, an either too weak or a too optimistic accuracy is then reported and the estimated model [...] Read more.
Outliers in the training or test set used to fit and evaluate a classifier on transcriptomics data can considerably change the estimated performance of the model. Hence, an either too weak or a too optimistic accuracy is then reported and the estimated model performance cannot be reproduced on independent data. It is then also doubtful whether a classifier qualifies for clinical usage. We estimate classifier performances in simulated gene expression data with artificial outliers and in two real-world datasets. As a new approach, we use two outlier detection methods within a bootstrap procedure to estimate the outlier probability for each sample and evaluate classifiers before and after outlier removal by means of cross-validation. We found that the removal of outliers changed the classification performance notably. For the most part, removing outliers improved the classification results. Taking into account the fact that there are various, sometimes unclear reasons for a sample to be an outlier, we strongly advocate to always report the performance of a transcriptomics classifier with and without outliers in training and test data. This provides a more diverse picture of a classifier’s performance and prevents reporting models that later turn out to be not applicable for clinical diagnoses. Full article
(This article belongs to the Collection Feature Papers in Bioinformatics)
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10 pages, 2352 KiB  
Case Report
De Novo Variant in the KCNJ9 Gene as a Possible Cause of Neonatal Seizures
by Taisiya O. Kochetkova, Dmitry N. Maslennikov, Ekaterina R. Tolmacheva, Jekaterina Shubina, Anna S. Bolshakova, Dzhenneta I. Suvorova, Anna V. Degtyareva, Irina V. Orlovskaya, Maria V. Kuznetsova, Anastasia A. Rachkova, Gennady T. Sukhikh, Denis V. Rebrikov and Dmitriy Yu. Trofimov
Genes 2023, 14(2), 366; https://doi.org/10.3390/genes14020366 - 31 Jan 2023
Cited by 1 | Viewed by 2324
Abstract
Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented [...] Read more.
Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented with convulsive syndrome on the third day of life. Generalized convulsive seizures were accompanied by electroencephalographic patterns corresponding to epileptiform activity. Proband WES expanded to trio sequencing was performed. Results: A differential diagnosis was made between symptomatic (dysmetabolic, structural, infectious) neonatal seizures and benign neonatal seizures. There were no data in favor of the dysmetabolic, structural, or infectious nature of seizures. Molecular karyotyping and whole exome sequencing were not informative. Trio WES revealed a de novo variant in the KCNJ9 gene (1:160087612T > C, p.Phe326Ser, NM_004983), for which, according to the OMIM database, no association with the disease has been described to date. Three-dimensional modeling was used to predict the structure of the KCNJ9 protein using the known structure of its homologs. According to the predictions, Phe326Ser change possibly disrupts the hydrophobic contacts with the valine side chain. Destabilization of the neighboring structures may undermine the formation of GIRK2/GIRK3 tetramers necessary for their proper functioning. Conclusions: We believe that the identified variant may be the cause of the disease in this patient but further studies, including the search for other patients with the KCNJ9 variants, are needed. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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20 pages, 13468 KiB  
Article
Making the Genome Huge: The Case of Triatoma delpontei, a Triatominae Species with More than 50% of Its Genome Full of Satellite DNA
by Pablo Mora, Sebastián Pita, Eugenia E. Montiel, José M. Rico-Porras, Teresa Palomeque, Francisco Panzera and Pedro Lorite
Genes 2023, 14(2), 371; https://doi.org/10.3390/genes14020371 - 31 Jan 2023
Cited by 19 | Viewed by 2564
Abstract
The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug [...] Read more.
The genome of Triatoma delpontei Romaña & Abalos 1947 is the largest within Heteroptera, approximately two to three times greater than other evaluated Heteroptera genomes. Here, the repetitive fraction of the genome was determined and compared with its sister species Triatoma infestans Klug 1834, in order to shed light on the karyotypic and genomic evolution of these species. The T. delpontei repeatome analysis showed that the most abundant component in its genome is satellite DNA, which makes up more than half of the genome. The T. delpontei satellitome includes 160 satellite DNA families, most of them also present in T. infestans. In both species, only a few satellite DNA families are overrepresented on the genome. These families are the building blocks of the C-heterochromatic regions. Two of these satellite DNA families that form the heterochromatin are the same in both species. However, there are satellite DNA families highly amplified in the heterochromatin of one species that in the other species are in low abundance and located in the euchromatin. Therefore, the present results depicted the great impact of the satellite DNA sequences in the evolution of Triatominae genomes. Within this scenario, satellitome determination and analysis led to a hypothesis that explains how satDNA sequences have grown on T. delpontei to reach its huge genome size within true bugs. Full article
(This article belongs to the Special Issue State-of-the-Art in Insect Cytogenetics)
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19 pages, 2999 KiB  
Review
Nonsense-Mediated mRNA Decay as a Mediator of Tumorigenesis
by Preeti Nagar, Md Rafikul Islam and Mohammad Alinoor Rahman
Genes 2023, 14(2), 357; https://doi.org/10.3390/genes14020357 - 30 Jan 2023
Cited by 16 | Viewed by 6659
Abstract
Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved and well-characterized biological mechanism that ensures the fidelity and regulation of gene expression. Initially, NMD was described as a cellular surveillance or quality control process to promote selective recognition and rapid degradation of erroneous transcripts [...] Read more.
Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved and well-characterized biological mechanism that ensures the fidelity and regulation of gene expression. Initially, NMD was described as a cellular surveillance or quality control process to promote selective recognition and rapid degradation of erroneous transcripts harboring a premature translation-termination codon (PTC). As estimated, one-third of mutated and disease-causing mRNAs were reported to be targeted and degraded by NMD, suggesting the significance of this intricate mechanism in maintaining cellular integrity. It was later revealed that NMD also elicits down-regulation of many endogenous mRNAs without mutations (~10% of the human transcriptome). Therefore, NMD modulates gene expression to evade the generation of aberrant truncated proteins with detrimental functions, compromised activities, or dominant-negative effects, as well as by controlling the abundance of endogenous mRNAs. By regulating gene expression, NMD promotes diverse biological functions during development and differentiation, and facilitates cellular responses to adaptation, physiological changes, stresses, environmental insults, etc. Mutations or alterations (such as abnormal expression, degradation, post-translational modification, etc.) that impair the function or expression of proteins associated with the NMD pathway can be deleterious to cells and may cause pathological consequences, as implicated in developmental and intellectual disabilities, genetic defects, and cancer. Growing evidence in past decades has highlighted NMD as a critical driver of tumorigenesis. Advances in sequencing technologies provided the opportunity to identify many NMD substrate mRNAs in tumor samples compared to matched normal tissues. Interestingly, many of these changes are tumor-specific and are often fine-tuned in a tumor-specific manner, suggesting the complex regulation of NMD in cancer. Tumor cells differentially exploit NMD for survival benefits. Some tumors promote NMD to degrade a subset of mRNAs, such as those encoding tumor suppressors, stress response proteins, signaling proteins, RNA binding proteins, splicing factors, and immunogenic neoantigens. In contrast, some tumors suppress NMD to facilitate the expression of oncoproteins or other proteins beneficial for tumor growth and progression. In this review, we discuss how NMD is regulated as a critical mediator of oncogenesis to promote the development and progression of tumor cells. Understanding how NMD affects tumorigenesis differentially will pave the way for the development of more effective and less toxic, targeted therapeutic opportunities in the era of personalized medicine. Full article
(This article belongs to the Special Issue RNA Splicing in Cancer and Targeted Therapies)
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16 pages, 2981 KiB  
Article
Phylogenetic Position of Haemaphysalis kashmirensis and Haemaphysalis cornupunctata, with Notes on Rickettsia spp.
by Shah Masood Khan, Mehran Khan, Abdulaziz Alouffi, Mashal M. Almutairi, Muhmmad Numan, Shafi Ullah, Muhammad Kashif Obaid, Zia Ul Islam, Haroon Ahmed, Tetsuya Tanaka and Abid Ali
Genes 2023, 14(2), 360; https://doi.org/10.3390/genes14020360 - 30 Jan 2023
Cited by 14 | Viewed by 2184
Abstract
Despite high diversity in the Oriental region, ticks of the genus Haemaphysalis have been neglected regarding their genetic data and vector potential. This study aimed to genetically characterize three species of the genus Haemaphysalis: Haemaphysalis cornupunctata, Haemaphysalis kashmirensis, and Haemaphysalis montgomeryi [...] Read more.
Despite high diversity in the Oriental region, ticks of the genus Haemaphysalis have been neglected regarding their genetic data and vector potential. This study aimed to genetically characterize three species of the genus Haemaphysalis: Haemaphysalis cornupunctata, Haemaphysalis kashmirensis, and Haemaphysalis montgomeryi infesting goats and sheep, and Rickettsia spp. associated with these tick species in the Hindu Kush Himalayan range of Pakistan. Altogether, 834 ticks were collected by examining 120 hosts including goats (64/120, 53.3%) and sheep (56/120, 46.6%), in which 86 (71.6%) hosts were found to be tick-infested. The morphologically identified ticks were subjected to DNA extraction and PCR for the amplification of partial 16S rDNA and cox fragments. Rickettsia spp. associated with the collected ticks were detected through the amplification of gltA, ompA and ompB partial fragments. The 16S rDNA of H. cornupunctata and H. montgomeryi showed a maximum identity of 100% with the sequences of the same species, whereas the 16S rDNA of H. kashmirensis showed the highest identity of 93–95% with Haemaphysalis sulcata. The cox sequence of H. montgomeryi displayed 100% identity with the same species. In comparison, the cox sequences of H. cornupunctata and H. kashmirensis showed maximum identities of 87.65–89.22% with Haemaphysalis punctata and 89.34% with H. sulcata, respectively. The gltA sequence of Rickettsia sp. from H. kashmirensis showed the highest identity of 97.89% with Rickettsia conorii subsp. raoultii, while the ompA and ompB fragments from the same DNA samples revealed 100% and 98.16% identity with Rickettsia sp. and “Candidatus Rickettsia longicornii”, respectively. Another gltA sequence amplified from H. montgomeryi ticks showed 100% identity with Rickettsia hoogstraalii, while the attempts to amplify ompA and ompB for R. hoogstraalii were unsuccessful. In the phylogenetic tree, the 16S rDNA of H. cornupunctata clustered with the corresponding species while its cox clustered with H. punctata. Both 16S rDNA and cox sequences of H. kashmirensis clustered with H. sulcata. The gltA sequence of Rickettsia sp. was clustered individually in the spotted fever (SF) group of Rickettsia, while the gltA sequence of R. hoogstraalii was clustered with the same species in the transition group of Rickettsia. In the SF group, the rickettsial ompA and ompB sequence clustered with undetermined Rickettsia sp. and “Candidatus Rickettsia longicornii”, respectively. This is the earliest study regarding the genetic characterization of H. kashmirensis. This study indicated that ticks belong to the genus Haemaphysalis have the potential of harboring and/or transmitting Rickettsia spp. in the region. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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18 pages, 1254 KiB  
Review
Histone Modifications in Alzheimer’s Disease
by Dalileia Aparecida Santana, Marilia de Arruda Cardoso Smith and Elizabeth Suchi Chen
Genes 2023, 14(2), 347; https://doi.org/10.3390/genes14020347 - 29 Jan 2023
Cited by 56 | Viewed by 6024
Abstract
Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications [...] Read more.
Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease’s onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer’s disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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11 pages, 1725 KiB  
Article
Response Surface Methodology for Optimization of Multiplex-PCR Protocols for Detection of TYLCV, TSWV and Fol Molecular Markers: Analytical Performance Evaluation
by Richecarde Lafrance, José Benigno Valdez-Torres, Claudia Villicaña, Raymundo Saúl García-Estrada, Mayra Janeth Esparza-Araiza and Josefina León-Félix
Genes 2023, 14(2), 337; https://doi.org/10.3390/genes14020337 - 28 Jan 2023
Cited by 3 | Viewed by 3508
Abstract
Molecular markers linked to disease resistance genes which affect economically important crops are of great interest. In the case of tomato, a major focus on resistance breeding to multiple fungal and viral pathogens such as Tomato yellow leaf curl virus (TYLCV), Tomato spotted [...] Read more.
Molecular markers linked to disease resistance genes which affect economically important crops are of great interest. In the case of tomato, a major focus on resistance breeding to multiple fungal and viral pathogens such as Tomato yellow leaf curl virus (TYLCV), Tomato spotted wilt virus (TSWV) and Fusarium oxysporum f. sp. lycopersici (Fol), have led to the introgression of several resistance genes; therefore, molecular markers have become important in molecular-assisted selection (MAS) of tomato varieties resistant to those pathogens. However, assays that allow simultaneous evaluation of resistant genotypes, such as multiplex PCR, need to be optimized and evaluated to demonstrate their analytical performance, as many factors can affect them. This work aimed to generate multiplex PCR protocols for the joint detection of the molecular markers associated with pathogen resistance genes in tomato plants that are sensitive, specific and repeatable. For the optimization a central composite design of a response surface methodology (RSM-CCD) was used. For analytical performance evaluation, specificity/selectivity and sensibility (limit of detection and dynamic range) were analyzed. Two protocols were optimized: the first one with a desirability of 1.00, contained two markers (At-2 and P7-43) linked to I- and I-3-resistant genes. The second one with a desirability of 0.99, contained markers (SSR-67, SW5 and P6-25) linked to I-, Sw-5-, and Ty-3-resistant genes. For protocol 1, all the commercial hybrids (7/7) were resistant to Fol, and for protocol 2, two hybrids were resistant to Fol, one to TSWV and one to TYLCV with good analytical performance. In both protocols, the varieties considered susceptible to the pathogens, no-amplicon or susceptible amplicons, were observed. The optimized multiplex PCR protocols showed dynamic ranges from 5.97 up to 161.3 ng DNA. The limit of detection was 17.92 ng and 53.76 ng DNA for protocols 1 and 2, respectively, giving 100% positive results in the test replicates. This method allowed to develop optimized multiplex PCR protocols with few assays which translates into less time and resources, without sacrificing method performance. Full article
(This article belongs to the Section Genes & Environments)
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13 pages, 957 KiB  
Article
The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation
by Natalia Bałdyga, Dominika Oziębło, Nina Gan, Mariusz Furmanek, Marcin L. Leja, Henryk Skarżyński and Monika Ołdak
Genes 2023, 14(2), 335; https://doi.org/10.3390/genes14020335 - 28 Jan 2023
Cited by 5 | Viewed by 2469
Abstract
The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause [...] Read more.
The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA (n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5′ region of SLC26A4) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4, together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes. Full article
(This article belongs to the Special Issue Genetics of Ear Development and Hearing Loss)
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11 pages, 752 KiB  
Article
Identification of Germline Variants in Patients with Hereditary Cancer Syndromes in Northeast Mexico
by Diana Cristina Pérez-Ibave, María Lourdes Garza-Rodríguez, María Fernanda Noriega-Iriondo, Sonia María Flores-Moreno, Manuel Ismael González-Geroniz, Absalon Espinoza-Velazco, Ana Lilia Castruita-Ávila, Fernando Alcorta-Núñez, Omar Alejandro Zayas-Villanueva, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, Oscar Vidal-Gutiérrez and Carlos Horacio Burciaga-Flores
Genes 2023, 14(2), 341; https://doi.org/10.3390/genes14020341 - 28 Jan 2023
Cited by 7 | Viewed by 2832
Abstract
Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic [...] Read more.
Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk syndromes. Genetic counseling in HCS is still a global challenge. Multigene panels are an essential tool to detect the variants frequency. Our program has a high detection rate of probands with HCS and pathogenic variants (40%), compared with other reports that detect 10% in other populations. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 2201 KiB  
Article
High Levels of Diversity in Anopheles Subgenus Kerteszia Revealed by Species Delimitation Analyses
by Brian P. Bourke, Richard C. Wilkerson, Fredy Ruiz-Lopez, Silvia A. Justi, David B. Pecor, Martha L. Quinones, Juan-Carlos Navarro, Joubert Alarcón Ormaza, Joubert Alarcón Ormaza, Jr., Ranulfo González, Carmen Flores-Mendoza, Fanny Castro, Jesús E. Escovar and Yvonne-Marie Linton
Genes 2023, 14(2), 344; https://doi.org/10.3390/genes14020344 - 28 Jan 2023
Cited by 4 | Viewed by 2610
Abstract
The Anopheles subgenus Kerteszia is a poorly understood group of mosquitoes that includes several species of medical importance. Although there are currently twelve recognized species in the subgenus, previous studies have shown that this is likely to be an underestimate of species diversity. [...] Read more.
The Anopheles subgenus Kerteszia is a poorly understood group of mosquitoes that includes several species of medical importance. Although there are currently twelve recognized species in the subgenus, previous studies have shown that this is likely to be an underestimate of species diversity. Here, we undertake a baseline study of species delimitation using the barcode region of the mtDNA COI gene to explore species diversity among a geographically and taxonomically diverse range of Kerteszia specimens. Beginning with 10 of 12 morphologically identified Kerteszia species spanning eight countries, species delimitation analyses indicated a high degree of cryptic diversity. Overall, our analyses found support for at least 28 species clusters within the subgenus Kerteszia. The most diverse taxon was Anopheles neivai, a known malaria vector, with eight species clusters. Five other species taxa showed strong signatures of species complex structure, among them Anopheles bellator, which is also considered a malaria vector. There was some evidence for species structure within An. homunculus, although the results were equivocal across delimitation analyses. The current study, therefore, suggests that species diversity within the subgenus Kerteszia has been grossly underestimated. Further work will be required to build on this molecular characterization of species diversity and will rely on genomic level approaches and additional morphological data to test these species hypotheses. Full article
(This article belongs to the Special Issue Advances in Evolutionary Genetics and Phylogenetics of Mosquito Species)
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16 pages, 741 KiB  
Article
Tumor Androgen Receptor Protein Level Is Positively Associated with a Better Overall Survival in Melanoma Patients
by Nupur Singh, Jude Khatib, Chi-Yang Chiu, Jianjian Lin, Tejesh Surender Patel and Feng Liu-Smith
Genes 2023, 14(2), 345; https://doi.org/10.3390/genes14020345 - 28 Jan 2023
Cited by 2 | Viewed by 2590
Abstract
Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the [...] Read more.
Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the relationship between AR expression and cutaneous melanoma. This study used genomics and proteomics data from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA), with 470 cutaneous melanoma patient data points. Cox regression analyses evaluated the association between AR protein level with overall survival and revealed that a higher level of AR protein was positively associated with a better overall survival (OS) (p = 0.003). When stratified by sex, the AR association with OS was only significant for both sexes. The multivariate Cox models with justifications of sex, age of diagnosis, stage of disease, and Breslow depth of the tumor confirmed the AR-OS association in all patients. However, the significance of AR was lost when ulceration was included in the model. When stratified by sex, the multivariate Cox models indicated significant role of AR in OS of female patients but not in males. AR-associated genes were identified and enrichment analysis revealed shared and distinct gene network in male and female patients. Furthermore, AR was found significantly associated with OS in RAS mutant subtypes of melanoma but not in BRAF, NF1, or triple-wild type subtypes of melanoma. Our study may provide insight into the well-known female survival advantage in melanoma patients. Full article
(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)
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23 pages, 651 KiB  
Review
Extracellular Vesicles as Potential Biomarkers in Amyotrophic Lateral Sclerosis
by Maruša Barbo and Metka Ravnik-Glavač
Genes 2023, 14(2), 325; https://doi.org/10.3390/genes14020325 - 27 Jan 2023
Cited by 23 | Viewed by 3662
Abstract
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, [...] Read more.
Amyotrophic lateral sclerosis (ALS) is described as a fatal and rapidly progressive neurodegenerative disorder caused by the degeneration of upper motor neurons in the primary motor cortex and lower motor neurons of the brainstem and spinal cord. Due to ALS’s slowly progressive characteristic, which is often accompanied by other neurological comorbidities, its diagnosis remains challenging. Perturbations in vesicle-mediated transport and autophagy as well as cell-autonomous disease initiation in glutamatergic neurons have been revealed in ALS. The use of extracellular vesicles (EVs) may be key in accessing pathologically relevant tissues for ALS, as EVs can cross the blood–brain barrier and be isolated from the blood. The number and content of EVs may provide indications of the disease pathogenesis, its stage, and prognosis. In this review, we collected a recent study aiming at the identification of EVs as a biomarker of ALS with respect to the size, quantity, and content of EVs in the biological fluids of patients compared to controls. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
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10 pages, 262 KiB  
Communication
Use of Next-Generation Sequencing to Support the Diagnosis of Familial Interstitial Pneumonia
by Ana Rita Gigante, Eduarda Milheiro Tinoco, Ana Fonseca, Inês Marques, Agostinho Sanches, Natália Salgueiro, Carla Nogueira, Sérgio Campainha and Sofia Neves
Genes 2023, 14(2), 326; https://doi.org/10.3390/genes14020326 - 27 Jan 2023
Viewed by 1791
Abstract
Familial interstitial pneumonia (FIP) is defined as idiopathic interstitial lung disease (ILD) in two or more relatives. Genetic studies on familial ILD discovered variants in several genes or associations with genetic polymorphisms. The aim of this study was to describe the clinical features [...] Read more.
Familial interstitial pneumonia (FIP) is defined as idiopathic interstitial lung disease (ILD) in two or more relatives. Genetic studies on familial ILD discovered variants in several genes or associations with genetic polymorphisms. The aim of this study was to describe the clinical features of patients with suspected FIP and to analyze the genetic variants detected through next-generation sequencing (NGS) genetic testing. A retrospective analysis was conducted in patients followed in an ILD outpatient clinic who had ILD and a family history of ILD in at least one first- or second-degree relative and who underwent NGS between 2017 and 2021. Only patients with at least one genetic variant were included. Genetic testing was performed on 20 patients; of these, 13 patients had a variant in at least one gene with a known association with familial ILD. Variants in genes implicated in telomere and surfactant homeostasis and MUC5B variants were detected. Most variants were classified with uncertain clinical significance. Probable usual interstitial pneumonia radiological and histological patterns were the most frequently identified. The most prevalent phenotype was idiopathic pulmonary fibrosis. Pulmonologists should be aware of familial forms of ILD and genetic diagnosis. Full article
(This article belongs to the Section Genetic Diagnosis)
14 pages, 562 KiB  
Article
Public Health Genetics: Surveying Preparedness for the Next Generation of Public Health Professionals
by Anastasia M. Jacko, Andrea L. Durst, Karen L. Niemchick, Stephen M. Modell and Amy H. Ponte
Genes 2023, 14(2), 317; https://doi.org/10.3390/genes14020317 - 26 Jan 2023
Cited by 1 | Viewed by 2240
Abstract
Since the Human Genome Project’s completion in 2003, the need for increased population genetic literacy has grown exponentially. To address this need, public health professionals must be educated appropriately to serve the public best. This study examines the current state of public health [...] Read more.
Since the Human Genome Project’s completion in 2003, the need for increased population genetic literacy has grown exponentially. To address this need, public health professionals must be educated appropriately to serve the public best. This study examines the current state of public health genetics education within existing master of public health (MPH) programs. A total of 171 MPH Council on Education for Public Health Accreditation (CEPH)-accredited programs across the nation were identified via a preliminary internet search. The American Public Health Association (APHA) Genomics Forum Policy Committee created 14 survey questions to assess the current status of incorporating genetics/genomics education within MPH programs. Using the Qualtrics survey system through the University of Pittsburgh, a link to the anonymous survey was sent to each director’s email address obtained from their program’s website. There were 41 survey responses, with 37 finished to completion, for a response rate of 21.6% (37/171). A total of 75.7% (28/37) of respondents reported having courses containing genetics/genomics information in their programs’ coursework. Only 12.6% reported such coursework to be required for program completion. Commonly listed barriers to incorporating genetics/genomics include limited faculty knowledge and lack of space in existing courses and programs. Survey results revealed the incongruous and limited incorporation of genetics/genomics within the context of graduate-level public health education. While most recorded programs report offering public health genetics coursework, the extent and requirement of such instruction are not considered necessary for program completion, thereby potentially limiting the genetic literacy of the current pool of public health professionals. Full article
(This article belongs to the Special Issue Public Health Genetics and Genomics)
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10 pages, 2295 KiB  
Article
Evidence for Strand Asymmetry in Different Plastid Genomes
by Cindy Ruan and Brian R. Morton
Genes 2023, 14(2), 320; https://doi.org/10.3390/genes14020320 - 26 Jan 2023
Cited by 1 | Viewed by 1644
Abstract
A common genome composition pattern in eubacteria is an asymmetry between the leading and lagging strands resulting in opposite skew patterns in the two replichores that lie between the origin and terminus of replication. Although this pattern has been reported for a couple [...] Read more.
A common genome composition pattern in eubacteria is an asymmetry between the leading and lagging strands resulting in opposite skew patterns in the two replichores that lie between the origin and terminus of replication. Although this pattern has been reported for a couple of isolated plastid genomes, it is not clear how widespread it is overall in this chromosome. Using a random walk approach, we examine plastid genomes outside of the land plants, which are excluded since they are known not to initiate replication at a single site, for such a pattern of asymmetry. Although it is not a common feature, we find that it is detectable in the plastid genome of species from several diverse lineages. The euglenozoa in particular show a strong skew pattern as do several rhodophytes. There is a weaker pattern in some chlorophytes but it is not apparent in other lineages. The ramifications of this for analyses of plastid evolution are discussed. Full article
(This article belongs to the Special Issue Plant Plastid Genome)
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15 pages, 21866 KiB  
Article
A Founder Intronic Variant in P3H1 Likely Results in Aberrant Splicing and Protein Truncation in Patients of Karen Descent with Osteogenesis Imperfecta Type VIII
by Piranit Nik Kantaputra, Salita Angkurawaranon, Worrachet Intachai, Chumpol Ngamphiw, Bjorn Olsen, Sissades Tongsima, Timothy C. Cox and James R. Ketudat Cairns
Genes 2023, 14(2), 322; https://doi.org/10.3390/genes14020322 - 26 Jan 2023
Cited by 1 | Viewed by 2362
Abstract
One of the most important steps in post-translational modifications of collagen type I chains is the hydroxylation of carbon-3 of proline residues by prolyl-3-hydroxylase-1 (P3H1). Genetic variants in P3H1 have been reported to cause autosomal recessive osteogenesis imperfecta (OI) type VIII. Clinical and [...] Read more.
One of the most important steps in post-translational modifications of collagen type I chains is the hydroxylation of carbon-3 of proline residues by prolyl-3-hydroxylase-1 (P3H1). Genetic variants in P3H1 have been reported to cause autosomal recessive osteogenesis imperfecta (OI) type VIII. Clinical and radiographic examinations, whole-exome sequencing (WES), and bioinformatic analysis were performed in 11 Thai children of Karen descent affected by multiple bone fractures. Clinical and radiographic findings in these patients fit OI type VIII. Phenotypic variability is evident. WES identified an intronic homozygous variant (chr1:43212857A > G; NM_022356.4:c.2055 + 86A > G) in P3H1 in all patients, with parents in each patient being heterozygous for the variant. This variant is predicted to generate a new “CAG” splice acceptor sequence, resulting in the incorporation of an extra exon that leads to a frameshift in the final exon and subsequent non-functional P3H1 isoform a. Alternative splicing of P3H1 resulting in the absence of functional P3H1 caused OI type VIII in 11 Thai children of Karen descent. This variant appears to be specific to the Karen population. Our study emphasizes the significance of considering intronic variants. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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10 pages, 2284 KiB  
Hypothesis
Microsatellite Instability and Aberrant Pre-mRNA Splicing: How Intimate Is It?
by Laurent Corcos, Enora Le Scanf, Gaël Quéré, Danielle Arzur, Gwennina Cueff, Catherine Le Jossic-Corcos and Cédric Le Maréchal
Genes 2023, 14(2), 311; https://doi.org/10.3390/genes14020311 - 25 Jan 2023
Cited by 1 | Viewed by 2271
Abstract
Cancers that belong to the microsatellite instability (MSI) class can account for up to 15% of all cancers of the digestive tract. These cancers are characterized by inactivation, through the mutation or epigenetic silencing of one or several genes from the DNA MisMatch [...] Read more.
Cancers that belong to the microsatellite instability (MSI) class can account for up to 15% of all cancers of the digestive tract. These cancers are characterized by inactivation, through the mutation or epigenetic silencing of one or several genes from the DNA MisMatch Repair (MMR) machinery, including MLH1, MLH3, MSH2, MSH3, MSH6, PMS1, PMS2 and Exo1. The unrepaired DNA replication errors turn into mutations at several thousand sites that contain repetitive sequences, mainly mono- or dinucleotides, and some of them are related to Lynch syndrome, a predisposition condition linked to a germline mutation in one of these genes. In addition, some mutations shortening the microsatellite (MS) stretch could occur in the 3′-intronic regions, i.e., in the ATM (ATM serine/threonine kinase), MRE11 (MRE11 homolog) or the HSP110 (Heat shock protein family H) genes. In these three cases, aberrant pre-mRNA splicing was observed, and it was characterized by the occurrence of selective exon skipping in mature mRNAs. Because both the ATM and MRE11 genes, which as act as players in the MNR (MRE11/NBS1 (Nibrin)/RAD50 (RAD50 double strand break repair protein) DNA damage repair system, participate in double strand breaks (DSB) repair, their frequent splicing alterations in MSI cancers lead to impaired activity. This reveals the existence of a functional link between the MMR/DSB repair systems and the pre-mRNA splicing machinery, the diverted function of which is the consequence of mutations in the MS sequences. Full article
(This article belongs to the Special Issue Reciprocal Links between RNA Metabolism and DNA Damage)
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14 pages, 834 KiB  
Review
miRNAs: The Road from Bench to Bedside
by Giuseppe Iacomino
Genes 2023, 14(2), 314; https://doi.org/10.3390/genes14020314 - 25 Jan 2023
Cited by 54 | Viewed by 9090
Abstract
miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids [...] Read more.
miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids has underscored their potential in the field of biomarker research. In addition, the therapeutic potential of miRNAs is receiving increasing attention in numerous conditions. On the other hand, many operative problems including stability, delivery systems, and bioavailability, still need to be solved. In this dynamic field, biopharmaceutical companies are increasingly engaged, and ongoing clinical trials point to anti-miR and miR-mimic molecules as an innovative class of molecules for upcoming therapeutic applications. This article aims to provide a comprehensive overview of current knowledge on several pending issues and new opportunities offered by miRNAs in the treatment of diseases and as early diagnostic tools in next-generation medicine. Full article
(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)
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23 pages, 4069 KiB  
Article
ABCB1 Amplicon Contains Cyclic AMP Response Element-Driven TRIP6 Gene in Taxane-Resistant MCF-7 Breast Cancer Sublines
by Petr Daniel, Kamila Balušíková, Radka Václavíková, Karolína Šeborová, Šárka Ransdorfová, Marie Valeriánová, Longfei Wei, Michael Jelínek, Tereza Tlapáková, Thomas Fleischer, Vessela N. Kristensen, Pavel Souček, Iwao Ojima and Jan Kovář
Genes 2023, 14(2), 296; https://doi.org/10.3390/genes14020296 - 23 Jan 2023
Cited by 1 | Viewed by 2644
Abstract
A limited number of studies are devoted to regulating TRIP6 expression in cancer. Hence, we aimed to unveil the regulation of TRIP6 expression in MCF-7 breast cancer cells (with high TRIP6 expression) and taxane-resistant MCF-7 sublines (manifesting even higher TRIP6 expression). We found [...] Read more.
A limited number of studies are devoted to regulating TRIP6 expression in cancer. Hence, we aimed to unveil the regulation of TRIP6 expression in MCF-7 breast cancer cells (with high TRIP6 expression) and taxane-resistant MCF-7 sublines (manifesting even higher TRIP6 expression). We found that TRIP6 transcription is regulated primarily by the cyclic AMP response element (CRE) in hypomethylated proximal promoters in both taxane-sensitive and taxane-resistant MCF-7 cells. Furthermore, in taxane-resistant MCF-7 sublines, TRIP6 co-amplification with the neighboring ABCB1 gene, as witnessed by fluorescence in situ hybridization (FISH), led to TRIP6 overexpression. Ultimately, we found high TRIP6 mRNA levels in progesterone receptor-positive breast cancer and samples resected from premenopausal women. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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20 pages, 475 KiB  
Systematic Review
Status Epilepticus in Chromosomal Disorders Associated with Epilepsy: A Systematic Review
by Luca Bergonzini, Jacopo Pruccoli, Ilaria Pettenuzzo, Rosa Pugliano, Luca Soliani, Anna Fetta and Duccio Maria Cordelli
Genes 2023, 14(2), 299; https://doi.org/10.3390/genes14020299 - 23 Jan 2023
Cited by 1 | Viewed by 2859
Abstract
Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding [...] Read more.
Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients. Full article
(This article belongs to the Collection Study on Genotypes and Phenotypes of Pediatric Clinical Rare Diseases)
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8 pages, 413 KiB  
Communication
RADX Gene Variant May Predispose to Familial Asperger Syndrome
by Alessia Azzarà, Roberto Rumore, Fulvia Brugnoletti, Elisabetta Tabolacci, Irene Bottillo, Eugenio Sangiorgi and Fiorella Gurrieri
Genes 2023, 14(2), 301; https://doi.org/10.3390/genes14020301 - 23 Jan 2023
Viewed by 2552
Abstract
Asperger syndrome (AS) is a pervasive developmental disorder characterized by general impairment in socialization, stereotypical behavior, defective adaptation to the social context usually without intellectual disability, and some high functioning areas related to memory and mathematics. Clinical criteria are not well defined and [...] Read more.
Asperger syndrome (AS) is a pervasive developmental disorder characterized by general impairment in socialization, stereotypical behavior, defective adaptation to the social context usually without intellectual disability, and some high functioning areas related to memory and mathematics. Clinical criteria are not well defined and the etiology is heterogeneous and mostly unknown. Like in typical autism spectrum disorders (ASD), the genetic background plays a crucial role in AS, and often an almost mendelian segregation can be observed in some families. We performed a whole exome sequencing (WES) in three relatives of a family with vertical transmission of AS-ASD to identify variants in candidate genes segregating with the phenotype. Variant p.(Cys834Ser) in the RADX gene was the only one segregating among all the affected family members. This gene encodes a single-strand DNA binding factor, which mediates the recruitment of genome maintenance proteins to sites of replication stress. Replication stress and genome instability have been reported recently in neural progenitor cells derived from ASD patients, leading to a disruption of long neural genes involved in cell–cell adhesion and migration. We propose RADX as a new gene that when mutated could represent a predisposing factor to AS-ASD. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
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19 pages, 3296 KiB  
Article
A Network-Based Approach for Improving Annotation of Transcription Factor Functions and Binding Sites in Arabidopsis thaliana
by Tanzira Najnin, Sakhawat Hossain Saimon, Garry Sunter and Jianhua Ruan
Genes 2023, 14(2), 282; https://doi.org/10.3390/genes14020282 - 21 Jan 2023
Viewed by 2109
Abstract
Transcription factors are an integral component of the cellular machinery responsible for regulating many biological processes, and they recognize distinct DNA sequence patterns as well as internal/external signals to mediate target gene expression. The functional roles of an individual transcription factor can be [...] Read more.
Transcription factors are an integral component of the cellular machinery responsible for regulating many biological processes, and they recognize distinct DNA sequence patterns as well as internal/external signals to mediate target gene expression. The functional roles of an individual transcription factor can be traced back to the functions of its target genes. While such functional associations can be inferred through the use of binding evidence from high-throughput sequencing technologies available today, including chromatin immunoprecipitation sequencing, such experiments can be resource-consuming. On the other hand, exploratory analysis driven by computational techniques can alleviate this burden by narrowing the search scope, but the results are often deemed low-quality or non-specific by biologists. In this paper, we introduce a data-driven, statistics-based strategy to predict novel functional associations for transcription factors in the model plant Arabidopsis thaliana. To achieve this, we leverage one of the largest available gene expression compendia to build a genome-wide transcriptional regulatory network and infer regulatory relationships among transcription factors and their targets. We then use this network to build a pool of likely downstream targets for each transcription factor and query each target pool for functionally enriched gene ontology terms. The results exhibited sufficient statistical significance to annotate most of the transcription factors in Arabidopsis with highly specific biological processes. We also perform DNA binding motif discovery for transcription factors based on their target pool. We show that the predicted functions and motifs strongly agree with curated databases constructed from experimental evidence. In addition, statistical analysis of the network revealed interesting patterns and connections between network topology and system-level transcriptional regulation properties. We believe that the methods demonstrated in this work can be extended to other species to improve the annotation of transcription factors and understand transcriptional regulation on a system level. Full article
(This article belongs to the Section Bioinformatics)
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18 pages, 1597 KiB  
Review
Novel Insights into Mitochondrial DNA: Mitochondrial Microproteins and mtDNA Variants Modulate Athletic Performance and Age-Related Diseases
by Hiroshi Kumagai, Brendan Miller, Su-Jeong Kim, Naphada Leelaprachakul, Naoki Kikuchi, Kelvin Yen and Pinchas Cohen
Genes 2023, 14(2), 286; https://doi.org/10.3390/genes14020286 - 21 Jan 2023
Cited by 20 | Viewed by 4828
Abstract
Sports genetics research began in the late 1990s and over 200 variants have been reported as athletic performance- and sports injuries-related genetic polymorphisms. Genetic polymorphisms in the α-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are well-established for athletic performance, while collagen-, inflammation-, and [...] Read more.
Sports genetics research began in the late 1990s and over 200 variants have been reported as athletic performance- and sports injuries-related genetic polymorphisms. Genetic polymorphisms in the α-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are well-established for athletic performance, while collagen-, inflammation-, and estrogen-related genetic polymorphisms are reported as genetic markers for sports injuries. Although the Human Genome Project was completed in the early 2000s, recent studies have discovered previously unannotated microproteins encoded in small open reading frames. Mitochondrial microproteins (also called mitochondrial-derived peptides) are encoded in the mtDNA, and ten mitochondrial microproteins, such as humanin, MOTS-c (mitochondrial ORF of the 12S rRNA type-c), SHLPs 1–6 (small humanin-like peptides 1 to 6), SHMOOSE (Small Human Mitochondrial ORF Over SErine tRNA), and Gau (gene antisense ubiquitous in mtDNAs) have been identified to date. Some of those microproteins have crucial roles in human biology by regulating mitochondrial function, and those, including those to be discovered in the future, could contribute to a better understanding of human biology. This review describes a basic concept of mitochondrial microproteins and discusses recent findings about the potential roles of mitochondrial microproteins in athletic performance as well as age-related diseases. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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17 pages, 3022 KiB  
Article
Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice
by Linn Amanda Syding, Agnieszka Kubik-Zahorodna, David Pajuelo Reguera, Petr Nickl, Bohdana Hruskova, Michaela Kralikova, Jana Kopkanova, Vendula Novosadova, Petr Kasparek, Jan Prochazka, Jan Rozman, Rostislav Turecek and Radislav Sedlacek
Genes 2023, 14(2), 285; https://doi.org/10.3390/genes14020285 - 21 Jan 2023
Viewed by 2513
Abstract
Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and [...] Read more.
Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and there are knowledge gaps regarding its regulation. It is known that the HPA axis is under GABAergic control, but the contribution of the individual subunits of the GABA receptor is largely unknown. In this study, we investigated the relationship between the α5 subunit and corticosterone levels in a new mouse model deficient for Gabra5, which is known to be linked to anxiety disorders in humans and phenologs observed in mice. We observed decreased rearing behavior, suggesting lower anxiety in the Gabra5−/− animals; however, such a phenotype was absent in the open field and elevated plus maze tests. In addition to decreased rearing behavior, we also found decreased levels of fecal corticosterone metabolites in Gabra5−/− mice indicating a lowered stress response. Moreover, based on the electrophysiological recordings where we observed a hyperpolarized state of hippocampal neurons, we hypothesize that the constitutive ablation of the Gabra5 gene leads to functional compensation with other channels or GABA receptor subunits in this model. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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15 pages, 8115 KiB  
Article
The Evolutionary History of a DNA Methylase Reveals Frequent Horizontal Transfer and Within-Gene Recombination
by Sophia P. Gosselin, Danielle R. Arsenault, Catherine A. Jennings and Johann Peter Gogarten
Genes 2023, 14(2), 288; https://doi.org/10.3390/genes14020288 - 21 Jan 2023
Cited by 2 | Viewed by 2272
Abstract
Inteins, often referred to as protein introns, are highly mobile genetic elements that invade conserved genes throughout the tree of life. Inteins have been found to invade a wide variety of key genes within actinophages. While in the process of conducting a survey [...] Read more.
Inteins, often referred to as protein introns, are highly mobile genetic elements that invade conserved genes throughout the tree of life. Inteins have been found to invade a wide variety of key genes within actinophages. While in the process of conducting a survey of these inteins in actinophages, we discovered that one protein family of methylases contained a putative intein, and two other unique insertion elements. These methylases are known to occur commonly in phages as orphan methylases (possibly as a form of resistance to restriction–modification systems). We found that the methylase family is not conserved within phage clusters and has a disparate distribution across divergent phage groups. We determined that two of the three insertion elements have a patchy distribution within the methylase protein family. Additionally, we found that the third insertion element is likely a second homing endonuclease, and that all three elements (the intein, the homing endonuclease, and what we refer to as the ShiLan domain) have different insertion sites that are conserved in the methylase gene family. Furthermore, we find strong evidence that both the intein and ShiLan domain are partaking in long-distance horizontal gene transfer events between divergent methylases in disparate phage hosts within the already dispersed methylase distribution. The reticulate evolutionary history of methylases and their insertion elements reveals high rates of gene transfer and within-gene recombination in actinophages. Full article
(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2023)
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20 pages, 1341 KiB  
Review
Effect of the Rho-Kinase/ROCK Signaling Pathway on Cytoskeleton Components
by Guangzhao Guan, Richard D. Cannon, Dawn E. Coates and Li Mei
Genes 2023, 14(2), 272; https://doi.org/10.3390/genes14020272 - 20 Jan 2023
Cited by 54 | Viewed by 8552
Abstract
The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate [...] Read more.
The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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20 pages, 5005 KiB  
Article
Functional Assessment of a New PBX1 Variant in a 46,XY Fetus with Severe Syndromic Difference of Sexual Development through CRISPR-Cas9 Gene Editing
by Laura Mary, Delphine Leclerc, Audrey Labalme, Pascale Bellaud, Séverine Mazaud-Guittot, Stéphane Dréano, Bertrand Evrard, Antoine Bigand, Aurélie Cauchoix, Philippe Loget, Anna Lokchine, Laurence Cluzeau, David Gilot, Marc-Antoine Belaud-Rotureau and Sylvie Jaillard
Genes 2023, 14(2), 273; https://doi.org/10.3390/genes14020273 - 20 Jan 2023
Cited by 1 | Viewed by 2641
Abstract
Sexual development is a complex process relying on numerous genes. Disruptions in some of these genes are known to cause differences of sexual development (DSDs). Advances in genome sequencing allowed the discovery of new genes implicated in sexual development, such as PBX1. We [...] Read more.
Sexual development is a complex process relying on numerous genes. Disruptions in some of these genes are known to cause differences of sexual development (DSDs). Advances in genome sequencing allowed the discovery of new genes implicated in sexual development, such as PBX1. We present here a fetus with a new PBX1 NM_002585.3: c.320G>A,p.(Arg107Gln) variant, presenting with severe DSD along with renal and lung malformations. Using CRISPR-Cas9 gene editing on HEK293T cells, we generated a KD cell line for PBX1. The KD cell line showed reduced proliferation and adhesion properties compared with HEK293T cells. HEK293T and KD cells were then transfected plasmids coding either PBX1 WT or PBX1-320G>A (mutant). WT or mutant PBX1 overexpression rescued cell proliferation in both cell lines. RNA-seq analyses showed less than 30 differentially expressed genes, in ectopic mutant-PBX1-expressing cells compared with WT-PBX1. Among them, U2AF1, encoding a splicing factor subunit, is an interesting candidate. Overall, mutant PBX1 seems to have modest effects compared with WT PBX1 in our model. However, the recurrence of PBX1 Arg107 substitution in patients with closely related phenotypes calls for its impact in human diseases. Further functional studies are needed to explore its effects on cellular metabolism. Full article
(This article belongs to the Special Issue Molecular Genetics of Infertility)
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23 pages, 1729 KiB  
Review
Adaptive Evolution of Rhizobial Symbiosis beyond Horizontal Gene Transfer: From Genome Innovation to Regulation Reconstruction
by Sheng Liu, Jian Jiao and Chang-Fu Tian
Genes 2023, 14(2), 274; https://doi.org/10.3390/genes14020274 - 20 Jan 2023
Cited by 11 | Viewed by 5921
Abstract
There are ubiquitous variations in symbiotic performance of different rhizobial strains associated with the same legume host in agricultural practices. This is due to polymorphisms of symbiosis genes and/or largely unexplored variations in integration efficiency of symbiotic function. Here, we reviewed cumulative evidence [...] Read more.
There are ubiquitous variations in symbiotic performance of different rhizobial strains associated with the same legume host in agricultural practices. This is due to polymorphisms of symbiosis genes and/or largely unexplored variations in integration efficiency of symbiotic function. Here, we reviewed cumulative evidence on integration mechanisms of symbiosis genes. Experimental evolution, in concert with reverse genetic studies based on pangenomics, suggests that gain of the same circuit of key symbiosis genes through horizontal gene transfer is necessary but sometimes insufficient for bacteria to establish an effective symbiosis with legumes. An intact genomic background of the recipient may not support the proper expression or functioning of newly acquired key symbiosis genes. Further adaptive evolution, through genome innovation and reconstruction of regulation networks, may confer the recipient of nascent nodulation and nitrogen fixation ability. Other accessory genes, either co-transferred with key symbiosis genes or stochastically transferred, may provide the recipient with additional adaptability in ever-fluctuating host and soil niches. Successful integrations of these accessory genes with the rewired core network, regarding both symbiotic and edaphic fitness, can optimize symbiotic efficiency in various natural and agricultural ecosystems. This progress also sheds light on the development of elite rhizobial inoculants using synthetic biology procedures. Full article
(This article belongs to the Special Issue Evolution of Root Nodule Symbioses)
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20 pages, 2837 KiB  
Article
Client Applications and Server-Side Docker for Management of RNASeq and/or VariantSeq Workflows and Pipelines of the GPRO Suite
by Ahmed Ibrahem Hafez, Beatriz Soriano, Aya Allah Elsayed, Ricardo Futami, Raquel Ceprian, Ricardo Ramos-Ruiz, Genis Martinez, Francisco Jose Roig, Miguel Angel Torres-Font, Fernando Naya-Catala, Josep Alvar Calduch-Giner, Lucia Trilla-Fuertes, Angelo Gamez-Pozo, Vicente Arnau, Jose Maria Sempere-Luna, Jaume Perez-Sanchez, Toni Gabaldon and Carlos Llorens
Genes 2023, 14(2), 267; https://doi.org/10.3390/genes14020267 - 19 Jan 2023
Cited by 1 | Viewed by 3619
Abstract
The GPRO suite is an in-progress bioinformatic project for -omics data analysis. As part of the continued growth of this project, we introduce a client- and server-side solution for comparative transcriptomics and analysis of variants. The client-side consists of two Java applications called [...] Read more.
The GPRO suite is an in-progress bioinformatic project for -omics data analysis. As part of the continued growth of this project, we introduce a client- and server-side solution for comparative transcriptomics and analysis of variants. The client-side consists of two Java applications called “RNASeq” and “VariantSeq” to manage pipelines and workflows based on the most common command line interface tools for RNA-seq and Variant-seq analysis, respectively. As such, “RNASeq” and “VariantSeq” are coupled with a Linux server infrastructure (named GPRO Server-Side) that hosts all dependencies of each application (scripts, databases, and command line interface software). Implementation of the Server-Side requires a Linux operating system, PHP, SQL, Python, bash scripting, and third-party software. The GPRO Server-Side can be installed, via a Docker container, in the user’s PC under any operating system or on remote servers, as a cloud solution. “RNASeq” and “VariantSeq” are both available as desktop (RCP compilation) and web (RAP compilation) applications. Each application has two execution modes: a step-by-step mode enables each step of the workflow to be executed independently, and a pipeline mode allows all steps to be run sequentially. “RNASeq” and “VariantSeq” also feature an experimental, online support system called GENIE that consists of a virtual (chatbot) assistant and a pipeline jobs panel coupled with an expert system. The chatbot can troubleshoot issues with the usage of each tool, the pipeline jobs panel provides information about the status of each computational job executed in the GPRO Server-Side, while the expert system provides the user with a potential recommendation to identify or fix failed analyses. Our solution is a ready-to-use topic specific platform that combines the user-friendliness, robustness, and security of desktop software, with the efficiency of cloud/web applications to manage pipelines and workflows based on command line interface software. Full article
(This article belongs to the Collection Feature Papers in Bioinformatics)
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14 pages, 1067 KiB  
Article
Framework of the Alu Subfamily Evolution in the Platyrrhine Three-Family Clade of Cebidae, Callithrichidae, and Aotidae
by Jessica M. Storer, Jerilyn A. Walker, Jasmine N. Baker, Shifat Hossain, Christian Roos, Travis J. Wheeler and Mark A. Batzer
Genes 2023, 14(2), 249; https://doi.org/10.3390/genes14020249 - 18 Jan 2023
Cited by 2 | Viewed by 2063
Abstract
The history of Alu retroposons has been choreographed by the systematic accumulation of inherited diagnostic nucleotide substitutions to form discrete subfamilies, each having a distinct nucleotide consensus sequence. The oldest subfamily, AluJ, gave rise to AluS after the split between Strepsirrhini [...] Read more.
The history of Alu retroposons has been choreographed by the systematic accumulation of inherited diagnostic nucleotide substitutions to form discrete subfamilies, each having a distinct nucleotide consensus sequence. The oldest subfamily, AluJ, gave rise to AluS after the split between Strepsirrhini and what would become Catarrhini and Platyrrhini. The AluS lineage gave rise to AluY in catarrhines and to AluTa in platyrrhines. Platyrrhine Alu subfamilies Ta7, Ta10, and Ta15 were assigned names based on a standardized nomenclature. However, with the subsequent intensification of whole genome sequencing (WGS), large scale analyses to characterize Alu subfamilies using the program COSEG identified entire lineages of subfamilies simultaneously. The first platyrrhine genome with WGS, the common marmoset (Callithrix jacchus; [caljac3]), resulted in Alu subfamily names sf0 to sf94 in an arbitrary order. Although easily resolved by alignment of the consensus sequences, this naming convention can become increasingly confusing as more genomes are independently analyzed. In this study, we reported Alu subfamily characterization for the platyrrhine three-family clade of Cebidae, Callithrichidae, and Aotidae. We investigated one species/genome from each recognized family of Callithrichidae and Aotidae and of both subfamilies (Cebinae and Saimiriinae) of the family Cebidae. Furthermore, we constructed a comprehensive network of Alu subfamily evolution within the three-family clade of platyrrhines to provide a working framework for future research. Alu expansion in the three-family clade has been dominated by AluTa15 and its derivatives. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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16 pages, 1521 KiB  
Article
Omics Data Preprocessing for Machine Learning: A Case Study in Childhood Obesity
by Álvaro Torres-Martos, Mireia Bustos-Aibar, Alberto Ramírez-Mena, Sofía Cámara-Sánchez, Augusto Anguita-Ruiz, Rafael Alcalá, Concepción M. Aguilera and Jesús Alcalá-Fdez
Genes 2023, 14(2), 248; https://doi.org/10.3390/genes14020248 - 18 Jan 2023
Cited by 14 | Viewed by 5100
Abstract
The use of machine learning techniques for the construction of predictive models of disease outcomes (based on omics and other types of molecular data) has gained enormous relevance in the last few years in the biomedical field. Nonetheless, the virtuosity of omics studies [...] Read more.
The use of machine learning techniques for the construction of predictive models of disease outcomes (based on omics and other types of molecular data) has gained enormous relevance in the last few years in the biomedical field. Nonetheless, the virtuosity of omics studies and machine learning tools are subject to the proper application of algorithms as well as the appropriate pre-processing and management of input omics and molecular data. Currently, many of the available approaches that use machine learning on omics data for predictive purposes make mistakes in several of the following key steps: experimental design, feature selection, data pre-processing, and algorithm selection. For this reason, we propose the current work as a guideline on how to confront the main challenges inherent to multi-omics human data. As such, a series of best practices and recommendations are also presented for each of the steps defined. In particular, the main particularities of each omics data layer, the most suitable preprocessing approaches for each source, and a compilation of best practices and tips for the study of disease development prediction using machine learning are described. Using examples of real data, we show how to address the key problems mentioned in multi-omics research (e.g., biological heterogeneity, technical noise, high dimensionality, presence of missing values, and class imbalance). Finally, we define the proposals for model improvement based on the results found, which serve as the bases for future work. Full article
(This article belongs to the Special Issue Selected Papers from the 9th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2022))
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13 pages, 1202 KiB  
Article
KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection
by Juan J. Velasco, Yupeng Li, Bulat A. Ziganshin, Mohammad A. Zafar, John A. Rizzo, Deqiong Ma, Hui Zang, Asanish Kalyanasundaram and John A. Elefteriades
Genes 2023, 14(2), 252; https://doi.org/10.3390/genes14020252 - 18 Jan 2023
Cited by 1 | Viewed by 2406
Abstract
Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) [...] Read more.
Background: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. Methods: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. Results: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). Conclusions: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable “non-size” criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter). Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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9 pages, 3542 KiB  
Case Report
Identification of a Small Supernumerary Marker Chromosome in a Turner Syndrome Patient with Karyotype mos 46,X,+mar/45,X
by María Teresa Alejandra González-Rodríguez, Sinhue Alejandro Brukman-Jiménez, Idalid Cuero-Quezada, Jorge Román Corona-Rivera, Alfredo Corona-Rivera, Graciela Serafín-Saucedo, Liuba M. Aguirre-Salas and Lucina Bobadilla-Morales
Genes 2023, 14(2), 253; https://doi.org/10.3390/genes14020253 - 18 Jan 2023
Cited by 1 | Viewed by 9557
Abstract
Turner Syndrome is characterized by a normal X chromosome and the partial or complete absence of a second sexual chromosome. Small supernumerary marker chromosomes are present in 6.6% of these patients. Because of the wide range of Turner syndrome karyotypes, it is difficult [...] Read more.
Turner Syndrome is characterized by a normal X chromosome and the partial or complete absence of a second sexual chromosome. Small supernumerary marker chromosomes are present in 6.6% of these patients. Because of the wide range of Turner syndrome karyotypes, it is difficult to establish a relationship with the phenotype of the patients. We present the case of a female patient with Turner syndrome, insulin resistance, type 2 diabetes, and intellectual disability. The karyotype revealed the presence of mosaicism with a monosomy X cell line and a second line with a small marker chromosome. FISH of two different tissues was used to identify the marker chromosome with probes for X and Y centromeres. Both tissues presented mosaicism for a two X chromosome signal, differing in the percentage of the monosomy X cell percentage. Comparative genomic hybridization with the CytoScanTMHD assay was performed in genomic DNA from peripheral blood, allowing us to determine the size and breakage points of the small marker chromosome. The patient presents a phenotype that combines classic Turner syndrome features and unlikely ones as intellectual disability. The size, implicated genes, and degree of inactivation of the X chromosome influence the broad spectrum of phenotypes resulting from these chromosomes. Full article
(This article belongs to the Section Genetic Diagnosis)
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7 pages, 1005 KiB  
Brief Report
Genome Survey Sequencing of the Mole Cricket Gryllotalpa orientalis
by Kuo Sun, De-Long Guan, Hua-Teng Huang and Sheng-Quan Xu
Genes 2023, 14(2), 255; https://doi.org/10.3390/genes14020255 - 18 Jan 2023
Cited by 1 | Viewed by 2507
Abstract
The mole cricket Gryllotalpa orientalis is an evolutionarily, medicinal, and agriculturally significant insect that inhabits underground environments and is distributed globally. This study measured genome size by flow cytometry and k-mer based on low-coverage sequencing, and nuclear repetitive elements were also identified. The [...] Read more.
The mole cricket Gryllotalpa orientalis is an evolutionarily, medicinal, and agriculturally significant insect that inhabits underground environments and is distributed globally. This study measured genome size by flow cytometry and k-mer based on low-coverage sequencing, and nuclear repetitive elements were also identified. The haploid genome size estimate is 3.14 Gb by flow cytometry, 3.17 Gb, and 3.77 Gb-based two k-mer methods, respectively, which is well within the range previously reported for other species of the suborder Ensifera. 56% of repetitive elements were found in G. orientalis, similar to 56.83% in Locusta migratoria. However, the great size of repetitive sequences could not be annotated to specific repeat element families. For the repetitive elements that were annotated, Class I-LINE retrotransposon elements were the most common families and more abundant than satellite and Class I-LTR. These results based on the newly developed genome survey could be used in the taxonomic study and whole genome sequencing to improve the understanding of the biology of G. orientalis. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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9 pages, 267 KiB  
Communication
Selected SNPs of FCN2 Associated with Chronic Tonsillitis in the Polish Adult Population
by Jadwiga Gaździcka, Karolina Gołąbek, Dorota Hudy, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Wojciech Tynior, Marek Asman, Maciej Misiołek and Joanna Katarzyna Strzelczyk
Genes 2023, 14(2), 242; https://doi.org/10.3390/genes14020242 - 17 Jan 2023
Cited by 2 | Viewed by 1653
Abstract
Chronic tonsillitis is a problem related to bacterial and viral infections. Ficolins play a key role in the defence against various pathogens. In the present study, we investigated the associations between the selected single nucleotide polymorphisms (SNPs) of the FCN2 gene and chronic [...] Read more.
Chronic tonsillitis is a problem related to bacterial and viral infections. Ficolins play a key role in the defence against various pathogens. In the present study, we investigated the associations between the selected single nucleotide polymorphisms (SNPs) of the FCN2 gene and chronic tonsillitis in the Polish population. The study included 101 patients with chronic tonsillitis and 101 healthy individuals. The selected SNPs of FCN2 (rs3124953, rs17514136 and rs3124954) were genotyped using TaqMan SNP Genotyping Assays (Applied Biosystem, Foster City, CA, USA). The analysis of rs17514136 and rs3124953 showed no significant differences in genotype frequencies between the chronic tonsillitis patients and controls (p > 0.01). The CT genotype of rs3124954 was significantly more frequent, while the CC genotype was less frequent in chronic tonsillitis patients (p = 0.003 and p = 0.001, respectively). The frequency of the A/G/T haplotype (rs17514136/rs3124953/rs3124954) was significantly more common in chronic tonsillitis patients (p = 0.0011). Moreover, the FCN2 CT genotype of rs3124954 was associated with a higher risk of chronic tonsillitis, while the CC genotype of rs3124954 decreased this risk. Our findings demonstrate that FCN2 rs3124954 may be associated with chronic tonsillitis in the Polish adult population. Full article
(This article belongs to the Special Issue Head and Neck Genetics)
12 pages, 10327 KiB  
Article
Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8
by Domizia Pasquetti, Giuseppe Marangi, Daniela Orteschi, Marina Carapelle, Federica Francesca L’Erario, Romina Venditti, Sabrina Maietta, Domenica Immacolata Battaglia, Ilaria Contaldo, Chiara Veredice and Marcella Zollino
Genes 2023, 14(2), 245; https://doi.org/10.3390/genes14020245 - 17 Jan 2023
Cited by 3 | Viewed by 2533
Abstract
Neuronal ceroid lipofuscinoses (CNL) are lysosomal storage diseases that represent the most common cause of dementia in children. To date, 13 autosomal recessive (AR) and 1 autosomal dominant (AD) gene have been characterized. Biallelic variants in MFSD8 cause CLN7 type, with nearly 50 [...] Read more.
Neuronal ceroid lipofuscinoses (CNL) are lysosomal storage diseases that represent the most common cause of dementia in children. To date, 13 autosomal recessive (AR) and 1 autosomal dominant (AD) gene have been characterized. Biallelic variants in MFSD8 cause CLN7 type, with nearly 50 pathogenic variants, mainly truncating and missense, reported so far. Splice site variants require functional validation. We detected a novel homozygous non-canonical splice-site variant in MFSD8 in a 5-year-old girl who presented with progressive neurocognitive impairment and microcephaly. The diagnostic procedure was elicited by clinical genetics first, and then confirmed by cDNA sequencing and brain imaging. Inferred by the common geographic origin of the parents, an autosomal recessive inheritance was hypothesized, and SNP-array was performed as the first-line genetic test. Only three AR genes lying within the observed 24 Mb regions of homozygosity were consistent with the clinical phenotype, including EXOSC9, SPATA5 and MFSD8. The cerebral and cerebellar atrophy detected in the meantime by MRI, along with the suspicion of accumulation of ceroid lipopigment in neurons, prompted us to perform targeted MFSD8 sequencing. Following the detection of a splice site variant of uncertain significance, skipping of exon 8 was demonstrated by cDNA sequencing, and the variant was redefined as pathogenic. Full article
(This article belongs to the Section RNA)
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10 pages, 14946 KiB  
Brief Report
Involvement of Mitochondrial Dysfunction in FOXG1 Syndrome
by Victoria A. Bjerregaard, Amanda M. Levy, Mille S. Batz, Ravina Salehi, Mathis Hildonen, Trine B. Hammer, Rikke S. Møller, Claus Desler and Zeynep Tümer
Genes 2023, 14(2), 246; https://doi.org/10.3390/genes14020246 - 17 Jan 2023
Viewed by 2697
Abstract
FOXG1 (Forkhead box g1) syndrome is a neurodevelopmental disorder caused by a defective transcription factor, FOXG1, important for normal brain development and function. As FOXG1 syndrome and mitochondrial disorders have shared symptoms and FOXG1 regulates mitochondrial function, we investigated whether defective FOXG1 leads [...] Read more.
FOXG1 (Forkhead box g1) syndrome is a neurodevelopmental disorder caused by a defective transcription factor, FOXG1, important for normal brain development and function. As FOXG1 syndrome and mitochondrial disorders have shared symptoms and FOXG1 regulates mitochondrial function, we investigated whether defective FOXG1 leads to mitochondrial dysfunction in five individuals with FOXG1 variants compared to controls (n = 6). We observed a significant decrease in mitochondrial content and adenosine triphosphate (ATP) levels and morphological changes in mitochondrial network in the fibroblasts of affected individuals, indicating involvement of mitochondrial dysfunction in FOXG1 syndrome pathogenesis. Further investigations are warranted to elucidate how FOXG1 deficiency impairs mitochondrial homeostasis. Full article
(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases)
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9 pages, 2646 KiB  
Communication
The Mitochondrial Genomes of Two Parasitoid Wasps Protapanteles immunis and Parapanteles hyposidrae (Hymenoptera: Braconidae) with Phylogenetic Implications and Novel Gene Rearrangements
by Dandan Xiao, Ziqi Wang, Jiachen Zhu, Xiaogui Zhou, Pu Tang and Xuexin Chen
Genes 2023, 14(1), 230; https://doi.org/10.3390/genes14010230 - 16 Jan 2023
Cited by 1 | Viewed by 2162
Abstract
Parapanteles hypsidrae (Wilkinson, 1928) and Protapanteles immunis (Haliday, 1834) are the most important parasitic wasps of Ectropis grisescens Warren and Ectropis obliqua (Prout). We sequenced and annotated the mitochondrial genomes of Pa. hyposidrae and Pr. immunis, which are 17,063 bp and 16,397 [...] Read more.
Parapanteles hypsidrae (Wilkinson, 1928) and Protapanteles immunis (Haliday, 1834) are the most important parasitic wasps of Ectropis grisescens Warren and Ectropis obliqua (Prout). We sequenced and annotated the mitochondrial genomes of Pa. hyposidrae and Pr. immunis, which are 17,063 bp and 16,397 bp in length, respectively, and possess 37 mitochondrial genes. We discovered two novel types of gene rearrangement, the local inversion of nad4L in Pa. hyposidrae and the remote inversion of the block cox3-nad3-nad5-nad4 in Pr. immunis, within the mitogenomes of Braconidae. The phylogenetic analysis supported the subfamily Microgastrinae is a monophyletic group, but the tribes Apantelini and Cotesiini within this subfamily are paraphyletic groups. Full article
(This article belongs to the Special Issue Advanced Research on Mitochondrial Genome)
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18 pages, 2558 KiB  
Article
Spectrum of Genetic Variants in the Dystrophin Gene: A Single Centre Retrospective Analysis of 750 Duchenne and Becker Patients from Southern Italy
by Emanuela Viggiano, Esther Picillo, Luigia Passamano, Maria Elena Onore, Giulio Piluso, Marianna Scutifero, Annalaura Torella, Vincenzo Nigro and Luisa Politano
Genes 2023, 14(1), 214; https://doi.org/10.3390/genes14010214 - 14 Jan 2023
Cited by 16 | Viewed by 4602
Abstract
Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are [...] Read more.
Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are available. We report a large single-centre study on the spectrum of DMD gene variants observed in 750 patients analyzed for suspected Duchenne (DMD) or Becker (BMD) muscular dystrophy, over the past 30 years, at the Cardiomyology and Medical Genetics of the University of Campania. We found 534 (71.21%) large deletions, 73 (9.73%) large duplications, and 112 (14.93%) point mutations, of which 44 (5.9%) were small ins/del causing frame-shifts, 57 (7.6%) nonsense mutations, 8 (1.1%) splice site and 3 (0.4%) intronic mutations, and 31 (4.13%) non mutations. Moreover, we report the prevalence of the different types of mutations in patients with DMD and BMD according to their decade of birth, from 1930 to 2020, and correlate the data to the different techniques used over the years. In the most recent decades, we observed an apparent increase in the prevalence of point mutations, probably due to the use of Next-Generation Sequencing (NGS). In conclusion, in southern Italy, deletions are the most frequent variation observed in DMD and BMD patients followed by point mutations and duplications, as elsewhere in the world. NGS was useful to identify point mutations in cases of strong suspicion of DMD/BMD negative on deletions/duplications analyses. In the era of personalized medicine and availability of new causative therapies, a collective effort is necessary to enable DMD and BMD patients to have timely genetic diagnoses and avoid late implementation of standard of care and late initiation of appropriate treatment. Full article
(This article belongs to the Special Issue Genetics of Muscular Dystrophies from Pathogenesis to Gene Therapy)
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12 pages, 2388 KiB  
Article
Genome-Wide Identification of DUF668 Gene Family and Expression Analysis under Drought and Salt Stresses in Sweet Potato [Ipomoea batatas (L.) Lam]
by Enliang Liu, Zhiqiang Li, Zhengqian Luo, Linli Xu, Ping Jin, Shun Ji, Guohui Zhou, Zhenyang Wang, Zhilin Zhou and Hua Zhang
Genes 2023, 14(1), 217; https://doi.org/10.3390/genes14010217 - 14 Jan 2023
Cited by 12 | Viewed by 3244
Abstract
The domain of unknown function 668 (DUF668) is a gene family that plays a vital role in responses to adversity coercion stresses in plant. However, the function of the DUF668 gene family is not fully understood in sweet potato. In this study, bioinformatics [...] Read more.
The domain of unknown function 668 (DUF668) is a gene family that plays a vital role in responses to adversity coercion stresses in plant. However, the function of the DUF668 gene family is not fully understood in sweet potato. In this study, bioinformatics methods were used to analyze the number, physicochemical properties, evolution, structure, and promoter cis-acting elements of the IbDUF668 family genes, and RNA-seq and qRT–PCR were performed to detect gene expression and their regulation under hormonal and abiotic stress. A total of 14 IbDUF668 proteins were identified in sweet potato, distributed on nine chromosomes. By phylogenetic analysis, IbDUF668 proteins can be divided into two subfamilies. Transcriptome expression profiling revealed that many genes from DUF668 in sweet potato showed specificity and differential expression under cold, heat, drought, salt and hormones (ABA, GA3 and IAA). Four genes (IbDUF668-6, 7, 11 and 13) of sweet potato were significantly upregulated by qRT-PCR under ABA, drought and NaCl stress. Results suggest that the DUF668 gene family is involved in drought and salt tolerance in sweet potato, and it will further provide the basic information of DUF668 gene mechanisms in plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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20 pages, 2181 KiB  
Review
Parvalbumin: A Major Fish Allergen and a Forensically Relevant Marker
by Subham Mukherjee, Petra Horka, Kamila Zdenkova and Eliska Cermakova
Genes 2023, 14(1), 223; https://doi.org/10.3390/genes14010223 - 14 Jan 2023
Cited by 28 | Viewed by 9488
Abstract
Parvalbumins (PVALBs) are low molecular weight calcium-binding proteins. In addition to their role in many biological processes, PVALBs play an important role in regulating Ca2+ switching in muscles with fast-twitch fibres in addition to their role in many biological processes. The PVALB gene [...] Read more.
Parvalbumins (PVALBs) are low molecular weight calcium-binding proteins. In addition to their role in many biological processes, PVALBs play an important role in regulating Ca2+ switching in muscles with fast-twitch fibres in addition to their role in many biological processes. The PVALB gene family is divided into two gene types, alpha (α) and beta (β), with the β gene further divided into two gene types, beta1 (β1) and beta2 (β2), carrying traces of whole genome duplication. A large variety of commonly consumed fish species contain PVALB proteins which are known to cause fish allergies. More than 95% of all fish-induced food allergies are caused by PVALB proteins. The authentication of fish species has become increasingly important as the seafood industry continues to grow and the growth brings with it many cases of food fraud. Since the PVALB gene plays an important role in the initiation of allergic reactions, it has been used for decades to develop alternate assays for fish identification. A brief review of the significance of the fish PVALB genes is presented in this article, which covers evolutionary diversity, allergic properties, and potential use as a forensic marker. Full article
(This article belongs to the Special Issue Genomics in Aquaculture and Fisheries)
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