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Genes, Volume 14, Issue 2 (February 2023) – 296 articles

Cover Story (view full-size image): RYR1-related myopathy (RYR1-RM) is now known to manifest itself in vastly heterogeneous forms, whose clinical interpretation is, therefore, highly challenging. We set out to develop a novel unsupervised cluster analysis method in a large patient population. The objective was to analyze the main RYR1-related characteristics to identify distinctive features of RYR1-RM and, thus, offer more precise genotype–phenotype correlations in a group of potentially life-threatening disorders. We studied 600 patients presenting with a suspicion of inherited myopathy, who were investigated using next-generation sequencing. In addressing the need for more specific genotype–phenotype correlations, we found clustering to overcome the limits of the “single-dimension” paradigm traditionally used to describe genotype–phenotype relationships. View this paper
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16 pages, 3618 KiB  
Article
Understanding Drug Resistance of Wild-Type and L38HL Insertion Mutant of HIV-1 C Protease to Saquinavir
by Sankaran Venkatachalam, Nisha Murlidharan, Sowmya R. Krishnan, C. Ramakrishnan, Mpho Setshedi, Ramesh Pandian, Debmalya Barh, Sandeep Tiwari, Vasco Azevedo, Yasien Sayed and M. Michael Gromiha
Genes 2023, 14(2), 533; https://doi.org/10.3390/genes14020533 - 20 Feb 2023
Cited by 1 | Viewed by 1597
Abstract
Acquired immunodeficiency syndrome (AIDS) is one of the most challenging infectious diseases to treat on a global scale. Understanding the mechanisms underlying the development of drug resistance is necessary for novel therapeutics. HIV subtype C is known to harbor mutations at critical positions [...] Read more.
Acquired immunodeficiency syndrome (AIDS) is one of the most challenging infectious diseases to treat on a global scale. Understanding the mechanisms underlying the development of drug resistance is necessary for novel therapeutics. HIV subtype C is known to harbor mutations at critical positions of HIV aspartic protease compared to HIV subtype B, which affects the binding affinity. Recently, a novel double-insertion mutation at codon 38 (L38HL) was characterized in HIV subtype C protease, whose effects on the interaction with protease inhibitors are hitherto unknown. In this study, the potential of L38HL double-insertion in HIV subtype C protease to induce a drug resistance phenotype towards the protease inhibitor, Saquinavir (SQV), was probed using various computational techniques, such as molecular dynamics simulations, binding free energy calculations, local conformational changes and principal component analysis. The results indicate that the L38HL mutation exhibits an increase in flexibility at the hinge and flap regions with a decrease in the binding affinity of SQV in comparison with wild-type HIV protease C. Further, we observed a wide opening at the binding site in the L38HL variant due to an alteration in flap dynamics, leading to a decrease in interactions with the binding site of the mutant protease. It is supported by an altered direction of motion of flap residues in the L38HL variant compared with the wild-type. These results provide deep insights into understanding the potential drug resistance phenotype in infected individuals. Full article
(This article belongs to the Collection Feature Papers in Bioinformatics)
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11 pages, 545 KiB  
Article
Genetic Lesions in Russian CLL Patients with the Most Common Stereotyped Antigen Receptors
by Bella V. Biderman, Ekaterina B. Likold, Nataliya A. Severina, Tatiana N. Obukhova and Andrey B. Sudarikov
Genes 2023, 14(2), 532; https://doi.org/10.3390/genes14020532 - 20 Feb 2023
Viewed by 1252
Abstract
Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of [...] Read more.
Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization. Full article
(This article belongs to the Special Issue Genetics of Blood Disorders)
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11 pages, 1758 KiB  
Article
Characterization of phi112, a Molecular Marker Tightly Linked to the o2 Gene of Maize, and Its Utilization in Multiplex PCR for Differentiating Normal Maize from QPM
by Alla Singh, Chikkappa Karjagi, Sehgeet Kaur, Gagan Jeet, Deepak Bhamare, Sonu Gupta, Sunil Kumar, Abhijit Das, Mamta Gupta, D. P. Chaudhary, Bharat Bhushan, B. S. Jat, Ramesh Kumar, M. C. Dagla and Manoj Kumar
Genes 2023, 14(2), 531; https://doi.org/10.3390/genes14020531 - 20 Feb 2023
Viewed by 1624
Abstract
Quality Protein Maize (QPM) contains higher amounts of essential amino acids lysine and tryptophan. The QPM phenotype is based on regulating zein protein synthesis by opaque2 transcription factor. Many gene modifiers act to optimize the amino acid content and agronomic performance. An SSR [...] Read more.
Quality Protein Maize (QPM) contains higher amounts of essential amino acids lysine and tryptophan. The QPM phenotype is based on regulating zein protein synthesis by opaque2 transcription factor. Many gene modifiers act to optimize the amino acid content and agronomic performance. An SSR marker, phi112, is present upstream of the opaque2 DNA gene. Its analysis has shown the presence of transcription factor activity. The functional associations of opaque2 have been determined. The putative transcription factor binding at phi112 marked DNA was identified through computational analysis. The present study is a step towards understanding the intricate network of molecular interactions that fine-tune the QPM genotype to influence maize protein quality. In addition, a multiplex PCR assay for differentiation of QPM from normal maize is shown, which can be used for Quality Control at various stages of the QPM value chain. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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19 pages, 1226 KiB  
Article
Genomic Insights of Alnus-Infective Frankia Strains Reveal Unique Genetic Features and New Evidence on Their Host-Restricted Lifestyle
by Sandra Kim Tiam, Hasna Boubakri, Lorine Bethencourt, Danis Abrouk, Pascale Fournier and Aude Herrera-Belaroussi
Genes 2023, 14(2), 530; https://doi.org/10.3390/genes14020530 - 20 Feb 2023
Cited by 2 | Viewed by 1463
Abstract
The present study aimed to use comparative genomics to explore the relationships between Frankia and actinorhizal plants using a data set made of 33 Frankia genomes. The determinants of host specificity were first explored for “Alnus-infective strains” (i.e., Frankia strains belonging [...] Read more.
The present study aimed to use comparative genomics to explore the relationships between Frankia and actinorhizal plants using a data set made of 33 Frankia genomes. The determinants of host specificity were first explored for “Alnus-infective strains” (i.e., Frankia strains belonging to Cluster Ia). Several genes were specifically found in these strains, including an agmatine deiminase which could possibly be involved in various functions as access to nitrogen sources, nodule organogenesis or plant defense. Within “Alnus-infective strains”, Sp+ Frankia genomes were compared to Sp− genomes in order to elucidate the narrower host specificity of Sp+ strains (i.e., Sp+ strains being capable of in planta sporulation, unlike Sp− strains). A total of 88 protein families were lost in the Sp+ genomes. The lost genes were related to saprophytic life (transcriptional factors, transmembrane and secreted proteins), reinforcing the proposed status of Sp+ as obligatory symbiont. The Sp+ genomes were also characterized by a loss of genetic and functional paralogs, highlighting a reduction in functional redundancy (e.g., hup genes) or a possible loss of function related to a saprophytic lifestyle (e.g., genes involved in gas vesicle formation or recycling of nutrients). Full article
(This article belongs to the Special Issue Evolution of Root Nodule Symbioses)
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12 pages, 2011 KiB  
Article
miR-33a Inhibits the Differentiation of Bovine Preadipocytes through the IRS2–Akt Pathway
by Wenzhen Zhang, Sayed Haidar Abbas Raza, Bingzhi Li, Bing Sun, Sihu Wang, Sameer D. Pant, Nouf S. Al-Abbas, Nehad A. Shaer and Linsen Zan
Genes 2023, 14(2), 529; https://doi.org/10.3390/genes14020529 - 20 Feb 2023
Cited by 2 | Viewed by 1472
Abstract
Several microRNAs (miRNAs) are known to participate in adipogenesis. However, their role in this process, especially in the differentiation of bovine preadipocytes, remains to be elucidated. This study was intended to clarify the effect of microRNA-33a (miR-33a) on the differentiation of bovine preadipocytes [...] Read more.
Several microRNAs (miRNAs) are known to participate in adipogenesis. However, their role in this process, especially in the differentiation of bovine preadipocytes, remains to be elucidated. This study was intended to clarify the effect of microRNA-33a (miR-33a) on the differentiation of bovine preadipocytes by cell culture, real-time fluorescent quantitative PCR (qPCR), Oil Red staining, BODIPY staining, and Western blotting. The results indicate that overexpression of miR-33a significantly inhibited lipid droplet accumulation and decreased the mRNA and protein expression of adipocyte differentiation marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and fatty acid-binding protein 4 (FABP4). In contrast, the interference expression of miR-33a promoted lipid droplet accumulation and increased the expression of marker genes. Additionally, miR-33a directly targeted insulin receptor substrate 2 (IRS2) and regulated the phosphorylation level of serine/threonine kinase (Akt). Furthermore, miR-33a inhibition could rescue defects in the differentiation of bovine preadipocytes and the Akt phosphorylation level caused by small interfering IRS2 (si-IRS2). Collectively, these results indicate that miR-33a could inhibit the differentiation of bovine preadipocytes, possibly through the IRS2–Akt pathway. These findings might help develop practical means to improve the quality of beef. Full article
(This article belongs to the Special Issue Genetics and Genomics in Livestock Production and Disease Resistance)
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16 pages, 4354 KiB  
Article
Root Metabolism and Effects of Root Exudates on the Growth of Ralstonia solanacearum and Fusarium moniliforme Were Significantly Different between the Two Genotypes of Peanuts
by Zhong Li, Wenfeng Guo, Changming Mo, Ronghua Tang, Liangqiong He, Lin Du, Ming Li, Haining Wu, Xiumei Tang, Zhipeng Huang and Xingjian Wu
Genes 2023, 14(2), 528; https://doi.org/10.3390/genes14020528 - 20 Feb 2023
Cited by 3 | Viewed by 1781
Abstract
Wild peanut species Arachis correntina (A. correntina) had a higher continuous cropping tolerance than peanut cultivars, closely correlating with the regulatory effects of its root exudates on soil microorganisms. To reveal the resistance mechanism of A. correntina to pathogens, we adopted transcriptomic [...] Read more.
Wild peanut species Arachis correntina (A. correntina) had a higher continuous cropping tolerance than peanut cultivars, closely correlating with the regulatory effects of its root exudates on soil microorganisms. To reveal the resistance mechanism of A. correntina to pathogens, we adopted transcriptomic and metabolomics approaches to analyze differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) between A. correntina and peanut cultivar Guihua85 (GH85) under hydroponic conditions. Interaction experiments of peanut root exudates with Ralstonia solanacearum (R. solanacearum) and Fusarium moniliforme (F. moniliforme) were carried out in this study. The result of transcriptome and metabolomics association analysis showed that there were fewer up-regulated DEGs and DEMs in A. correntina compared with GH85, which were closely associated with the metabolism of amino acids and phenolic acids. Root exudates of GH85 had stronger effects on promoting the growth of R. solanacearum and F. moniliforme than those of A. correntina under 1 and 5 percent volume (1% and 5%) of root exudates treatments. Thirty percent volume (30%) of A. correntina and GH85 root exudates significantly inhibited the growth of two pathogens. The exogenous amino acids and phenolic acids influenced R. solanacearum and F. moniliforme showing concentration effects from growth promotion to inhibition as with the root exudates. In conclusion, the greater resilience of A. correntina) to changes in metabolic pathways for amino acids and phenolic acids might aid in the repression of pathogenic bacteria and fungi. Full article
(This article belongs to the Special Issue Peanut Genetics and Omics)
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15 pages, 1286 KiB  
Review
Genetic Ethnic Differences in Human 2′-5′-Oligoadenylate Synthetase and Disease Associations: A Systematic Review
by Anmol Gokul, Thilona Arumugam and Veron Ramsuran
Genes 2023, 14(2), 527; https://doi.org/10.3390/genes14020527 - 19 Feb 2023
Cited by 3 | Viewed by 2056
Abstract
Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious [...] Read more.
Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious diseases within Africa. Understanding the host genetic mechanisms that offer protection against infectious diseases provides an opportunity to develop unique therapeutic interventions. Over the past two decades, several studies have linked the 2′-5′-oligoadenylate synthetase (OAS) family with a range of infectious diseases. More recently, the OAS-1 gene has also been associated with disease severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a global pandemic. The OAS family serves as an antiviral factor through the interaction with Ribonuclease-Latent (RNase-L). This review explores the genetic variants observed within the OAS genes and the associations with various viral infections and how previously reported ethnic-specific polymorphisms drive clinical significance. This review provides an overview of OAS genetic association studies with a particular focus on viral diseases affecting individuals of African descent. Full article
(This article belongs to the Special Issue Host Genetics and Infectious Disease)
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16 pages, 5874 KiB  
Article
De Novo Assembly and Comparative Analysis of the Complete Mitochondrial Genome of Chaenomeles speciosa (Sweet) Nakai Revealed the Existence of Two Structural Isomers
by Pei Cao, Yuan Huang, Mei Zong and Zilong Xu
Genes 2023, 14(2), 526; https://doi.org/10.3390/genes14020526 - 19 Feb 2023
Cited by 2 | Viewed by 1772
Abstract
As a valuable Chinese traditional medicinal species, Chaenomeles speciosa (Sweet) Nakai (C. speciosa) is a natural resource with significant economic and ornamental value. However, its genetic information is not well understood. In this study, the complete mitochondrial genome of C. speciosa [...] Read more.
As a valuable Chinese traditional medicinal species, Chaenomeles speciosa (Sweet) Nakai (C. speciosa) is a natural resource with significant economic and ornamental value. However, its genetic information is not well understood. In this study, the complete mitochondrial genome of C. speciosa was assembled and characterized to explore the repeat sequences, recombination events, rearrangements, and IGT, to predict RNA editing sites, and to clarify the phylogenetic and evolutionary relationship. The C. speciosa mitochondrial genome was found to have two circular chromosomes as its major conformation, with a total length of 436,464 bp and 45.2% GC content. The mitochondrial genome contained 54 genes, including 33 unique protein-coding genes, 18 tRNAs, and 3 rRNA genes. Seven pairs of repeat sequences involving recombination events were analyzed. Both the repeat pairs, R1 and R2, played significant roles in mediating the major and minor conformations. In total, 18 MTPTs were identified, 6 of which were complete tRNA genes. There were 454 RNA editing sites in the 33 protein-coding sequences predicted by the PREPACT3 program. A phylogenetic analysis based on 22 species of mitochondrial genomes was constructed and indicated highly conserved PCG sequences. Synteny analyses showed extensive genomic rearrangements in the mitochondrial genome of C. speciosa and closely related species. This work is the first to report the C. speciosa mitochondrial genome, which is of great significance for conducting additional genetic studies on this organism. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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12 pages, 1494 KiB  
Article
The Circulating Level of Klotho Is Not Dependent upon Physical Fitness and Age-Associated Methylation Increases at the Promoter Region of the Klotho Gene
by Dora Aczel, Ferenc Torma, Matyas Jokai, Kristen McGreevy, Anita Boros, Yasuhiro Seki, Istvan Boldogh, Steve Horvath and Zsolt Radak
Genes 2023, 14(2), 525; https://doi.org/10.3390/genes14020525 - 19 Feb 2023
Cited by 2 | Viewed by 1947
Abstract
(1) Background: Higher levels of physical fitness are believed to increase the physiological quality of life and impact the aging process with a wide range of adaptive mechanisms, including the regulation of the expression of the age-associated klotho (KL) gene and protein levels. [...] Read more.
(1) Background: Higher levels of physical fitness are believed to increase the physiological quality of life and impact the aging process with a wide range of adaptive mechanisms, including the regulation of the expression of the age-associated klotho (KL) gene and protein levels. (2) Methods: Here, we tested the relationship between the DNA methylation-based epigenetic biomarkers PhenoAge and GrimAge and methylation of the promoter region of the KL gene, the circulating level of KL, and the stage of physical fitness and grip force in two groups of volunteer subjects, trained (TRND) and sedentary (SED), aged between 37 and 85 years old. (3) Results: The circulating KL level is negatively associated with chronological age in the TRND group (r = −0.19; p = 0.0295) but not in the SED group (r = −0.065; p = 0.5925). The age-associated decrease in circulating KL is partly due to the increased methylation of the KL gene. In addition, higher plasma KL is significantly related to epigenetic age-deceleration in the TRND group, assessed by the biomarker of PhenoAge (r = −0.21; p = 0.0192). (4) Conclusions: The level of physical fitness, on the other hand, does not relate to circulating KL levels, nor to the rate of the methylation of the promoter region of the KL gene, only in males. Full article
(This article belongs to the Section Epigenomics)
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11 pages, 471 KiB  
Article
Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study
by Alejandra Villagómez Vega, Jorge Iván Gámez Nava, Francisco Ruiz González, Misael Pérez Romero, Walter Ángel Trujillo Rangel and Ismael Nuño Arana
Genes 2023, 14(2), 524; https://doi.org/10.3390/genes14020524 - 19 Feb 2023
Cited by 2 | Viewed by 1489
Abstract
Background: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do [...] Read more.
Background: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. Aim: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. Methods: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. Results: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). Conclusions: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis. Full article
(This article belongs to the Special Issue Genetics and Pharmacogenetics in Primary Care)
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14 pages, 4421 KiB  
Article
Phylogenetic Relationships among TnpB-Containing Mobile Elements in Six Bacterial Species
by Yali Wang, Mengke Guo, Naisu Yang, Zhongxia Guan, Han Wu, Numan Ullah, Emmanuel Asare, Shasha Shi, Bo Gao and Chengyi Song
Genes 2023, 14(2), 523; https://doi.org/10.3390/genes14020523 - 19 Feb 2023
Cited by 1 | Viewed by 1895
Abstract
Some families of mobile elements in bacterial genomes encode not only a transposase but also an accessory TnpB gene. This gene has been shown to encode an RNA-guided DNA endonuclease, co-evolving with Y1 transposase and serine recombinase in mobile elements IS605 and IS607 [...] Read more.
Some families of mobile elements in bacterial genomes encode not only a transposase but also an accessory TnpB gene. This gene has been shown to encode an RNA-guided DNA endonuclease, co-evolving with Y1 transposase and serine recombinase in mobile elements IS605 and IS607. In this paper, we reveal the evolutionary relationships among TnpB-containing mobile elements (TCMEs) in well-assembled genomes of six bacterial species: Bacillus cereus, Clostridioides difficile, Deinococcus radiodurans, Escherichia coli, Helicobacter pylori and Salmonella enterica. In total, 9996 TCMEs were identified in 4594 genomes. They belonged to 39 different insertion sequences (ISs). Based on their genetic structures and sequence identities, the 39 TCMEs were classified into three main groups and six subgroups. According to our phylogenetic analysis, TnpBs include two main branches (TnpB-A and TnpB-B) and two minor branches (TnpB-C and TnpB-D). The key TnpB motifs and the associated Y1 and serine recombinases were highly conserved across species, even though their overall sequence identities were low. Substantial variation was observed for the rate of invasion across bacterial species and strains. Over 80% of the genomes of B. cereus, C. difficile, D. radiodurans and E. coli contained TCMEs; however, only 64% of the genomes of H. pylori and 44% of S. enterica genomes contained TCMEs. IS605 showed the largest rate of invasion in these species, while IS607 and IS1341 had a relatively narrow distribution. Co-invasions of IS605, IS607 and IS1341 elements were observed in various genomes. The largest average copy number was observed for IS605b elements in C. difficile. The average copy numbers of most other TCMEs were smaller than four. Our findings have important implications for understanding the co-evolution of TnpB-containing mobile elements and their biological roles in host genome evolution. Full article
(This article belongs to the Special Issue Co-evolution of Mobilome and Genome)
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15 pages, 1227 KiB  
Article
Genome-Wide Association Analysis Identified Variants Associated with Body Measurement and Reproduction Traits in Shaziling Pigs
by Qun Lan, Qiuchun Deng, Shijin Qi, Yuebo Zhang, Zhi Li, Shishu Yin, Yulian Li, Hong Tan, Maisheng Wu, Yulong Yin, Jun He and Mei Liu
Genes 2023, 14(2), 522; https://doi.org/10.3390/genes14020522 - 18 Feb 2023
Cited by 2 | Viewed by 1692
Abstract
With the increasing popularity of genomic sequencing, breeders pay more attention to identifying the crucial molecular markers and quantitative trait loci for improving the body size and reproduction traits that could affect the production efficiency of pig-breeding enterprises. Nevertheless, for the Shaziling pig, [...] Read more.
With the increasing popularity of genomic sequencing, breeders pay more attention to identifying the crucial molecular markers and quantitative trait loci for improving the body size and reproduction traits that could affect the production efficiency of pig-breeding enterprises. Nevertheless, for the Shaziling pig, a well-known indigenous breed in China, the relationship between phenotypes and their corresponding genetic architecture remains largely unknown. Herein, in the Shaziling population, a total of 190 samples were genotyped using the Geneseek Porcine 50K SNP Chip, obtaining 41857 SNPs for further analysis. For phenotypes, two body measurement traits and four reproduction traits in the first parity from the 190 Shaziling sows were measured and recorded, respectively. Subsequently, a genome-wide association study (GWAS) between the SNPs and the six phenotypes was performed. The correlation between body size and reproduction phenotypes was not statistically significant. A total of 31 SNPs were found to be associated with body length (BL), chest circumference (CC), number of healthy births (NHB), and number of stillborns (NSB). Gene annotation for those candidate SNPs identified 18 functional genes, such as GLP1R, NFYA, NANOG, COX7A2, BMPR1B, FOXP1, SLC29A1, CNTNAP4, and KIT, which exert important roles in skeletal morphogenesis, chondrogenesis, obesity, and embryonic and fetal development. These findings are helpful to better understand the genetic mechanism for body size and reproduction phenotypes, while the phenotype-associated SNPs could be used as the molecular markers for the pig breeding programs. Full article
(This article belongs to the Special Issue Genetics and Genomics of Pig Breeding)
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10 pages, 336 KiB  
Article
The Telomeric Repeats of HHV-6A Do Not Determine the Chromosome into Which the Virus Is Integrated
by Aleksey V. Kusakin, Olga V. Goleva, Lavrentii G. Danilov, Andrey V. Krylov, Victoria V. Tsay, Roman S. Kalinin, Natalia S. Tian, Yuri A. Eismont, Anna L. Mukomolova, Alexei B. Chukhlovin, Aleksey S. Komissarov and Oleg S. Glotov
Genes 2023, 14(2), 521; https://doi.org/10.3390/genes14020521 - 18 Feb 2023
Viewed by 1405
Abstract
Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DRR) region. It has been shown experimentally that perfect telomeric [...] Read more.
Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DRR) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DRR region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DRR may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DRR regions were examined. We also compared TMR within the herpes virus DRR and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DRR in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration. Full article
(This article belongs to the Special Issue Genetic Architecture in Complex Traits)
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17 pages, 2424 KiB  
Article
Characterization of NDM-5-Producing Escherichia coli Strains Isolated from Pediatric Patients with Bloodstream Infections in a Chinese Hospital
by Lili Huang, Hongye Hu, Chen Xu, Mi Zhou, Yuanyuan Li, Yunbing Li, Shuyan Wu and Ning Dong
Genes 2023, 14(2), 520; https://doi.org/10.3390/genes14020520 - 18 Feb 2023
Cited by 5 | Viewed by 1577
Abstract
Escherichia coli (E. coli) bloodstream infections (BSIs) are among the most predominant causes of death in infants and children worldwide. NDM-5 (New Delhi Metallo-lactamase-5) is responsible for one of the main mechanisms of carbapenem resistance in E. coli. To analyze [...] Read more.
Escherichia coli (E. coli) bloodstream infections (BSIs) are among the most predominant causes of death in infants and children worldwide. NDM-5 (New Delhi Metallo-lactamase-5) is responsible for one of the main mechanisms of carbapenem resistance in E. coli. To analyze the phenotypic and genomic characteristics of NDM-5-producing E. coli from bloodstream infections (BSIs), a total of 114 E. coli strains was collected from a children’s hospital in Jiangsu province, China. Eight blaNDM-5-carrying E. coli strains were identified which were all carbapenem-resistant and carried diverse antimicrobial resistance genes apart from blaNDM-5. They belonged to six distinct sequence types (STs) and serotypes including one each for ST38/O7:H8, ST58/O?:H37, ST131/O25:H4, ST156/O11:H25 and ST361/O9:H30 and three strains are originating from a single clone belonging to ST410/O?:H9. Apart from blaNDM-5, the E. coli strains isolated from BSIs also carried other β-lactamase genes, including blaCMY-2 (n = 4), blaCTX-M-14 (n = 2), blaCTX-M-15 (n = 3), blaCTX-M-65 (n = 1), blaOXA-1 (n = 4) and blaTEM-1B (n = 5). The blaNDM-5 genes were located on three different types of plasmids, which were IncFII/I1 (n = 1), IncX3 (n = 4) and IncFIA/FIB/FII/Q1 (n = 3). The former two types were conjugatively transferable at frequencies of 10−3 and 10−6, respectively. The dissemination of NDM-producing strains, which exhibit resistance to the last-line antibiotics, carbapenems, may increase the muti-antimicrobial resistance burden among E. coli BSIs and further threaten public health. Full article
(This article belongs to the Special Issue Genetics and Genomics of Antimicrobial Resistance)
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14 pages, 2361 KiB  
Article
Clinical and Genetic Features of Korean Patients with Achromatopsia
by Yong Je Choi, Kwangsic Joo, Hyun Taek Lim, Sung Soo Kim, Jinu Han and Se Joon Woo
Genes 2023, 14(2), 519; https://doi.org/10.3390/genes14020519 - 18 Feb 2023
Cited by 1 | Viewed by 1387
Abstract
This multicenter study aimed to characterize Korean patients with achromatopsia. The patients’ genotypes and phenotypes were retrospectively evaluated. Twenty-one patients (with a mean age at the baseline of 10.9 years) were enrolled and followed up for a mean of 7.3 years. A targeted [...] Read more.
This multicenter study aimed to characterize Korean patients with achromatopsia. The patients’ genotypes and phenotypes were retrospectively evaluated. Twenty-one patients (with a mean age at the baseline of 10.9 years) were enrolled and followed up for a mean of 7.3 years. A targeted gene panel or exome sequencing was performed. The pathogenic variants of the four genes and their frequencies were identified. CNGA3 and PDE6C were equally the most prevalent genes: CNGA3 (N = 8, 38.1%), PDE6C (N = 8, 38.1%), CNGB3 (N = 3, 14.3%), and GNAT2 (N = 2, 9.5%). The degree of functional and structural defects varied among the patients. The patients’ age exhibited no significant correlation with structural defects. During the follow-up, the visual acuity and retinal thickness did not change significantly. In CNGA3-achromatopsia patients, a proportion of patients with a normal foveal ellipsoid zone on the OCT was significantly higher than that of patients with other causative genes (62.5% vs. 16.7%; p = 0.023). In PDE6C-achromatopsia patients, the same proportion was significantly lower than that of patients with other causative genes (0% vs. 58.3%; p = 0.003). Korean patients with achromatopsia showed similar clinical features but a higher prevalence of PDE6C variants than those of other ethnic groups. The retinal phenotypes of the PDE6C variants were more likely to be worse than those of other genes. Full article
(This article belongs to the Special Issue Study of Inherited Retinal Disease (IRD))
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20 pages, 2842 KiB  
Article
Genetic Interaction of tRNA-Dependent Mistranslation with Fused in Sarcoma Protein Aggregates
by Jeremy T. Lant, Farah Hasan, Julia Briggs, Ilka U. Heinemann and Patrick O’Donoghue
Genes 2023, 14(2), 518; https://doi.org/10.3390/genes14020518 - 18 Feb 2023
Viewed by 1840
Abstract
High-fidelity protein synthesis requires properly aminoacylated transfer RNAs (tRNAs), yet diverse cell types, from bacteria to humans, show a surprising ability to tolerate errors in translation resulting from mutations in tRNAs, aminoacyl-tRNA synthetases, and other components of protein synthesis. Recently, we characterized a [...] Read more.
High-fidelity protein synthesis requires properly aminoacylated transfer RNAs (tRNAs), yet diverse cell types, from bacteria to humans, show a surprising ability to tolerate errors in translation resulting from mutations in tRNAs, aminoacyl-tRNA synthetases, and other components of protein synthesis. Recently, we characterized a tRNASerAGA G35A mutant (tRNASerAAA) that occurs in 2% of the human population. The mutant tRNA decodes phenylalanine codons with serine, inhibits protein synthesis, and is defective in protein and aggregate degradation. Here, we used cell culture models to test our hypothesis that tRNA-dependent mistranslation will exacerbate toxicity caused by amyotrophic lateral sclerosis (ALS)-associated protein aggregation. Relative to wild-type tRNA, we found cells expressing tRNASerAAA showed slower but effective aggregation of the fused in sarcoma (FUS) protein. Despite reduced levels in mistranslating cells, wild-type FUS aggregates showed similar toxicity in mistranslating cells and normal cells. The aggregation kinetics of the ALS-causative FUS R521C variant were distinct and more toxic in mistranslating cells, where rapid FUS aggregation caused cells to rupture. We observed synthetic toxicity in neuroblastoma cells co-expressing the mistranslating tRNA mutant and the ALS-causative FUS R521C variant. Our data demonstrate that a naturally occurring human tRNA variant enhances cellular toxicity associated with a known causative allele for neurodegenerative disease. Full article
(This article belongs to the Special Issue Emerging Roles of tRNAs in Health and Disease)
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15 pages, 668 KiB  
Review
An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling
by Brian G. Hunt, Levi H. Fox, James C. Davis, Angelle Jones, Zhixin Lu and Susan E. Waltz
Genes 2023, 14(2), 517; https://doi.org/10.3390/genes14020517 - 17 Feb 2023
Cited by 2 | Viewed by 2269
Abstract
RON is a receptor tyrosine kinase (RTK) of the MET receptor family that is canonically involved in mediating growth and inflammatory signaling. RON is expressed at low levels in a variety of tissues, but its overexpression and activation have been associated with malignancies [...] Read more.
RON is a receptor tyrosine kinase (RTK) of the MET receptor family that is canonically involved in mediating growth and inflammatory signaling. RON is expressed at low levels in a variety of tissues, but its overexpression and activation have been associated with malignancies in multiple tissue types and worse patient outcomes. RON and its ligand HGFL demonstrate cross-talk with other growth receptors and, consequentially, positions RON at the intersection of numerous tumorigenic signaling programs. For this reason, RON is an attractive therapeutic target in cancer research. A better understanding of homeostatic and oncogenic RON activity serves to enhance clinical insights in treating RON-expressing cancers. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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16 pages, 7179 KiB  
Review
Palm-Plant Pain, Sign of a Severe Systemic Disease? Case Report and Review of Literature
by Iuliana Magdalena Starcea, Lavinia Bodescu Amancei Ionescu, Tudor Ilie Lazaruc, Vasile Valeriu Lupu, Roxana Alexandra Bogos, Ileana Ioniuc, Felicia Dragan, Ancuta Lupu, Laura Stefana Galatanu, Ingrith Crenguta Miron and Adriana Mocanu
Genes 2023, 14(2), 516; https://doi.org/10.3390/genes14020516 - 17 Feb 2023
Cited by 1 | Viewed by 1546
Abstract
Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will [...] Read more.
Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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11 pages, 2583 KiB  
Article
Histological and Microscopic Analysis of Fats in Heart, Liver Tissue, and Blood Parameters in Experimental Mice
by Sehrish Basheer, Imran Riaz Malik, Fazli Rabbi Awan, Kalsoom Sughra, Sadia Roshan, Adila Khalil, Muhammad Javed Iqbal and Zahida Parveen
Genes 2023, 14(2), 515; https://doi.org/10.3390/genes14020515 - 17 Feb 2023
Viewed by 1459
Abstract
The intake of various types and amounts of dietary fats influences metabolic and cardiovascular health. Hence, this study evaluated the impact of routinely consumed Pakistani dietary fats on their cardiometabolic impact. For this, we made four groups of mice, each comprising 5 animals: [...] Read more.
The intake of various types and amounts of dietary fats influences metabolic and cardiovascular health. Hence, this study evaluated the impact of routinely consumed Pakistani dietary fats on their cardiometabolic impact. For this, we made four groups of mice, each comprising 5 animals: (1) C-ND: Control mice on a normal diet, (2) HFD-DG: High-fat diet mice on a normal diet plus 10% (w/w) desi ghee, (3) HFD-O: Mice on normal diet plus 10% (w/w) plant oil (4) HFD-BG: Mice on normal diet plus 10% (w/w) banaspati ghee. Mice were fed for 16 weeks, and blood, liver, and heart samples were collected for biochemical, histological, and electron microscopic analysis. The physical factors indicated that mice fed on HFD gained more body weight than the C-ND group. Blood parameters do not show significant differences, but overall, the glucose and cholesterol concentrations were raised in the mice fed with a fat-rich diet, with the highest concentrations in the HFD-BG group. The mice fed with HFD-BG and HFD-O had more lipid droplets in the liver, compared to HFD-DG and C-ND. Full article
(This article belongs to the Special Issue Molecular Genetics & Diagnosis of Infectious Diseases)
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4 pages, 201 KiB  
Editorial
Special Issue “Genomics of Stroke” 2022
by Svetlana A. Limborska and Ivan B. Filippenkov
Genes 2023, 14(2), 514; https://doi.org/10.3390/genes14020514 - 17 Feb 2023
Viewed by 895
Abstract
Stroke is one of the greatest medical threats to human health and quality of life in modern society [...] Full article
(This article belongs to the Special Issue Genomics of Stroke)
15 pages, 987 KiB  
Article
Association of Single-Nucleotide Polymorphisms Rs2779249 (chr17:26128581 C>A) and Rs rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 Gene with Tension-Type Headache and Arterial Hypertension Overlap Syndrome in Eastern Siberia
by Polina V. Alyabyeva, Marina M. Petrova, Diana V. Dmitrenko, Natalia P. Garganeeva, Galina A. Chumakova, Mustafa Al-Zamil, Vera V. Trefilova, Regina F. Nasyrova and Natalia A. Shnayder
Genes 2023, 14(2), 513; https://doi.org/10.3390/genes14020513 - 17 Feb 2023
Cited by 2 | Viewed by 1535
Abstract
Inducible nitric oxide (NO) synthase (iNOS), encoded by the NOS2 gene, promotes the generation of high levels of NO to combat harmful environmental influences in a wide range of cells. iNOS can cause adverse effects, such as falling blood pressure, if overexpressed. Thus, [...] Read more.
Inducible nitric oxide (NO) synthase (iNOS), encoded by the NOS2 gene, promotes the generation of high levels of NO to combat harmful environmental influences in a wide range of cells. iNOS can cause adverse effects, such as falling blood pressure, if overexpressed. Thus, according to some data, this enzyme is an important precursor of arterial hypertension (AH) and tension-type headache (TTH), which are the most common multifactorial diseases in adults. The purpose of this study was to investigate the association of rs2779249 (chr17:26128581 C>A) and rs2297518 (chr17: chr17:27769571 G>A) of the NOS2 gene with TTH and AH overlap syndrome (OS) in Caucasians in Eastern Siberia. The sample size was 91 participants: the first group—30 patients with OS; the second group—30 patients AH; and the third group—31 healthy volunteers. RT-PCR was used for the determination of alleles and genotypes of the SNPs rs2779249 and rs2297518 of the NOS2 gene in all groups of participants. We showed that the frequency of allele A was significantly higher among patients with AH compared with healthy volunteers (p-value < 0.05). The frequency of the heterozygous genotype CA of rs2779249 was higher in the first group vs. the control (p-value = 0.03), and in the second group vs. the control (p-value = 0.045). The frequency of the heterozygous genotype GA of rs2297518 was higher in the first group vs. the control (p-value = 0.035), and in the second group vs. the control (p-value = 0.001). The allele A of rs2779249 was associated with OS (OR = 3.17 [95% CI: 1.31–7.67], p-value = 0.009) and AH (OR = 2.94 [95% CI: 1.21–7.15], p-value = 0.015) risks compared with the control. The minor allele A of rs2297518 was associated with OS (OR = 4.0 [95% CI: 0.96–16.61], p-value = 0.035) and AH (OR = 8.17 [95% CI: 2.03–32.79], p-value = 0.001) risks compared with the control. Therefore, our pilot study demonstrated that the SNPs rs2779249 and rs229718 of the NOS2 gene could be promising genetic biomarkers for this OS risk in Caucasians from Eastern Siberia. Full article
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13 pages, 2529 KiB  
Article
Effect of 11-Deoxycorticosterone in the Transcriptomic Response to Stress in Rainbow Trout Skeletal Muscle
by Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina and Juan Antonio Valdés
Genes 2023, 14(2), 512; https://doi.org/10.3390/genes14020512 - 17 Feb 2023
Cited by 2 | Viewed by 1525
Abstract
In aquaculture, many stressors can negatively affect growth in teleosts. It is believed that cortisol performs glucocorticoid and mineralocorticoid functions because teleosts do not synthesize aldosterone. However, recent data suggest that 11-deoxycorticosterone (DOC) released during stress events may be relevant to modulate the [...] Read more.
In aquaculture, many stressors can negatively affect growth in teleosts. It is believed that cortisol performs glucocorticoid and mineralocorticoid functions because teleosts do not synthesize aldosterone. However, recent data suggest that 11-deoxycorticosterone (DOC) released during stress events may be relevant to modulate the compensatory response. To understand how DOC modifies the skeletal muscle molecular response, we carried out a transcriptomic analysis. Rainbow trout (Oncorhynchus mykiss) were intraperitoneally treated with physiological doses of DOC in individuals pretreated with mifepristone (glucocorticoid receptor antagonist) or eplerenone (mineralocorticoid receptor antagonist). RNA was extracted from the skeletal muscles, and cDNA libraries were constructed from vehicle, DOC, mifepristone, mifepristone plus DOC, eplerenone, and eplerenone plus DOC groups. The RNA-seq analysis revealed 131 differentially expressed transcripts (DETs) induced by DOC with respect to the vehicle group, mainly associated with muscle contraction, sarcomere organization, and cell adhesion. In addition, a DOC versus mifepristone plus DOC analysis revealed 122 DETs related to muscle contraction, sarcomere organization, and skeletal muscle cell differentiation. In a DOC versus eplerenone plus DOC analysis, 133 DETs were associated with autophagosome assembly, circadian regulation of gene expression, and regulation of transcription from RNA pol II promoter. These analyses indicate that DOC has a relevant function in the stress response of skeletal muscles, whose action is differentially modulated by GR and MR and is complementary to cortisol. Full article
(This article belongs to the Special Issue Aquaculture Genetics: Latest Advances and Prospects)
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14 pages, 2995 KiB  
Article
Novel Haplotype in the HHEX Gene Promoter Associated with Body Length in Pigs
by Yabiao Luo, Qiao Xu, Mingming Xue, Yubei Wang, Xiaoyang Yang, Shuheng Chan, Qiguo Tang, Feng Wang, Ruiping Sun, Zhe Chao and Meiying Fang
Genes 2023, 14(2), 511; https://doi.org/10.3390/genes14020511 - 17 Feb 2023
Cited by 1 | Viewed by 1318
Abstract
The screening of important candidate genes and the identification of genetic markers are important for molecular selection in the pig industry. The hematopoietically expressed homeobox (HHEX) gene plays an important role in embryonic development and organogenesis; however, the genetic variation and [...] Read more.
The screening of important candidate genes and the identification of genetic markers are important for molecular selection in the pig industry. The hematopoietically expressed homeobox (HHEX) gene plays an important role in embryonic development and organogenesis; however, the genetic variation and expression pattern of the porcine HHEX gene remains to be clarified. In this study, semiquantitative RT-PCR and immunohistochemistry results showed the specific expression of the HHEX gene in porcine cartilage tissues. A novel haplotype consisting of two SNPs rs80901185 (T > C) and rs80934526 (A > G) was detected in the promoter region of the HHEX gene. The expression of the HHEX gene was significantly higher in Yorkshire pigs (TA haplotype) than in Wuzhishan pigs (CG haplotype), and a population analysis showed that this haplotype was significantly associated with body length. An analysis subsequently revealed that the –586 to –1 bp region of the HHEX gene promoter showed the highest activity. Furthermore, we found that the activity of the TA haplotype was significantly higher than that of the CG haplotype by changing the potential binding of transcription factors YY1 and HDAC2. In summary, we conclude that the porcine HHEX gene may contribute to the breeding of pigs for body length traits. Full article
(This article belongs to the Special Issue Genetics and Genomics of Pig Breeding)
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14 pages, 2642 KiB  
Article
A Novel Homozygous Nonsense Variant in the DYM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family
by Abu Bakar, Sulaiman Shams, Nousheen Bibi, Asmat Ullah, Wasim Ahmad, Musharraf Jelani, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Turki S. Abujamel, Absarul Haque, Muhammad Imran Naseer and Bushra Khan
Genes 2023, 14(2), 510; https://doi.org/10.3390/genes14020510 - 17 Feb 2023
Cited by 1 | Viewed by 1767
Abstract
(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In [...] Read more.
(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community. Full article
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16 pages, 724 KiB  
Review
Histories of Dermatan Sulfate Epimerase and Dermatan 4-O-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome
by Shuji Mizumoto and Shuhei Yamada
Genes 2023, 14(2), 509; https://doi.org/10.3390/genes14020509 - 16 Feb 2023
Cited by 1 | Viewed by 1941
Abstract
Dermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these enzymes, dermatan sulfate epimerase [...] Read more.
Dermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these enzymes, dermatan sulfate epimerase (DSE) and dermatan 4-O-sulfotranserase (D4ST) are rate-limiting factors of DS biosynthesis. Pathogenic variants in human genes encoding DSE and D4ST cause the musculocontractural type of Ehlers-Danlos syndrome, characterized by tissue fragility, joint hypermobility, and skin hyperextensibility. DS-deficient mice exhibit perinatal lethality, myopathy-related phenotypes, thoracic kyphosis, vascular abnormalities, and skin fragility. These findings indicate that DS is essential for tissue development as well as homeostasis. This review focuses on the histories of DSE as well as D4ST, and their knockout mice as well as human congenital disorders. Full article
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11 pages, 278 KiB  
Article
The rs3825807 Polymorphism of ADAMTS7 as a Potential Genetic Marker for Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus
by David Petrovič, Petra Nussdorfer and Danijel Petrovič
Genes 2023, 14(2), 508; https://doi.org/10.3390/genes14020508 - 16 Feb 2023
Cited by 2 | Viewed by 1240
Abstract
Background: A disintegrin and metalloprotease with thrombospondin motif 7 (ADAMTS-7) was reported to play a role in the migration of vascular smooth muscle cells and neointimal formation. The object of the study was to investigate the association between the rs3825807 polymorphism of ADAMTS7 [...] Read more.
Background: A disintegrin and metalloprotease with thrombospondin motif 7 (ADAMTS-7) was reported to play a role in the migration of vascular smooth muscle cells and neointimal formation. The object of the study was to investigate the association between the rs3825807 polymorphism of ADAMTS7 and myocardial infarction among patients with type 2 diabetes mellitus in a Slovenian cohort. Methods: 1590 Slovenian patients with type 2 diabetes mellitus were enrolled in this retrospective cross-sectional case–control study. In total, 463 had a history of recent myocardial infarction, and 1127 of the subjects in the control group had no clinical signs of coronary artery disease. Genetic analysis of an rs3825807 polymorphism of ADAMTS7 was performed with logistic regression. Results: Patients with the AA genotype had a higher prevalence of myocardial infarction than those in the control group in recessive [odds ratio (OR) 1.647; confidence interval (CI) 1.120–2.407; p = 0.011] and co-dominant (OR 2.153; CI 1.215–3.968; p = 0.011) genetic models. Conclusion: We found a statistically significant association between rs3825807 and myocardial infarction in a cohort of Slovenian patients with type 2 diabetes mellitus. We report that the AA genotype might be a genetic risk factor for myocardial infarction. Full article
(This article belongs to the Special Issue Omics Studies of Type 2 Diabetes and Diabetes-Related Complications)
11 pages, 4568 KiB  
Article
Insights into the Genetic Determination of the Autotetraploid Potato Plant Height
by Long Zhao, Meiling Zou, Sirong Jiang, Xiaorui Dong, Ke Deng, Tiancang Na, Jian Wang, Zhiqiang Xia and Fang Wang
Genes 2023, 14(2), 507; https://doi.org/10.3390/genes14020507 - 16 Feb 2023
Viewed by 1657
Abstract
Plant height is an important characteristic, the modification of which can improve the ability of stress adaptation as well as the yield. In this study, genome-wide association analysis was performed for plant height traits in 370 potato cultivars using the tetraploid potato genome [...] Read more.
Plant height is an important characteristic, the modification of which can improve the ability of stress adaptation as well as the yield. In this study, genome-wide association analysis was performed for plant height traits in 370 potato cultivars using the tetraploid potato genome as a reference. A total of 92 significant single nucleotide polymorphism (SNP) loci for plant height were obtained, which were particularly significant in haplotypes A3 and A4 on chromosome 1 and A1, A2, and A4 on chromosome 5. Thirty-five candidate genes were identified that were mainly involved in the gibberellin and brassinolide signal transduction pathways, including the FAR1 gene, methyltransferase, ethylene response factor, and ubiquitin protein ligase. Among them, PIF3 and GID1a were only present on chromosome 1, with PIF3 in all four haplotypes and GID1a in haplotype A3. This could lead to more effective genetic loci for molecular marker-assisted selection breeding as well as more precise localization and cloning of genes for plant height traits in potatoes. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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20 pages, 1068 KiB  
Article
Attention-Based Graph Neural Network for Label Propagation in Single-Cell Omics
by Rahul Bhadani, Zhuo Chen and Lingling An
Genes 2023, 14(2), 506; https://doi.org/10.3390/genes14020506 - 16 Feb 2023
Cited by 1 | Viewed by 1706
Abstract
Single-cell data analysis has been at forefront of development in biology and medicine since sequencing data have been made available. An important challenge in single-cell data analysis is the identification of cell types. Several methods have been proposed for cell-type identification. However, these [...] Read more.
Single-cell data analysis has been at forefront of development in biology and medicine since sequencing data have been made available. An important challenge in single-cell data analysis is the identification of cell types. Several methods have been proposed for cell-type identification. However, these methods do not capture the higher-order topological relationship between different samples. In this work, we propose an attention-based graph neural network that captures the higher-order topological relationship between different samples and performs transductive learning for predicting cell types. The evaluation of our method on both simulation and publicly available datasets demonstrates the superiority of our method, scAGN, in terms of prediction accuracy. In addition, our method works best for highly sparse datasets in terms of F1 score, precision score, recall score, and Matthew’s correlation coefficients as well. Further, our method’s runtime complexity is consistently faster compared to other methods. Full article
(This article belongs to the Special Issue Machine Learning Applications in Genetics)
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12 pages, 2461 KiB  
Article
Efficient Delivery of FMR1 across the Blood Brain Barrier Using AAVphp Construct in Adult FMR1 KO Mice Suggests the Feasibility of Gene Therapy for Fragile X Syndrome
by Kathryn K. Chadman, Tatyana Adayev, Aishwarya Udayan, Rida Ahmed, Chun-Ling Dai, Jeffrey H. Goodman, Harry Meeker, Natalia Dolzhanskaya and Milen Velinov
Genes 2023, 14(2), 505; https://doi.org/10.3390/genes14020505 - 16 Feb 2023
Cited by 2 | Viewed by 1998
Abstract
Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.eb-hSyn-mFMR1IOS7 vector and an empty control were injected into the tail [...] Read more.
Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism. Gene therapy may offer an efficient method to ameliorate the symptoms of this disorder. Methods An AAVphp.eb-hSyn-mFMR1IOS7 vector and an empty control were injected into the tail vein of adult Fmr1 knockout (KO) mice and wildtype (WT) controls. The KO mice were injected with 2 × 1013 vg/kg of the construct. The control KO and WT mice were injected with an empty vector. Four weeks following treatment, the animals underwent a battery of tests: open field, marble burying, rotarod, and fear conditioning. The mouse brains were studied for levels of the Fmr1 product FMRP. Results: No significant levels of FMRP were found outside the CNS in the treated animals. The gene delivery was highly efficient, and it exceeded the control FMRP levels in all tested brain regions. There was also improved performance in the rotarod test and partial improvements in the other tests in the treated KO animals. Conclusion: These experiments demonstrate efficient, brain-specific delivery of Fmr1 via peripheral administration in adult mice. The gene delivery led to partial alleviation of the Fmr1 KO phenotypical behaviors. FMRP oversupply may explain why not all behaviors were significantly affected. Since AAV.php vectors are less efficient in humans than in the mice used in the current experiment, studies to determine the optimal dose using human-suitable vectors will be necessary to further demonstrate feasibility. Full article
(This article belongs to the Special Issue Fragile X Syndrome Genetics)
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14 pages, 8347 KiB  
Article
Candidate Genes and Gene Networks Change with Age in Japanese Black Cattle by Blood Transcriptome Analysis
by Chencheng Chang, Yanda Yang, Le Zhou, Batu Baiyin, Zaixia Liu, Lili Guo, Fengying Ma, Jie Wang, Yuan Chai, Caixia Shi and Wenguang Zhang
Genes 2023, 14(2), 504; https://doi.org/10.3390/genes14020504 - 16 Feb 2023
Cited by 1 | Viewed by 1403
Abstract
Age is an important physiological factor that affects the metabolism and immune function of beef cattle. While there have been many studies using the blood transcriptome to study the effects of age on gene expression, few have been reported on beef cattle. To [...] Read more.
Age is an important physiological factor that affects the metabolism and immune function of beef cattle. While there have been many studies using the blood transcriptome to study the effects of age on gene expression, few have been reported on beef cattle. To this end, we used the blood transcriptomes of Japanese black cattle at different ages as the study subjects and screened 1055, 345, and 1058 differential expressed genes (DEGs) in the calf vs. adult, adult vs. old, and calf vs. old comparison groups, respectively. The weighted co-expression network consisted of 1731 genes. Finally, blue, brown, and yellow age-specific modules were obtained, in which genes were enriched in signaling pathways related to growth and development and immune metabolic dysfunction, respectively. Protein-protein interaction (PPI) analysis showed gene interactions in each specific module, and 20 of the highest connectivity genes were chosen as potential hub genes. Finally, we identified 495, 244, and 1007 genes by exon-wide selection signature (EWSS) analysis of different comparison groups. Combining the results of hub genes, we found that VWF, PARVB, PRKCA, and TGFB1I1 could be used as candidate genes for growth and development stages of beef cattle. CORO2B and SDK1 could be used as candidate marker genes associated with aging. In conclusion, by comparing the blood transcriptome of calves, adult cattle, and old cattle, the candidate genes related to immunity and metabolism affected by age were identified, and the gene co-expression network of different age stages was constructed. It provides a data basis for exploring the growth, development, and aging of beef cattle. Full article
(This article belongs to the Special Issue Genetics and Breeding of Cattle)
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