Genes

17 pages, 4606 KiB

Open AccessEditor’s ChoiceArticle

Multi-Omics Revealed Regulatory Mechanisms Underlying the Flowering of Ferula sinkiangensis across Three Dimensions

by Congzhao Fan, Yanfei Li, Jizhao Zhang, Yaqin Zhao, Yigong Zhang, Jun Zhu, Xingwang Gao, Yan Liang, Yuanjin Qiu, Jingyuan Song and Guoping Wang

Genes 2024, 15(10), 1275; https://doi.org/10.3390/genes15101275 - 28 Sep 2024

Cited by 1 | Viewed by 1025

Abstract

Backgroud/Objectives: Ferula spp. is an essential crop in Central Asia with pronounced economic benefits governed by its flowering process. However, the mechanisms of the flowering phenotype remain unclear. Methods: In this study, using F. sinkiangensis as a model plant, we integrated transcriptome, proteome, [...] Read more.

Backgroud/Objectives: Ferula spp. is an essential crop in Central Asia with pronounced economic benefits governed by its flowering process. However, the mechanisms of the flowering phenotype remain unclear. Methods: In this study, using F. sinkiangensis as a model plant, we integrated transcriptome, proteome, and metabolome analyses to compare the multilayer differences in leaves and roots of plants with flowering and unflowering phenotypes. Results: We found that several variations in the transcriptome, proteome, and metabolome were closely associated with flowering. The Photosynthesis and Phenylpropanoid biosynthesis pathways in plants with the flowering phenotype were more active. Additionally, three flowering genes, named FL2–FL4, were upregulated in the leaves of flowering plants. Notably, six transcription factors were potentially responsible for regulating the expression of FL2–FL4 in the leaves to mediate flowering process of F. sinkiangensis. Moreover, genes relevant to Photosynthesis and Phenylpropanoid biosynthesis were also involved in regulating the expression of FL2–FL4 in flowering plants. Conclusions: The active regulation network together with Photosynthesis and Phenylpropanoid biosynthesis were essential for inducing the expression of flowering-related genes in leaves to promote the flowering process of F. sinkiangensis. Full article

(This article belongs to the Special Issue Genomics and Genetics of Medicinal Plants)

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14 pages, 2103 KiB

Open AccessEditor’s ChoiceSystematic Review

The Association between Post-Traumatic Stress Disorder, 5HTTLPR, and the Role of Ethnicity: A Meta-Analysis

by Marta Landoni, Sonia Di Tella, Giulia Ciuffo and Chiara Ionio

Genes 2024, 15(10), 1270; https://doi.org/10.3390/genes15101270 - 27 Sep 2024

Viewed by 1069

Abstract

Background/Objectives: The current meta-analysis looks at the effect of ethnicity on the connection between 5-HTTLPR SNPs and PTSD patients in all published genetic association studies. Techniques: In accordance with PRISMA principles, the literature was searched in PubMed, Scopus, and ScienceDirect. A consistent method [...] Read more.

Background/Objectives: The current meta-analysis looks at the effect of ethnicity on the connection between 5-HTTLPR SNPs and PTSD patients in all published genetic association studies. Techniques: In accordance with PRISMA principles, the literature was searched in PubMed, Scopus, and ScienceDirect. A consistent method was followed by two reviewers who independently chose publications for inclusion and extracted data. Using a random-effects model, a meta-analysis of the biallelic and triallelic studies was conducted in order to determine the pooled OR and the associated 95% CI. The impact estimates were corrected for minor study effects, including publication bias, using the trim-and-fill approach. Findings: After 17 studies were deemed eligible for inclusion, the overall sample size was 8838 controls and 2586 PTSD patients, as opposed to 627 and 3524 in the triallelic meta-analysis. The results of our meta-analysis and comprehensive review do not point to a direct main effect of the 5-HTTLPR polymorphisms on PTSD. Nonetheless, preliminary data suggest that ethnicity influences the association between 5-HTTLPR and PTSD. Conclusions: According to our findings, ethnicity—especially African ethnicity—has a major influence on the relationship between 5-HTTLPR and PTSD and needs to be taken into account as a crucial moderating factor in further studies. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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15 pages, 1066 KiB

Open AccessEditor’s ChoiceReview

The Microphthalmia-Associated Transcription Factor (MITF) and Its Role in the Structure and Function of the Eye

by Andrea García-Llorca and Thor Eysteinsson

Genes 2024, 15(10), 1258; https://doi.org/10.3390/genes15101258 - 27 Sep 2024

Cited by 1 | Viewed by 1819

Abstract

Background/Objectives: The microphthalmia-associated transcription factor (Mitf) has been found to play an important role in eye development, structure, and function. The Mitf gene is responsible for controlling cellular processes in a range of cell types, contributing to multiple eye development processes. [...] Read more.

Background/Objectives: The microphthalmia-associated transcription factor (Mitf) has been found to play an important role in eye development, structure, and function. The Mitf gene is responsible for controlling cellular processes in a range of cell types, contributing to multiple eye development processes. In this review, we survey what is now known about the impact of Mitf on eye structure and function in retinal disorders. Several mutations in the human and mouse Mitf gene are now known, and the effects of these on eye phenotype are addressed. We discuss the importance of Mitf in regulating ion transport across the retinal pigment epithelium (RPE) and the vasculature of the eye. Methods: The literature was searched using the PubMed, Scopus, and Google Scholar databases. Fundus and Optical Coherence Tomography (OCT) images from mice were obtained with a Micron IV rodent imaging system. Results: Defects in neural-crest-derived melanocytes resulting from any Mitf mutations lead to hypopigmentation in the eye, coat, and inner functioning of the animals. While many Mitf mutations target RPE cells in the eye, fewer impact osteoclasts at the same time. Some of the mutations in mice lead to microphthalmia, and ultimately vision loss, while other mice show a normal eye size; however, the latter, in some cases, show hypopigmentation in the fundus and the choroid is depigmented and thickened, and in rare cases Mitf mutations lead to progressive retinal degeneration. Conclusions: The Mitf gene has an impact on the structure and function of the retina and its vasculature, the RPE, and the choroid in the adult eye. Full article

(This article belongs to the Special Issue Genetics in Retinal Diseases—2nd Edition)

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6 pages, 195 KiB

Open AccessEditor’s ChoiceCase Report

New Mutation Associated with Polycystic Kidney Disease Type I: A Case Report

by Vanya Rai, Manisha Singh and Joseph H. Holthoff

Genes 2024, 15(10), 1262; https://doi.org/10.3390/genes15101262 - 27 Sep 2024

Cited by 1 | Viewed by 1540

Abstract

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent heritable disorders, characterized by the progressive development of kidney cysts leading to renal failure. It is primarily caused by mutations in the PKD1 and PKD2 genes, which account for approximately [...] Read more.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent heritable disorders, characterized by the progressive development of kidney cysts leading to renal failure. It is primarily caused by mutations in the PKD1 and PKD2 genes, which account for approximately 85% and 15% of cases, respectively. This case report describes a previously unreported mutation in the PKD1 gene, identified in a family involving an aunt and her niece with ADPKD. Case Presentation: The index case, a 56-year-old female with chronic kidney disease stage 3b secondary to ADPKD and hypertension, exhibited a strong family history of polycystic kidney disease (PKD). Initial genetic evaluations did not identify any recognized pathogenic mutations, leading to a more detailed investigation which revealed a novel mutation in the PKD1 gene. This mutation was also found in her niece, who presented with early-onset disease. Conclusions: The identification of a heterozygous six-nucleotide deletion, c.2084_2089del, resulting in the in-frame deletion of two amino acids, p.Pro695_Ala696del, in the PKD1 gene, has been linked with ADPKD in these patients. This report emphasizes the need for continuous updates to genetic data for a deeper understanding of the diagnosis and prognosis of ADPKD that could potentially aid in targeted therapy. Full article

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

10 pages, 2083 KiB

Open AccessEditor’s ChoiceArticle

Molecular Phylogenetics and Mitochondrial Genomic Evolution in the Endemic Genus Pielomastax (Orthoptera: Eumastacoidea) in China

by Jun-Hui Lu, Keyao Zhang, Sheng-Quan Xu and Ying Ding

Genes 2024, 15(10), 1260; https://doi.org/10.3390/genes15101260 - 27 Sep 2024

Viewed by 949

Abstract

Background/Objectives: The genus Pielomastax Chang (Orthoptera: Eumastacoidea, 1937) is endemic to China, which is mainly distributed in low- and medium-altitude areas in central and eastern China. However, there are relatively few molecular data studies on the genus Pielomastax. Methods: In this study, [...] Read more.

Background/Objectives: The genus Pielomastax Chang (Orthoptera: Eumastacoidea, 1937) is endemic to China, which is mainly distributed in low- and medium-altitude areas in central and eastern China. However, there are relatively few molecular data studies on the genus Pielomastax. Methods: In this study, three species of the genus Pielomastax were collected from Hubei and Henan, China, namely Pielomastax sp., Pielomastax shennongjiaensis Wang (1995) and Pielomastax tenuicerca Hsia and Liu (1989). Both Pielomastax sp. and Pielomastax shennongjiaensis were collected from the Shennongjia area of Hubei, but they exhibit some differences in morphological characteristics. Results: We obtained the mitochondrial genome structures of the three species, which were similar to those of the published mitochondrial genome structures of species within Eumastacoidea with 37 typical mitochondrial genes, including 13 PCGs, 22 tRNAs, and 2 ribosomal RNAs. The results of the maximum likelihood (ML) tree and the Bayesian inference (BI) tree showed that the families Eumastacidae, Chorotypidae and Episactinae in Eumastacoidea are a monophyletic group, and Thericleinae and Episactinae are sister clades. The time-calibrated phylogeny results indicated that the divergence time between Thericleinae and Episactinae was 95.58 Ma (56.71–128.02 Ma). Conclusions: These phylogenetic tree results indicate that Pielomastax sp. and Pielomastax shennongjiaensis are the same species. And the time-calibrated phylogeny tree and the species distribution map of the genus Pielomastax indicate that the species of the genus Pielomastax spread from eastern to central China and diversified. These studies fill the gap in molecular data for the genus Pielomastax and the taxonomic status of Episactidae. Full article

(This article belongs to the Section Bioinformatics)

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12 pages, 259 KiB

Open AccessEditor’s ChoiceReview

Sudden Cardiac Death and Channelopathies: What Lies behind the Clinical Significance of Rare Splice-Site Alterations in the Genes Involved?

by Mauro Pesaresi, Alessia Bernini Di Michele, Filomena Melchionda, Valerio Onofri, Federica Alessandrini and Chiara Turchi

Genes 2024, 15(10), 1272; https://doi.org/10.3390/genes15101272 - 27 Sep 2024

Viewed by 1460

Abstract

Background and objectives: Sudden cardiac death (SCD) is a natural and unexpected death of cardiac origin that occurs within 1 h from the onset of acute symptoms. The major leading causes of SCD are cardiomyopathies and channelopathies. In this review, we focus [...] Read more.

Background and objectives: Sudden cardiac death (SCD) is a natural and unexpected death of cardiac origin that occurs within 1 h from the onset of acute symptoms. The major leading causes of SCD are cardiomyopathies and channelopathies. In this review, we focus on channelopathies, inherited diseases caused by mutations affecting genes encoding membrane ion channels (sodium, potassium or calcium channels) or cellular structures that affect Ca²⁺ availability. The diagnosis of diseases such as long QT, Brugada syndrome, short QT and catecholaminergic polymorphic ventricular tachycardia (CPVT) is still challenging. Currently, genetic testing and next-generation sequencing allow us to identify many rare alterations. However, some non-coding variants, e.g., splice-site variants, are usually difficult to interpret and to classify. Methods: In our review, we searched for splice-site variants of genes involved in channelopathies, focusing on variants of unknown significance (VUSs) registered on ClinVar up to now. Results: The research led to a high number of splice-site VUSs of genes involved in channelopathies, suggesting the performance of deeper studies. Conclusions: In order to interpret the correlation between variants and pathologies, we discuss experimental studies, such as RNA sequencing and functional analysis of proteins. Unfortunately, as these in vitro analyses cannot always be performed, we draw attention to in silico studies as future perspectives in genetics. This review has the aim of discussing the potential methods of detection and interpretation of VUSs, bringing out the need for a future reclassification of variants with currently unknown significance. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics Volume II)

10 pages, 1850 KiB

Open AccessEditor’s ChoiceArticle

De Novo Genome Assembly and Phylogenetic Analysis of Cirsium nipponicum

by Bae Young Choi, Jaewook Kim, Hyeonseon Park, Jincheol Kim, Seahee Han, Ick-Hyun Jo and Donghwan Shim

Genes 2024, 15(10), 1269; https://doi.org/10.3390/genes15101269 - 27 Sep 2024

Viewed by 1214

Abstract

Background: Cirsium nipponicum, a pharmaceutically valuable plant from the Asteraceae family, has been utilized for over 2000 years. Unlike other thistles, it is native to East Asia and found exclusively on Ulleung Island on the Korea Peninsula. Despite its significance, the genome [...] Read more.

Background: Cirsium nipponicum, a pharmaceutically valuable plant from the Asteraceae family, has been utilized for over 2000 years. Unlike other thistles, it is native to East Asia and found exclusively on Ulleung Island on the Korea Peninsula. Despite its significance, the genome information of C. nipponicum has remained unclear. Methods: In this study, we assembled the genome of C. nipponicum using both short reads from Illumina sequencing and long reads from Nanopore sequencing. Results: The assembled genome is 929.4 Mb in size with an N50 length of 0.7 Mb, covering 95.1% of BUSCO core groups listed in edicots_odb10. Repeat sequences accounted for 70.94% of the assembled genome. We curated 31,263 protein-coding genes, of which 28,752 were functionally annotated using public databases. Phylogenetic analysis of 11 plant species using single-copy orthologs revealed that C. nipponicum diverged from Cynara cardunculus approximately 15.9 million years ago. Gene family evolutionary analysis revealed significant expansion and contraction in genes involved in abscisic acid biosynthesis, late endosome to vacuole transport, response to nitrate, and abaxial cell fate specification. Conclusions: This study provides a reference genome of C. nipponicum, enhancing our understanding of its genetic background and facilitating an exploration of genetic resources for beneficial phytochemicals. Full article

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

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12 pages, 273 KiB

Open AccessEditor’s ChoiceArticle

The Association of the Oral Microbiota with Cognitive Functioning in Adolescence

by Oxana Y. Naumova, Pavel V. Dobrynin, Galina V. Khafizova and Elena L. Grigorenko

Genes 2024, 15(10), 1263; https://doi.org/10.3390/genes15101263 - 27 Sep 2024

Cited by 2 | Viewed by 1354

Abstract

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host’s cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged [...] Read more.

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host’s cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota. Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12–18 years and explored the associations between the microbiome and the youths’ cognitive performance captured with the Kaufman Assessment Battery for Children II (KABC-II). Results: Several bacterial species of the oral microbiota and related metabolic pathways were associated with cognitive function. In particular, we found negative associations between indicators of general intelligence and the relative abundance of Bacteroidetes and Lachnospiraceae and positive associations with Bifidobacteriaceae and Prevotella histicola sp. Among metabolic pathways, the super pathways related to bacterial cell division and GABA metabolism were linked to cognitive function. Conclusions: The results of our work are consistent with the literature reporting on the association between microbiota and cognitive function and support further population work to elucidate the potential for a healthy oral microbiome to improve cognitive health. Full article

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

13 pages, 9328 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome and Metabolome Analysis of BmFAMeT6 Overexpression in Bombyx mori

by Yang Yu, Tian Li and Ping Chen

Genes 2024, 15(10), 1261; https://doi.org/10.3390/genes15101261 - 27 Sep 2024

Cited by 1 | Viewed by 914

Abstract

Background/Objectives: The gene-encoding farnesyl diphosphate O-methyltransferase 6 (FAMeT 6) is a member of the farnesyl diphosphate O-methyltransferase family. Our previous studies have demonstrated its influence on juvenile hormone levels in third instar silkworm larvae. Methods: we utilized transcriptomic and metabolomic techniques to investigate [...] Read more.

Background/Objectives: The gene-encoding farnesyl diphosphate O-methyltransferase 6 (FAMeT 6) is a member of the farnesyl diphosphate O-methyltransferase family. Our previous studies have demonstrated its influence on juvenile hormone levels in third instar silkworm larvae. Methods: we utilized transcriptomic and metabolomic techniques to investigate the changes in third instar larvae at 0, 12, and 24 h following BmFAMeT6 overexpression. Results: (1) The differentially expressed homologous genes were enriched in detoxification-related pathways at all three time points. (2) Transcription factor analysis of DEGs indicated a predominant presence of ZF-C2H2. (3) The metabolite-related network suggested that BmFAMeT6 may influence the metabolism of silkworm larvae through the ABC transporters, purine metabolism, and tyrosine metabolism pathways. (4) The differential gene count, differential metabolite count, and types of metabolites at the three time points indicated a shift in the regulatory focus within the larvae as time progresses, with the inflection point of regulation occurring at the third instar larval stage, 12 h. Conclusion: In summary, our research indicates that the regulatory role of BmFAMeT6 occurs within the context of the domestic silkworm’s own growth and development regulation. Full article

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

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15 pages, 16488 KiB

Open AccessEditor’s ChoiceArticle

YELLOW LEAF AND DWARF 7, Encoding a Novel Ankyrin Domain-Containing Protein, Affects Chloroplast Development in Rice

by Yongtao Cui, Jian Song, Liqun Tang and Jianjun Wang

Genes 2024, 15(10), 1267; https://doi.org/10.3390/genes15101267 - 27 Sep 2024

Viewed by 1116

Abstract

Background: The proper development of grana and stroma within chloroplasts is critical for plant vitality and crop yield in rice and other cereals. While the molecular mechanisms underpinning these processes are known, the genetic networks governing them require further exploration. Methods and Results: [...] Read more.

Background: The proper development of grana and stroma within chloroplasts is critical for plant vitality and crop yield in rice and other cereals. While the molecular mechanisms underpinning these processes are known, the genetic networks governing them require further exploration. Methods and Results: In this study, we characterize a novel rice mutant termed yellow leaf and dwarf 7 (yld7), which presents with yellow, lesion-like leaves and a dwarf growth habit. The yld7 mutant shows reduced photosynthetic activity, lower chlorophyll content, and abnormal chloroplast structure. Transmission electron microscopy (TEM) analysis revealed defective grana stacking in yld7 chloroplasts. Additionally, yld7 plants accumulate high levels of hydrogen peroxide (H₂O₂) and exhibit an up-regulation of senescence-associated genes, leading to accelerated cell death. Map-based cloning identified a C-to-T mutation in the LOC_Os07g33660 gene, encoding the YLD7 protein, which is a novel ankyrin domain-containing protein localized to the chloroplast. Immunoblot analysis of four LHCI proteins indicated that the YLD7 protein plays an important role in the normal biogenesis of chloroplast stroma and grana, directly affecting leaf senescence and overall plant stature. Conclusions: This study emphasizes the significance of YLD7 in the intricate molecular mechanisms that regulate the structural integrity of chloroplasts and the senescence of leaves, thus providing valuable implications for the enhancement of rice breeding strategies and cultivation. Full article

(This article belongs to the Special Issue Genetics and Breeding of Rice)

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22 pages, 1537 KiB

Open AccessEditor’s ChoiceReview

Canonical and Non-Canonical Roles of Human DNA Polymerase η

by Salma Bedaiwi, Anam Usmani and Michael P. Carty

Genes 2024, 15(10), 1271; https://doi.org/10.3390/genes15101271 - 27 Sep 2024

Viewed by 1758

Abstract

DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is [...] Read more.

DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is mediated by specialised DNA polymerases that can accommodate altered DNA structures during DNA synthesis, and are important in allowing replication to proceed after fork arrest, preventing fork collapse that can generate more deleterious double-strand breaks in the genome. TLS may occur directly at the fork, or at gaps remaining behind the fork, in the process of post-replication repair. Inactivating mutations in the human POLH gene encoding the Y-family DNA polymerase Pol η causes the skin cancer-prone genetic disease xeroderma pigmentosum variant (XPV). Pol η also contributes to chemoresistance during cancer treatment by bypassing DNA lesions induced by anti-cancer drugs including cisplatin. We review the current understanding of the canonical role of Pol η in translesion synthesis following replication arrest, as well as a number of emerging non-canonical roles of the protein in other aspects of DNA metabolism. Full article

(This article belongs to the Special Issue Mechanisms and Regulation of Human DNA Replication)

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20 pages, 278 KiB

Open AccessEditor’s ChoiceArticle

Metabolomic Changes Associated with AGXT2 Genotype Variants and Stone Formation in a Colony of Cats

by Jean A. Hall, Jeffrey A. Brockman, John J. Brejda and Dennis E. Jewell

Genes 2024, 15(10), 1264; https://doi.org/10.3390/genes15101264 - 27 Sep 2024

Viewed by 1363

Abstract

Objective: The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats [...] Read more.

Objective: The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats with uroliths. Methods: AGXT2 genotypes of 445 cats in the colony at Hill’s Pet Nutrition, Inc. (Topeka, KS, USA) were assessed in a genome-wide association study. Additionally, the serum chemistries and metabolic profiles of each cat were determined, along with their lifetime history of stone incidence. Factor analysis was used as a data-reduction method for metabolites in order to perform statistical hypothesis testing and to select significant metabolites from the more than 600 serum metabolites identified. Results: Of the 82 cats forming stones in the colony (18.4%), the majority were calcium oxalate. Results showed that approximately one third of the cats with the AA variant of the AGXT2 gene have stones, that chronic kidney disease (CKD) is more common in cats with stones, and that having stones results in a shorter lifespan. A discriminant variable selection process was performed to determine the complete blood count, serum biochemistries, and serum metabolomic factors that best discriminated among the three genotypes (AA, AG, GG) and between cats forming stones and non-stone formers. Several of the highly ranked discriminating factors included metabolites related to decreased aminotransferase activity in cats with the AA variant of the AGXT2 gene. Another factor that ranked highly for discriminating between stone formers and non-stone formers contained lipid metabolites, consisting of multiple sphingomyelin species and cholesterol. Conclusions: These findings support the results of feeding studies in cats, whereby CKD cats fed food supplemented with betaine and prebiotics have experienced an increase in total body mass, reduced uremic toxins, and altered sphingomyelin concentrations. Full article

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

13 pages, 2409 KiB

Open AccessEditor’s ChoiceArticle

Systematic Analysis of miR-506-3p Target Genes Identified Key Mediators of Its Differentiation-Inducing Function

by Daniela F. Cardus, Mitchell T. Smith, Alexandra Vernaza, Jadyn L. Smith, Brynn Del Buono, Anupa Parajuli, Emma G. Lewis, Nakya Mesa-Diaz and Liqin Du

Genes 2024, 15(10), 1268; https://doi.org/10.3390/genes15101268 - 27 Sep 2024

Cited by 1 | Viewed by 1382

Abstract

Background/Objectives: miR-506-3p has been demonstrated to be a strong inducer of neuroblastoma cell differentiation, highlighting the potential of applying miR-506-3p mimics to neuroblastoma differentiation therapy. However, the target genes of miR-506-3p that mediate its differentiation-inducing function have not been fully defined. This [...] Read more.

Background/Objectives: miR-506-3p has been demonstrated to be a strong inducer of neuroblastoma cell differentiation, highlighting the potential of applying miR-506-3p mimics to neuroblastoma differentiation therapy. However, the target genes of miR-506-3p that mediate its differentiation-inducing function have not been fully defined. This study aims to comprehensively investigate the targetome of miR-506-3p regarding its role in regulating neuroblastoma cell differentiation. Methods: We combined gene expression profiling and functional high-content screening (HCS) to identify miR-506-3p target genes that have differentiation-modulating functions. For evaluating the potential clinical relevance of the identified genes, we analyzed the correlations of gene expressions with neuroblastoma patient survival. Results: We identified a group of 19 target genes with their knockdown significantly inducing cell differentiation, suggesting that these genes play a key role in mediating the differentiation-inducing activity of miR-506-3p. We observed significant correlations of higher mRNA levels with lower patient survival with 13 of the 19 genes, suggesting that overexpression of these 13 genes plays important roles in promoting neuroblastoma development by disrupting the cell differentiation pathways. Conclusions: Through this study, we identified novel target genes of miR-506-3p that function as strong modulators of neuroblastoma cell differentiation. Our findings represent a significant advancement in understanding the mechanisms by which miR-506-3p induces neuroblastoma cell differentiation. Future investigations of the identified 13 genes are needed to fully define their functions and mechanisms in controlling neuroblastoma cell differentiation, the understanding of which may reveal additional targets for developing novel differentiation therapeutic agents. Full article

(This article belongs to the Special Issue Emerging Concepts in miRNA-Based Therapeutics)

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10 pages, 947 KiB

Open AccessEditor’s ChoiceArticle

by Yaqi Wang, Zihong He, Tao Mei, Xiaolin Yang, Zhuangzhuang Gu, Zhihao Zhang and Yanchun Li

Genes 2024, 15(10), 1251; https://doi.org/10.3390/genes15101251 - 26 Sep 2024

Cited by 1 | Viewed by 1785

Abstract

Objectives: The aim of this study was to assess the relationship between variant loci significantly associated with sports-related traits in the GWAS Catalog database and sprint/power athlete status, as well as to explore the polygenic profile of elite athletes. Methods: Next-generation sequencing and [...] Read more.

Objectives: The aim of this study was to assess the relationship between variant loci significantly associated with sports-related traits in the GWAS Catalog database and sprint/power athlete status, as well as to explore the polygenic profile of elite athletes. Methods: Next-generation sequencing and microarray technology were used to genotype samples from 211 elite athletes who had achieved success in national or international competitions in power-based sports and from 522 non-athletes, who were healthy university students with no history of professional sports training. Variant loci collected from databases were extracted after imputation. Subsequently, 80% of the samples were randomly selected as the training set, and the remaining 20% as the validation set. Results: Association analysis of variant loci was conducted in the training set, and individual Total Genotype Score (TGS) were calculated using genotype dosage and lnOR, followed by the establishment of a logistic model, with predictive performance evaluated in the validation set. Association analysis was performed on 2075 variant loci, and after removing linked loci (r² > 0.2), 118 Tag SNPs (p ≤ 0.05) were identified. A logistic model built using 30 Tag SNPs (p ≤ 0.01) showed better performance in the validation set (AUC = 0.707). Conclusions: Our study identified 30 new genetic molecular markers and demonstrated that elite sprint/power athlete status is polygenic. Full article

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

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19 pages, 8631 KiB

Open AccessEditor’s ChoiceArticle

Integrated Transcriptomics and Metabolomics Reveal Key Insights into Iridoid Biosynthesis in Gentiana crassicaulis Seeds during Germination

by Lechen Xuan, Hongyang Xiao, Zhili Zhao, Jingxian Feng, Lianghong Ni and Jinrong Wu

Genes 2024, 15(10), 1255; https://doi.org/10.3390/genes15101255 - 26 Sep 2024

Cited by 1 | Viewed by 1061

Abstract

Background: Gentiana crassicaulis Duthie ex Burk., a key species used in traditional Chinese medicine for treating rheumatic pain and stroke, contains iridoids as its primary active component. However, the biosynthetic mechanisms underlying iridoid production are not fully understood. Methods: This study focused on [...] Read more.

Background: Gentiana crassicaulis Duthie ex Burk., a key species used in traditional Chinese medicine for treating rheumatic pain and stroke, contains iridoids as its primary active component. However, the biosynthetic mechanisms underlying iridoid production are not fully understood. Methods: This study focused on iridoid biosynthesis during the germination of G. crassicaulis seeds, integrating metabolomic and transcriptomic analyses to uncover the underlying pathways and key candidate genes. Results: 196,132 unigenes and 10 iridoid compounds were identified through RNA-seq and ultra performance liquid chromatography-quadrupole time of flight-mass spectrometer (UPLC-Q-TOF-MS), respectively. The intersection of results from Pearson correlation analysis and weighted gene co-expression network analysis (WGCNA) revealed a significant correlation between 26 genes and iridoid levels, suggesting their potential role in the iridoid metabolism. Notably, six highly expressed candidate genes (DL7H, SLS, CYP76, CYP72A2, CYP84A1, and 13-LOX3) and five iridoids (loganic acid, sweroside, swertiamarin, gentiopicroside, and 6′-O-β-D-glucosyl-gentiopicroside) responded to methyl jasmonate stimulation in G. crassicaulis seedlings. Conclusions: by combining the known functions of candidate gene families, It is hypothesized that the CYP716 and LOX families exert indirect influences on iridoid metabolism, while the CYP71, CYP81, CYP72, CYP76, CYP710 families, 2OG-FeII family, and the glucosyltransferase family are likely to play direct roles in the biosynthetic transformations of the five iridoids. This study provides a theoretical basis for further functional gene validation and metabolic engineering aimed at enhancing iridoid production. The insights gained could lead to improved iridoid production efficiency in medicinal plants, ultimately benefiting the quality and efficacy of medicinal materials. Full article

(This article belongs to the Special Issue Genomics and Genetics of Medicinal Plants)

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13 pages, 5488 KiB

Open AccessEditor’s ChoiceArticle

Characterization of the Rat Osteosarcoma Cell Line UMR-106 by Long-Read Technologies Identifies a Large Block of Amplified Genes Associated with Human Disease

by Alan F. Scott, David W. Mohr, William A. Littrell, Reshma Babu, Michelle Kokosinski, Victoria Stinnett, Janvi Madhiwala, John Anderson, Ying S. Zou and Kathleen L. Gabrielson

Genes 2024, 15(10), 1254; https://doi.org/10.3390/genes15101254 - 26 Sep 2024

Viewed by 1472

Abstract

Background/Objectives: The rat osteosarcoma cell line UMR-106 is widely used for the study of bone cancer biology but it has not been well characterized with modern genomic methods. Methods: To better understand the biology of UMR-106 cells we used a combination of optical [...] Read more.

Background/Objectives: The rat osteosarcoma cell line UMR-106 is widely used for the study of bone cancer biology but it has not been well characterized with modern genomic methods. Methods: To better understand the biology of UMR-106 cells we used a combination of optical genome mapping (OGM), long-read sequencing nanopore sequencing and RNA sequencing.The UMR-106 genome was compared to a strain-matched Sprague-Dawley rat for variants associated with human osteosarcoma while expression data were contrasted with a public osteoblast dataset. Results: Using the COSMIC database to identify the most affected genes in human osteosarcomas we found somatic mutations in Tp53 and H3f3a. OGM identified a relatively small number of differences between the cell line and a strain-matched control animal but did detect a ~45 Mb block of amplification that included Myc on chromosome 7 which was confirmed by long-read sequencing. The amplified region showed several blocks of non-contiguous rearranged sequence implying complex rearrangements during their formation and included 14 genes reported as biomarkers in human osteosarcoma, many of which also showed increased transcription. A comparison of 5mC methylation from the nanopore reads of tumor and control samples identified genes with distinct differences including the OS marker Cdkn2a. Conclusions: This dataset illustrates the value of long DNA methods for the characterization of cell lines and how inter-species analysis can inform us about the genetic nature underlying mutations that underpin specific tumor types. The data should be a valuable resource for investigators studying osteosarcoma, in general, and specifically the UMR-106 model. Full article

(This article belongs to the Special Issue Advances of Optical Genome Mapping in Human Genetics)

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15 pages, 3605 KiB

Open AccessEditor’s ChoiceArticle

Diversity, Distribution and Structural Prediction of the Pathogenic Bacterial Effectors EspN and EspS

by Zhan Li, Yuru Hu, Yuan Song, Deyu Li, Xiaolan Yang, Liangyan Zhang, Tao Li and Hui Wang

Genes 2024, 15(10), 1250; https://doi.org/10.3390/genes15101250 - 26 Sep 2024

Viewed by 1331

Abstract

Background: Many Gram-negative enterobacteria translocate virulence proteins (effectors) into intestinal epithelial cells using a type III secretion system (T3SS) to subvert the activity of various cell functions possess. Many T3SS effectors have been extensively characterized, but there are still some effector proteins whose [...] Read more.

Background: Many Gram-negative enterobacteria translocate virulence proteins (effectors) into intestinal epithelial cells using a type III secretion system (T3SS) to subvert the activity of various cell functions possess. Many T3SS effectors have been extensively characterized, but there are still some effector proteins whose functional information is completely unknown. Methods: In this study, two predicted effectors of unknown function, EspN and EspS (Escherichia coli secreted protein N and S), were selected for analysis of translocation, distribution and structure prediction. Results: The TEM1 (β-lactamase) translocation assay was performed, which showed that EspN and EspS are translocated into host cells in a T3SS-dependent manner during bacterial infection. A phylogenetic tree analysis revealed that homologs of EspN and EspS are widely distributed in pathogenic bacteria. Multiple sequence alignment revealed that EspN and its homologs share a conserved C-terminal region (673–1133 a.a.). Furthermore, the structure of EspN (673–1133 a.a.) was also predicted and well-defined, which showed that it has three subdomains connected by a loop region. EspS and its homologs share a sequence-conserved C-terminal (146–291 a.a.). The predicted structure of EspS (146–291 a.a.) is composed of a β-sheet consisting of four β-strands and several short helices, which has a TM score of 0.5014 with the structure of the Vibrio cholerae RTX cysteine protease domain (PDBID: 3eeb). Conclusions: These results suggest that EspN and EspS may represent two important classes of T3SS effectors associated with pathogen virulence, and our findings provide important clues to understanding the potential functions of EspN and EspS. Full article

(This article belongs to the Special Issue Genomics of Microbial Diversity, Evolution and Function)

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19 pages, 849 KiB

Open AccessEditor’s ChoiceSystematic Review

Molecular Mechanism of Radioresponsiveness in Colorectal Cancer: A Systematic Review

by Matthew Y. H. Lau, Md Zahirul Islam Khan and Helen K. W. Law

Genes 2024, 15(10), 1257; https://doi.org/10.3390/genes15101257 - 26 Sep 2024

Cited by 1 | Viewed by 1809

Abstract

Background/Objectives: Colorectal cancer (CRC) is the third most diagnosed cancer globally. Radiotherapy is a common treatment strategy for patients but factors such as gene expressions and molecular mechanism effects may affect tumor radioresponse. The aim of this review is to systematically identify [...] Read more.

Background/Objectives: Colorectal cancer (CRC) is the third most diagnosed cancer globally. Radiotherapy is a common treatment strategy for patients but factors such as gene expressions and molecular mechanism effects may affect tumor radioresponse. The aim of this review is to systematically identify genes suggested to have molecular mechanism effects on the radioresponsiveness of CRC patients. Methods: By following the PRISMA guidelines, a comprehensive literature search was conducted on Pubmed, EMBASE and Cochrane Library. After exclusion and inclusion criteria sorting and critical appraisal for study quality, data were extracted from seven studies. A gene set analysis was conducted on reported genes. Results: From the seven studies, 56 genes were found to have an effect on CRC radioresponsiveness. Gene set analysis show that out of these 56 genes, 24 genes have roles in pathways which could affect cancer radioresponse. These are AKT1, APC, ATM, BRAF, CDKN2A, CTNNB1, EGFR, ERBB2, FLT3, KRAS, MET, mTOR, MYC, NFKB1, KRAS, PDGFRA, PIK3CA, PTEN, PTGS1, PTGS2, RAF1, RET, SMAD4 and TP53. The current project was conducted between the period May 2024 to August 2024. Conclusions: The current review systematically presented 56 genes which have been reported to be related to RT or CRT treatment effectiveness in rectal cancer patients. Gene set analysis shows that nearly half of the genes were involved in apoptosis, DNA damage response and repair, inflammation and cancer metabolism molecular pathways that could affect cancer radioresponse. The gene cohort identified in this study may be used as a foundation for future works focusing on the molecular mechanism of specific pathways contributing to the radioresponse of CRC. Full article

(This article belongs to the Special Issue Genetic and Genomic Research on Colorectal Cancer)

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17 pages, 6964 KiB

Open AccessEditor’s ChoiceArticle

Peculiar k-mer Spectra Are Correlated with 3D Contact Frequencies and Breakpoint Regions in the Human Genome

by Wisam Mohammed Hikmat, Aaron Sievers, Michael Hausmann and Georg Hildenbrand

Genes 2024, 15(10), 1247; https://doi.org/10.3390/genes15101247 - 25 Sep 2024

Viewed by 1320

Abstract

Background: It is widely accepted that the 3D chromatin organization in human cell nuclei is not random and recent investigations point towards an interactive relation of epigenetic functioning and chromatin (re-)organization. Although chromatin organization seems to be the result of self-organization of the [...] Read more.

Background: It is widely accepted that the 3D chromatin organization in human cell nuclei is not random and recent investigations point towards an interactive relation of epigenetic functioning and chromatin (re-)organization. Although chromatin organization seems to be the result of self-organization of the entirety of all molecules available in the cell nucleus, a general question remains open as to what extent chromatin organization might additionally be predetermined by the DNA sequence and, if so, if there are characteristic differences that distinguish typical regions involved in dysfunction-related aberrations from normal ones, since typical DNA breakpoint regions involved in disease-related chromosome aberrations are not randomly distributed along the DNA sequence. Methods: Highly conserved k-mer patterns in intronic and intergenic regions have been reported in eukaryotic genomes. In this article, we search and analyze regions deviating from average spectra (ReDFAS) of k-mer word frequencies in the human genome. This includes all assembled regions, e.g., telomeric, centromeric, genic as well as intergenic regions. Results: A positive correlation between k-mer spectra and 3D contact frequencies, obtained exemplarily from given Hi-C datasets, has been found indicating a relation of ReDFAS to chromatin organization and interactions. We also searched and found correlations of known functional annotations, e.g., genes correlating with ReDFAS. Selected regions known to contain typical breakpoints on chromosomes 9 and 5 that are involved in cancer-related chromosomal aberrations appear to be enriched in ReDFAS. Since transposable elements like ALUs are often assigned as major players in 3D genome organization, we also studied their impact on our examples but could not find a correlation between ALU regions and breakpoints comparable to ReDFAS. Conclusions: Our findings might show that ReDFAS are associated with instable regions of the genome and regions with many chromatin contacts which is in line with current research indicating that chromatin loop anchor points lead to genomic instability. Full article

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

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16 pages, 4739 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Studies of Hair Whorl in Pigs

by Wenyu Jiang, Xidi Yang, Liangyu Zhu, Yiting Yang, Chengming Liu, Yong Du, Yan Wang, Lili Niu, Ye Zhao, Yihui Liu, Mailin Gan, Linyuan Shen and Li Zhu

Genes 2024, 15(10), 1249; https://doi.org/10.3390/genes15101249 - 25 Sep 2024

Viewed by 1528

Abstract

Background: In pigs, a hair whorl refers to hairs that form a ring of growth around the direction of the hair follicle at the dorsal hip. In China, a hair whorl is considered a negative trait that affects marketing, and no studies have [...] Read more.

Background: In pigs, a hair whorl refers to hairs that form a ring of growth around the direction of the hair follicle at the dorsal hip. In China, a hair whorl is considered a negative trait that affects marketing, and no studies have been conducted to demonstrate whether hair whorl affects pig performance and provide an explanation for its genetic basis. Methods: Performance-measured traits and slaughter-measured traits of hair whorl and non-hair whorl pigs were differentially analyzed, followed by genome-wide association analysis (GWAS) and copy number variation (CNV) methods to investigate the genetic basis of hair whorl in pigs. Results: Differential analysis of 2625 pigs (171 hair whorl and 2454 non-hair whorl) for performance measures showed that hair whorl and non-hair whorl pigs differed significantly (p < 0.05) in traits such as live births, total litter size, and healthy litter size (p < 0.05), while differential analysis of carcass and meat quality traits showed a significant difference only in the 45 min pH (p = 0.0265). GWAS identified 4 SNP loci significantly associated with the hair whorl trait, 2 of which reached genome-significant levels, and 23 candidate genes were obtained by annotation with the Ensembl database. KEGG and GO enrichment analyses showed that these genes were mainly enriched in the ErbB signaling, endothelial apoptosis regulation, and cell proliferation pathways. In addition, CNV analysis identified 652 differential genes between hair whorl and non-hair whorl pigs, which were mainly involved in the signal transduction, transcription factor activity, and nuclear and cytoplasmic-related pathways. Conclusions: The candidate genes and copy number variation differences identified in this study provide a new theoretical basis for pig breeding efforts. Full article

(This article belongs to the Special Issue Advances in Pig Genetics and Breeding)

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11 pages, 4358 KiB

Open AccessEditor’s ChoiceArticle

Visual Integration of Genome-Wide Association Studies and Differential Expression Results with the Hidecan R Package

by Olivia Angelin-Bonnet, Matthieu Vignes, Patrick J. Biggs, Samantha Baldwin and Susan Thomson

Genes 2024, 15(10), 1244; https://doi.org/10.3390/genes15101244 - 25 Sep 2024

Cited by 1 | Viewed by 1141

Abstract

Background/Objectives: We present hidecan, an R package for generating visualisations that summarise the results of one or more genome-wide association studies (GWAS) and differential expression analyses, as well as manually curated candidate genes, e.g., extracted from the literature. This tool is applicable to [...] Read more.

Background/Objectives: We present hidecan, an R package for generating visualisations that summarise the results of one or more genome-wide association studies (GWAS) and differential expression analyses, as well as manually curated candidate genes, e.g., extracted from the literature. This tool is applicable to all ploidy levels; we notably provide functionalities to facilitate the visualisation of GWAS results obtained for autotetraploid organisms with the GWASpoly package. Results: We illustrate the capabilities of hidecan with examples from two autotetraploid potato datasets. Conclusions: The hidecan package is implemented in R and is publicly available on the CRAN repository and on GitHub. A description of the package, as well as a detailed tutorial, is made available alongside the package. It is also part of the VIEWpoly tool for the visualisation and exploration of results from polyploids computational tools. Full article

(This article belongs to the Special Issue Genetics and Genomics of Polyploid Plants)

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12 pages, 901 KiB

Open AccessEditor’s ChoiceReview

Utilization of Microfluidic Droplet-Based Methods in Diagnosis and Treatment Methods of Hepatocellular Carcinoma: A Review

by Akvilė Zajanckauskaite, Miah Lingelbach, Dovilė Juozapaitė, Algirdas Utkus, Greta Rukšnaitytė, Goda Jonuškienė and Aistė Gulla

Genes 2024, 15(10), 1242; https://doi.org/10.3390/genes15101242 - 25 Sep 2024

Viewed by 1817

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is associated with high morbidity and mortality. One of the main challenges in the management of HCC is late clinical presentation and thus diagnosis of the disease, which results in poor [...] Read more.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is associated with high morbidity and mortality. One of the main challenges in the management of HCC is late clinical presentation and thus diagnosis of the disease, which results in poor survival. The pathogenesis of HCC is complex and involves chronic liver injury and genetic alterations. Diagnosis of HCC can be made either by biopsy or imaging; however, conventional tissue-based biopsy methods and serological biomarkers such as AFP have limited clinical applications. While hepatocellular carcinoma is associated with a range of molecular alterations, including the activation of oncogenic signaling pathways, such as Wnt-TGFβ, PI3K-AKT-mTOR, RAS-MAPK, MET, IGF, and Wnt-β-catenin and TP53 and TERT promoter mutations, microfluidic applications have been limited. Early diagnosis is crucial for advancing treatments that would address the heterogeneity of HCC. In this context, microfluidic droplet-based methods are crucial, as they enable comprehensive analysis of the genome and transcriptome of individual cells. Single-cell RNA sequencing (scRNA-seq) allows the examination of individual cell transcriptomes, identifying their heterogeneity and cellular evolutionary relationships. Other microfluidic methods, such as Drop-seq, InDrop, and ATAC-seq, are also employed for single-cell analysis. Here, we examine and compare these microfluidic droplet-based methods, exploring their advantages and limitations in liver cancer research. These technologies provide new opportunities to understand liver cancer biology, diagnosis, treatment, and prognosis, contributing to scientific efforts in combating this challenging disease. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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15 pages, 1268 KiB

Open AccessEditor’s ChoiceReview

MicroRNA and Rare Human Diseases

by Himanshu Goel and Amy Goel

Genes 2024, 15(10), 1243; https://doi.org/10.3390/genes15101243 - 25 Sep 2024

Cited by 6 | Viewed by 2299

Abstract

Background: The role of microRNAs (miRNAs) in the pathogenesis of rare genetic disorders has been gradually discovered. MiRNAs, a class of small non-coding RNAs, regulate gene expression by silencing target messenger RNAs (mRNAs). Their biogenesis involves transcription into primary miRNA (pri-miRNA), processing by [...] Read more.

Background: The role of microRNAs (miRNAs) in the pathogenesis of rare genetic disorders has been gradually discovered. MiRNAs, a class of small non-coding RNAs, regulate gene expression by silencing target messenger RNAs (mRNAs). Their biogenesis involves transcription into primary miRNA (pri-miRNA), processing by the DROSHA–DGCR8 (DiGeorge syndrome critical region 8) complex, exportation to the cytoplasm, and further processing by DICER to generate mature miRNAs. These mature miRNAs are incorporated into the RNA-induced silencing complex (RISC), where they modulate gene expression. Methods/Results: The dysregulation of miRNAs is implicated in various Mendelian disorders and familial diseases, including DICER1 syndrome, neurodevelopmental disorders (NDDs), and conditions linked to mutations in miRNA-binding sites. We summarized a few mechanisms how miRNA processing and regulation abnormalities lead to rare genetic disorders. Examples of such genetic diseases include hearing loss associated with MIR96 mutations, eye disorders linked to MIR184 mutations, and skeletal dysplasia involving MIR140 mutations. Conclusions: Understanding these molecular mechanisms is crucial, as miRNA dysregulation is a key factor in the pathogenesis of these conditions, offering significant potential for the diagnosis and potential therapeutic intervention. Full article

(This article belongs to the Special Issue Genetics and Therapy of Neurodevelopmental Disorders)

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13 pages, 7132 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of Peroxidase (PRX) Gene Family in Cucumber

by Weirong Luo, Junjun Liu, Wenchen Xu, Shenshen Zhi, Xudong Wang and Yongdong Sun

Genes 2024, 15(10), 1245; https://doi.org/10.3390/genes15101245 - 25 Sep 2024

Viewed by 1037

Abstract

Background: The Peroxidase (PRX) gene family is essential for plant growth and significantly contributes to defense against stresses. However, information about PRX genes in cucumber (Cucumis sativus L.) remains limited. Methods: In this present study, CsPRX genes were [...] Read more.

Background: The Peroxidase (PRX) gene family is essential for plant growth and significantly contributes to defense against stresses. However, information about PRX genes in cucumber (Cucumis sativus L.) remains limited. Methods: In this present study, CsPRX genes were identified and characterized using bioinformatics analysis. The expression pattern analysis of CsPRX genes were examined utilizing the RNA-seq data of cucumber from public databases and real-time quantitative PCR (qRT-PCR) analysis. Results: Here, we identified 60 CsPRX genes and mapped them onto seven chromosomes of cucumber. The CsPRX proteins exhibited the presence of 10 conserved motifs, with motif 8, motif 2, motif 5, and motif 3 consistently appearing across all 60 CsPRX protein sequences, indicating the conservation of CsPRX proteins. Furthermore, RNA-seq analysis revealed that differential expression of CsPRX genes in various tissues. Notably, a majority of the CsPRX genes exhibited significantly higher expression levels in the root compared to the other plant tissues, suggesting a potential specialization of these genes in root function. In addition, qRT-PCR analysis for four selected CsPRX genes under different stress conditions indicated that these selected CsPRX genes demonstrated diverse expression levels when subjected to NaCl, CdCl₂, and PEG treatments, and the CsPRX17 gene was significantly induced by NaCl, CdCl₂, and PEG stresses, suggesting a vital role of the CsPRX17 gene in response to environmental stresses. Conclusions: These findings will contribute valuable insights for future research into the functions and regulatory mechanisms associated with CsPRX genes in cucumber. Full article

(This article belongs to the Special Issue Molecular Biology of Crop Abiotic Stress Resistance)

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16 pages, 3296 KiB

Open AccessEditor’s ChoiceArticle

Whole-Genome Bisulfite Sequencing (WGBS) Analysis of Gossypium hirsutum under High-Temperature Stress Conditions

by Zhaolong Gong, Juyun Zheng, Ni Yang, Xueyuan Li, Shuaishuai Qian, Fenglei Sun, Shiwei Geng, Yajun Liang and Junduo Wang

Genes 2024, 15(10), 1241; https://doi.org/10.3390/genes15101241 - 24 Sep 2024

Viewed by 1378

Abstract

Background: DNA methylation is an important part of epigenetic regulation and plays an important role in the response of plants to adverse stress. Methods: In this study, whole-genome bisulfite sequencing (WGBS) was performed on the high-temperature-resistant material Xinluzao 36 and the high-temperature-sensitive material [...] Read more.

Background: DNA methylation is an important part of epigenetic regulation and plays an important role in the response of plants to adverse stress. Methods: In this study, whole-genome bisulfite sequencing (WGBS) was performed on the high-temperature-resistant material Xinluzao 36 and the high-temperature-sensitive material Che 61–72 at 0 h and 12 h under high-temperature stress conditions. Results: The results revealed that the Gossypium hirsutum methylation levels of CG and CHG (H = A, C, or T) decreased after the high-temperature stress treatment, and the methylation level of the A subgenome was significantly greater than that of the D subgenome. The methylation level of CHH increased, and the methylation level of CHH in the D subgenome was significantly greater than that in the A subgenome after high-temperature stress treatment. The methylation density of CG is lower than that of CHG and CHH, and the methylation density of the middle region of chromosomes is greater than that of both ends, which is opposite to the distribution density of genes. There were 124 common differentially methylated genes in the CG, CHG, and CHH groups, and 5130 common DEGs and differentially methylated genes were found via joint analysis with RNA-seq; these genes were significantly enriched in the biosynthesis of plant hormones, thiamine metabolism, glutathione metabolism, and tyrosine metabolism pathways. DNA methylation did not affect the expression of many genes (accounting for 85.68% of the differentially methylated genes), DNA methylation-promoted gene expression was located mainly in the downstream region of the gene or gene body, and the expression of inhibitory genes was located mainly in the upstream region of the gene. Conclusions: This study provides a theoretical basis for further exploration of the gene expression and functional regulatory mechanism of G. hirsutum DNA methylation under high-temperature stress conditions. Full article

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

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12 pages, 2422 KiB

Open AccessEditor’s ChoiceReview

The Clinical Spectrum of Mosaic Genetic Disease

by Hanabi Geiger, Yutaka Furuta, Suné van Wyk, John A. Phillips III and Rory J. Tinker

Genes 2024, 15(10), 1240; https://doi.org/10.3390/genes15101240 - 24 Sep 2024

Viewed by 3888

Abstract

Genetic mosaicism is defined as the presence of two or more cell lineages with different genotypes arising from a single zygote. Mosaicism has been implicated in hundreds of genetic diseases with diverse genetic etiologies affecting every organ system. Mosaic genetic disease (MDG) is [...] Read more.

Genetic mosaicism is defined as the presence of two or more cell lineages with different genotypes arising from a single zygote. Mosaicism has been implicated in hundreds of genetic diseases with diverse genetic etiologies affecting every organ system. Mosaic genetic disease (MDG) is a spectrum that, on the extreme ends, enables survival from genetic severe disorders that would be lethal in a non-mosaic form. On the milder end of the spectrum, mosaicism can result in little if any phenotypic effects but increases the risk of transmitting a pathogenic genotype. In the middle of the spectrum, mosaicism has been implicated in reducing the phenotypic severity of genetic disease. In this review will describe the spectrum of mosaic genetic disease whilst discussing the status of the detection and prevalence of mosaic genetic disease. Full article

(This article belongs to the Special Issue Genomic Mosaicism in Human Development and Diseases)

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18 pages, 3222 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification of the Rehmannia glutinosa miRNA Family and Exploration of Their Expression Characteristics Caused by the Replant Disease Formation-Related Principal Factor

by Li Gu, Yanlin Lai, Guojun Zhang, Yanhui Yang, Bao Zhang, Jianming Wang, Zhongyi Zhang and Mingjie Li

Genes 2024, 15(9), 1239; https://doi.org/10.3390/genes15091239 - 23 Sep 2024

Cited by 1 | Viewed by 1278

Abstract

Background/Objectives: Rehmannia glutinosa, a highly valuable medicinal plant in China, is encountering severe replant disease. Replant disease represents a complex stress driven by multiple principal factors (RDFs), including allelochemicals, microbes, and their interactions. miRNAs are recognized as key regulators of plant response [...] Read more.

Background/Objectives: Rehmannia glutinosa, a highly valuable medicinal plant in China, is encountering severe replant disease. Replant disease represents a complex stress driven by multiple principal factors (RDFs), including allelochemicals, microbes, and their interactions. miRNAs are recognized as key regulators of plant response to stresses; however, their specific roles within RDFs are not entirely clear. Methods: This study builds six RDF treatments, comprising R. glutinosa continuously planted (SP), normally planted (NP), and NP treated with ferulic acid (FA), Fusarium oxysporum (FO), and a combination of FA with FO (FAFO). sRNA-seq technology was used to identify crucial miRNAs in response to diverse RDFs. Results: In total, 30 sRNA datasets were generated from the SP, NP, FA, FO, and FAFO samples. A total of 160 known and 41 novel miRNAs (RgmiRNAs) were identified in the R. glutinosa genome based on the sRNA database. Abundance analysis revealed that RgmiRNAs in SP exhibited a distinct expression profile in comparison with others. Of these, 124, 86, 86, and 90 RgmiRNAs were differentially expressed in SP, FA, FO, and FAFO compared with NP. Target analysis indicated that RgmiRNAs downregulated in both SP and RDFs impede the organism growth of R. glutinosa. RgmiRNAs upregulated in SP can disrupt root formation and nutrient metabolism, in which, two RgmiR398 were uniquely expressed in SP. It was confirmed to target RgCSD genes. The expression patterns of RgmiR398 and RgCSD indicated that replant disease induces the oxidative damage of R. glutinosa through RgmiR398. Conclusions: RgmiRNA profiling under RDFs provides a theoretical basis for the further clarification of RgmiRNA function in replant disease. Full article

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

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24 pages, 2625 KiB

Open AccessEditor’s ChoiceArticle

Revision of the Most Primitive Taxa of the Family Gyrodactylidae (van Beneden et Hesse, 1864) (Platyhelminthes, Monopisthocotyla) Based on ITS rDNA Phylogeny

by Jakub Janulewicz, Maciej Pietkiewicz and Marek S. Ziętara

Genes 2024, 15(9), 1236; https://doi.org/10.3390/genes15091236 - 23 Sep 2024

Cited by 1 | Viewed by 1420

Abstract

Background: For the past 25 years, the ITS rDNA (ITS1-5.8S-ITS2) of Gyrodactylidae has been crucial for species identification, description, and phylogeny. This family includes 25 genera parasitizing marine and freshwater fish, initially distinguished by morphological differences in attachment and/or male copulatory organs. Gyrodactylus [...] Read more.

Background: For the past 25 years, the ITS rDNA (ITS1-5.8S-ITS2) of Gyrodactylidae has been crucial for species identification, description, and phylogeny. This family includes 25 genera parasitizing marine and freshwater fish, initially distinguished by morphological differences in attachment and/or male copulatory organs. Gyrodactylus Nordmann, 1832, the most species-rich genus, has approximately 500 described species and an additional 25,000 species suspected. The genus is not monophyletic, and the functionally adaptive nature of morphological diagnostic characters complicates the delimitation of new genera. Methods: A phylogeny based on ITS rDNA was proposed to address these challenges, using only complete sequences of primitive taxa. Fifty-four sequences were aligned with the MUSCLE v5.1 algorithm, creating a 1590 ps long matrix. Maximum Likelihood (ML) and Bayesian Inference (BI) methods with the models TVM+F+G4 and SYM+G4 for ITS1–ITS2 and 5.8S, respectively, were inferred using IQ-TREE v2.3.5 and BEAST v2.7.6.0. Results: The findings revealed eleven main lineages. Four of them are proposed for classification into new genera: Cichlidarus gen. nov., Iraqemembranatus gen. nov., Macracanthus gen. nov., and Rysavyius gen. nov. Elevating the subgenus G. (Gyrodactylus) to genus rank was supported. Conclusions: The presented phylogeny provides a foundation for developing a classification system within Gyrodactylidae that is both reasonable and comprehensive. Full article

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

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10 pages, 5121 KiB

Open AccessEditor’s ChoiceArticle

The Ca²⁺-Regulated Protein Kinase CIPK1 Modulates Plant Response to Nitrate Deficiency in Arabidopsis

by Hang Su, Qian Wang, Lihu Wang and Junjun Cui

Genes 2024, 15(9), 1235; https://doi.org/10.3390/genes15091235 - 23 Sep 2024

Viewed by 1497

Abstract

Background/Objectives: Nitrogen is an essential macroelement for plant growth and productivity. Calcium (Ca²⁺) acts as a critical second messenger in numerous adaptations and developmental processes in plants. The Calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway has been demonstrated to [...] Read more.

Background/Objectives: Nitrogen is an essential macroelement for plant growth and productivity. Calcium (Ca²⁺) acts as a critical second messenger in numerous adaptations and developmental processes in plants. The Calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway has been demonstrated to be involved in multiple intracellular ion homeostasis of plants in response to stresses. However, whether CIPKs are involved in nitrate deficiency stress remains largely unknown. Methods: In this study, we screened Arabidopsis thaliana T-DNA insertion mutants of the CIPK family under nitrate deficiency conditions by a reverse genetic strategy. Results: We found that the cipk1 mutant showed a shorter primary root and had a lower fresh weight and total N content compared with wildtype (WT) plants under nitrate deficiency. The CIPK1 complementation lines completely rescued the sensitive phenotype. Additionally, CIPK1 mutation caused nitrogen-starvation marker genes to be decreased under nitrate deficiency. We further found that CIPK1 interacted with teosintebranched 1/cycloidea/proliferating cell factor 1-20 (TCP20) in a yeast two-hybrid system. Conclusions: Collectively, our results reveal a novel role of CIPK1 in response to nitrate deficiency in Arabidopsis. Full article

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

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18 pages, 2977 KiB

Open AccessEditor’s ChoiceArticle

Silicon Modifies Photosynthesis Efficiency and hsp Gene Expression in European Beech (Fagus sylvatica) Seedlings Exposed to Drought Stress

by Justyna Nowakowska, Monika Dang, Piotr Kiełtyk, Marzena Niemczyk, Tadeusz Malewski, Wiesław Szulc, Beata Rutkowska, Piotr Borowik and Tomasz Oszako

Genes 2024, 15(9), 1233; https://doi.org/10.3390/genes15091233 - 21 Sep 2024

Cited by 1 | Viewed by 1240

Abstract

Background: Climate change is leading to severe and long-term droughts in European forest ecosystems. can have profound effects on various physiological processes, including photosynthesis, gene expression patterns, and nutrient uptake at the developmental stage of young trees. Objectives: Our study aimed to test [...] Read more.

Background: Climate change is leading to severe and long-term droughts in European forest ecosystems. can have profound effects on various physiological processes, including photosynthesis, gene expression patterns, and nutrient uptake at the developmental stage of young trees. Objectives: Our study aimed to test the hypothesis that the application of silica (SiO₂) influences photosynthetic efficiency and gene expression in 1- to 2-year-old Fagus sylvatica (L.) seedlings. Additionally, we aimed to assess whether silicon application positively influences the structural properties of leaves and roots. To determine whether the plant physiological responses are genotype-specific, seedlings of four geographically different provenances were subjected to a one-year evaluation under greenhouse conditions. Methods: We used the Kruskal–Wallis test followed by Wilcoxon’s test to evaluate the differences in silicon content and ANOVA followed by Tukey’s test to evaluate the physiological responses of seedlings depending on treatment and provenance. Results: Our results showed a significantly higher Si content in the roots compared with the leaves, regardless of provenance and treatment. The most significant differences in photosynthetic performance were found in trees exposed to Si treatment, but the physiological responses were generally nuanced and provenance-dependent. Expression of hsp70 and hsp90 was also increased in leaf tissues of all provenances. These results provide practical insights that Si can improve the overall health and resilience of beech seedlings in nursery and forest ecosystems, with possible differences in the beneficial role of silicon application arising from the large differences in wild populations of forest tree species. Full article

(This article belongs to the Special Issue Genes and Genomics of Plants Under Abiotic Stresses)

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50 pages, 1227 KiB

Open AccessEditor’s ChoiceReview

Menin in Cancer

by Ariana D. Majer, Xianxin Hua and Bryson W. Katona

Genes 2024, 15(9), 1231; https://doi.org/10.3390/genes15091231 - 21 Sep 2024

Cited by 4 | Viewed by 4858

Abstract

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area [...] Read more.

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin’s function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation. Full article

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

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19 pages, 2318 KiB

Open AccessEditor’s ChoiceArticle

Impacts of Nucleosome Positioning Elements and Pre-Assembled Chromatin States on Expression and Retention of Transgenes

by Ronard Kwizera, Junkai Xie, Nathan Nurse, Chongli Yuan and Ann L. Kirchmaier

Genes 2024, 15(9), 1232; https://doi.org/10.3390/genes15091232 - 21 Sep 2024

Viewed by 1631

Abstract

Background/Objectives: Transgene applications, ranging from gene therapy to the development of stable cell lines and organisms, rely on maintaining the expression of transgenes. To date, the use of plasmid-based transgenes has been limited by the loss of their expression shortly after their delivery [...] Read more.

Background/Objectives: Transgene applications, ranging from gene therapy to the development of stable cell lines and organisms, rely on maintaining the expression of transgenes. To date, the use of plasmid-based transgenes has been limited by the loss of their expression shortly after their delivery into the target cells. The short-lived expression of plasmid-based transgenes has been largely attributed to host-cell-mediated degradation and/or silencing of transgenes. The development of chromatin-based strategies for gene delivery has the potential to facilitate defining the requirements for establishing epigenetic states and to enhance transgene expression for numerous applications. Methods: To assess the impact of “priming” plasmid-based transgenes to adopt accessible chromatin states to promote gene expression, nucleosome positioning elements were introduced at promoters of transgenes, and vectors were pre-assembled into nucleosomes containing unmodified histones or mutants mimicking constitutively acetylated states at residues 9 and 14 of histone H3 or residue 16 of histone H4 prior to their introduction into cells, then the transgene expression was monitored over time. Results: DNA sequences capable of positioning nucleosomes could positively impact the expression of adjacent transgenes in a distance-dependent manner in the absence of their pre-assembly into chromatin. Intriguingly, the pre-assembly of plasmids into chromatin facilitated the prolonged expression of transgenes relative to plasmids that were not pre-packaged into chromatin. Interactions between pre-assembled chromatin states and nucleosome positioning-derived effects on expression were also assessed and, generally, nucleosome positioning played the predominant role in influencing gene expression relative to priming with hyperacetylated chromatin states. Conclusions: Strategies incorporating nucleosome positioning elements and the pre-assembly of plasmids into chromatin prior to nuclear delivery can modulate the expression of plasmid-based transgenes. Full article

(This article belongs to the Special Issue Feature Papers: Molecular Genetics and Genomics 2024)

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16 pages, 2934 KiB

Open AccessEditor’s ChoiceArticle

Hepatic Transcriptome Reveals Potential Key Genes Contributing to Differential Milk Production

by Chao Du, A La Teng Zhu La, Shengtao Gao, Wenshuo Gao, Lu Ma, Dengpan Bu and Wenju Zhang

Genes 2024, 15(9), 1229; https://doi.org/10.3390/genes15091229 - 20 Sep 2024

Cited by 1 | Viewed by 1134

Abstract

Background: Despite the widespread adoption of TMR or PMR and the formulas designed to sufficiently cover the cows’ requirements, individual dairy cows’ milk production varies significantly. The liver is one of the most important organs in cow lactation metabolism and plays an essential [...] Read more.

Background: Despite the widespread adoption of TMR or PMR and the formulas designed to sufficiently cover the cows’ requirements, individual dairy cows’ milk production varies significantly. The liver is one of the most important organs in cow lactation metabolism and plays an essential role in the initiation of lactation. Objectives: This study aimed to investigate the potential key genes in the liver contributing to the different milk production. Methods: We enrolled 64 cows and assigned them to high or low milk yield (MY) groups according to their first 3 weeks of milk production. We performed RNAseq for 35 liver samples with 18 from prepartum and 17 from postpartum cows. Results: The continuous milk yield observation showed a persistently higher milk yield in high MY cows than low MY cows in the first 3 weeks. High MY cows showed better feed conversion efficiency. We identified 795 differentially expressed genes (DGEs) in the liver of high MY cows compared with low MY cows, with up-regulated genes linked to morphogenesis and development pathways. Weighted gene co-expression network analysis (WGCNA) revealed four gene modules positively correlating with milk yield, and protein and lactose yield (p < 0.05). Using the intersected genes between the four gene modules and DEGs, we constructed the linear mixed-effects models and identified six hub genes positively associated and two hub genes negatively associated with milk yield (Coefficients > 0.25, p < 0.05). Random forest machine learning model training based on these eight hub genes could efficiently predict the milk yield (p < 0.001, R² = 0.946). Interestingly, the expression patterns of these eight hub genes remained remarkably similar before and after parturition. Conclusions: The present study indicated the critical role of liver in milk production. Activated processes involved in morphogenesis and development in liver may contribute to the higher milk production. Eight hub genes identified in this study may provide genetic research materials for dairy cow breeding. Full article

(This article belongs to the Special Issue Functional Genomics and Breeding of Animals)

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17 pages, 1016 KiB

Open AccessEditor’s ChoiceReview

The Role of Single Nucleotide Polymorphisms in MicroRNA Genes in Head and Neck Squamous Cell Carcinomas: Susceptibility and Prognosis

by Elżbieta Szmida, Dorota Butkiewicz, Paweł Karpiński, Tomasz Rutkowski, Małgorzata Oczko-Wojciechowska and Maria Małgorzata Sąsiadek

Genes 2024, 15(9), 1226; https://doi.org/10.3390/genes15091226 - 20 Sep 2024

Cited by 1 | Viewed by 1655

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. [...] Read more.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. MicroRNAs (miRNAs), which belong to the group of important post-transcriptional regulators of human gene expression, seem to be valuable options for consideration as key modifiers of individual cancer risk, and therefore may be helpful in predicting inter-individual differences in cancer risk, response to treatment and prognosis. Methods: There have not been many studies focused on the relationship between miRNA variants and HNSCC published in PubMed within the last 15 years. We found and analyzed 30 reviews, meta-analyses and research papers and revealed 14 SNPs which have been reported as significant in the context of HNSCC susceptibility and/or prognosis. Results: These 14 SNPs were located in 13 separate miRNAs. Among them, four were the most frequently studied (miRNA-146, -196, -149 and -499) and have been shown to have the greatest impact on the course of HNSCC. However, the presented results have been conflicting. Conclusions: It must be concluded that, despite the years of studies, there are no conclusive reports demonstrating a significant role of SNPs in miRNAs in the context of the susceptibility to HNSCC or its prognosis. Full article

(This article belongs to the Special Issue The Role of miRNAs in Human Cancer)

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13 pages, 5252 KiB

Open AccessEditor’s ChoiceArticle

Selection of Reference Genes of Flower Development in Ludisia discolor

by Rui Gao, Wenyan He, Wen-Tao Zhu, Xuewei Zhao, Chen Chen, You Wu, Shasha Wu, Jun-Wen Zhai and Zhong-Jian Liu

Genes 2024, 15(9), 1225; https://doi.org/10.3390/genes15091225 - 19 Sep 2024

Viewed by 1122

Abstract

Background: RT-qPCR is a powerful strategy for recognizing the most appropriate reference genes, which can successfully minimize experimental mistakes through accurate normalization. Ludisia discolor, recognized for its ornamental value, features little, distinctive blossoms with twisted lips and gynostemium showing chiral asymmetry, together [...] Read more.

Background: RT-qPCR is a powerful strategy for recognizing the most appropriate reference genes, which can successfully minimize experimental mistakes through accurate normalization. Ludisia discolor, recognized for its ornamental value, features little, distinctive blossoms with twisted lips and gynostemium showing chiral asymmetry, together with striking blood-red fallen leaves periodically marked with golden blood vessels. Methods and Results: To ensure the accuracy of qRT-PCR, selecting appropriate reference genes for quantifying target gene expression levels is essential. This study aims to identify stable reference genes during the development of L. discolor. In this study, the entire floral buds, including the lips and gynostemium from different development stages, were taken as materials. Based upon the transcriptome information of L. discolor, nine housekeeping genes, ACT, HIS, EF1-α1, EF1-α2, PP2A, UBQ1, UBQ2, UBQ3, and TUB, were selected in this research study as prospect interior referral genes. The expression of these nine genes were found by RT-qPCR and afterwards comprehensively examined by four software options: geNorm, NormFinder, BestKeeper, and ΔCt. The outcomes of the analysis showed that ACT was the most steady gene, which could be the most effective inner referral gene for the expression evaluation of flower advancement in L. discolor. Conclusions: The results of this study will contribute to the molecular biology research of flower development in L. discolor and closely related species. Full article

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

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20 pages, 302 KiB

Open AccessEditor’s ChoiceReview

Ethical Aspects of Human Genome Research in Sports—A Narrative Review

by Aleksandra Bojarczuk

Genes 2024, 15(9), 1216; https://doi.org/10.3390/genes15091216 - 18 Sep 2024

Cited by 4 | Viewed by 3870

Abstract

Human genome research in sports raises complex ethical considerations regarding the intersection of genetics and athletic performance. Pursuing genetic enhancements must uphold fairness, equality, and respect for human dignity. This narrative review explores the ethical dimensions of human genome research in sports, its [...] Read more.

Human genome research in sports raises complex ethical considerations regarding the intersection of genetics and athletic performance. Pursuing genetic enhancements must uphold fairness, equality, and respect for human dignity. This narrative review explores the ethical dimensions of human genome research in sports, its potential implications on athletes, and the integrity of sports. As a narrative review, this study synthesizes the existing literature and expert insights to examine the ethical aspects of human genome research in sports. This study extensively examined the current literature on genetics, sports performance, ethical concerns, human rights, and legal regulations within the European context. The literature was searched using the SPORTDiscus, Scopus, Google Scholar, and PubMed databases. Exploring human genome research in sports reveals significant ethical implications, including potential genetic discrimination, impacts on human rights, and creating a genetic underclass of athletes. There are also definite benefits surrounding genetic testing. In conclusion, this review contends that integrating ethical considerations into developing and applying genetic technologies in sports is crucial to upholding fundamental principles of fairness, equality, and respect for human dignity. It stresses the importance of open and inclusive dialogue about the potential consequences of genetic advancements on athletic performance, future generations, and the integrity of sports. Full article

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

15 pages, 2085 KiB

Open AccessEditor’s ChoiceArticle

IL-10 A-Allele as a Biomarker for Periodontitis Severity in Bulgarian Patients

by Zdravka Pashova-Tasseva, Velitchka Dosseva-Panova, Antoaneta Mlachkova, Alexey Savov and Ekaterina Tosheva

Genes 2024, 15(9), 1221; https://doi.org/10.3390/genes15091221 - 18 Sep 2024

Viewed by 1127

Abstract

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular [...] Read more.

Background: Periodontitis is a complex disease, and bacterial factors play a crucial role in its initiation. The contributions of genetic and epigenetic factors to the pathogenesis of periodontal disease are increasingly recognized. Single-nucleotide polymorphisms (SNPs) in various molecules, including cytokines, are of particular interest due to their established involvement in numerous diseases. This study investigates the influence of SNPs in the IL-10 gene at positions −592 (rs1800872) C>A and −1082 (rs1800896) T>C (also referred to as 1082A>G) on the severity of periodontitis in a cohort of Bulgarian patients. Methods: In the recent study, both clinical and paraclinical methodologies were employed to comprehensively assess the periodontal status of the participants. The genotypic characterization of IL-10 polymorphisms was performed by PCR RFLP analysis. Statistical analyses, including principal component analysis (PCA), were executed utilizing IBM SPSS Statistics Version 21. Results: We have established a statistically significant association between the presence of at least one A-allele in the patients’ genotype and the incidence of severe periodontitis (p = 0.047). Conclusions: IL-10 single-nucleotide polymorphisms (SNPs) could be effectively considered as biomarkers for the severity of periodontitis. Full article

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

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16 pages, 2726 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Efficacy of Target Capture Sequencing for Genotyping in Cattle

by Yan Ren, Mehar S. Khatkar, Callum MacPhillamy, Haofei Wang, Rudi A. McEwin, Tong Chen, Wayne S. Pitchford and Wai Yee Low

Genes 2024, 15(9), 1218; https://doi.org/10.3390/genes15091218 - 18 Sep 2024

Viewed by 1417

Abstract

(1) Background: Target capture sequencing (TCS) is potentially a cost-effective way to detect single-nucleotide polymorphisms (SNPs) and an alternative to SNP array-based genotyping. (2) Methods: We evaluated the effectiveness and reliability of TCS in cattle breeding scenarios using 48 female and 8 male [...] Read more.

(1) Background: Target capture sequencing (TCS) is potentially a cost-effective way to detect single-nucleotide polymorphisms (SNPs) and an alternative to SNP array-based genotyping. (2) Methods: We evaluated the effectiveness and reliability of TCS in cattle breeding scenarios using 48 female and 8 male samples. DNA was extracted from blood samples, targeted for 71,746 SNPs with TWIST probes, and sequenced on an MGI platform. GATK and BCFtools were evaluated for the best genotyping calling tool. The genotypes were compared to existing genotypes from the Versa50K SNP array of the same animals by measuring accuracy as concordance (%) and R². (3) Results: In this study, 71,553 SNPs and 166 indels were identified. The genotype comparison of 37,130 common SNPs between TCS and SNP arrays yielded high agreement, with a mean concordance of 98%, R² of 0.98 and Cohen’s kappa of 0.97. The concordances of sex prediction, parent verification and validation of five genotype markers of interest important for Wagyu breeding were 100% between TCS and SNP array. The elements of the genomic relationship matrix (GRM) constructed from the SNP array and TCS data demonstrated a correlation coefficient approaching unity (r = 0.9998). (4) Conclusions: Compared to the SNP array, TCS is a comparable, cost-effective and flexible platform for genotyping SNPs, including non-model organisms and underrepresented commercial animal populations. Full article

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

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17 pages, 1330 KiB

Open AccessEditor’s ChoiceReview

A Review and Meta-Analysis of Genotype by Environment Interaction in Commercial Shrimp Breeding

by Md. Mehedi Hasan, Peter C. Thomson, Herman W. Raadsma and Mehar S. Khatkar

Genes 2024, 15(9), 1222; https://doi.org/10.3390/genes15091222 - 18 Sep 2024

Cited by 2 | Viewed by 1356

Abstract

(1) Background: Genotype-by-environment interaction (G×E) can adversely impact genetic improvement programs. The presence of G×E is mainly measured as the genetic correlation between the same trait measured in different environments where departure from unity can be taken as presence of G×E. (2) Methods: [...] Read more.

(1) Background: Genotype-by-environment interaction (G×E) can adversely impact genetic improvement programs. The presence of G×E is mainly measured as the genetic correlation between the same trait measured in different environments where departure from unity can be taken as presence of G×E. (2) Methods: To understand the extent of G×E in shrimp production, a review and meta-analysis was conducted using the results from 32 peer-reviewed studies. (3) Results: Of these, 22 G×E studies were conducted on Pacific white shrimp (Litopenaeus vannamei) with fewer studies reported in other shrimp species. The most frequently studied traits were growth and survival, with relatively few studies on traits of economic importance. The meta-analysis demonstrated a moderately high genetic correlation (r_g = 0.72 ± 0.05) for growth, indicating low to moderate levels of G×E with some re-ranking of breeding values across environments. However, substantial G×E was evident for survival where only a moderate genetic correlation (r_g = 0.58 ± 0.07) was observed for survival across different environments. A re-ranking of breeding values is likely for this trait and genetic improvement of shrimp for survival in one environment may not be effective in other environments. The results from ANOVA-based studies show that G×E accounted for 6.42 ± 1.05% and 7.13 ± 3.46% of the variation for growth and survival traits, respectively. (4) Conclusion: The significance of G×E necessitates tailored genetic improvement programs in commercial shrimp breeding. We discuss the scope and challenges of G×E for shrimp breeding programs, including opportunities of implementing G×E in genomic selection programs. Full article

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

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24 pages, 3052 KiB

Open AccessEditor’s ChoiceArticle

Comparison of B-Cell Lupus and Lymphoma Using a Novel Immune Imbalance Transcriptomics Algorithm Reveals Potential Therapeutic Targets

by Naomi Rapier-Sharman, Sehi Kim, Madelyn Mudrow, Michael T. Told, Lane Fischer, Liesl Fawson, Joseph Parry, Brian D. Poole, Kim L. O’Neill, Stephen R. Piccolo and Brett E. Pickett

Genes 2024, 15(9), 1215; https://doi.org/10.3390/genes15091215 - 17 Sep 2024

Cited by 1 | Viewed by 1979

Abstract

Background/Objectives: Systemic lupus erythematosus (lupus) and B-cell lymphoma (lymphoma) co-occur at higher-than-expected rates and primarily depend on B cells for their pathology. These observations implicate shared inflammation-related B cell molecular mechanisms as a potential cause of co-occurrence. Methods: We consequently implemented a novel [...] Read more.

Background/Objectives: Systemic lupus erythematosus (lupus) and B-cell lymphoma (lymphoma) co-occur at higher-than-expected rates and primarily depend on B cells for their pathology. These observations implicate shared inflammation-related B cell molecular mechanisms as a potential cause of co-occurrence. Methods: We consequently implemented a novel Immune Imbalance Transcriptomics (IIT) algorithm and applied IIT to lupus, lymphoma, and healthy B cell RNA-sequencing (RNA-seq) data to find shared and contrasting mechanisms that are potential therapeutic targets. Results: We observed 7143 significantly dysregulated genes in both lupus and lymphoma. Of those genes, we found 5137 to have a significant immune imbalance, defined as a significant dysregulation by both diseases, as analyzed by IIT. Gene Ontology (GO) term and pathway enrichment of the IIT genes yielded immune-related “Neutrophil Degranulation” and “Adaptive Immune System”, which validates that the IIT algorithm isolates biologically relevant genes in immunity and inflammation. We found that 344 IIT gene products are known targets for established and/or repurposed drugs. Among our results, we found 48 known and 296 novel lupus targets, along with 151 known and 193 novel lymphoma targets. Known disease drug targets in our IIT results further validate that IIT isolates genes with disease-relevant mechanisms. Conclusions: We anticipate the IIT algorithm, together with the shared and contrasting gene mechanisms uncovered here, will contribute to the development of immune-related therapeutic options for lupus and lymphoma patients. Full article

(This article belongs to the Special Issue Bioinformatics of Human Diseases)

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11 pages, 1312 KiB

Open AccessEditor’s ChoiceArticle

Co-Occurrence of Two Plasmids Encoding Transferable bla_NDM-1 and tet(Y) Genes in Carbapenem-Resistant Acinetobacter bereziniae

by Andrés Opazo-Capurro, Kyriaki Xanthopoulou, Rocío Arazo del Pino, Paulina González-Muñoz, Maximiliano Matus-Köhler, Luis Amsteins-Romero, Christian Jerez-Olate, Juan Carlos Hormazábal, Rodrigo Vera, Felipe Aguilera, Sebastián Fuller, Paul G. Higgins and Gerardo González-Rocha

Genes 2024, 15(9), 1213; https://doi.org/10.3390/genes15091213 - 17 Sep 2024

Viewed by 1621

Abstract

Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the bla_NDM-1 and tet(Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile [...] Read more.

Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the bla_NDM-1 and tet(Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile during the COVID-19 pandemic. Methods: Antibiotic susceptibility testing was conducted on UCO-553 and UCO-554. Both isolates underwent whole-genome sequencing to ascertain their sequence type (ST), core genome multilocus sequence-typing (cgMLST) profile, antibiotic resistance genes, plasmids, and mobile genetic elements. Conjugation experiments were performed for both isolates. Results: Both isolates exhibited broad resistance, including resistance to carbapenems, third-generation cephalosporins, fluoroquinolones, tetracycline, cotrimoxazole, and aminoglycosides. Both isolates belong to sequence type ST^PAS1761, with a difference of 17 out of 2984 alleles. Each isolate carried a 47,274 bp plasmid with bla_NDM-1 and aph(3′)-VI genes and two highly similar plasmids: a 35,184 bp plasmid with tet(Y), sul2, aph(6)-Id, and aph(3″)-Ib genes, and a 6078 bp plasmid containing the ant(2″)-Ia gene. Quinolone-resistance mutations were identified in the gyrA and parC genes of both isolates. Importantly, bla_NDM-1 was located within a Tn125 transposon, and tet(Y) was embedded in a Tn5393 transposon. Conjugation experiments successfully transferred bla_NDM-1 and tet(Y) into the A. baumannii ATCC 19606 strain, indicating the potential for horizontal gene transfer. Conclusions: This study highlights the critical role of plasmids in disseminating resistance genes in A. bereziniae and underscores the need for the continued genomic surveillance of this emerging pathogen. The findings emphasize the importance of monitoring A. bereziniae for its potential to cause difficult-to-treat infections and its capacity to spread resistance determinants against clinically significant antibiotics. Full article

(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Antimicrobial Resistance in Bacteria)

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12 pages, 4992 KiB

Open AccessEditor’s ChoiceCase Report

Unambiguous Interpretation of the Pathogenicity of the GLA c.547+3A>G Variant Causing Fabry Disease

by Mario Urtis, Claudia Cavaliere, Viviana Vilardo, Chiara Paganini, Alexandra Smirnova, Carmelina Giorgianni, Alessandro Di Toro, Luisa Chiapparini, Carlo Pellegrini, Maurizia Grasso and Eloisa Arbustini

Genes 2024, 15(9), 1212; https://doi.org/10.3390/genes15091212 - 17 Sep 2024

Viewed by 1672

Abstract

Objectives: This study aims to demonstrate the role of case-level American College of Medical Genetics (ACMG) criteria, such as familial segregation and pathology data, in providing conclusive evidence for the pathogenicity of ultrarare GLA variants causing Anderson–Fabry disease when gene-level and variant-level criteria [...] Read more.

Objectives: This study aims to demonstrate the role of case-level American College of Medical Genetics (ACMG) criteria, such as familial segregation and pathology data, in providing conclusive evidence for the pathogenicity of ultrarare GLA variants causing Anderson–Fabry disease when gene-level and variant-level criteria provide ambiguous or discrepant results. Case/family description: A 52-year-old woman presented with new-onset shortness of breath, chest pain, and palpitations. Echocardiography revealed mild left ventricular wall thickening (14 mm) and mild diastolic dysfunction. She was the second of three siblings born to unrelated parents, both of whom died from malignancies. Family screening identified brothers, one affected 55-year-old with hypertension and asthma and one unaffected 47-year-old. The 15-year-old son of the proband complained of exercise-induced burning feet acral pain his electrocardiogram showed a short PR interval and signs of early hypertrophy. Results: Endomyocardial biopsies of the proband and the affected sibling demonstrated substrate accumulation (globotriaosylceramide). The anti-α-galactosidase-A immunostain showed a total loss of the enzyme in the hemizygous male and a mosaic pattern in the heterozygous female. The next-generation sequencing short-read multigene panel identified the c.547+3A>G variant in the GLA gene and excluded variants in other genes; Oxford-Nanopore long-read sequencing excluded known pathogenic deep intronic variants. A Multiplex-Ligation-dependent-Probe-Amplification assay excluded copy number variations. Based on the variant-level and gene-level ACMG criteria, the variant was classified as a Variant of Uncertain Significance or Likely Benign using different bioinformatic tools. By adding case-level functional data (endomyocardial biopsy, PS3_VeryStrong) and familial data (segregation of genotype with phenotype, PP2_Moderate), the variant was classified as Likely Pathogenic/Pathogenic. Conclusion: ACMG case-level data can unambiguously resolve uncertain interpretations of GLA variants. Full article

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

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16 pages, 14888 KiB

Open AccessEditor’s ChoiceArticle

Molecular Cloning of the scd1 Gene and Its Expression in Response to Feeding Artificial Diets to Mandarin Fish (Siniperca chuatsi)

by Jiangjiang Wang, Lihan Zhang, Xiaowei Gao, Yanfeng Sun, Chunlong Zhao, Xiaotian Gao and Chengbin Wu

Genes 2024, 15(9), 1211; https://doi.org/10.3390/genes15091211 - 16 Sep 2024

Cited by 1 | Viewed by 1519

Abstract

Background/Objectives: Stearoyl-coenzyme A desaturase 1 (SCD1) plays a crucial role in fatty acid metabolism. However, its roles in the feeding habit transformation of mandarin fish (Siniperca chuatsi) remain largely unknown. Methods: Juvenile mandarin fish (10.37 ± 0.54)g were trained to [...] Read more.

Background/Objectives: Stearoyl-coenzyme A desaturase 1 (SCD1) plays a crucial role in fatty acid metabolism. However, its roles in the feeding habit transformation of mandarin fish (Siniperca chuatsi) remain largely unknown. Methods: Juvenile mandarin fish (10.37 ± 0.54)g were trained to feed on an artificial diet and then divided into artificial diet feeders and nonfeeders according to their feed preference. Afterwards, the scd1 gene of mandarin fish (Sc-scd1) was identified and characterized, and its transcription difference was determined between S. chuatsi fed live artificial diets and those fed prey fish. Results: Our results show that Sc-scd1 coding sequence is 1002 bp long, encoding 333 amino acids. The assumed Sc-SCD1 protein lacks a signal peptide, and it contains 1 N-linked glycosylation site, 24 phosphorylation sites, 4 transmembrane structures, and 3 conserved histidine elements. We found that Sc-SCD1 exhibits a high similarity with its counterparts in other fish by multiple alignments and phylogenetic analysis. The expression level of Sc-scd1 was detected with different expression levels in all tested tissues between male and female individuals fed either live prey fish or artificial diets. Conclusions: In particular, the Sc-scd1 expression level was the highest in the liver of both male and female mandarin fish fed artificial diets, indicating that scd1 genes may be associated with feed adaption of mandarin fish. Taken together, our findings offer novel perspectives on the potential roles of scd1 in specific domestication, and they provide valuable genetic information on feeding habits for the domestication of mandarin fish. Full article

(This article belongs to the Special Issue Genetics and Molecular Breeding in Fisheries and Aquaculture)

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12 pages, 9310 KiB

Open AccessEditor’s ChoiceArticle

NR0B2 Is a Key Factor for Gastric Diseases: A GEO Database Analysis Combined with Drug-Target Mendelian Randomization

by Zhengwen Li, Lijia Xu, Dongliang Huang, Chujie Li, Guido R. M. M. Haenen and Ming Zhang

Genes 2024, 15(9), 1210; https://doi.org/10.3390/genes15091210 - 16 Sep 2024

Viewed by 2001

Abstract

Small Heterodimer Partner (SHP; NR0B2) is an orphan receptor that acts as a transcriptional regulator, controlling various metabolic processes, and is a potential therapeutic target for cancer. Examining the correlation between the expression of NR0B2 and the risk of gastric diseases could [...] Read more.

Small Heterodimer Partner (SHP; NR0B2) is an orphan receptor that acts as a transcriptional regulator, controlling various metabolic processes, and is a potential therapeutic target for cancer. Examining the correlation between the expression of NR0B2 and the risk of gastric diseases could open a new path for treatment and drug development. The Gene Expression Omnibus (GEO) database was utilized to explore NR0B2 gene expression profiles in gastric diseases. Co-expressed genes were identified through Weighted Correlation Network Analysis (WGCNA), and GO enrichment was performed to identify potential pathways. The Xcell method was employed to analyze immune infiltration relationships. To determine the potential causal relationship between NR0B2 expression and gastric diseases, we identified six single-nucleotide polymorphisms (SNPs) as a proxy for NR0B2 expression located within 100 kilobases of NR0B2 and which are associated with triglyceride homeostasis and performed drug-target Mendelian randomization (MR). Bioinformatics analysis revealed that NR0B2 expression levels were reduced in gastric cancer and increased in gastritis. GO analysis and Gene Set Enrichment Analysis (GSEA) showed that NR0B2 is widely involved in oxidation-related processes. Immune infiltration analyses found that NR0B2 was associated with Treg. Prognostic analyses showed that a low expression of NR0B2 is a risk factor for the poor prognoses of gastric cancer. MR analyses revealed that NR0B2 expression is associated with a risk of gastric diseases (NR0B2 vs. gastric cancer, p = 0.006, OR: 0.073, 95%CI: 0.011–0.478; NR0B2 vs. gastric ulcer, p = 0.03, OR: 0.991, 95%CI: 0.984–0.999; NR0B2 vs. other gastritis, p = 0.006, OR:3.82, 95%CI: 1.468–9.942). Our study confirms the causal relationship between the expression of NR0B2 and the risk of gastric diseases, and highlights its role in the progression of gastric cancer. The present study opens new avenues for exploring the potential of drugs that either activate or inhibit the NR0B2 receptor in the treatment of gastric diseases. Full article

(This article belongs to the Section Bioinformatics)

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6 pages, 896 KiB

Open AccessEditor’s ChoiceCase Report

Constitutional Mutation of PIK3CA: A Variant of Cowden Syndrome?

by Elena Vida-Navas, Verónica Barca-Tierno, Victoria López-Gómez, María Teresa Salazar, Miguel A. Moreno-Pelayo and Carmen Guillén-Ponce

Genes 2024, 15(9), 1209; https://doi.org/10.3390/genes15091209 - 15 Sep 2024

Viewed by 1449

Abstract

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer [...] Read more.

We present a family in which four individuals have been identified with the same likely pathogenic genetic alteration in the PIK3CA gene at the germinal level; specifically, c.1145G>A p.(Arg382Lys) missense type. The index case patient was diagnosed with multinodular goiter and breast cancer at 61 years old. Among the other three carrier relatives: one has been diagnosed with serous cystadenoma of the ovary and a thyroid nodule with no radiological suspicion of malignancy; the other two present multinodular goiter. Additionally, a sister of three of the carriers suffered from an ovarian teratoma, follicular thyroid carcinoma on multinodular goiter, and high-grade serous ovarian carcinoma. No direct mutation study was performed on her as she had died due to ovarian carcinoma. This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes. Full article

(This article belongs to the Topic Advances in Genetics and Precision Medicine in Human Diseases)

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20 pages, 9201 KiB

Open AccessEditor’s ChoiceArticle

Epidermal Growth Factor Receptor Emerges as a Viable Target for Reducing Tumorigenicity of MDCK Cells

by Di Yang, Yuejiao Liao, Lingwei Huang, Jiachen Shi, Jiamin Wang, Zilin Qiao, Zhongren Ma and Sijiu Yu

Genes 2024, 15(9), 1208; https://doi.org/10.3390/genes15091208 - 14 Sep 2024

Viewed by 1563

Abstract

The MDCK cell line is perceived as better than the embryos of hen eggs for the production of influenza vaccines, but the tumorigenicity of these cells is concerning. Epidermal growth factor receptor (EGFR) is likely to be a crucial target that contributes to [...] Read more.

The MDCK cell line is perceived as better than the embryos of hen eggs for the production of influenza vaccines, but the tumorigenicity of these cells is concerning. Epidermal growth factor receptor (EGFR) is likely to be a crucial target that contributes to the tumorigenicity of MDCK cells. In this study, EGFR-knockdown and EGFR-overexpression cell lines were established. EGFR’s influence on cell growth, migration, clonogenic ability, and flu virus susceptibility was evaluated in vitro, and its role in cell tumorigenicity was examined in nude mice. GST pull-down coupled with mass spectrometry (MS) and bioinformatics analysis identified EGFR-interacting proteins. The expression levels of these proteins, as well as those of PI3K–AKT- and MAPK–ERK-signaling-pathway-related molecules, were confirmed at both gene and protein levels. The result indicates that EGFR overexpression can enhance cell proliferation, migration, and clonal formation; EGFR knockdown could effectively curtail tumorigenesis and amplify the titers of influenza viruses in MDCK cells. An analysis of the underlying mechanism identified a total of 21 interacting proteins implicated in tumor formation, and among these, AKT1, CDK4, GNB2, and MAPK8 were confirmed at both gene and protein levels. EGFR can activate key factors of the PI3K–AKT signaling pathway, AKT and PI3K, and promote their phosphorylation levels. Consequently, we concluded that EGFR interacts with GNB2, facilitating transmembrane signal transduction, activating the PI3K–AKT signaling cascade, controlling cell cycle alterations, stimulating cell proliferation, and promoting tumorigenesis. Full article

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

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13 pages, 1365 KiB

Open AccessEditor’s ChoiceArticle

CD33 and SHP-1/PTPN6 Interaction in Alzheimer’s Disease

by Lien Beckers, Mamunur Rashid, Annie J. Lee, Zena K. Chatila, Kirstin A. Tamucci, Ryan C. Talcoff, Jennifer L. Hall, David A. Bennett, Badri N. Vardarajan and Elizabeth M. Bradshaw

Genes 2024, 15(9), 1204; https://doi.org/10.3390/genes15091204 - 13 Sep 2024

Cited by 2 | Viewed by 2015

Abstract

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer’s disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk [...] Read more.

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer’s disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer’s disease. Several studies explored the molecular outcomes of genetic variation at the CD33 locus. It has been determined that the risk variant associated with AD increases the expression of the large isoform of CD33 (CD33M) in innate immune cells and alters its biological functions. CD33 is thought to signal via the interaction of its ITIM motif and the protein tyrosine phosphatase, SHP-1. Here, we utilize different molecular and computational approaches to investigate how AD-associated genetic variation in CD33 affects its interaction with SHP-1 in human microglia and microglia-like cells. Our findings demonstrate a genotype-dependent interaction between CD33 and SHP-1, which may functionally contribute to the AD risk associated with this CD33 variant. We also found that CD33-PTPN6 (SHP-1) gene–gene interactions impact AD-related traits, while CD33-PTPN11 (SHP-2) interactions do not. Full article

(This article belongs to the Special Issue Genetic Basis of Neurodegenerative Disorders)

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17 pages, 16291 KiB

Open AccessEditor’s ChoiceArticle

Tumor Heterogeneity in Gastrointestinal Cancer Based on Multimodal Data Analysis

by Dongmei Ai, Yang Du, Hongyu Duan, Juan Qi and Yuduo Wang

Genes 2024, 15(9), 1207; https://doi.org/10.3390/genes15091207 - 13 Sep 2024

Viewed by 1361

Abstract

Background: Gastrointestinal cancer cells display both morphology and physiology diversity, thus posing a significant challenge for precise representation by a single data model. We conducted an in-depth study of gastrointestinal cancer heterogeneity by integrating and analyzing data from multiple modalities. Methods: We used [...] Read more.

Background: Gastrointestinal cancer cells display both morphology and physiology diversity, thus posing a significant challenge for precise representation by a single data model. We conducted an in-depth study of gastrointestinal cancer heterogeneity by integrating and analyzing data from multiple modalities. Methods: We used a modified Canny algorithm to identify edges from tumor images, capturing intricate nonlinear interactions between pixels. These edge features were then combined with differentially expressed mRNA, miRNA, and immune cell data. Before data integration, we used the K-medoids algorithm to pre-cluster individual data types. The results of pre-clustering were used to construct the kernel matrix. Finally, we applied spectral clustering to the fusion matrix to identify different tumor subtypes. Furthermore, we identified hub genes linked to these subtypes and their biological roles through the application of Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Ontology (GO) enrichment analysis. Results: Our investigation categorized patients into three distinct tumor subtypes and pinpointed hub genes associated with each. Genes MAGI2-AS3, MALAT1, and SPARC were identified as having a differential impact on the metastatic and invasive capabilities of cancer cells. Conclusion: By harnessing multimodal features, our study enhances the understanding of gastrointestinal tumor heterogeneity and identifies biomarkers for personalized medicine and targeted treatments. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 57494 KiB

Open AccessEditor’s ChoiceArticle

CHIR99021 and Brdu Are Critical in Chicken iPSC Reprogramming via Small-Molecule Screening

by Kai Jin, Jing Zhou, Gaoyuan Wu, Zeyu Li, Xilin Zhu, Youchen Liang, Tingting Li, Guohong Chen, Qisheng Zuo, Yingjie Niu, Jiuzhou Song and Wei Han

Genes 2024, 15(9), 1206; https://doi.org/10.3390/genes15091206 - 13 Sep 2024

Viewed by 1566

Abstract

Background/Objectives: Induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells into cells with most of the ESC (embryonic stem cell) characteristics show promise toward solving ethical problems currently facing stem cell research and eventually yield clinical grade pluripotent stem cells for therapies and [...] Read more.

Background/Objectives: Induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells into cells with most of the ESC (embryonic stem cell) characteristics show promise toward solving ethical problems currently facing stem cell research and eventually yield clinical grade pluripotent stem cells for therapies and regenerative medicine. In recent years, an increasing body of research suggests that the chemical induction of pluripotency (CIP) method can yield iPSCs in vitro, yet its application in avian species remains unreported. Methods: Herein, we successfully obtained stably growing chicken embryonic fibroblasts (CEFs) using the tissue block adherence method and employed 12 small-molecule compounds to induce chicken iPSC formation. Results: The final optimized iPSC induction system was bFGF (10 ng/mL), CHIR99021 (3 μM), RepSox (5 μM), DZNep (0.05 μM), BrdU (10 μM), BMP4 (10 ng/mL), vitamin C (50 μg/mL), EPZ-5676 (5 μM), and VPA (0.1 mM). Optimization of the induction system revealed that the highest number of clones was induced with 8 × 10⁴ cells per well and at 1.5 times the original concentration. Upon characterization, these clones exhibited iPSC characteristics, leading to the development of a stable compound combination for iPSC generation in chickens. Concurrently, employing a deletion strategy to investigate the functionality of small-molecule compounds during induction, we identified CHIR99021 and BrdU as critical factors for inducing chicken iPSC formation. Conclusions: In conclusion, this study provides a reference method for utilizing small-molecule combinations in avian species to reprogram cells and establish a network of cell fate determination mechanisms. Full article

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

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16 pages, 1402 KiB

Open AccessEditor’s ChoiceReview

Research Progress on miRNAs and Artificial miRNAs in Insect and Disease Resistance and Breeding in Plants

by Zengfeng Ma, Jianyu Wang and Changyan Li

Genes 2024, 15(9), 1200; https://doi.org/10.3390/genes15091200 - 12 Sep 2024

Cited by 8 | Viewed by 2217

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that are expressed in a tissue- and temporal-specific manner during development. They have been found to be highly conserved during the evolution of different species. miRNAs regulate the expression of several genes in various organisms, with some [...] Read more.

MicroRNAs (miRNAs) are small, non-coding RNAs that are expressed in a tissue- and temporal-specific manner during development. They have been found to be highly conserved during the evolution of different species. miRNAs regulate the expression of several genes in various organisms, with some regulating the expression of multiple genes with similar or completely unrelated functions. Frequent disease and insect pest infestations severely limit agricultural development. Thus, cultivating resistant crops via miRNA-directed gene regulation in plants, insects, and pathogens is an important aspect of modern breeding practices. To strengthen the application of miRNAs in sustainable agriculture, plant endogenous or exogenous miRNAs have been used for plant breeding. Consequently, the development of biological pesticides based on miRNAs has become an important avenue for future pest control methods. However, selecting the appropriate miRNA according to the desired target traits in the target organism is key to successfully using this technology for pest control. This review summarizes the progress in research on miRNAs in plants and other species involved in regulating plant disease and pest resistance pathways. We also discuss the molecular mechanisms of relevant target genes to provide new ideas for future research on pest and disease resistance and breeding in plants. Full article

(This article belongs to the Special Issue Plant Small RNAs: Biogenesis and Functions)

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