Genes

Article

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 1069

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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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 1425

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)

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 986

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, 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 1428

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)

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 1163

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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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 1450

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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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 963

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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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 1265

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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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 1548

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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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 1890

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 1129

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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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

Cited by 1 | Viewed by 1389

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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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 1110

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, 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 1593

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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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 1370

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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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 1232

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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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

Cited by 1 | Viewed by 1466

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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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 1346

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 2 | Viewed by 1482

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 1553

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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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 1707

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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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 2 | Viewed by 1314

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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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 1179

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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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 1186

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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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 1196

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 1522

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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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

Cited by 1 | Viewed by 1730

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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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 2077

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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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 2108

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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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 1584

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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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 1614

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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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 1416

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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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 2128

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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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 1714

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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10 pages, 651 KiB

Open AccessEditor’s ChoiceArticle

Phylo-Epigenetics in Phylogeny Analyses and Evolution

by Simeon Santourlidis

Genes 2024, 15(9), 1198; https://doi.org/10.3390/genes15091198 - 12 Sep 2024

Viewed by 1474

Abstract

Long-standing, continuous blurring and controversies in the field of phylogenetic interspecies relations, associated with insufficient explanations for dynamics and variability of speeds of evolution in mammals, hint at a crucial missing link. It has been suggested that transgenerational epigenetic inheritance and the concealed [...] Read more.

Long-standing, continuous blurring and controversies in the field of phylogenetic interspecies relations, associated with insufficient explanations for dynamics and variability of speeds of evolution in mammals, hint at a crucial missing link. It has been suggested that transgenerational epigenetic inheritance and the concealed mechanisms behind play a distinct role in mammalian evolution. Here, a comprehensive sequence alignment approach in hominid species, i.e., Homo sapiens, Homo neanderthalensis, Denisovan human, Pan troglodytes, Pan paniscus, Gorilla gorilla, and Pongo pygmaeus, comprising conserved CpG islands of housekeeping genes, uncover evidence for a distinct variability of CpG dinucleotides. Applying solely these evolutionary consistent and inconsistent CpG sites in a classic phylogenetic analysis, calibrated by the divergence time point of the common chimpanzee (P. troglodytes) and the bonobo or pygmy chimpanzee (P. paniscus), a “phylo-epigenetic” tree has been generated, which precisely recapitulates branch points and branch lengths, i.e., divergence events and relations, as they have been broadly suggested in the current literature, based on comprehensive molecular phylogenomics and fossil records of many decades. It is suggested here that CpG dinucleotide changes at CpG islands are of superior importance for evolutionary developments. These changes are successfully inherited through the germ line, determining emerging methylation profiles, and they are a central component of transgenerational epigenetic inheritance. It is hidden in the DNA, what will happen on it later. Full article

(This article belongs to the Section Epigenomics)

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22 pages, 3832 KiB

Open AccessEditor’s ChoiceArticle

Developing a Machine Learning ‘Smart’ Polymerase Chain Reaction Thermocycler Part 2: Putting the Theoretical Framework into Practice

by Caitlin McDonald, Duncan Taylor, Russell S. A. Brinkworth and Adrian Linacre

Genes 2024, 15(9), 1199; https://doi.org/10.3390/genes15091199 - 12 Sep 2024

Viewed by 2174

Abstract

The introduction of PCR into forensic science and the rapid increases in the sensitivity, specificity and discrimination power of DNA profiling that followed have been fundamental in shaping the field of forensic biology. Despite these developments, the challenges associated with the DNA profiling [...] Read more.

The introduction of PCR into forensic science and the rapid increases in the sensitivity, specificity and discrimination power of DNA profiling that followed have been fundamental in shaping the field of forensic biology. Despite these developments, the challenges associated with the DNA profiling of trace, inhibited and degraded samples remain. Thus, any improvement to the performance of sub-optimal samples in DNA profiling would be of great value to the forensic community. The potential exists to optimise the PCR performance of samples by altering the cycling conditions used. If the effects of changing cycling conditions upon the quality of a DNA profile can be well understood, then the PCR process can be manipulated to achieve a specific goal. This work is a proof-of-concept study for the development of a smart PCR system, the theoretical foundations of which are outlined in part 1 of this publication. The first steps needed to demonstrate the performance of our smart PCR goal involved the manual alteration of cycling conditions and assessment of the DNA profiles produced. In this study, the timing and temperature of the denaturation and annealing stages of the PCR were manually altered to achieve the goal of reducing PCR runtime while maintaining an acceptable quality and quantity of DNA product. A real-time feedback system was also trialled using an STR PCR and qPCR reaction mix, and the DNA profiles generated were compared to profiles produced using the standard STR PCR kits. The aim of this work was to leverage machine learning to enable real-time adjustments during a PCR, allowing optimisation of cycling conditions towards predefined user goals. A set of parameters was found that yielded similar results to the standard endpoint PCR methodology but was completed 30 min faster. The development of an intelligent system would have significant implications for the various biological disciplines that are reliant on PCR technology. Full article

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

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34 pages, 12575 KiB

Open AccessEditor’s ChoiceArticle

A Proposal for the RNAome at the Dawn of the Last Universal Common Ancestor

by Miryam Palacios-Pérez and Marco V. José

Genes 2024, 15(9), 1195; https://doi.org/10.3390/genes15091195 - 11 Sep 2024

Viewed by 1347

Abstract

From the most ancient RNAs, which followed an RNY pattern and folded into small hairpins, modern RNA molecules evolved by two different pathways, dubbed Extended Genetic Code 1 and 2, finally conforming to the current standard genetic code. Herein, we describe the evolutionary [...] Read more.

From the most ancient RNAs, which followed an RNY pattern and folded into small hairpins, modern RNA molecules evolved by two different pathways, dubbed Extended Genetic Code 1 and 2, finally conforming to the current standard genetic code. Herein, we describe the evolutionary path of the RNAome based on these evolutionary routes. In general, all the RNA molecules analysed contain portions encoded by both genetic codes, but crucial features seem to be better recovered by Extended 2 triplets. In particular, the whole Peptidyl Transferase Centre, anti-Shine–Dalgarno motif, and a characteristic quadruplet of the RNA moiety of RNAse-P are clearly unveiled. Differences between bacteria and archaea are also detected; in most cases, the biological sequences are more stable than their controls. We then describe an evolutionary trajectory of the RNAome formation, based on two complementary evolutionary routes: one leading to the formation of essentials, while the other complemented the molecules, with the cooperative assembly of their constituents giving rise to modern RNAs. Full article

(This article belongs to the Special Issue Tools for Evolutionary Genetics)

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24 pages, 3565 KiB

Open AccessEditor’s ChoiceArticle

Developing a Machine-Learning ‘Smart’ PCR Thermocycler, Part 1: Construction of a Theoretical Framework

by Caitlin McDonald, Duncan Taylor, Gershom Mwachari Masawi, Ayesha Khalid Ahmed Khan, Richard Leibbrandt, Adrian Linacre and Russell S. A. Brinkworth

Genes 2024, 15(9), 1196; https://doi.org/10.3390/genes15091196 - 11 Sep 2024

Viewed by 3037

Abstract

The use of PCR is widespread in biological fields. Some fields, such as forensic biology, push PCR to its limits as DNA profiling may be required in short timeframes, may be produced from minute amounts of starting material, and may be required to [...] Read more.

The use of PCR is widespread in biological fields. Some fields, such as forensic biology, push PCR to its limits as DNA profiling may be required in short timeframes, may be produced from minute amounts of starting material, and may be required to perform in the presence of inhibitory compounds. Due to the extreme high-throughput of samples using PCR in forensic science, any small improvement in the ability of PCR to address these challenges can have dramatic effects for the community. At least part of the improvement in PCR performance could potentially come by altering PCR cycling conditions. These alterations could be general, in that they are applied to all samples, or they could be tailored to individual samples for maximum targeted effect. Further to this, there may be the ability to respond in real time to the conditions of PCR for a sample and make cycling parameters change on the fly. Such a goal would require both a means to track the conditions of the PCR in real time, and the knowledge of how cycling parameters should be altered, given the current conditions. In Part 1 of our work, we carry out the theoretical groundwork for the ambitious goal of creating a smart PCR system that can respond appropriately to features within individual samples in real time. We approach this task using an open qPCR instrument to provide real-time feedback and machine learning to identify what a successful PCR ‘looks like’ at different stages of the process. We describe the fundamental steps to set up a real-time feedback system, devise a method of controlling PCR cycling conditions from cycle to cycle, and to develop a system of defining PCR goals, scoring the performance of the system towards achieving those goals. We then present three proof-of-concept studies that prove the feasibility of this overall method. In a later Part 2 of our work, we demonstrate the performance of the theory outlined in this paper on a large-scale PCR cycling condition alteration experiment. The aim is to utilise machine learning so that throughout the process of PCR automatic adjustments can be made to best alter cycling conditions towards a user-defined goal. The realisation of smart PCR systems will have large-scale ramifications for biological fields that utilise PCR. Full article

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

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14 pages, 15725 KiB

Open AccessEditor’s ChoiceArticle

Downregulation of RhoB Inhibits Cervical Cancer Progression and Enhances Cisplatin Sensitivity

by Weijiao Wang, Yubin Jia, Yuhuan Liu, Xiaofeng Lv, Lili Guo, Silu Meng and Changyu Wang

Genes 2024, 15(9), 1186; https://doi.org/10.3390/genes15091186 - 10 Sep 2024

Viewed by 1713

Abstract

RhoB, a member of the Rho GTPase family, has been implicated in the malignant progression of various cancer types. However, its role in cervical cancer (CC) remains unclear. Therefore, this study aims to elucidate the biological function of RhoB in CC and its [...] Read more.

RhoB, a member of the Rho GTPase family, has been implicated in the malignant progression of various cancer types. However, its role in cervical cancer (CC) remains unclear. Therefore, this study aims to elucidate the biological function of RhoB in CC and its relationship with cisplatin sensitivity. We analyzed data from the TCGA, GTEx, and GEO databases, revealing that RhoB mRNA expression is downregulated in CC tissues compared to normal cervical tissues. The further analysis of the TCGA database and Tongji samples showed that CC patients with a high RhoB expression had a shorter overall survival (OS). Subsequently, we found that the knockdown of RhoB inhibited the proliferation, migration, and invasion of cancer cells, while increasing apoptosis. Through Western blot (WB) analysis, we found that knocking down RhoB resulted in an increased expression of the epithelial marker E-cadherin, while the levels of N-cadherin, MMP2, MMP9, Vimentin, and Snail1 were reduced. Additionally, RhoB mRNA expression was upregulated in CC tissues after chemotherapy compared to CC tissues before chemotherapy. In CC cells, RhoB expression increased with cisplatin concentration, and the IC50 value decreased following RhoB knockdown. Moreover, the knockdown of RhoB could enhance the cellular apoptosis triggered by cisplatin. This study demonstrated that RhoB plays an oncogenic role in CC and that its knockdown could enhance the sensitivity of CC cells to cisplatin. Full article

(This article belongs to the Special Issue Genetic Biomarkers and Their Expression for Human Diseases: From the Laboratory to the Patient’s Bedside)

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17 pages, 3251 KiB

Open AccessEditor’s ChoiceArticle

17α-Ethynylestradiol and Levonorgestrel Exposure of Rainbow Trout RTL-W1 Cells at 18 °C and 21 °C Mainly Reveals Thermal Tolerance, Absence of Estrogenic Effects, and Progestin-Induced Upregulation of Detoxification Genes

by Margarida Vilaça, Célia Lopes, Rosária Seabra and Eduardo Rocha

Genes 2024, 15(9), 1189; https://doi.org/10.3390/genes15091189 - 10 Sep 2024

Cited by 3 | Viewed by 1222

Abstract

Fish are exposed to increased water temperatures and aquatic pollutants, including endocrine-disrupting compounds (EDCs). Although each stressor can disturb fish liver metabolism independently, combined effects may exist. To unveil the molecular mechanisms behind the effects of EDCs and temperature, fish liver cell lines [...] Read more.

Fish are exposed to increased water temperatures and aquatic pollutants, including endocrine-disrupting compounds (EDCs). Although each stressor can disturb fish liver metabolism independently, combined effects may exist. To unveil the molecular mechanisms behind the effects of EDCs and temperature, fish liver cell lines are potential models needing better characterisation. Accordingly, we exposed the rainbow trout RTL-W1 cells (72 h), at 18 °C and 21 °C, to ethynylestradiol (EE2), levonorgestrel (LNG), and a mixture of both hormones (MIX) at 10 µM. The gene expression of a selection of targets related to detoxification (CYP1A, CYP3A27, GST, UGT, CAT, and MRP2), estrogen exposure (ERα, VtgA), lipid metabolism (FAS, FABP1, FATP1), and temperature stress (HSP70b) was analysed by RT-qPCR. GST expression was higher after LNG exposure at 21 °C than at 18 °C. LNG further enhanced the expression of CAT, while both LNG and MIX increased the expressions of CYP3A27 and MRP2. In contrast, FAS expression only increased in MIX, compared to the control. ERα, VtgA, UGT, CYP1A, HSP70b, FABP1, and FATP1 expressions were not influenced by the temperature or the tested EDCs. The RTL-W1 model was unresponsive to EE2 alone, sensitive to LNG (in detoxification pathway genes), and mainly insensitive to the temperature range but had the potential to unveil specific interactions. Full article

(This article belongs to the Section Genes & Environments)

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17 pages, 2484 KiB

Open AccessEditor’s ChoiceArticle

Limb Perfusion Delivery of a rAAV1 Alpha-1 Antitrypsin Vector in Non-Human Primates Is Safe but Insufficient for Therapy

by Debora Pires-Ferreira, Darcy Reil, Qiushi Tang, Meghan Blackwood, Thomas Gallagher, Allison M. Keeler, Jessica A. Chichester, Kristin K. Vyhnal, Jane A. Lindborg, Janet Benson, Dongtao Fu, Terence R. Flotte and Alisha M. Gruntman

Genes 2024, 15(9), 1188; https://doi.org/10.3390/genes15091188 - 10 Sep 2024

Viewed by 1508

Abstract

Background/Objectives: α-1 antitrypsin (AAT) deficiency is an inherited, genetic condition characterized by reduced serum levels of AAT and increased risk of developing emphysema and liver disease. AAT is normally synthesized primarily in the liver, but muscle-targeting with a recombinant adeno-associated virus (rAAV) vector [...] Read more.

Background/Objectives: α-1 antitrypsin (AAT) deficiency is an inherited, genetic condition characterized by reduced serum levels of AAT and increased risk of developing emphysema and liver disease. AAT is normally synthesized primarily in the liver, but muscle-targeting with a recombinant adeno-associated virus (rAAV) vector for α-1 antitrypsin (AAT) gene therapy has been used to minimize liver exposure to the virus and hepatotoxicity. Clinical trials of direct intramuscular (IM) administration of rAAV1-hAAT have demonstrated its overall safety and transgene expression for 5 years. However, the failure to reach the therapeutic target level after 100 large-volume (1.5 mL) IM injections of maximally concentrated vector led us to pursue a muscle-targeting approach using isolated limb perfusion. This targets the rAAV to a greater muscle mass and allows for a higher total volume (and thereby a higher dose) than is tolerable by multiple direct IM injections. Limb perfusion has been shown to be feasible in non-human primates using the rAAV1 serotype and a ubiquitous promoter expressing an epitope-tagged AAT matched to the host species. Methods: In this study, we performed a biodistribution and preclinical safety study in non-human primates with a clinical candidate rAAV1-human AAT (hAAT) vector at doses ranging from 3.0 × 10¹² to 1.3 × 10¹³ vg/kg, bracketing those used in our clinical trials. Results: We found that limb perfusion delivery of rAAV1-hAAT was safe and showed a biodistribution pattern similar to previous studies. However, serum levels of AAT obtained with high-dose limb perfusion still reached only ~50% of the target serum levels. Conclusions: Our results suggest that clinically effective AAT gene therapy may ultimately require delivery at doses between 3.5 × 10¹³–1 × 10¹⁴ vg/kg, which is within the dose range used for approved rAAV gene therapies. Muscle-targeting strategies could be incorporated when delivering systemic administration of high-dose rAAV gene therapies to increase transduction of muscle tissues and reduce the burden on the liver, especially in diseases that can present with hepatotoxicity such as AAT deficiency. Full article

(This article belongs to the Special Issue Gene Therapy for Childhood Diseases)

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13 pages, 1395 KiB

Open AccessEditor’s ChoiceArticle

A Novel KIDINS220 Pathogenic Variant Associated with the Syndromic Spastic Paraplegia SINO: An Expansion of the Brain Malformation Spectrum and a Literature Review

by Maria Teresa Bonati, Cristina Baldoli, Jacopo Taurino, Daniela Marchetti, Lidia Larizza, Palma Finelli and Maria Iascone

Genes 2024, 15(9), 1190; https://doi.org/10.3390/genes15091190 - 10 Sep 2024

Viewed by 1302

Abstract

Background/Objectives: Identifying novel variants in very rare disease genes can be challenging when patients exhibit a complex phenotype that expands the one described, and we provide such an example here. A few terminal truncating variants in KIDINS220 cause spastic paraplegia (SP), intellectual disability [...] Read more.

Background/Objectives: Identifying novel variants in very rare disease genes can be challenging when patients exhibit a complex phenotype that expands the one described, and we provide such an example here. A few terminal truncating variants in KIDINS220 cause spastic paraplegia (SP), intellectual disability (ID), nystagmus, and obesity (SINO, MIM #617296). Prompted by the result of next-generation sequencing on a patient referred for SP associated with complex brain dysmorphisms, we reviewed the phenotype of SINO patients focusing on their brain malformations, mainly described in prenatal age and first years of life, and tried to understand if the predicted effect of the mutant kidins220 may have caused them. Methods: We performed whole exome sequencing (WES) and a literature and mutation databases review. Results: We report a young adult with SP, severe ID, strabismus, and macrocephaly exhibiting brain malformations at follow-up, partially overlapping with those described in TUBB3 tubulinopathy. WES analysis of the proband and parents identified the heterozygous de novo variant (NM_020738.4: c. 4144G > T) p. Glu 1382* in KIDINS220 that was predicted to be causative of SINO. Conclusions: The progression of myelination and the development of brain structures turned out to be crucial for identifying, at follow-up, the whole KIDINS220-related brain malformations. The truncated proteins associated with SINO lack a portion fundamental for the interaction of kidins220 with tubulins and microtubule-associated proteins. The complexity of the brain malformations displayed by our patient, and possibly by other reported SINO patients, could result from an impaired dynamic modulation of the microtubule cytoskeleton during embryogenesis. Brain malformations must be considered as part of the SINO spectrum phenotype. Full article

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

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11 pages, 8076 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversity and Divergence between Southern Japonica and Northern Japonica Rice Varieties in China

by Zhiqiang Yan, Ruyue Deng, Huihui Tang and Susong Zhu

Genes 2024, 15(9), 1182; https://doi.org/10.3390/genes15091182 - 9 Sep 2024

Viewed by 1145

Abstract

Given the notable ecological and breeding disparities between southern and northern rice regions, delving into the genetic diversity and divergence between southern and northern japonica rice contributes to enhancing the genetic pool for japonica rice breeding. In this study, we analyzed 90 southern [...] Read more.

Given the notable ecological and breeding disparities between southern and northern rice regions, delving into the genetic diversity and divergence between southern and northern japonica rice contributes to enhancing the genetic pool for japonica rice breeding. In this study, we analyzed 90 southern and 51 northern japonica rice varieties, focusing on nucleotide diversity (Pi), agronomic trait variations, population structure, genetic divergence, and a neutral test. For genetic diversity, the results demonstrated higher Pi in northern japonica rice varieties (NJRVs) on Chr2, Chr5, Chr6, Chr8, and Chr10, whereas in southern japonica rice varieties (SJRVs) on Chr7 and Chr9. In addition, SJRVs exhibited higher grain width and thickness, whereas NJRVs featured a higher grain aspect ratio, filled grain number, and grain number per panicle. Regarding genetic divergence, geographic differentiation existed between NJRVs and SJRVs, with Chr5 exhibiting numerous higher genetic differentiation windows, including cloned grain shape-controlling genes RGA1 and SFD5, stemming from intensified selection pressure on SJRVs. In summary, SJRVs and NJRVs exhibited diversity differences and genetic differentiation. Hence, it was suggested to conduct genetic introgression between NJRVs and SJRVs to broaden the genetic basis of the local japonica rice germplasm. By exploiting their heterotic advantage, new japonica rice cultivars with superior comprehensive traits could be developed. Full article

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

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25 pages, 5732 KiB

Open AccessEditor’s ChoiceArticle

SVA Regulation of Transposable Element Clustered Transcription within the Major Histocompatibility Complex Genomic Class II Region of the Parkinson’s Progression Markers Initiative

by Jerzy K. Kulski, Abigail L. Pfaff and Sulev Koks

Genes 2024, 15(9), 1185; https://doi.org/10.3390/genes15091185 - 9 Sep 2024

Cited by 3 | Viewed by 1659

Abstract

SINE-VNTR-Alu (SVA) retrotransposons can regulate expression quantitative trait loci (eQTL) of coding and noncoding genes including transposable elements (TEs) distributed throughout the human genome. Previously, we reported that expressed SVAs and human leucocyte antigen (HLA) class II genotypes on chromosome 6 were associated [...] Read more.

SINE-VNTR-Alu (SVA) retrotransposons can regulate expression quantitative trait loci (eQTL) of coding and noncoding genes including transposable elements (TEs) distributed throughout the human genome. Previously, we reported that expressed SVAs and human leucocyte antigen (HLA) class II genotypes on chromosome 6 were associated significantly with Parkinson’s disease (PD). Here, our aim was to follow-up our previous study and evaluate the SVA associations and their regulatory effects on the transcription of TEs within the HLA class II genomic region. We reanalyzed the transcriptome data of peripheral blood cells from the Parkinson’s Progression Markers Initiative (PPMI) for 1530 subjects for TE and gene RNAs with publicly available computing packages. Four structurally polymorphic SVAs regulate the transcription of 20 distinct clusters of 235 TE loci represented by LINES (37%), SINES (28%), LTR/ERVs (23%), and ancient transposon DNA elements (12%) that are located in close proximity to HLA genes. The transcribed TEs were mostly short length, with an average size of 389 nucleotides. The numbers, types and profiles of positive and negative regulation of TE transcription varied markedly between the four regulatory SVAs. The expressed SVA and TE RNAs in blood cells appear to be enhancer-like elements that are coordinated differentially in the regulation of HLA class II genes. Future work on the mechanisms underlying their regulation and potential impact is essential for elucidating their roles in normal cellular processes and disease pathogenesis. Full article

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

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16 pages, 4210 KiB

Open AccessEditor’s ChoiceArticle

Physiological and Transcriptome Analyses Reveal the Effects of Fertilization on the Yield of Winter Wheat and on the Photosynthetic Performance of Leaves during the Flowering Period

by Lihong Wang, Jia Shi, Hongzhi Zhang, Xunji Chen, Jianfeng Li, Zhong Wang, Xiaorong Li, Xin Gao, Chunsheng Wang, Jianqiang Xia, Zhun Zhao, Yueqiang Zhang, Zheru Fan and Qi Zhao

Genes 2024, 15(9), 1179; https://doi.org/10.3390/genes15091179 - 8 Sep 2024

Cited by 1 | Viewed by 1232

Abstract

Fertilization significantly affects the growth and development of wheat. However, the precise mechanisms underlying gene regulation during flowering in response to fertilization deficiency remain elusive. In this study, fertilization (F) and non-fertilization (CK) ) treatments were set up to reveal examine the effect [...] Read more.

Fertilization significantly affects the growth and development of wheat. However, the precise mechanisms underlying gene regulation during flowering in response to fertilization deficiency remain elusive. In this study, fertilization (F) and non-fertilization (CK) ) treatments were set up to reveal examine the effect of fertilization on the photosynthetic capacity of winter wheat during the flowering period through physiological, biochemical, and transcriptome analyses. Upon analyzing analysing their yield, leaf photosynthetic system exchange parameters during flowering, antioxidant enzyme activity, and endogenous hormone parameters, we found that the F treatment resulted in higher net photosynthetic rates during flowering periods than the CK treatment. The superoxide dismutase (SOD) (83.92%), peroxidase (POD) (150.75%), and catalase (CAT) (22.74%) activities of leaves in treated with F during the flowering period were notably elevated compared to those of CK-treated leaves. Abscisic acid (ABA) (1.86%) and gibberellin acid (GA3) (33.69%) levels were reduced, whereas Auxin auxin (IAA) (98.27%) content was increasedwas increased under F treatment compared to those the results under the CK treatment. The chlorophyll a (32.53%), chlorophyll b (56%), total chlorophyll (37.96%), and carotenoid contents (29.80%) under F treatment were also increased compared to CK., exceeded exceeding those obtained under the CK treatment. Furthermore, transcriptional differences between the F and CK conditions were analyzed, and key genes were screened and validated by using q-PCR. Transcriptome analysis identified 2281 differentially expressed genes (DEGs), with enriched pathways related to photosynthesis and light harvesting. DEGs were subjected to cluster simulation, which revealed that 53 DEGS, both up- and down-regulated, responded to the F treatment. qRT-PCR-based validation confirmed the differential expression of genes associated with carbohydrate transport and metabolism, lipid transport, and signal transduction. This study revealed distinctive transcriptional patterns and crucial gene regulation networks in wheat during flowering under fertilization, providing transcriptomic guidance for the precise regulation of wheat breeding. Full article

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

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9 pages, 6139 KiB

Open AccessEditor’s ChoiceArticle

Multimodal Evaluation and Management of Wagner Syndrome—Three Patients from an Affected Family

by Tomasz Szeligowski, Jasmina Cehajic-Kapetanovic, Shabnam Raji, Ravi Purohit, Hoda Amin, Chetan K. Patel and Kanmin Xue

Genes 2024, 15(9), 1178; https://doi.org/10.3390/genes15091178 - 8 Sep 2024

Cited by 1 | Viewed by 1425

Abstract

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old [...] Read more.

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old mother (P1), 12-year-old daughter (P2), and a 2-year-old son (P3). The phenotype included early-onset cataract (P1), optically empty vitreous with avascular membranes (P1, 2), nasal dragging of optic nerve heads associated with foveal hypoplasia (P1, 2), tractional retinoschisis on optical coherence tomography (P2), and peripheral circumferential vitreo-retinal interface abnormality resembling white-without-pressure (P3) progressing to pigmented chorio-retinal atrophy (P1, 2). P2 developed a macula-off retinal detachment, which was treated initially with encircling band + vitrectomy + gas, followed by vitrectomy + heavy silicone oil tamponade for re-detachment from new inferior breaks. Strong vitreo-retinal adhesion was noted intraoperatively, which prevented the separation of posterior hyaloid beyond the equator. Electroretinograms from P1&2 demonstrated attenuated b-waves, a-waves, and flicker responses in light- and dark-adapted conditions, suggestive of generalised retinal dysfunction. Our patients demonstrated the clinical spectrum of Wagner syndrome, highlighting nasal dragging with foveal disruption as a distinguishing feature from other inherited vitreoretinopathies. Surgical outcomes demonstrate significant challenges in managing vitreo-retinal traction and need for further research into strategies to prevent sight loss. Full article

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

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22 pages, 7304 KiB

Open AccessEditor’s ChoiceArticle

Integration of Transcriptomics and WGCNA to Characterize Trichoderma harzianum-Induced Systemic Resistance in Astragalus mongholicus for Defense against Fusarium solani

by Jingping Niu, Xiang Yan, Yuguo Bai, Wandi Li, Genglong Lu, Yuanyuan Wang, Hongjun Liu, Zhiyong Shi and Jianping Liang

Genes 2024, 15(9), 1180; https://doi.org/10.3390/genes15091180 - 8 Sep 2024

Viewed by 1753

Abstract

Beneficial fungi of the genus Trichoderma are among the most widespread biocontrol agents that induce a plant’s defense response against pathogens. Fusarium solani is one of the main pathogens that can negatively affect Astragalus mongholicus production and quality. To investigate the impact of [...] Read more.

Beneficial fungi of the genus Trichoderma are among the most widespread biocontrol agents that induce a plant’s defense response against pathogens. Fusarium solani is one of the main pathogens that can negatively affect Astragalus mongholicus production and quality. To investigate the impact of Trichoderma harzianum on Astragalus mongholicus defense responses to Fusarium solani, A. mongholicus roots under T. harzianum + F. solani (T + F) treatment and F. solani (F) treatment were sampled and subjected to transcriptomic analysis. A differential expression analysis revealed that 6361 differentially expressed genes (DEGs) responded to T. harzianum induction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the 6361 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant–pathogen interaction pathway, phenylpropanoid biosynthesis pathway, flavonoid biosynthesis pathway, isoflavonoid biosynthesis pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and plant hormone signal transduction pathway. Pathway analysis revealed that the PR1, formononetin biosynthesis, biochanin A biosynthesis, and CHIB, ROS production, and HSP90 may be upregulated by T. harzianum and play important roles in disease resistance. Our study further revealed that the H₂O₂ content was significantly increased by T. harzianum induction. Formononetin and biochanin A had the potential to suppress F. solani. Weighted gene coexpression network analysis (WGCNA) revealed one module, including 58 DEGs associated with T. harzianum induction. One core hub gene, RPS25, was found to be upregulated by T. harzianum, SA (salicylic acid) and ETH (ethephon). Overall, our data indicate that T. harzianum can induce induced systemic resistance (ISR) and systemic acquired resistance (SAR) in A. mongholicus. The results of this study lay a foundation for a further understanding of the molecular mechanism by which T. harzianum induces resistance in A. mongholicus. Full article

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

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16 pages, 1389 KiB

Open AccessEditor’s ChoiceArticle

A Genome-Wide Association Study Approach to Identify Novel Major-Effect Quantitative Trait Loci for End-Use Quality Traits in Soft Red Winter Wheat

by Madhav Subedi, John White Bagwell, Benjamin Lopez, Byung-Kee Baik, Md. Ali Babar and Mohamed Mergoum

Genes 2024, 15(9), 1177; https://doi.org/10.3390/genes15091177 - 7 Sep 2024

Cited by 2 | Viewed by 1699

Abstract

Wheat is used for making many food products due to its diverse quality profile among different wheat classes. Since laboratory analysis of these end-use quality traits is costly and time-consuming, genetic dissection of the traits is preferential. This study used a genome-wide association [...] Read more.

Wheat is used for making many food products due to its diverse quality profile among different wheat classes. Since laboratory analysis of these end-use quality traits is costly and time-consuming, genetic dissection of the traits is preferential. This study used a genome-wide association study (GWAS) of ten end-use quality traits, including kernel protein, flour protein, flour yield, softness equivalence, solvent’s retention capacity, cookie diameter, and top-grain, in soft red winter wheat (SRWW) adapted to US southeast. The GWAS included 266 SRWW genotypes that were evaluated in two locations over two years (2020–2022). A total of 27,466 single nucleotide markers were used, and a total of 80 significant marker-trait associations were identified. There were 13 major-effect quantitative trait loci (QTLs) explaining >10% phenotypic variance, out of which, 12 were considered to be novel. Five of the major-effect QTLs were found to be stably expressed across multiple datasets, and four showed associations with multiple traits. Candidate genes were identified for eight of the major-effect QTLs, including genes associated with starch biosynthesis and nutritional homeostasis in plants. These findings increase genetic comprehension of these end-use quality traits and could potentially be used for improving the quality of SRWW. Full article

(This article belongs to the Special Issue Quality Gene Mining and Breeding of Wheat)

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16 pages, 4020 KiB

Open AccessEditor’s ChoiceArticle

Epidemiological Study on the Interaction between the PNPLA3 (rs738409) and Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease

by Satoshi Sato, Chikara Iino, Takafumi Sasada, Go Soma, Keisuke Furusawa, Kenta Yoshida, Kaori Sawada, Tatsuya Mikami, Shigeyuki Nakaji, Hirotake Sakuraba and Shinsaku Fukuda

Genes 2024, 15(9), 1172; https://doi.org/10.3390/genes15091172 - 6 Sep 2024

Cited by 3 | Viewed by 1816

Abstract

Many factors are associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, genetics and gut microbiota are representative factors. Recent studies have highlighted the link between host genes and the gut microbiota. Although there have been many studies [...] Read more.

Many factors are associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, genetics and gut microbiota are representative factors. Recent studies have highlighted the link between host genes and the gut microbiota. Although there have been many studies on the separate effects of single nucleotide polymorphisms (SNPs) and gut bacteria on MASLD, few epidemiological studies have examined how SNPs and gut bacteria interact in the development and progression of MASLD. This study aimed to investigate the association between PNPLA3 rs738409, a representative MASLD-related SNP, and gut bacteria in MASLD using a cross-sectional study of the general population. The 526 participants (318 normal and 208 MASLD groups) were grouped into the PNPLA3 rs738409 SNP, CC, CG, and GG genotypes, and the differences in the gut microbiota were investigated in each group. The PNPLA3 rs738409 CC and CG genotypes were associated with decreased Blautia and Ruminococcaceae in the MASLD group. They were negatively correlated with controlled attenuation parameter levels, body mass index, serum blood glucose, and triglycerides. In contrast, there was no association between the normal and MASLD groups and the gut bacteria in the PNPLA3 rs738409, the GG genotype group. This finding implies that dietary interventions and probiotics may be more effective in preventing and treating MASLD in individuals with the PNPLA3 rs738409 CC and CG genotypes. In contrast, their efficacy may be limited in those with the GG genotype. Full article

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

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25 pages, 2311 KiB

Open AccessEditor’s ChoiceArticle

A Capacity Audit of Medical Geneticists and Genetic Counsellors in South Africa, 2024: A National Crisis

by Marianne C. M. Gomes, Byron J. Gomes, Arnold L. Christianson, Claude Bailly, Neil McKerrow and Helen L. Malherbe

Genes 2024, 15(9), 1173; https://doi.org/10.3390/genes15091173 - 6 Sep 2024

Cited by 2 | Viewed by 1692

Abstract

Community genetic services were introduced in South Africa almost seven decades ago, with medical geneticists and genetic counsellors being formally recognized for the past 30 years. Initial training platforms were established at academic centres countrywide, and posts for relevant healthcare professionals, including medical [...] Read more.

Community genetic services were introduced in South Africa almost seven decades ago, with medical geneticists and genetic counsellors being formally recognized for the past 30 years. Initial training platforms were established at academic centres countrywide, and posts for relevant healthcare professionals, including medical geneticists and genetic counsellors were created in the public sector. Despite these early advances, the number of these specialists required to address the rising burden of congenital disorders in the country remains far below required targets established by the National Department of Health. The aim of this study was to analyse the retrospective, current and projected number of medical geneticists and genetic counsellors in South Africa. The results indicate the number of practicing medical geneticists (n = 13) and genetic counsellors (n = 28) are currently at 10% and 5% of capacity targets, respectively. There is unequal distribution of these specialists between the public and private healthcare sectors, and geographical maldistribution. An alarming trend of emigration is particularly prevalent among newly qualified genetic counsellors. With the proportion of congenital disorders expected to continue to rise in coming years, together with the increasing proportion of ageing South Africans, it is imperative that health workforce planning addresses the ever-widening gap between the supply, demand and unmet need for these crucial specialists in South Africa. Full article

(This article belongs to the Special Issue Human Genetics: Diseases, Community, and Counseling)

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