Genes

3 pages, 154 KiB

Open AccessEditor’s ChoiceEditorial

Editorial for the “Genetics, Phylogeny, and Evolution of Insects” Special Issue

by Zhiteng Chen

Genes 2024, 15(8), 1000; https://doi.org/10.3390/genes15081000 - 30 Jul 2024

Viewed by 1095

The rapid advancement of sequencing technologies has revolutionized our understanding of the phylogeny and evolution of insects, enabling researchers to generate extensive molecular data with unprecedented detail [...] Full article

(This article belongs to the Special Issue Genetics, Phylogeny, and Evolution of Insects)

26 pages, 1492 KiB

Open AccessEditor’s ChoiceReview

Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges

by Umme Sabrina Haque and Toshifumi Yokota

Genes 2024, 15(8), 999; https://doi.org/10.3390/genes15080999 - 30 Jul 2024

Cited by 6 | Viewed by 5869

Abstract

Spinal muscular atrophy (SMA) is a severe genetic disorder characterized by the loss of motor neurons, leading to progressive muscle weakness, loss of mobility, and respiratory complications. In its most severe forms, SMA can result in death within the first two years of [...] Read more.

Spinal muscular atrophy (SMA) is a severe genetic disorder characterized by the loss of motor neurons, leading to progressive muscle weakness, loss of mobility, and respiratory complications. In its most severe forms, SMA can result in death within the first two years of life if untreated. The condition arises from mutations in the SMN1 (survival of motor neuron 1) gene, causing a deficiency in the survival motor neuron (SMN) protein. Humans possess a near-identical gene, SMN2, which modifies disease severity and is a primary target for therapies. Recent therapeutic advancements include antisense oligonucleotides (ASOs), small molecules targeting SMN2, and virus-mediated gene replacement therapy delivering a functional copy of SMN1. Additionally, recognizing SMA’s broader phenotype involving multiple organs has led to the development of SMN-independent therapies. Evidence now indicates that SMA affects multiple organ systems, suggesting the need for SMN-independent treatments along with SMN-targeting therapies. No single therapy can cure SMA; thus, combination therapies may be essential for comprehensive treatment. This review addresses the SMA etiology, the role of SMN, and provides an overview of the rapidly evolving therapeutic landscape, highlighting current achievements and future directions. Full article

(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)

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16 pages, 2071 KiB

Open AccessEditor’s ChoiceReview

Bioinformatics for Inosine: Tools and Approaches to Trace This Elusive RNA Modification

by Enrico Bortoletto and Umberto Rosani

Genes 2024, 15(8), 996; https://doi.org/10.3390/genes15080996 - 29 Jul 2024

Viewed by 2085

Abstract

Inosine is a nucleotide resulting from the deamination of adenosine in RNA. This chemical modification process, known as RNA editing, is typically mediated by a family of double-stranded RNA binding proteins named Adenosine Deaminase Acting on dsRNA (ADAR). While the presence of ADAR [...] Read more.

Inosine is a nucleotide resulting from the deamination of adenosine in RNA. This chemical modification process, known as RNA editing, is typically mediated by a family of double-stranded RNA binding proteins named Adenosine Deaminase Acting on dsRNA (ADAR). While the presence of ADAR orthologs has been traced throughout the evolution of metazoans, the existence and extension of RNA editing have been characterized in a more limited number of animals so far. Undoubtedly, ADAR-mediated RNA editing plays a vital role in physiology, organismal development and disease, making the understanding of the evolutionary conservation of this phenomenon pivotal to a deep characterization of relevant biological processes. However, the lack of direct high-throughput methods to reveal RNA modifications at single nucleotide resolution limited an extended investigation of RNA editing. Nowadays, these methods have been developed, and appropriate bioinformatic pipelines are required to fully exploit this data, which can complement existing approaches to detect ADAR editing. Here, we review the current literature on the “bioinformatics for inosine” subject and we discuss future research avenues in the field. Full article

(This article belongs to the Special Issue Bioinformatics of RNA Modifications and Epitranscriptome)

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20 pages, 4926 KiB

Open AccessEditor’s ChoiceArticle

Optimizing Genomic Parental Selection for Categorical and Continuous–Categorical Multi-Trait Mixtures

by Bartolo de Jesús Villar-Hernández, Paulino Pérez-Rodríguez, Paolo Vitale, Guillermo Gerard, Osval A. Montesinos-Lopez, Carolina Saint Pierre, José Crossa and Susanne Dreisigacker

Genes 2024, 15(8), 995; https://doi.org/10.3390/genes15080995 - 29 Jul 2024

Viewed by 1588

Abstract

This study presents a novel approach for the optimization of genomic parental selection in breeding programs involving categorical and continuous–categorical multi-trait mixtures (CMs and CCMMs). Utilizing the Bayesian decision theory (BDT) and latent trait models within a multivariate normal distribution framework, we address [...] Read more.

This study presents a novel approach for the optimization of genomic parental selection in breeding programs involving categorical and continuous–categorical multi-trait mixtures (CMs and CCMMs). Utilizing the Bayesian decision theory (BDT) and latent trait models within a multivariate normal distribution framework, we address the complexities of selecting new parental lines across ordinal and continuous traits for breeding. Our methodology enhances precision and flexibility in genetic selection, validated through extensive simulations. This unified approach presents significant potential for the advancement of genetic improvements in diverse breeding contexts, underscoring the importance of integrating both categorical and continuous traits in genomic selection frameworks. Full article

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

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17 pages, 4068 KiB

Open AccessEditor’s ChoiceArticle

Genomic and Pathogenic Characterization of Akanthomyces muscarius Isolated from Living Mite Infesting Hazelnut Big Buds

by Silvia Turco, Mounira Inas Drais, Luca Rossini, Nicolò Di Sora, Federico Brugneti, Stefano Speranza, Mario Contarini and Angelo Mazzaglia

Genes 2024, 15(8), 993; https://doi.org/10.3390/genes15080993 - 28 Jul 2024

Cited by 3 | Viewed by 1399

Abstract

The capability of entomopathogenic fungi to live as plant endophytes is well established. However, their presence in undiscovered environmental niches represents the beginning of a new challenging research journey. Recently, Akanthomyces muscarius (Ascomycota, Cordycipitaceae) (Petch) Spatafora, Kepler & B. Shrestha was isolated from [...] Read more.

The capability of entomopathogenic fungi to live as plant endophytes is well established. However, their presence in undiscovered environmental niches represents the beginning of a new challenging research journey. Recently, Akanthomyces muscarius (Ascomycota, Cordycipitaceae) (Petch) Spatafora, Kepler & B. Shrestha was isolated from hazelnut buds infested by the big bud mite pest Phytoptus avellanae Nalepa, which makes the buds swollen, reddish, and unable to further develop. Gall formation is known to be regulated by a consortium of microbes and mites, and to better understand the possible role of A. muscarius within the infested gall, its whole genome sequence was obtained using a hybrid approach of Illumina and Nanopore reads. The functional and comparative genomics analysis provided within this study may help answer questions related to the ecology and the entomopathogenicity of this fungus. Full article

(This article belongs to the Special Issue Advances in Genomics of Pathogenic Fungi)

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14 pages, 4172 KiB

Open AccessEditor’s ChoiceArticle

Network of Interactions between the Mut Domains of the E2 Protein of Atypical Porcine Pestivirus and Host Proteins

by Yuai Yang, Guangfei Jiang, Weiqi He, Xin Tian, Huanli Zheng, Bin Xiang and Yongke Sun

Genes 2024, 15(8), 991; https://doi.org/10.3390/genes15080991 - 27 Jul 2024

Viewed by 1170

Abstract

Atypical porcine pestivirus (APPV) can cause congenital tremor type A-II in neonatal piglets, posing a significant threat to swine herd health globally. Our previous study demonstrated that the Mut domains, comprising 112 amino acids at the N-terminus, are the primary functional regions of [...] Read more.

Atypical porcine pestivirus (APPV) can cause congenital tremor type A-II in neonatal piglets, posing a significant threat to swine herd health globally. Our previous study demonstrated that the Mut domains, comprising 112 amino acids at the N-terminus, are the primary functional regions of the E2 protein of APPV. This study identified 14 host cellular proteins that exhibit potential interactions with the Mut domains of the E2 protein using yeast two-hybrid screening. Using bioinformatics analysis, we discovered that the Mut domains of the E2 protein might exert regulatory effects on apoptosis by modulating energy metabolism within the mitochondria. We also conducted co-immunoprecipitation, glutathione S-transferase pull-down, and immunofluorescence assays to confirm the interaction between the Mut domains of the E2 protein and cathepsin H and signal sequence receptor subunit 4 (SSR4). Ultimately, SSR4 enhanced APPV replication in vitro. In summary, our study successfully elucidated the interactions between the Mut domains of the E2 protein and host cell protein, predicted the potential pathways implicated in these interactions, and demonstrated SSR4 involvement in APPV infection. These significant findings contribute valuable knowledge toward a deeper understanding of APPV pathogenesis and the role of the Mut domains of the E2 protein in this intricate process. Full article

(This article belongs to the Special Issue Animal Viruses Molecular Biology)

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12 pages, 1839 KiB

Open AccessEditor’s ChoiceArticle

Dynamic Changes in Histone Modifications Are Associated with Differential Chromatin Interactions

by Yumin Nie and Mengjie Wang

Genes 2024, 15(8), 988; https://doi.org/10.3390/genes15080988 - 26 Jul 2024

Viewed by 1521

Abstract

Eukaryotic genomes are organized into chromatin domains through long-range chromatin interactions which are mediated by the binding of architectural proteins, such as CTCF and cohesin, and histone modifications. Based on the published Hi-C and ChIP-seq datasets in human monocyte-derived macrophages, we identified 206 [...] Read more.

Eukaryotic genomes are organized into chromatin domains through long-range chromatin interactions which are mediated by the binding of architectural proteins, such as CTCF and cohesin, and histone modifications. Based on the published Hi-C and ChIP-seq datasets in human monocyte-derived macrophages, we identified 206 and 127 differential chromatin interactions (DCIs) that were not located within transcription readthrough regions in influenza A virus- and interferon β-treated cells, respectively, and found that the binding positions of CTCF and RAD21 within more than half of the DCI sites did not change. However, five histone modifications, H3K4me3, H3K27ac, H3K36me3, H3K9me3, and H3K27me3, showed significantly more dramatic changes than CTCF and RAD21 within the DCI sites. For H3K4me3, H3K27ac, H3K36me3, and H3K27me3, significantly more dramatic changes were observed outside than within the DCI sites. We further applied a motif scanning approach to discover proteins that might correlate with changes in histone modifications and chromatin interactions and found that PRDM9, ZNF384, and STAT2 frequently bound to DNA sequences corresponding to 1 kb genomic intervals with gains or losses of a histone modification within the DCI sites. This study explores the dynamic regulation of chromatin interactions and extends the current knowledge of the relationship between histone modifications and chromatin interactions. Full article

(This article belongs to the Section Epigenomics)

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13 pages, 1494 KiB

Open AccessEditor’s ChoiceArticle

The High-Molecular-Weight Glutenin Subunits of the T. timopheevii (A^uA^uGG) Group

by Benedetta Margiotta, Giuseppe Colaprico, Marcella Urbano, Daniela Panichi, Francesco Sestili and Domenico Lafiandra

Genes 2024, 15(8), 986; https://doi.org/10.3390/genes15080986 - 26 Jul 2024

Viewed by 1016

Abstract

Polyploid wheats include a group of tetraploids known as Timopheevii (A^uA^uGG), which are represented by two subspecies: Triticum timopheevii ssp. timopheevii (cultivated) and Triticum timopheevii ssp. araraticum (wild). The combined use of electrophoretic (SDS-PAGE) and chromatographic (RP-HPLC) techniques carried [...] Read more.

Polyploid wheats include a group of tetraploids known as Timopheevii (A^uA^uGG), which are represented by two subspecies: Triticum timopheevii ssp. timopheevii (cultivated) and Triticum timopheevii ssp. araraticum (wild). The combined use of electrophoretic (SDS-PAGE) and chromatographic (RP-HPLC) techniques carried out on high-molecular-weight glutenin subunits (HMW-GSs) permitted the association of different x- and y-type subunits to the A and G genomes and the assessment of allelic variation present at corresponding loci. The results also revealed that in both subspecies, accessions are present that possess expressed y-type subunits at the Glu-A1 locus. Genes corresponding to these subunits were amplified and amplicons corresponding to x- and y-type genes associated with the A genome were detected in all accessions, including those without expressed x- and y-type subunits. The comparison with genes of polyploid wheats confirmed the structural characteristics of typical y-type genes, with the presence of seven cysteine residues and with hexapeptide and nonapeptide repeat motifs. The identification of wild and cultivated T. timopheevii with both x- and y-type glutenin subunits at the Glu-A1 and Glu-G1 loci represents a useful source for the modification of the allelic composition of HMW-GSs in cultivated wheats with the ultimate objective of improving technological properties. Full article

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

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17 pages, 2947 KiB

Open AccessEditor’s ChoiceArticle

New Insights into the Mechanism by Which the Pituitary Gland Copes with Hypoxia Stress Based on a Transcriptomic Analysis of Megalobrama amblycephala

by Ruilin Xie, Huandi Guo, Yuanyuan Luo, Wen Huang, Zhuohao Ruan and Wensheng Liu

Genes 2024, 15(8), 987; https://doi.org/10.3390/genes15080987 - 26 Jul 2024

Viewed by 1247

Abstract

Hypoxia is a common environmental stressor in aquatic ecosystems, and during the cultivation process, Megalobrama amblycephala is prone to death because it is hypoxia-intolerant, which brings huge economic losses to farmers. The pituitary gland is a crucial endocrine gland in fish, and it [...] Read more.

Hypoxia is a common environmental stressor in aquatic ecosystems, and during the cultivation process, Megalobrama amblycephala is prone to death because it is hypoxia-intolerant, which brings huge economic losses to farmers. The pituitary gland is a crucial endocrine gland in fish, and it is mainly involved in the secretion, storage, and regulation of hormones. In the present study, we compared the transcriptional responses to serious hypoxia in the pituitary gland among hypoxia-sensitive (HS) and hypoxia-tolerant (HT) M. amblycephala and a control group that received a normal oxygen supply (C0). The fish were categorized according to the time required to lose balance during a hypoxia treatment. A total of 129,251,170 raw reads were obtained. After raw sequence filtering, 43,461,745, 42,609,567, and 42,730,282 clean reads were obtained for the HS, HT, and C0 groups, respectively. A transcriptomic comparison revealed 1234 genes that were differentially expressed in C0 vs. HS, while 1646 differentially expressed genes were obtained for C0 vs. HT. In addition, the results for HS vs. HT showed that 367 upregulated and 41 downregulated differentially expressed genes were obtained for a total of 408 differentially expressed genes. A KEGG analysis of C0 vs. HS, C0 vs. HT, and HS vs. HT identified 315, 322, and 219 enriched pathways, respectively. Similar hypoxia-induced transcription patterns suggested that the downregulated DEGs and enriched pathways were related to pathways of neurodegeneration in multiple diseases, pathways in cancer, thermogenesis, microRNAs in cancer, diabetic cardiomyopathy, and renin secretion. However, in the upregulated DEGs, the PI3K-Akt signaling pathway (C0 vs. HS), microRNAs in cancer (C0 vs. HT), and HIF-1 signaling pathway (HS vs. HT) were significantly enriched. There is a lack of clarity regarding the role of the pituitary gland in hypoxic stress. These results not only provide new insights into the mechanism by which pituitary tissue copes with hypoxia stress in M. amblycephala but also offer a basis for breeding M. amblycephala with hypoxia-resistant traits. Full article

(This article belongs to the Collection Feature Papers in ‘Animal Genetics and Genomics’)

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13 pages, 3505 KiB

Open AccessEditor’s ChoiceArticle

Integrating Multi-Omics Data to Identify Key Functional Variants Affecting Feed Efficiency in Large White Boars

by Yue Xiang, Jiahui Sun, Guojian Ma, Xueting Dai, Yuan Meng, Chong Fu, Yan Zhang, Qiulin Zhao, Jingjin Li, Saixian Zhang, Zhuqing Zheng, Xinyun Li, Liangliang Fu, Kui Li and Xiaolong Qi

Genes 2024, 15(8), 980; https://doi.org/10.3390/genes15080980 - 25 Jul 2024

Cited by 4 | Viewed by 1810

Abstract

Abstract: Optimizing feed efficiency through the feed conversion ratio (FCR) is paramount for economic viability and sustainability. In this study, we integrated RNA-seq, ATAC-seq, and genome-wide association study (GWAS) data to investigate key functional variants associated with feed efficiency in pigs. Identification of [...] Read more.

Abstract: Optimizing feed efficiency through the feed conversion ratio (FCR) is paramount for economic viability and sustainability. In this study, we integrated RNA-seq, ATAC-seq, and genome-wide association study (GWAS) data to investigate key functional variants associated with feed efficiency in pigs. Identification of differentially expressed genes in the duodenal and muscle tissues of low- and high-FCR pigs revealed that pathways related to digestion of dietary carbohydrate are responsible for differences in feed efficiency between individuals. Differential open chromatin regions identified by ATAC-seq were linked to genes involved in glycolytic and fatty acid processes. GWAS identified 211 significant single-nucleotide polymorphisms associated with feed efficiency traits, with candidate genes PPP1R14C, TH, and CTSD. Integration of duodenal ATAC-seq data and GWAS data identified six key functional variants, particularly in the 1500985–1509676 region on chromosome 2. In those regions, CTSD was found to be highly expressed in the duodenal tissues of pigs with a high feed conversion ratio, suggesting its role as a potential target gene. Overall, the integration of multi-omics data provided insights into the genetic basis of feed efficiency, offering valuable information for breeding more efficient pig breeds. Full article

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

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14 pages, 4279 KiB

Open AccessEditor’s ChoiceArticle

A Comprehensive Systematic Review Coupled with an Interacting Network Analysis Identified Candidate Genes and Biological Pathways Related to Bovine Temperament

by Gilberto Ruiz-De-La-Cruz, Thomas H. Welsh, Jr., Ronald D. Randel and Ana María Sifuentes-Rincón

Genes 2024, 15(8), 981; https://doi.org/10.3390/genes15080981 - 25 Jul 2024

Viewed by 1448

Abstract

Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review [...] Read more.

Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to analyze candidate genes related to bovine temperament, using bovine as the population, SNPs and genes as the exposure, and temperament test as the outcome, as principal search terms for population, exposure, and outcome (PEO) categories to define the scope of the search. The search results allowed the selection of 36 articles after removing duplicates and filtering by relevance. One hundred-two candidate genes associated with temperament traits were identified. The genes were further analyzed to construct an interaction network using the STRING database, resulting in 113 nodes and 346 interactions and the identification of 31 new candidate genes for temperament. Notably, the main genes identified were SST and members of the Kelch family. The candidate genes displayed interactions with pathways associated with different functions such as AMPA receptors, hormones, neuronal maintenance, protein signaling, neuronal regulation, serotonin synthesis, splicing, and ubiquitination activities. These new findings demonstrate the complexity of interconnected biological processes that regulate behavior and stress response in mammals. This insight now enables our targeted analysis of these newly identified temperament candidate genes in bovines. Full article

(This article belongs to the Special Issue Advances in Cattle, Sheep, and Goats Molecular Genetics and Breeding)

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21 pages, 6349 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Characterization of Maize Long-Chain Acyl-CoA Synthetases and Their Expression Profiles in Different Tissues and in Response to Multiple Abiotic Stresses

by Zhenwei Yan, Jing Hou, Bingying Leng, Guoqi Yao, Changle Ma, Yue Sun, Qiantong Liu, Fajun Zhang, Chunhua Mu and Xia Liu

Genes 2024, 15(8), 983; https://doi.org/10.3390/genes15080983 - 25 Jul 2024

Cited by 2 | Viewed by 1236

Abstract

Long-chain acyl-CoA synthetases (LACSs) are essential enzymes that activate free fatty acids to fatty acyl-CoA thioesters, playing key roles in fatty acid (FA) catabolism, lipid synthesis and storage, epidermal wax synthesis, and stress tolerance. Despite their importance, comprehensive information about LACS genes in [...] Read more.

Long-chain acyl-CoA synthetases (LACSs) are essential enzymes that activate free fatty acids to fatty acyl-CoA thioesters, playing key roles in fatty acid (FA) catabolism, lipid synthesis and storage, epidermal wax synthesis, and stress tolerance. Despite their importance, comprehensive information about LACS genes in maize, a primary food crop, remains scarce. In the present work, eleven maize LACS genes were identified and mapped across five chromosomes. Three pairs of segmentally duplicated genes were detected in the maize LACS gene family, which underwent significant purifying selection (Ka/Ks < 1). Subsequently, phylogenetic analysis indicated that ZmLACS genes were divided into four subclasses, as supported by highly conserved motifs and gene structures. On the basis of the PlantCARE database, analysis of the ZmLACS promoter regions revealed various cis-regulatory elements related to tissue-specific expression, hormonal regulation, and abiotic stress response. RT-qPCR analysis showed that ZmLACS genes exhibit tissue-specific expression patterns and respond to diverse abiotic stresses including drought and salt, as well as phytohormone abscisic acid. Furthermore, using the STRING database, several proteins involved in fatty acid and complex lipid synthesis were identified to be the potential interaction partners of ZmLACS proteins, which was also confirmed by the yeast two-hybrid (Y2H) assay, enhancing our understanding of wax biosynthesis and regulatory mechanisms in response to abiotic stresses in maize. These findings provide a comprehensive understanding of ZmLACS genes and offer a theoretical foundation for future research on the biological functions of LACS genes in maize environmental adaptability. Full article

(This article belongs to the Special Issue Maize Molecular Genetics and Functional Genomics in 2024)

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17 pages, 904 KiB

Open AccessEditor’s ChoiceReview

Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease

by Valerio Caruso, Accursio Raia and Luciana Rigoli

Genes 2024, 15(8), 984; https://doi.org/10.3390/genes15080984 - 25 Jul 2024

Cited by 2 | Viewed by 1598

Abstract

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of [...] Read more.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease’s progression and improve symptomatology. Moreover, genetic counseling should be provided to the patient’s relatives to extend multidisciplinary care to their first-degree family members. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric symptoms commonly associated with WS1. A thorough understanding of WS1’s neurophysiopathology is critical for achieving the goal of improving patients’ quality of life and life expectancy. Full article

(This article belongs to the Special Issue Advances in Neurogenetics)

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9 pages, 2639 KiB

Open AccessEditor’s ChoiceArticle

In Silico Analysis of the Missense Variants of Uncertain Significance of CTNNB1 Gene Reported in GnomAD Database

by Arturo Caballero-Avendaño, Melva Gutiérrez-Angulo, María de la Luz Ayala-Madrigal, José Miguel Moreno-Ortiz, Anahí González-Mercado and Jorge Peregrina-Sandoval

Genes 2024, 15(8), 972; https://doi.org/10.3390/genes15080972 - 24 Jul 2024

Viewed by 1428

Abstract

CTNNB1 pathogenic variants are related to the improper functioning of the WNT/β-catenin pathway, promoting the development of different types of cancer of somatic origin. Bioinformatics analyses of genetic variation are a great tool to understand the possible consequences of these variants on protein [...] Read more.

CTNNB1 pathogenic variants are related to the improper functioning of the WNT/β-catenin pathway, promoting the development of different types of cancer of somatic origin. Bioinformatics analyses of genetic variation are a great tool to understand the possible consequences of these variants on protein structure and function and their probable implication in pathologies. The objective of this study is to describe the impact of the missense variants of uncertain significance (VUS) of the CTNNB1 gene on structure and function of the β-catenin protein. The CTNNB1 variants were obtained from the GnomAD v2.1.1 database; subsequently, a bioinformatic analysis was performed using the VarSome, UCSC Genome Browser, UniProt, the Kinase Library database, and DynaMut2 platforms to evaluate clinical significance, gene conservation, consensus sites for post-translational modifications, and the dynamics and stability of proteins. The GnomAD v2.1.1 database included 826 variants of the CTNNB1 gene, of which 385 were in exons and exon/intron boundaries. Among these variants, 214 were identified as missense, of which 146 were classified as VUS. Notably, 12 variants were in proximity to consensus sites for post-translational modifications (PTMs). The in silico analysis showed a slight tendency towards probably pathogenic for c.59C>T (p.Ala20Val) and c.983T>C (p.Met328Thr) missense VUS. These findings provide possible functional implications of these variants in some types of cancer. Full article

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

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11 pages, 966 KiB

Open AccessEditor’s ChoiceArticle

Medical Genetics in Brazil in the 21st Century: A Thriving Specialty and Its Incorporation in Public Health Policies

by Dafne Dain Gandelman Horovitz, Têmis Maria Félix and Victor Evangelista de Faria Ferraz

Genes 2024, 15(8), 973; https://doi.org/10.3390/genes15080973 - 24 Jul 2024

Cited by 4 | Viewed by 2323

Abstract

Brazil is a continent-size country with 203 million inhabitants, classified as a developing upper-middle-income country, although inequities remain significant. Most of the population is assisted by the public Unified Health System (SUS), along with a thriving private health sector. Congenital malformations are the [...] Read more.

Brazil is a continent-size country with 203 million inhabitants, classified as a developing upper-middle-income country, although inequities remain significant. Most of the population is assisted by the public Unified Health System (SUS), along with a thriving private health sector. Congenital malformations are the second leading cause of infant mortality and chronic/genetic disorders and a significant burden in hospital admissions. The past two decades have been crucial for formalizing medical genetics as a recognized medical specialty in the SUS, as well as for implementing a new health policy by the Ministry of Health for comprehensive care for rare diseases. These public health policies had the broad support of the Brazilian Society of Medical Genetics and Genomics and patient organizations. Most comprehensive genetic services are concentrated in large urban centers in the South and Southeast regions of Brazil; with this new policy, new services throughout the country are progressively being integrated. The number of medical geneticists increased by 103% in a decade. Details on the policy and an overview of the availability of services, testing, human resources, newborn screening, research projects, patient organizations, and relevant issues regarding medical genetics in this vast and diverse country are presented. Full article

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

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19 pages, 4445 KiB

Open AccessEditor’s ChoiceArticle

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease

by Candice G. T. Tahimic, Sonette Steczina, Aimy Sebastian, Nicholas R. Hum, Metadel Abegaz, Masahiro Terada, Maria Cimini, David A. Goukassian, Ann-Sofie Schreurs, Tana M. Hoban-Higgins, Charles A. Fuller, Gabriela G. Loots, Ruth K. Globus and Yasaman Shirazi-Fard

Genes 2024, 15(8), 975; https://doi.org/10.3390/genes15080975 - 24 Jul 2024

Cited by 1 | Viewed by 2010

Abstract

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of [...] Read more.

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long–Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space. Full article

(This article belongs to the Topic Animal Models of Human Disease 2.0)

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8 pages, 460 KiB

Open AccessEditor’s ChoiceReview

Auditory and Language Abilities in Children with Takenouchi–Kosaki Syndrome: A Systematic Review

by Valeria Caragli, Elisabetta Genovese, Sara Parretta, Michele Pellegrino and Andrea Ciorba

Genes 2024, 15(8), 974; https://doi.org/10.3390/genes15080974 - 24 Jul 2024

Cited by 2 | Viewed by 1098

Abstract

Takenouchi–Kosaki syndrome (TKS) is a rare congenital disease caused by a de novo mutation in the Cell Division Cycle 42 (CDC42) gene. Patients with TKS present facial and body dysmorphisms, hematologic and immune dysregulation, intellectual disability, neurodevelopmental delay and hearing loss. The aim [...] Read more.

Takenouchi–Kosaki syndrome (TKS) is a rare congenital disease caused by a de novo mutation in the Cell Division Cycle 42 (CDC42) gene. Patients with TKS present facial and body dysmorphisms, hematologic and immune dysregulation, intellectual disability, neurodevelopmental delay and hearing loss. The aim of this study is to review the literature, focusing on hearing and language abilities in children with TKS. A systematic search on PubMed, Scopus and Web of Science databases was performed, including twelve studies for a total of 13 patients. Hearing loss (HL) occurs in a great percentage of patients (84.6%); nonetheless, auditory threshold, severity of HL and language abilities were reported in a few cases. In two studies, auditory rehabilitation strategies were described. Although several studies have investigated the hematological features of TKS, still only a few authors have focused on the audiological and language abilities of these children. Given the fact that HL has a significant impact on behaviors, communications skills, and quality of life, it is important to adequately assess and rehabilitate patients early with this syndrome. Further studies are needed to improve the knowledge about this topic and improve the quality of life of patients with TKS. Full article

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

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16 pages, 2542 KiB

Open AccessEditor’s ChoiceCase Report

Identification of KSR2 Variants in Pediatric Patients with Severe Early-Onset Obesity from Qatar

by Lubna I. Abu-Rub, Tara Al-Barazenji, Sumaya Abiib, Ayat S Hammad, Alaa Abbas, Khalid Hussain and Mashael Al-Shafai

Genes 2024, 15(8), 966; https://doi.org/10.3390/genes15080966 - 23 Jul 2024

Cited by 1 | Viewed by 1452

Abstract

The kinase suppressor of Ras 2 (KSR2) gene is associated with monogenic obesity, and loss-of-function variants in KSR2 have been identified in individuals with severe early-onset obesity. This study investigated KSR2 variants in 9 pediatric patients with severe early-onset obesity in [...] Read more.

The kinase suppressor of Ras 2 (KSR2) gene is associated with monogenic obesity, and loss-of-function variants in KSR2 have been identified in individuals with severe early-onset obesity. This study investigated KSR2 variants in 9 pediatric patients with severe early-onset obesity in Qatar using whole genome sequencing among a cohort of 240 individuals. We focused on KSR2 variants with a minor allele frequency (MAF) below 1% and a Combined Annotation Dependent Depletion (CADD) score above 13 to identify potential causative variants. Our analysis identified four KSR2 variants: one intronic (c.1765-8G>A) and three missense variants (c.1057G>A, c.1673G>A, and c.923T>C) in nine patients. The intronic variant c.1765-8G>A was the most frequent (seen in six individuals) and had a CADD score of 21.10, suggesting possible pathogenicity. This variant showed a significantly higher allele frequency in the Qatari population compared to the Genome Aggregation Database (gnomAD), indicating a possible founder effect. Molecular modeling of the missense variants revealed structural changes in the protein structure. The study concludes that these four KSR2 variants are associated with monogenic obesity, with an autosomal dominant inheritance pattern. The c.1765-8G>A variant’s prevalence in Qatar underscores its importance in genetic screening for severe obesity. This research advances the understanding of genetic factors in severe early-onset obesity and may inform better management strategies. Full article

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

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7 pages, 203 KiB

Open AccessEditor’s ChoiceOpinion

Population Screening for Hereditary Haemochromatosis—Should It Be Carried Out, and If So, How?

by Martin B. Delatycki and Katrina J. Allen

Genes 2024, 15(8), 967; https://doi.org/10.3390/genes15080967 - 23 Jul 2024

Cited by 1 | Viewed by 2161

Abstract

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted [...] Read more.

The Human Genome Project, completed in 2003, heralded a new era in precision medicine. Somewhat tempering the excitement of the elucidation of the human genome is the emerging recognition that there are fewer single gene disorders than first anticipated, with most diseases predicted to be polygenic or at least gene-environment modified. Hereditary haemochromatosis (HH) is an inherited iron overload disorder, for which the vast majority of affected individuals (>90%) have homozygosity for a single pathogenic variant in the HFE gene, resulting in p.Cys282Tyr. Further, there is significant benefit to an individual in identifying the genetic risk of HH, since the condition evolves over decades, and the opportunity to intervene and prevent disease is both simple and highly effective through regular venesection. Add to that the immediate benefit to society of an increased pool of ready blood donors (blood obtained from HH venesections can generally be used for donation), and the case for population screening to identify those genetically at risk for HH becomes more cogent. Concerns about genetic discrimination, creating a cohort of “worried well”, antipathy to acting on medical advice to undertake preventive venesection or simply not understanding the genetic risk of the condition adequately have all been allayed by a number of investigations. So why then has HH population genetic screening not been routinely implemented anywhere in the world? The answer is complex, but in this article we explore the pros and cons of screening for HH and the different views regarding whether it should be phenotypic (screening for iron overload by serum ferritin and/or transferrin saturation) or genotypic (testing for HFE p.Cys282Tyr). We argue that now is the time to give this poster child for population genetic screening the due consideration required to benefit the millions of individuals at risk of HFE-related iron overload. Full article

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

14 pages, 5773 KiB

Open AccessEditor’s ChoiceArticle

Integrated Metagenomic and Metabolomics Profiling Reveals Key Gut Microbiota and Metabolites Associated with Weaning Stress in Piglets

by Xianrui Zheng, Liming Xu, Qingqing Tang, Kunpeng Shi, Ziyang Wang, Lisha Shi, Yueyun Ding, Zongjun Yin and Xiaodong Zhang

Genes 2024, 15(8), 970; https://doi.org/10.3390/genes15080970 - 23 Jul 2024

Cited by 2 | Viewed by 1922

Abstract

(1) Background: Weaning is a challenging and stressful event in the pig’s life, which disrupts physiological balance and induces oxidative stress. Microbiota play a significant role during the weaning process in piglets. Therefore, this study aimed to investigate key gut microbiota and metabolites [...] Read more.

(1) Background: Weaning is a challenging and stressful event in the pig’s life, which disrupts physiological balance and induces oxidative stress. Microbiota play a significant role during the weaning process in piglets. Therefore, this study aimed to investigate key gut microbiota and metabolites associated with weaning stress in piglets. (2) Methods: A total of ten newborn piglet littermates were randomly assigned to two groups: S (suckling normally) and W (weaned at 21 d; all euthanized at 23 d). Specimens of the cecum were dehydrated with ethanol, cleared with xylene, embedded in paraffin, and cut into 4 mm thick serial sections. After deparaffinization, the sections were stained with hematoxylin and eosin (H&E) for morphometric analysis. Cecal metagenomic and liver LC-MS-based metabolomics were employed in this study. Statistical comparisons were performed by a two-tailed Student’s t-test, and p < 0.05 indicated statistical significance. (3) Results: The results showed that weaning led to intestinal morphological damage in piglets. The intestinal villi of suckling piglets were intact, closely arranged in an orderly manner, and finger-shaped, with clear contours of columnar epithelial cells. In contrast, the intestines of weaned piglets showed villous atrophy and shedding, as well as mucosal bleeding. Metagenomics and metabolomics analyses showed significant differences in composition and function between suckling and weaned piglets. The W piglets showed a decrease and increase in the relative abundance of Bacteroidetes and Proteobacteria (p < 0.05), respectively. The core cecal flora in W piglets were Campylobacter and Clostridium, while those in S piglets were Prevotella and Lactobacillus. At the phylum level, the relative abundance of Bacteroidetes significantly decreased (p < 0.05) in weaned piglets, while Proteobacteria significantly increased (p < 0.05). Significant inter-group differences were observed in pathways and glycoside hydrolases in databases, such as the KEGG and CAZymes, including fructose and mannose metabolism, salmonella infection, antifolate resistance, GH135, GH16, GH32, and GH84. We identified 757 differential metabolites between the groups through metabolomic analyses—350 upregulated and 407 downregulated (screened in positive ion mode). In negative ion mode, 541 differential metabolites were identified, with 270 upregulated and 271 downregulated. Major differential metabolites included glycerophospholipids, histidine, nitrogen metabolism, glycine, serine, threonine, β-alanine, and primary bile acid biosynthesis. The significant differences in glycine, serine, and threonine metabolites may be potentially related to dysbiosis caused by weaning stress. Taken together, the identification of microbiome and metabolome signatures of suckling and weaned piglets has paved the way for developing health-promoting nutritional strategies, focusing on enhancing bacterial metabolite production in early life stages. Full article

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

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15 pages, 4465 KiB

Open AccessEditor’s ChoiceArticle

A Global Identification of Protein Disulfide Isomerases from ‘duli’ Pear (Pyrus betulaefolia) and Their Expression Profiles under Salt Stress

by Hao Zhang, Yuyue Zhang, Kexin Cui, Chang Liu, Mengya Chen, Yufan Fu, Zhenjie Li, Hui Ma, Haixia Zhang, Baoxiu Qi and Jianfeng Xu

Genes 2024, 15(8), 968; https://doi.org/10.3390/genes15080968 - 23 Jul 2024

Viewed by 933

Abstract

Protein disulfide isomerases (PDIs) and PDI-like proteins catalyze the oxidation and reduction in protein disulfide bonds, inhibit aggregation of misfolded proteins, and participate in isomerization and abiotic stress responses. The wild type ‘duli’ pear (Pyrus betulaefolia) is an important rootstock commonly [...] Read more.

Protein disulfide isomerases (PDIs) and PDI-like proteins catalyze the oxidation and reduction in protein disulfide bonds, inhibit aggregation of misfolded proteins, and participate in isomerization and abiotic stress responses. The wild type ‘duli’ pear (Pyrus betulaefolia) is an important rootstock commonly used for commercial pear tree grafting in northern China. In this study, we identified 24 PDI genes, named PbPDIs, from the genome of ‘duli’ pear. With 12 homologous gene pairs, these 24 PbPDIs distribute on 12 of its 17 chromosomes. Phylogenetic analysis placed the 24 PbPDIs into four clades and eleven groups. Collinearity analysis of the PDIs between P. betulaefolia, Arabidopsis thaliana, and Oryza sativa revealed that the PbPDIs of ‘duli’ pear show a strong collinear relationship with those from Arabidopsis, a dicot; but a weak collinear relationship with those from rice, a monocot. Quantitative RT-PCR analysis showed that most of the PbPDIs were upregulated by salt stress. Identification and expression analysis of ‘duli’ pear PbPDIs under salt stress conditions could provide useful information for further research in order to generate salt-resistant rootstock for pear grafting in the future. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Molecular Genetics and Genomics)

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17 pages, 3250 KiB

Open AccessEditor’s ChoiceArticle

A Penalized Regression Method for Genomic Prediction Reduces Mismatch between Training and Testing Sets

by Osval A. Montesinos-López, Cristian Daniel Pulido-Carrillo, Abelardo Montesinos-López, Jesús Antonio Larios Trejo, José Cricelio Montesinos-López, Afolabi Agbona and José Crossa

Genes 2024, 15(8), 969; https://doi.org/10.3390/genes15080969 - 23 Jul 2024

Viewed by 1086

Abstract

Genomic selection (GS) is changing plant breeding by significantly reducing the resources needed for phenotyping. However, its accuracy can be compromised by mismatches between training and testing sets, which impact efficiency when the predictive model does not adequately reflect the genetic and environmental [...] Read more.

Genomic selection (GS) is changing plant breeding by significantly reducing the resources needed for phenotyping. However, its accuracy can be compromised by mismatches between training and testing sets, which impact efficiency when the predictive model does not adequately reflect the genetic and environmental conditions of the target population. To address this challenge, this study introduces a straightforward method using binary-Lasso regression to estimate β coefficients. In this approach, the response variable assigns 1 to testing set inputs and 0 to training set inputs. Subsequently, Lasso, Ridge, and Elastic Net regression models use the inverse of these β coefficients (in absolute values) as weights during training (WLasso, WRidge, and WElastic Net). This weighting method gives less importance to features that discriminate more between training and testing sets. The effectiveness of this method is evaluated across six datasets, demonstrating consistent improvements in terms of the normalized root mean square error. Importantly, the model’s implementation is facilitated using the glmnet library, which supports straightforward integration for weighting β coefficients. Full article

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

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11 pages, 5149 KiB

Open AccessEditor’s ChoiceArticle

The Role of IRF9 Upregulation in Modulating Sensitivity to Olaparib and Platinum-Based Chemotherapies in Breast Cancer

by SeokGyeong Choi, Han-Gyu Bae, Dong-Gyu Jo and Woo-Young Kim

Genes 2024, 15(7), 959; https://doi.org/10.3390/genes15070959 - 22 Jul 2024

Viewed by 2077

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors [...] Read more.

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors in breast cancer cell lines. Our findings indicated that the interferon (IFN) signaling gene IRF9 was critically involved in modulating sensitivity to these inhibitors. We revealed that the loss of IRF9 leads to increased resistance to the PARP inhibitor in MDA-MB-468 cells, and a similar desensitization was observed in another breast cancer cell line, MDA-MB-231. Further analysis indicated that while the basal expression of IRF9 did not correlate with the response to the PARP inhibitor olaparib, its transcriptional induction was significantly associated with increased sensitivity to the DNA-damaging agent cisplatin in the NCI-60 cell line panel. This finding suggests a mechanistic link between IRF9 induction and cellular responses to DNA damage. Additionally, data from the METABRIC patient tissue study revealed a complex network of IFN-responsive gene expressions postchemotherapy, with seven upregulated genes, including IRF9, and three downregulated genes. These findings underscore the intricate role of IFN signaling in the cellular response to chemotherapy. Collectively, our CRISPR screening data and subsequent bioinformatic analyses suggest that IRF9 is a novel biomarker for sensitivity to DNA-damaging agents, such as olaparib and platinum-based chemotherapeutic agents. Our findings for IRF9 not only enhance our understanding of the genetic basis of drug sensitivity, but also elucidate the role of IRF9 as a critical effector within IFN signaling pathways, potentially influencing the association between the host immune system and chemotherapeutic efficacy. Full article

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

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13 pages, 11009 KiB

Open AccessEditor’s ChoiceArticle

Molecular Cloning, Characterization, and Function of Insulin-Related Peptide 1 (IRP1) in the Haliotis discus hanna

by Jianfang Huang, Mingcan Zhou, Jianming Chen and Caihuan Ke

Genes 2024, 15(7), 960; https://doi.org/10.3390/genes15070960 - 22 Jul 2024

Viewed by 1211

Abstract

Abalone is a popular mollusk in the marine aquaculture industry of China. However, existing challenges, like slow growth, individual miniaturization, and the absence of abundant abalone, have emerged as significant obstacles impeding its long-term progress in aquaculture. Studies have demonstrated that insulin-related peptide [...] Read more.

Abalone is a popular mollusk in the marine aquaculture industry of China. However, existing challenges, like slow growth, individual miniaturization, and the absence of abundant abalone, have emerged as significant obstacles impeding its long-term progress in aquaculture. Studies have demonstrated that insulin-related peptide (IRP) is a crucial factor in the growth of marine organisms. However, limited studies have been conducted on IRP in abalone. This study indicated that the hdh-MIRP1 open reading frame (ORF) was composed of 456 base pairs, which encoded 151 amino acids. Based on the gene expression and immunofluorescence analyses, the cerebral ganglion of Haliotis discus hannai (H. discus hannai) was the primary site of hdh-MIRP1 mRNA expression. Moreover, hdh-MIRP1 expression was observed to be higher in the larger group than in the smaller group abalones. Only single nucleotide polymorphism (SNP) was related to their growth characteristics. However, approximately 82 proteins that may interact with hdh-MIRP1 were identified. The functional enrichment analysis of the 82 genes indicated that hdh-MIRP1 may be involved in the regulation of glucose metabolism and the process of growth. This study established a benchwork for further investigating the role of IRP in the growth of abalone. Full article

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

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15 pages, 2757 KiB

Open AccessEditor’s ChoiceArticle

Identification and Comprehensive Analysis of circRNA-miRNA-mRNA Regulatory Networks in A2780 Cells Treated with Resveratrol

by Weihua Zhu, Yuanting Zhang, Qianqian Zhou, Cheng Zhen, Herong Huang and Xiaoying Liu

Genes 2024, 15(7), 965; https://doi.org/10.3390/genes15070965 - 22 Jul 2024

Cited by 1 | Viewed by 1548

Abstract

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations [...] Read more.

Ovarian cancer (OC) is one of the most commonplace gynecological malignancies. This study explored the effects of resveratrol (RES) on OC cell proliferation and apoptosis. Proliferation activity was measured for A2780 cells treated with RES for 24 h and 48 h at concentrations of 0, 10, 25, 50, 75, 100, 150, 200, and 300

μ

M. RNA sequencing (RNA-seq) was performed to analyze the circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) expression spectrum. The differentially expressed genes included 460 circRNAs, 1988 miRNAs, and 1671 mRNAs, and they were subjected to analyses including Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment. We selected signaling pathways enriched in the cell processes by mRNA KEGG, comprehensively analyzed the circRNA-miRNA-mRNA regulatory network, and verified several miRNAs expressed in the regulatory network diagram using the quantitative real-time polymerase chain reaction. The data showed that the cell proliferation of A2780 cells treated with RES for 24 h or 48 h decreased with increasing concentrations of RES. The circRNA-miRNA-mRNA regulatory network that we constructed provides new insights into the ability of RES to inhibit cell proliferation and promote apoptosis in A2780 cells. Full article

(This article belongs to the Section RNA)

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14 pages, 4077 KiB

Open AccessEditor’s ChoiceArticle

Identification of Two Potential Gene Insertion Sites for Gene Editing on the Chicken Z/W Chromosomes

by Gaoyuan Wu, Youchen Liang, Chen Chen, Guohong Chen, Qisheng Zuo, Yingjie Niu, Jiuzhou Song, Wei Han, Kai Jin and Bichun Li

Genes 2024, 15(7), 962; https://doi.org/10.3390/genes15070962 - 22 Jul 2024

Viewed by 1728

Abstract

The identification of accurate gene insertion sites on chicken sex chromosomes is crucial for advancing sex control breeding materials. In this study, the intergenic region NC_006127.4 on the chicken Z chromosome and the non-repetitive sequence EE0.6 on the W chromosome were selected as [...] Read more.

The identification of accurate gene insertion sites on chicken sex chromosomes is crucial for advancing sex control breeding materials. In this study, the intergenic region NC_006127.4 on the chicken Z chromosome and the non-repetitive sequence EE0.6 on the W chromosome were selected as potential gene insertion sites. Gene knockout vectors targeting these sites were constructed and transfected into DF-1 cells. T7E1 enzyme cleavage and luciferase reporter enzyme analyses revealed knockout efficiencies of 80.00% (16/20), 75.00% (15/20), and 75.00% (15/20) for the three sgRNAs targeting the EE0.6 site. For the three sgRNAs targeting the NC_006127.4 site, knockout efficiencies were 70.00% (14/20), 60.00% (12/20), and 45.00% (9/20). Gel electrophoresis and high-throughput sequencing were performed to detect potential off-target effects, showing no significant off-target effects for the knockout vectors at the two sites. EdU and CCK-8 proliferation assays revealed no significant difference in cell proliferation activity between the knockout and control groups. These results demonstrate that the EE0.6 and NC_006127.4 sites can serve as gene insertion sites on chicken sex chromosomes for gene editing without affecting normal cell proliferation. Full article

(This article belongs to the Special Issue Genetic Breeding of Poultry)

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18 pages, 5887 KiB

Open AccessEditor’s ChoiceArticle

Phylogenetic and Comparative Genomics Study of Papilionidae Based on Mitochondrial Genomes

by Zhen-Tian Yan, Xiao-Ya Tang, Dong Yang, Zhen-Huai Fan, Si-Te Luo and Bin Chen

Genes 2024, 15(7), 964; https://doi.org/10.3390/genes15070964 - 22 Jul 2024

Cited by 1 | Viewed by 1640

Abstract

Most species of Papilionidae are large and beautiful ornamental butterflies. They are recognized as model organisms in ecology, evolutionary biology, genetics, and conservation biology but present numerous unresolved phylogenetic problems. Complete mitochondrial genomes (mitogenomes) have been widely used in phylogenetic studies of butterflies, [...] Read more.

Most species of Papilionidae are large and beautiful ornamental butterflies. They are recognized as model organisms in ecology, evolutionary biology, genetics, and conservation biology but present numerous unresolved phylogenetic problems. Complete mitochondrial genomes (mitogenomes) have been widely used in phylogenetic studies of butterflies, but mitogenome knowledge within the family Papilionidae is limited, and its phylogeny is far from resolved. In this study, we first report the mitogenome of Byasa confusa from the subfamily Papilioninae of Papilionidae. The mitogenome of B. confusa is 15,135 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and an AT-rich control region (CR), closely mirroring the genomic structure observed in related butterfly species. Comparative analysis of 77 Papilionidae mitogenomes shows gene composition and order to be identical to that of an ancestral insect, and the AT bias, Ka/Ks, and relative synonymous codon usage (RSCU) are all consistent with that of other reported butterfly mitogenomes. We conducted phylogenetic analyses using maximum-likelihood (ML) and Bayesian-inference (BI) methods, with 77 Papilionidae species as ingroups and two species of Nymphalidae and Lycaenidae as outgroups. The phylogenetic analysis indicated that B. confusa were clustered within Byasa. The phylogenetic trees show the monophyly of the subfamily Papilioninae and the tribes Leptocircini, Papilionini, and Troidini. The data supported the following relationships in tribe level on Papilioninae: (((Troidini + Papilionini) + Teinopalpini) + Leptocircini). The divergence time analysis suggests that Papilionidae originated in the late Creataceous. Overall, utilizing the largest number of Papilionidae mitogenomes sequenced to date, with the current first exploration in a phylogenetic analysis on Papilionidae (including four subfamilies), this study comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny, providing information for further studies on the mitogenome, phylogeny, evolution, and taxonomic revision of the Papilionidae family. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)

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15 pages, 3078 KiB

Open AccessEditor’s ChoiceArticle

Liver Transcriptomic Profiles of Ruminant Species Fed Spent Hemp Biomass Containing Cannabinoids

by Agung Irawan and Massimo Bionaz

Genes 2024, 15(7), 963; https://doi.org/10.3390/genes15070963 - 22 Jul 2024

Viewed by 1578

Abstract

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appears to be safe with minor effects on the metabolism, including a decrease in circulating cholesterol and increase bilirubinemia, both [...] Read more.

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appears to be safe with minor effects on the metabolism, including a decrease in circulating cholesterol and increase bilirubinemia, both associated with liver metabolism. Those effects could be consequence of the presence of cannabinoids, particularly Δ⁹-tetrahydrocannabinol (THC) and CBD in the SHB. This study aimed to study the transcriptional profile of the liver of dairy cows and lambs fed SHB. Dairy cows received SHB or alfalfa pellet for four weeks of intervention (IP) and four weeks of withdrawal periods (WP). Finishing lambs were fed a control diet (CON), 10% (LH2), or 20% (HH2) SHB for 2 months or 1 month followed by 1-month SHB withdrawal (LH1 and HH1, respectively). RNA sequencing was performed, and the mRNA was annotated using the latest reference genomes. The RNAseq data were filtered, normalized for library size and composition, and statistically analyzed by DESeq2. The bioinformatic analysis was performed by using DAVID, Gene Set Enrichment Analysis (GSEA), and the Dynamic Impact Approach. Using a 0.2 FDR cut-off, we identified only ≤24 differentially expressed genes (DEG) in the liver by feeding SHB in dairy cows and a larger number of DEGs in lambs (from 71 in HH1 vs. CON to 552 in LH1 vs. CON). The KEGG analysis demonstrated that feeding SHB in dairy cows and lambs had relatively minor to moderate metabolic alterations in dairy cows and lambs mainly associated with amino acids and lipid metabolism whereas cholesterol synthesis was overall activated in lambs. GSEA identified activation of the PPAR signaling pathway only in dairy cows. We found an opposite effect on activation of metabolism of drug and xenobiotics by cytochrome P450 enzymes in dairy cows and lambs receiving less SHB but an inhibition in HH2 lambs. Immune system-related pathways were inhibited by feeding SHB in lambs, but the impact was minor. Cumulatively, inclusion of SHB containing cannabinoids in dairy and lambs demonstrate very little effects on the alteration of transcriptomic profile of the liver. Full article

(This article belongs to the Special Issue Livestock Genomics, Genetics and Breeding)

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18 pages, 3664 KiB

Open AccessEditor’s ChoiceArticle

Uncovering Porphyrin Accumulation in the Tumor Microenvironment

by Swamy R. Adapa, Abdus Sami, Pravin Meshram, Gloria C. Ferreira and Rays H. Y. Jiang

Genes 2024, 15(7), 961; https://doi.org/10.3390/genes15070961 - 22 Jul 2024

Cited by 2 | Viewed by 1722

Abstract

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), [...] Read more.

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed “Porphyrin Overdrive”. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME’s stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention. Full article

(This article belongs to the Special Issue Genetics of Complex Human Disease 2024)

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19 pages, 4953 KiB

Open AccessEditor’s ChoiceArticle

ECPUB5 Polyubiquitin Gene in Euphorbia characias: Molecular Characterization and Seasonal Expression Analysis

by Faustina Barbara Cannea, Daniela Diana, Rossano Rossino and Alessandra Padiglia

Genes 2024, 15(7), 957; https://doi.org/10.3390/genes15070957 - 21 Jul 2024

Viewed by 1484

Abstract

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and [...] Read more.

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and expressed protein in E. characias. Using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) and rapid amplification of cDNA ends (5′/3′-RACE), we reconstructed the entire open reading frame (ORF) and noncoding regions. Our analysis revealed that the polyubiquitin gene encodes five tandemly repeated sequences, each coding for a ubiquitin monomer with amino acid variations in four of the five repeats. In silico studies have suggested functional differences among monomers. Gene expression peaked during the summer, correlating with high temperatures and suggesting a role in heat stress response. Western blotting confirmed the presence of polyubiquitin in the latex and leaf tissues, indicating active ubiquitination processes. These findings enhance our understanding of polyubiquitin’s regulatory mechanisms and functions in E. characias, highlighting its unique structural and functional features. Full article

(This article belongs to the Special Issue Abiotic Stress in Land Plants: Molecular Genetics and Genomics)

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39 pages, 2514 KiB

Open AccessEditor’s ChoiceReview

Advances in CircRNAs in the Past Decade: Review of CircRNAs Biogenesis, Regulatory Mechanisms, and Functions in Plants

by Dongqin Zhang, Yue Ma, Misbah Naz, Nazeer Ahmed, Libo Zhang, Jing-Jiang Zhou, Ding Yang and Zhuo Chen

Genes 2024, 15(7), 958; https://doi.org/10.3390/genes15070958 - 21 Jul 2024

Viewed by 2483

Abstract

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable [...] Read more.

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control. Full article

(This article belongs to the Special Issue Genetic Regulation of Biotic Stress Responses)

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12 pages, 970 KiB

Open AccessEditor’s ChoiceReview

The MET Family of Receptor Tyrosine Kinases Promotes a Shift to Pro-Tumor Metabolism

by James C. Davis and Susan E. Waltz

Genes 2024, 15(7), 953; https://doi.org/10.3390/genes15070953 - 20 Jul 2024

Cited by 1 | Viewed by 2012

Abstract

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor [...] Read more.

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor that is implicated in this shift to pro-tumor metabolism. RTKs are important drivers of cancer growth and metastasis. One such family of RTKs is the MET family, which consists of MET and RON (MST1R). The overexpression of either MET or RON has been associated with worse cancer patient prognosis in a variety of tumor types. Both MET and RON signaling promote increased glycolysis by upregulating the expression of key glycolytic enzymes via increased MYC transcription factor activity. Additionally, both MET and RON signaling promote increased cholesterol biosynthesis downstream of glycolysis by upregulating the expression of SREBP2-induced cholesterol biosynthesis enzymes via CTTNB1. These changes in metabolism, driven by RTK activity, provide potential targets in limiting tumor growth and metastasis via pharmacological inhibition or modifications in diet. This review summarizes pro-tumor changes in metabolism driven by the MET family of RTKs. In doing so, we will offer our unique perspective on metabolic pathways that drive worse patient prognosis and provide suggestions for future study. Full article

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

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17 pages, 3069 KiB

Open AccessEditor’s ChoiceArticle

Exonic Short Interspersed Nuclear Element Insertion in FAM161A Is Associated with Autosomal Recessive Progressive Retinal Atrophy in the English Shepherd

by Katherine Stanbury, Ellen C. Schofield, Bryan McLaughlin, Oliver P. Forman and Cathryn S. Mellersh

Genes 2024, 15(7), 952; https://doi.org/10.3390/genes15070952 - 20 Jul 2024

Cited by 1 | Viewed by 5025

Abstract

Progressive retinal atrophies (PRAs) are a genetically heterogeneous group of inherited eye diseases that affect over 100 breeds of dog. The initial clinical sign is visual impairment in scotopic conditions, as a consequence of rod photoreceptor cell degeneration. Photopic vision degeneration then follows, [...] Read more.

Progressive retinal atrophies (PRAs) are a genetically heterogeneous group of inherited eye diseases that affect over 100 breeds of dog. The initial clinical sign is visual impairment in scotopic conditions, as a consequence of rod photoreceptor cell degeneration. Photopic vision degeneration then follows, due to progression of the disease to the cone photoreceptors, and ultimately results in complete blindness. Two full-sibling English Shepherds were diagnosed with PRA at approximately 5 years old and tested clear of all published PRA genetic variants. This study sought to identify the novel PRA-associated variant segregating in the breed. We utilised a combined approach of whole genome sequencing of the probands and homozygosity mapping of four cases and 22 controls and identified a short interspersed nuclear element within an alternatively spliced exon in FAM161A. The XP_005626197.1 c.17929_ins210 variant was homozygous in six PRA cases and heterozygous or absent in control dogs, consistent with a recessive mode of inheritance. The insertion is predicted to extend exon 4 by 39 aberrant amino acids followed by an early termination stop codon. PRA is intractable to treatment, so the development of a genetic screening test, based on the associated variant, is significant, because it provides dog breeders/owners with a means of reducing the frequency of the disease variant within this breed as well as minimising the risk of breeding puppies that will develop this blinding disease. Full article

(This article belongs to the Special Issue Advances in Canine Genetics)

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14 pages, 2146 KiB

Open AccessEditor’s ChoiceArticle

Divergence of Phyllosphere Microbial Community Assemblies and Components of Volatile Organic Compounds between the Invasive Sphagneticola trilobata, the Native Sphagneticola calendulacea and Their Hybrids, and Its Implications for Invasiveness

by Hui Zhang, Shanshan Li, Sheng Zhou, Wei Guo, Ping Chen, Yongquan Li and Wei Wu

Genes 2024, 15(7), 955; https://doi.org/10.3390/genes15070955 - 20 Jul 2024

Viewed by 1292

Abstract

Closely-related plant groups with distinct microbiomes, chemistries and ecological characteristics represent tractable models to explore mechanisms shaping species spread, competitive dynamics and community assembly at the interface of native and introduced ranges. We investigated phyllosphere microbial communities, volatile organic compound (VOC) compositions, and [...] Read more.

Closely-related plant groups with distinct microbiomes, chemistries and ecological characteristics represent tractable models to explore mechanisms shaping species spread, competitive dynamics and community assembly at the interface of native and introduced ranges. We investigated phyllosphere microbial communities, volatile organic compound (VOC) compositions, and potential interactions among introduced S. trilobata, native S. calendulacea and their hybrid in South China. S. trilobata exhibited higher α diversity but significantly different community composition compared to the native and hybrid groups. However, S. calendulacea and the hybrid shared certain microbial taxa, suggesting potential gene flow or co-existence. The potent antimicrobial VOC profile of S. trilobata, including unique compounds like p-cymene (13.33%), likely contributes to its invasion success. The hybrid’s intermediate microbial and VOC profiles suggest possible consequences for species distribution, genetic exchange, and community assembly in heterogeneous environments. This hybrid deserves further study as both an opportunity for and threat to diversity maintenance. These differentiating yet connected plant groups provide insight into ecological and evolutionary dynamics shaping microbiome structure, species co-occurrence and competitive outcomes during biological exchange and habitat transformation. An interdisciplinary approach combining chemical and microbial ecology may reveal mechanisms underlying community stability and change, informing management of species spread in a globalized world. Full article

(This article belongs to the Special Issue Genome-Wide Identifications: Recent Trends in Genomic Studies)

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25 pages, 10990 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases

by Vaishnavi Aradhyula, Joshua D. Breidenbach, Bella Z. Khatib-Shahidi, Julia N. Slogar, Sonia A. Eyong, Dhilhani Faleel, Prabhatchandra Dube, Rajesh Gupta, Samer J. Khouri, Steven T. Haller and David J. Kennedy

Genes 2024, 15(7), 954; https://doi.org/10.3390/genes15070954 - 20 Jul 2024

Cited by 5 | Viewed by 2591

Abstract

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce [...] Read more.

Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes. Full article

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

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13 pages, 20689 KiB

Open AccessEditor’s ChoiceArticle

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping

by Mario Cuk, Busra Unal, Andjela Bevanda, Connor P. Hayes, McKenzie Walker, Feruza Abraamyan, Robert Beluzic, Kristina Crkvenac Gornik, David Ozretic, Maja Prutki, Qian Nie, Honey V. Reddi and Arezou A. Ghazani

Genes 2024, 15(7), 946; https://doi.org/10.3390/genes15070946 - 19 Jul 2024

Cited by 1 | Viewed by 1655

Abstract

Purpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged [...] Read more.

Purpose: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2–15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes. Full article

(This article belongs to the Special Issue Precision Medicine and Genetics)

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11 pages, 2787 KiB

Open AccessEditor’s ChoiceArticle

The Missense Variant in the Signal Peptide of α-GLA Gene, c.13 A/G, Promotes Endoplasmic Reticular Stress and the Related Pathway’s Activation

by Sabrina Bossio, Ida Daniela Perrotta, Danilo Lofaro, Daniele La Russa, Vittoria Rago, Renzo Bonofiglio, Rosita Greco, Michele Andreucci, Antonio Aversa, Antonella La Russa and Anna Perri

Genes 2024, 15(7), 947; https://doi.org/10.3390/genes15070947 - 19 Jul 2024

Cited by 2 | Viewed by 1559

Abstract

Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could [...] Read more.

Anderson–Fabry disease (AFD) is an X-linked multisystemic disorder with a heterogeneous phenotype, resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) and leading to globotriaosylceramide systemic accumulation. Lysosomal storage is not the unique player in organ failure and different mechanisms could drive tissue damage, including endoplasmic reticulum (ER) stress and its related signaling pathway’s activation. We identified a new missense variant in the signal peptide of α-GLA gene, c.13 A/G, in a 55-year-old woman affected by chronic kidney disease, acroparesthesia, hypohidrosis, and deafness and exhibiting normal values of lysoGb3 and αGLA activity. The functional study of the new variant performed by its overexpression in HEK293T cells showed an increased protein expression of a key ER stress marker, GRP78, the pro-apoptotic BAX, the negative regulator of cell cycle p21, the pro-inflammatory cytokine, IL1β, together with pNFkB, and the pro-fibrotic marker, N-cadherin. Transmission electron microscopy showed signs of ER injury and intra-lysosomal inclusions. The proband’s PBMC exhibited higher expression of TGFβ 1 and pNFkB compared to control. Our findings suggest that the new variant, although it did not affect enzymatic activity, could cause cellular damage by affecting ER homeostasis and promoting apoptosis, inflammation, and fibrosis. Further studies are needed to demonstrate the variant’s contribution to cellular and tissue damage. Full article

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

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16 pages, 5151 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome Analysis Reveals Genes and Pathways Associated with Drought Tolerance of Early Stages in Sweet Potato (Ipomoea batatas (L.) Lam.)

by Peng Cheng, Fanna Kong, Yang Han, Xiaoping Liu and Jiaping Xia

Genes 2024, 15(7), 948; https://doi.org/10.3390/genes15070948 - 19 Jul 2024

Cited by 1 | Viewed by 1817

Abstract

The yield of sweet potato [Ipomoea batatas (L.) Lam] can be easily threatened by drought stress. Typically, early stages like the seedling stage and tuber-root expansion stage are more vulnerable to drought stress. In this study, a highly drought-tolerant sweet potato cultivar [...] Read more.

The yield of sweet potato [Ipomoea batatas (L.) Lam] can be easily threatened by drought stress. Typically, early stages like the seedling stage and tuber-root expansion stage are more vulnerable to drought stress. In this study, a highly drought-tolerant sweet potato cultivar “WanSu 63” was subjected to drought stress at both the seedling stage (15 days after transplanting, 15 DAT) and the tuber-root expansion stage (45 DAT). Twenty-four cDNA libraries were constructed from leaf segments and root tissues at 15 and 45 DAT for Next-Generation Sequencing. A total of 663, 063, and 218 clean reads were obtained and then aligned to the reference genome with a total mapped ratio greater than 82.73%. A sum of 7119, 8811, 5463, and 930 differentially expressed genes were identified from leaves in 15 days (L15), roots in 15 days (R15), leaves in 45 days (L45), and roots in 45 days (R45), respectively, in drought stress versus control. It was found that genes encoding heat shock proteins, sporamin, LEA protein dehydrin, ABA signaling pathway protein gene NCED1, as well as a group of receptor-like protein kinases genes were enriched in differentially expressed genes. ABA content was significantly higher in drought-treated tissues than in the control. The sweet potato biomass declined sharply to nearly one-quarter after drought stress. In conclusion, this study is the first to identify the differentially expressed drought-responsive genes and signaling pathways in the leaves and roots of sweet potato at the seedling and root expansion stages. The results provide potential resources for drought resistance breeding of sweet potato. Full article

(This article belongs to the Special Issue Advances in Genetic Breeding of Sweetpotato)

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14 pages, 6380 KiB

Open AccessEditor’s ChoiceArticle

Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases

by María Domínguez-Ruiz, Margarita Olarte, Esther Onecha, Irene García-Vaquero, Nancy Gelvez, Greizy López, Manuela Villamar, Matías Morín, Miguel A. Moreno-Pelayo, Carmelo Morales-Angulo, Rubén Polo, Martha L. Tamayo and Ignacio del Castillo

Genes 2024, 15(7), 951; https://doi.org/10.3390/genes15070951 - 19 Jul 2024

Cited by 1 | Viewed by 1365

Abstract

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of [...] Read more.

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety of phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with a predominance of neurological signs. The diversity of roles that are played by these moonlighting enzymes and the fact that most pathogenic variants are missense and affect different domains of these proteins in diverse compound heterozygous combinations make it difficult to establish genotype–phenotype correlations. We used a targeted gene-sequencing panel to investigate the presence of pathogenic variants in those four genes in cohorts of 175 Spanish and 18 Colombian familial cases with non-DFNB1 autosomal recessive NSHI. Disease-associated variants were found in five cases. Five mutations were novel as follows: c.766C>T in KARS1, c.475C>T, c.728A>C and c.1012G>A in HARS2, and c.795A>G in LARS2. We provide audiograms from patients at different ages to document the evolution of the hearing loss, which is mostly prelingual and progresses from moderate/severe to profound, the middle frequencies being more severely affected. No additional clinical sign was observed in any affected subject. Our results confirm the involvement of KARS1 in DFNB89 NSHI, for which until now there was limited evidence. Full article

(This article belongs to the Section Cytogenomics)

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22 pages, 4152 KiB

Open AccessEditor’s ChoiceArticle

Dissecting the Genetic Architecture of Morphological Traits in Sunflower (Helianthus annuus L.)

by Yavuz Delen, Semra Palali-Delen, Gen Xu, Mohamed Neji, Jinliang Yang and Ismail Dweikat

Genes 2024, 15(7), 950; https://doi.org/10.3390/genes15070950 - 19 Jul 2024

Cited by 2 | Viewed by 1726

Abstract

The sunflower (Helianthus annuus L.) is one of the most essential oil crops in the world. Several component traits, including flowering time, plant height, stem diameter, seed weight, and kernel weight, determine sunflower seed and oil yield. Although the genetic mechanisms governing [...] Read more.

The sunflower (Helianthus annuus L.) is one of the most essential oil crops in the world. Several component traits, including flowering time, plant height, stem diameter, seed weight, and kernel weight, determine sunflower seed and oil yield. Although the genetic mechanisms governing the variation of these yield-related traits have been studied using various approaches, genome-wide association studies (GWAS) have not been widely applied to sunflowers. In this study, a set of 342 sunflower accessions was evaluated in 2019 and 2020 using an incomplete randomized block design, and GWAS was conducted utilizing two complementary approaches: the mixed linear model (MLM) and the fixed and random model circulating probability unification (farmCPU) model by fitting 226,779 high-quality SNPs. As a result, GWAS identified a number of trait-associated SNPs. Those SNPs were located close to several genes that may serve as a basis for further molecular characterization and provide promising targets for sunflower yield improvement. Full article

(This article belongs to the Collection Feature Papers in Bioinformatics)

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11 pages, 3336 KiB

Open AccessEditor’s ChoiceArticle

Hepatopancreas Transcriptome Analysis of Spinibarbus sinensis to Reveal Different Growth-Related Genes

by Bo Zhou, Leyan Ling, Bin Wang, Fei Yang, Mengdan Hou, Fan Liu, Yu Li, Hui Luo, Wenping He and Hua Ye

Genes 2024, 15(7), 949; https://doi.org/10.3390/genes15070949 - 19 Jul 2024

Viewed by 1390

Abstract

Spinibarbus sinensis, also known as Qingbo, is an important economic fish in China. However, the detailed mechanisms underlying its growth are still unknown. To excavate the genes and signaling pathways related to its growth, we compared the transcriptome profiles of the hepatopancreas [...] Read more.

Spinibarbus sinensis, also known as Qingbo, is an important economic fish in China. However, the detailed mechanisms underlying its growth are still unknown. To excavate the genes and signaling pathways related to its growth, we compared the transcriptome profiles of the hepatopancreas tissues of S. sinensis, with two groups of growth rate for evaluation. An average of 66,304,909 and 68,739,585 clean reads were obtained in the fast growth (FG) and slow growth (SG) group, respectively. The differential gene expression analysis results showed that 272 differentially expressed genes (DEGs) were screened between the FG and SG groups, including 101 up-regulated genes and 171 down-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that GO terms related to metabolic process, organic substance metabolic process, and catalytic activity were enriched, pathway signals related to steroid biosynthesis and protein digestion and absorption were also detected. Meanwhile, the potential key regulatory genes sst2, fndc4, and cckra related to the growth of S. sinensis were screened. Reverse transcript fluorescence quantitative PCR (RT-qPCR) validation of 18 DEGs associated with growth differences showed that the RT-qPCR results were consistent with RNA-seq analysis, and nine genes, stk31, gpr149, angptl1, fstl1, sik1, ror2, nlrc3, pdlim2, and nav2 were significantly expressed in the FG group. bmp1, stc1, gpatch8, sstrt2, s100a1, ktf6, cckar6, sync1, bhlha15, a total of nine genes were significantly expressed in the SG group. This study provides basic information for improving the growth characteristics of S. sinensis and the functional research of candidate genes. Full article

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

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12 pages, 855 KiB

Open AccessEditor’s ChoiceArticle

Validation of Gene Expression Patterns for Oral Feeding Readiness: Transcriptional Analysis of Set of Genes in Neonatal Salivary Samples

by Leonardo Henrique Ferreira Gomes, Andressa Brito Marques, Isabel Cristina de Meireles Dias, Sanny Cerqueira de O. Gabeira, Tamara Rosa Barcelos, Mariana de Oliveira Guimarães, Igor Ribeiro Ferreira, Letícia Cunha Guida, Sabrina Lopes Lucena and Adriana Duarte Rocha

Genes 2024, 15(7), 936; https://doi.org/10.3390/genes15070936 - 18 Jul 2024

Cited by 1 | Viewed by 1812

Abstract

Background: Neonatal health assessment is crucial for detecting and intervening in various disorders. Traditional gene expression analysis methods often require invasive procedures during sample collection, which may not be feasible or ideal for preterm infants. In recent years, saliva has emerged as a [...] Read more.

Background: Neonatal health assessment is crucial for detecting and intervening in various disorders. Traditional gene expression analysis methods often require invasive procedures during sample collection, which may not be feasible or ideal for preterm infants. In recent years, saliva has emerged as a promising noninvasive biofluid for assessing gene expression. Another trend that has been growing is the use of “omics” technologies such as transcriptomics in the analysis of gene expression. The costs for carrying out these analyses and the difficulty of analysis make the detection of candidate genes necessary. These genes act as biomarkers for the maturation stages of the oral feeding issue. Methodology: Salivary samples (n = 225) were prospectively collected from 45 preterm (<34 gestational age) infants from five predefined feeding stages and submitted to RT-qPCR. A better description of the targeted genes and results from RT-qPCR analyses were included. The six genes previously identified as predictive of feeding success were tested. The genes are AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1, along with two reference genes: GAPDH and 18S. RT-qPCR amplification enabled the analysis of the gene expression of AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 in neonatal saliva. Expression results were correlated with the feeding status during sample collection. Conclusions: In summary, the genes AMPK, FOXP2, WNT3, NPHP4, NPY2R, and PLXNA1 play critical roles in regulating oral feeding and the development of premature infants. Understanding the influence of these genes can provide valuable insights for improving nutritional care and support the development of these vulnerable babies. Evidence suggests that saliva-based gene expression analysis in newborns holds great promise for early detection and monitoring of disease and understanding developmental processes. More research and standardization of protocols are needed to fully explore the potential of saliva as a noninvasive biomarker in neonatal care. Full article

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

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15 pages, 721 KiB

Open AccessEditor’s ChoiceArticle

Challenges of Preimplantation Genetic Counselling in the Context of Cystic Fibrosis and Other CFTR-Related Disorders: A Monocentric Experience in a Cohort of 92 Couples

by Ugo Sorrentino, Massimo Menegazzo, Ilaria Gabbiato, Davide Calosci, Carlo Federico Zambon and Daniela Zuccarello

Genes 2024, 15(7), 937; https://doi.org/10.3390/genes15070937 - 18 Jul 2024

Viewed by 2020

Abstract

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced [...] Read more.

Cystic fibrosis is a highly prevalent genetic disorder caused by biallelic pathogenic variants in the CFTR gene, causing an altered function of the exocrine glands and a subsequent spectrum of hypofunctional and degenerative manifestations. The increasing availability of carrier screening programmes, the enhanced life expectancy of patients due to improved treatment and care strategies and the development of more precise and affordable molecular diagnostic tools have prompted a rise in demand of prenatal diagnosis procedures for at-risk couples, including Preimplantation Genetic Testing (PGT). However, challenges remain: heterogeneity among screening programmes, nuances of variant interpretation and availability of novel treatments demand a considerate and knowledgeable approach to genetic counselling. In this work, we retrospectively evaluated the molecular data of 92 unselected couples who received a diagnosis of CFTR-related status and were referred to the genetics clinic at the University Hospital of Padua for genetic counselling on eligibility for PGT. A total of 50 couples were considered eligible for the procedure based on risk of transmitting biallelic pathogenic variants. We report and discuss our experience with this case series in the context of the Italian medical care system and present an overview of the most relevant issues regarding genetic counselling for PGT in CFTR-related disorders. Full article

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

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18 pages, 8420 KiB

Open AccessEditor’s ChoiceArticle

Intraspecific Differentiation of Styrax japonicus (Styracaceae) as Revealed by Comparative Chloroplast and Evolutionary Analyses

by Hao-Zhi Zheng, Wei Dai, Meng-Han Xu, Yu-Ye Lin, Xing-Li Zhu, Hui Long, Li-Li Tong and Xiao-Gang Xu

Genes 2024, 15(7), 940; https://doi.org/10.3390/genes15070940 - 18 Jul 2024

Cited by 4 | Viewed by 1254

Abstract

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. [...] Read more.

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus, we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus. The results demonstrated that the four chloroplast genomes (157,914–157,962 bp) exhibited a typical quadripartite structure consisting of a large single copy (LSC) region, a small single copy (SSC) region, and a pair of reverse repeats (IRa and IRb), and the structure was highly conserved. DNA polymorphism analysis revealed that three coding genes (infA, psbK, and rpl33) and five intergene regions (petA-psbJ, trnC-petN, trnD-trnY, trnE-trnT, and trnY-trnE) were identified as mutation hotspots. These genetic fragments have the potential to be utilized as DNA barcodes for future identification purposes. When comparing the boundary genes, a small contraction was observed in the IR region of four S. japonicus. Selection pressure analysis indicated positive selection for ycf1 and ndhD. These findings collectively suggest the adaptive evolution of S. japonicus. The phylogenetic structure revealed conflicting relationships among several S. japonicus, indicating divergent evolutionary paths within this species. Our study concludes by uncovering the genetic traits of the chloroplast genome in the differentiation of S. japonicus variety, offering fresh perspectives on the evolutionary lineage of this species. Full article

(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)

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12 pages, 3540 KiB

Open AccessEditor’s ChoiceArticle

GENet: A Graph-Based Model Leveraging Histone Marks and Transcription Factors for Enhanced Gene Expression Prediction

by Mahdieh Labani, Amin Beheshti and Tracey A. O’Brien

Genes 2024, 15(7), 938; https://doi.org/10.3390/genes15070938 - 18 Jul 2024

Viewed by 1524

Abstract

Understanding the regulatory mechanisms of gene expression is a crucial objective in genomics. Although the DNA sequence near the transcription start site (TSS) offers valuable insights, recent methods suggest that analyzing only the surrounding DNA may not suffice to accurately predict gene expression [...] Read more.

Understanding the regulatory mechanisms of gene expression is a crucial objective in genomics. Although the DNA sequence near the transcription start site (TSS) offers valuable insights, recent methods suggest that analyzing only the surrounding DNA may not suffice to accurately predict gene expression levels. We developed GENet (Gene Expression Network from Histone and Transcription Factor Integration), a novel approach that integrates essential regulatory signals from transcription factors and histone modifications into a graph-based model. GENet extends beyond simple DNA sequence analysis by incorporating additional layers of genetic control, which are vital for determining gene expression. Our method markedly enhances the prediction of mRNA levels compared to previous models that depend solely on DNA sequence data. The results underscore the significance of including comprehensive regulatory information in gene expression studies. GENet emerges as a promising tool for researchers, with potential applications extending from fundamental biological research to the development of medical therapies. Full article

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

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15 pages, 29526 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Characterization of CCT Gene Family from Microalgae to Legumes

by Yi Xu, Huiying Yao, Yanhong Lan, Yu Cao, Qingrui Xu, Hui Xu, Dairong Qiao and Yi Cao

Genes 2024, 15(7), 941; https://doi.org/10.3390/genes15070941 - 18 Jul 2024

Cited by 1 | Viewed by 1762

Abstract

The CCT (CO, COL and TOC1) gene family has been elucidated to be involved in the functional differentiation of the products in various plant species, but their specific mechanisms are poorly understood. In the present investigation, we conducted a genome-wide identification and phylogenetic [...] Read more.

The CCT (CO, COL and TOC1) gene family has been elucidated to be involved in the functional differentiation of the products in various plant species, but their specific mechanisms are poorly understood. In the present investigation, we conducted a genome-wide identification and phylogenetic analysis of CCT genes from microalgae to legumes. A total of 700 non-redundant members of the CCT gene family from 30 species were identified through a homology search. Phylogenetic clustering with Arabidopsis and domain conservation analysis categorized the CCT genes into three families. Multiple sequence alignment showed that the CCT domain contains important amino acid residues, and each CCT protein contains 24 conserved motifs, as demonstrated by the motif analysis. Whole-genome/segment duplication, as well as tandem duplication, are considered to be the driving forces in the evolutionary trajectory of plant species. This comprehensive investigation into the proliferation of the CCT gene family unveils the evolutionary dynamics whereby WGD/segment duplication is the predominant mechanism contributing to the expansion of the CCT genes. Meanwhile, the examination of the gene expression patterns revealed that the expression patterns of CCT genes vary in different tissues and at different developmental stages of plants, with high expression in leaves, which is consistent with the molecular regulation of flowering in photosynthesis by CCT. Based on the protein–protein interaction analysis of CCT genes in model plants, we propose that the CCT gene family synergistically regulates plant development and flowering with light-signaling factors (PHYs and PIFs) and MYB family transcription factors. Understanding the CCT gene family’s molecular evolution enables targeted gene manipulation for enhanced plant traits, including optimized flowering and stress resistance. Full article

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

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18 pages, 644 KiB

Open AccessEditor’s ChoiceReview

Using Genetics to Investigate Relationships between Phenotypes: Application to Endometrial Cancer

by Kelsie Bouttle, Nathan Ingold and Tracy A. O’Mara

Genes 2024, 15(7), 939; https://doi.org/10.3390/genes15070939 - 18 Jul 2024

Cited by 1 | Viewed by 1972

Abstract

Genome-wide association studies (GWAS) have accelerated the exploration of genotype–phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various phenotypes, focusing [...] Read more.

Genome-wide association studies (GWAS) have accelerated the exploration of genotype–phenotype associations, facilitating the discovery of replicable genetic markers associated with specific traits or complex diseases. This narrative review explores the statistical methodologies developed using GWAS data to investigate relationships between various phenotypes, focusing on endometrial cancer, the most prevalent gynecological malignancy in developed nations. Advancements in analytical techniques such as genetic correlation, colocalization, cross-trait locus identification, and causal inference analyses have enabled deeper exploration of associations between different phenotypes, enhancing statistical power to uncover novel genetic risk regions. These analyses have unveiled shared genetic associations between endometrial cancer and many phenotypes, enabling identification of novel endometrial cancer risk loci and furthering our understanding of risk factors and biological processes underlying this disease. The current status of research in endometrial cancer is robust; however, this review demonstrates that further opportunities exist in statistical genetics that hold promise for advancing the understanding of endometrial cancer and other complex diseases. Full article

(This article belongs to the Special Issue Statistical Methods for Genetic Epidemiology)

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15 pages, 3180 KiB

Open AccessEditor’s ChoiceReview

MicroRNA166: Old Players and New Insights into Crop Agronomic Traits Improvement

by Zhanhui Zhang, Tianxiao Yang, Na Li, Guiliang Tang and Jihua Tang

Genes 2024, 15(7), 944; https://doi.org/10.3390/genes15070944 - 18 Jul 2024

Cited by 1 | Viewed by 1920

Abstract

MicroRNA (miRNA), a type of non-coding RNA, is crucial for controlling gene expression. Among the various miRNA families, miR166 stands out as a highly conserved group found in both model and crop plants. It plays a key role in regulating a wide range [...] Read more.

MicroRNA (miRNA), a type of non-coding RNA, is crucial for controlling gene expression. Among the various miRNA families, miR166 stands out as a highly conserved group found in both model and crop plants. It plays a key role in regulating a wide range of developmental and environmental responses. In this review, we explore the diverse sequences of MIR166s in major crops and discuss the important regulatory functions of miR166 in plant growth and stress responses. Additionally, we summarize how miR166 interacts with other miRNAs and highlight the potential for enhancing agronomic traits by manipulating the expression of miR166 and its targeted HD-ZIP III genes. Full article

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

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17 pages, 2221 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

In Silico Prediction of BRCA1 and BRCA2 Variants with Conflicting Clinical Interpretation in a Cohort of Breast Cancer Patients

by Stefania Stella, Silvia Rita Vitale, Michele Massimino, Federica Martorana, Irene Tornabene, Cristina Tomarchio, Melissa Drago, Giuliana Pavone, Cristina Gorgone, Chiara Barone, Sebastiano Bianca and Livia Manzella

Genes 2024, 15(7), 943; https://doi.org/10.3390/genes15070943 - 18 Jul 2024

Cited by 1 | Viewed by 2187

Abstract

Germline BRCA1/2 alteration has been linked to an increased risk of hereditary breast and ovarian cancer syndromes. As a result, genetic testing, based on NGS, allows us to identify a high number of variants of uncertain significance (VUS) or conflicting interpretation of pathogenicity [...] Read more.

Germline BRCA1/2 alteration has been linked to an increased risk of hereditary breast and ovarian cancer syndromes. As a result, genetic testing, based on NGS, allows us to identify a high number of variants of uncertain significance (VUS) or conflicting interpretation of pathogenicity (CIP) variants. The identification of CIP/VUS is often considered inconclusive and clinically not actionable for the patients’ and unaffected carriers’ management. In this context, their assessment and classification remain a significant challenge. The aim of the study was to investigate whether the in silico prediction tools (PolyPhen-2, SIFT, Mutation Taster and PROVEAN) could predict the potential clinical impact and significance of BRCA1/2 CIP/VUS alterations, eventually impacting the clinical management of Breast Cancer subjects. In a cohort of 860 BC patients, 10.6% harbored BRCA1 or BRCA2 CIP/VUS alterations, mostly observed in BRCA2 sequences (85%). Among them, forty-two out of fifty-five alterations were predicted as damaging, with at least one in silico that used tools. Prediction agreement of the four tools was achieved in 45.5% of patients. Moreover, the highest consensus was obtained in twelve out of forty-two (28.6%) mutations by considering three out of four in silico algorithms. The use of prediction tools may help to identify variants with a potentially damaging effect. The lack of substantial agreement between the different algorithms suggests that the bioinformatic approaches should be combined with the personal and family history of the cancer patients. Full article

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

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19 pages, 595 KiB

Open AccessEditor’s ChoiceReview

A Review of Experimental Studies on Natural Chalcone-Based Therapeutic Targeting of Genes and Signaling Pathways in Type 2 Diabetes Complications

by Naser A. Alsharairi

Genes 2024, 15(7), 942; https://doi.org/10.3390/genes15070942 - 18 Jul 2024

Cited by 1 | Viewed by 2065

Abstract

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and β-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the [...] Read more.

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and β-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the cause of increasing mortality. Diabetic nephropathy (DNE), neuropathy (DNU), and retinopathy (DR) are the most common complications of diabetic microangiopathy, while diabetic cardiomyopathy (DCM) and peripheral vascular diseases are the major diabetic macroangiopathy complications. Chalcones (CHs) are in the flavonoid family and are commonly found in certain plant species as intermediate metabolites in the biosynthesis of flavonoids and their derivatives. Natural CHs with different substituents exert diverse therapeutic activities, including antidiabetic ones. However, the therapeutic mechanisms of natural CHs through influencing genes and/or signaling pathways in T2DM complications remain unknown. Therefore, this review summarizes the existing results from experimental models which highlight the mechanisms of natural CHs as therapeutic agents for T2DM complications. Full article

(This article belongs to the Special Issue Omics Studies of Type 2 Diabetes and Diabetes-Related Complications)

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