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Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing
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Immunogenetic Aspects of Sarcopenic Obesity
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Homozygous CNP Mutation and Neurodegeneration in Weimaraners: Myelin Abnormalities and Accumulation of Lipofuscin-like Inclusions
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The Intriguing Mystery of RPA Phosphorylation in DNA Double-Strand Break Repair
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Male Pedigree Toolbox: A Versatile Software for Y-STR Data Analyses
Journal Description
Genes
Genes
is a peer-reviewed, open access journal of genetics and genomics published monthly online by MDPI. The Spanish Society for Biochemistry and Molecular Biology (SEBBM) is affiliated with Genes and their members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, and other databases.
- Journal Rank: JCR - Q2 (Genetics and Heredity) / CiteScore - Q2 (Genetics (clinical))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.3 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: Reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
2.8 (2023);
5-Year Impact Factor:
3.3 (2023)
Latest Articles
Comparative Metabolome and Transcriptome Analyses of the Regulatory Mechanism of Light Intensity in the Synthesis of Endogenous Hormones and Anthocyanins in Anoectochilus roxburghii (Wall.) Lindl
Genes 2024, 15(8), 989; https://doi.org/10.3390/genes15080989 - 26 Jul 2024
Abstract
To explore the regulatory mechanism of endogenous hormones in the synthesis of anthocyanins in Anoectochilus roxburghii (Wall.) Lindl (A. roxburghii) under different light intensities, this study used metabolomics and transcriptomics techniques to identify the key genes and transcription factors involved in
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To explore the regulatory mechanism of endogenous hormones in the synthesis of anthocyanins in Anoectochilus roxburghii (Wall.) Lindl (A. roxburghii) under different light intensities, this study used metabolomics and transcriptomics techniques to identify the key genes and transcription factors involved in anthocyanin biosynthesis. We also analyzed the changes in and correlations between plant endogenous hormones and anthocyanin metabolites under different light intensities. The results indicate that light intensity significantly affects the levels of anthocyanin glycosides and endogenous hormones in leaves. A total of 38 anthocyanin-related differential metabolites were identified. Under 75% light transmittance (T3 treatment), the leaves exhibited the highest anthocyanin content and differentially expressed genes such as chalcone synthase (CHS), flavonol synthase (FLS), and flavonoid 3′-monooxygenase (F3′H) exhibited the highest expression levels. Additionally, 13 transcription factors were found to have regulatory relationships with 7 enzyme genes, with 11 possessing cis-elements responsive to plant hormones. The expression of six genes and two transcription factors was validated using qRT-PCR, with the results agreeing with those obtained using RNA sequencing. This study revealed that by modulating endogenous hormones and transcription factors, light intensity plays a pivotal role in regulating anthocyanin glycoside synthesis in A. roxburghii leaves. These findings provide insights into the molecular mechanisms underlying light-induced changes in leaf coloration and contribute to our knowledge of plant secondary metabolite regulation caused by environmental factors.
Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle
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
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
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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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Open AccessArticle
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
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
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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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Open AccessArticle
The High-Molecular-Weight Glutenin Subunits of the T. timopheevii (AuAuGG) 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
Abstract
Polyploid wheats include a group of tetraploids known as Timopheevii (AuAuGG), 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
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Polyploid wheats include a group of tetraploids known as Timopheevii (AuAuGG), 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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Open AccessArticle
High Prevalence of ESBL Genes in Commensal Escherichia coli of the Urinary Tract: Implications for Antibiotic Stewardship among Residents of Ghanaian Elderly Nursing Care Homes
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Emmanuel Armah, Lawrencia Osae-Nyarko, Bright Idun, Mawutor Kwame Ahiabu, Isaac Agyapong, Freda Boampong Kwarteng, Mercy Oppong, Naael Mohammed, Fleischer C. N. Kotey, Mike Yaw Osei-Atweneboana and Nicholas T. K. D. Dayie
Genes 2024, 15(8), 985; https://doi.org/10.3390/genes15080985 - 26 Jul 2024
Abstract
The emergence and spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) pose significant challenges to the treatment and control of urinary tract infections, particularly among vulnerable populations, such as the elderly living in nursing care homes. In this study, we
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The emergence and spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) pose significant challenges to the treatment and control of urinary tract infections, particularly among vulnerable populations, such as the elderly living in nursing care homes. In this study, we investigated the occurrence of ESBL genes in commensal E. coli isolated from urine samples of 118 elderly individuals residing in Ghanaian nursing care homes. A total of 195 ESBL genes were detected among 41 E. coli isolated from the study participants. All the isolates harboured at least one ESBL gene, and the majority of them (70.1%) carried at least four ESBL genes. Among the ESBL genes detected, CTXM825 was the predominant (14.1%). In antimicrobial susceptibility testing, 65.9% of the isolates showed resistance to cefepime, a fourth-generation cephalosporin, while 56.1% showed resistance to cefotaxime, a third-generation cephalosporin. Additionally, 46.3% of the isolates were multidrug-resistant, indicating resistance to antibiotics from multiple classes. In summary, we observed relatively high rates of resistance to antibiotics as well as alarming rates of ESBL genes in the isolated pathogens. These findings emphasise the urgent need for antimicrobial stewardship and infection control programmes to mitigate the spread of multidrug-resistant pathogens in nursing care homes.
Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessReview
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
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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Open AccessArticle
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
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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
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
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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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Open AccessArticle
Impact of Hepatitis Delta Virus Infection on the Selection of Hepatitis B Surface Antigen Mutations
by
Kabo Baruti, Wonderful T. Choga, Bonolo B. Phinius, Basetsana Phakedi, Lynnette Bhebhe, Gorata G. A. Mpebe, Patience C. Motshosi, Tsholofelo Ratsoma, Sikhulile Moyo, Mosimanegape Jongman, Motswedi Anderson and Simani Gaseitsiwe
Genes 2024, 15(8), 982; https://doi.org/10.3390/genes15080982 - 25 Jul 2024
Abstract
The interaction of multiple viruses in one host is thought to enhance the development of mutations. However, the impact of hepatitis D virus (HDV) positivity on the development of unique hepatitis B virus (HBV) mutations among people living with human immunodeficiency virus (HIV)
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The interaction of multiple viruses in one host is thought to enhance the development of mutations. However, the impact of hepatitis D virus (HDV) positivity on the development of unique hepatitis B virus (HBV) mutations among people living with human immunodeficiency virus (HIV) (PLWH) remains poorly understood in African countries, including Botswana. We used HBV sequences generated from the Botswana Combination Prevention Project (BCPP), which is the largest pair-matched cluster-randomized HIV trial in Botswana. Only participants with available HBV sequences (n = 55) were included in our study ([HIV/HBV-positive (n = 50) and HIV/HBV/HDV-positive (n = 5)]. Geno2pheno was used to determine HBV genotypes, and HBV surface region sequences (all subgenotype A1) were aligned in AliView for mutational analysis, while the impact of mutations was assessed using Phyre2. Our results identified 182 common mutations between the two groups. In the HIV/HBV/HDV cohort, only three mutations (L95W, W156Q, C221Y) were classified as deleterious, with only L95W being the most frequent. In the HIV/HBV cohort, four mutations (W199R, C221A, C221S, W223G) were also classified as deleterious. Our results demonstrate the presence of unique HBV mutations among the HIV/HBV/HDV-positive cohort. Functional characterization of these mutations is recommended to determine their effect on HDV.
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(This article belongs to the Special Issue Molecular Epidemiology, Genome and Evolution of Viruses)
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Open AccessArticle
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
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
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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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Open AccessArticle
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
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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Open AccessCommunication
GhWRKY40 Interacts with an Asparaginase GhAPD6 Involved in Fiber Development in Upland Cotton (Gossypium hirsutum L.)
by
Sujun Zhang, Xiao Cai, Jingyan Wei, Haitao Wang, Cunjing Liu, Xinghe Li, Liyuan Tang, Xiaodong Zhou and Jianhong Zhang
Genes 2024, 15(8), 979; https://doi.org/10.3390/genes15080979 - 24 Jul 2024
Abstract
Fiber quality improvement is a primary goal in cotton breeding. Identification of fiber quality-related genes and understanding the underlying molecular mechanisms are essential prerequisites. Previously, studies determined that silencing the gene GhWRKY40 resulted in longer cotton fibers; however, both the underlying mechanisms and
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Fiber quality improvement is a primary goal in cotton breeding. Identification of fiber quality-related genes and understanding the underlying molecular mechanisms are essential prerequisites. Previously, studies determined that silencing the gene GhWRKY40 resulted in longer cotton fibers; however, both the underlying mechanisms and whether this transcription factor is additionally involved in the regulation of cotton fiber strength/fineness are unknown. In the current study, we verified that GhWRKY40 influences the fiber strength, fiber fineness, and fiber surface structure by using virus-induced gene silencing (VIGS). Potential proteins that may interact with the nucleus-localized GhWRKY40 were screened in a yeast two-hybrid (Y2H) nuclear-system cDNA library constructed from fibers at 0, 10, and 25 days post-anthesis (DPA) in two near-isogenic lines differing in fiber length and strength. An aspartyl protease/asparaginase-related protein, GhAPD6, was identified and confirmed by Y2H and split-luciferase complementation assays. The expression of GhAPD6 was approximately 30-fold higher in the GhWRKY40-VIGS lines at 10 DPA and aspartyl protease activity was significantly upregulated in the GhWRKY40-VIGS lines at 10–20 DPA. This study suggested that GhWRKY40 may interact with GhAPD6 to regulate fiber development in cotton. The results provide a theoretical reference for the selection and breeding of high-quality cotton fibers assisted by molecular technology.
Full article
(This article belongs to the Collection Feature Papers: 'Plant Genetics and Genomics' Section)
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Open AccessArticle
Identification of Gene Regulatory Networks in B-Cell Progenitor Differentiation and Leukemia
by
Stefan Nagel and Corinna Meyer
Genes 2024, 15(8), 978; https://doi.org/10.3390/genes15080978 - 24 Jul 2024
Abstract
Pro-B- and pre-B-cells are consecutive entities in early B-cell development, representing cells of origin for B-cell precursor acute lymphoid leukemia (BCP-ALL). Normal B-cell differentiation is critically regulated by specific transcription factors (TFs). Accordingly, TF-encoding genes are frequently deregulated or mutated in BCP-ALL. Recently,
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Pro-B- and pre-B-cells are consecutive entities in early B-cell development, representing cells of origin for B-cell precursor acute lymphoid leukemia (BCP-ALL). Normal B-cell differentiation is critically regulated by specific transcription factors (TFs). Accordingly, TF-encoding genes are frequently deregulated or mutated in BCP-ALL. Recently, we described TF-codes which delineate physiological activities of selected groups of TF-encoding genes in hematopoiesis including B-cell development. Here, we exploited these codes to uncover regulatory connections between particular TFs in pro-B- and pre-B-cells via an analysis of developmental TFs encoded by NKL and TALE homeobox genes and by ETS and T-box genes. Comprehensive expression analyses in BCP-ALL cell lines helped identify validated models to study their mutual regulation in vitro. Knockdown and overexpression experiments and subsequent RNA quantification of TF-encoding genes in selected model cell lines revealed activating, inhibitory or absent connections between nine TFs operating in early B-cell development, including HLX, MSX1, IRX1, MEIS1, ETS2, ERG, SPIB, EOMES, and TBX21. In addition, genomic profiling revealed BCP-ALL subtype-specific copy number alterations of ERG at 21q22, while a deletion of the TGFbeta-receptor gene TGFBR2 at 3p24 resulted in an upregulation of EOMES. Finally, we combined the data to uncover gene regulatory networks which control normal differentiation of early B-cells, collectively endorsing more detailed evaluation of BCP-ALL subtypes.
Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Open AccessReview
Homoeologs in Allopolyploids: Navigating Redundancy as Both an Evolutionary Opportunity and a Technical Challenge—A Transcriptomics Perspective
by
Gaetano Aufiero, Carmine Fruggiero, Davide D’Angelo and Nunzio D’Agostino
Genes 2024, 15(8), 977; https://doi.org/10.3390/genes15080977 - 24 Jul 2024
Abstract
Allopolyploidy in plants involves the merging of two or more distinct parental genomes into a single nucleus, a significant evolutionary process in the plant kingdom. Transcriptomic analysis provides invaluable insights into allopolyploid plants by elucidating the fate of duplicated genes, revealing evolutionary novelties
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Allopolyploidy in plants involves the merging of two or more distinct parental genomes into a single nucleus, a significant evolutionary process in the plant kingdom. Transcriptomic analysis provides invaluable insights into allopolyploid plants by elucidating the fate of duplicated genes, revealing evolutionary novelties and uncovering their environmental adaptations. By examining gene expression profiles, scientists can discern how duplicated genes have evolved to acquire new functions or regulatory roles. This process often leads to the development of novel traits and adaptive strategies that allopolyploid plants leverage to thrive in diverse ecological niches. Understanding these molecular mechanisms not only enhances our appreciation of the genetic complexity underlying allopolyploidy but also underscores their importance in agriculture and ecosystem resilience. However, transcriptome profiling is challenging due to genomic redundancy, which is further complicated by the presence of multiple chromosomes sets and the variations among homoeologs and allelic genes. Prior to transcriptome analysis, sub-genome phasing and homoeology inference are essential for obtaining a comprehensive view of gene expression. This review aims to clarify the terminology in this field, identify the most challenging aspects of transcriptome analysis, explain their inherent difficulties, and suggest reliable analytic strategies. Furthermore, bulk RNA-seq is highlighted as a primary method for studying allopolyploid gene expression, focusing on critical steps like read mapping and normalization in differential gene expression analysis. This approach effectively captures gene expression from both parental genomes, facilitating a comprehensive analysis of their combined profiles. Its sensitivity in detecting low-abundance transcripts allows for subtle differences between parental genomes to be identified, crucial for understanding regulatory dynamics and gene expression balance in allopolyploids.
Full article
(This article belongs to the Special Issue Genetics and Genomics of Polyploid Plants)
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Open AccessArticle
Comparison of Mutations Induced by Different Doses of Fast-Neutron Irradiation in the M1 Generation of Sorghum (Sorghum bicolor)
by
Na Yuan, Shuaiqiang Liang, Ling Zhou, Xingxing Yuan, Chunhong Li, Xin Chen and Han Zhao
Genes 2024, 15(8), 976; https://doi.org/10.3390/genes15080976 - 24 Jul 2024
Abstract
Sorghum is an important C4 crop with various food and nonfood uses. Although improvements through hybridization and selection have been exploited, the introduction of genetic variation and the development of new genotypes in sorghum are still limited. Fast-neutron (FN) mutagenesis is a
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Sorghum is an important C4 crop with various food and nonfood uses. Although improvements through hybridization and selection have been exploited, the introduction of genetic variation and the development of new genotypes in sorghum are still limited. Fast-neutron (FN) mutagenesis is a very effective method for gene functional studies and to create genetic variability. However, the full spectrum of FN-induced mutations in sorghum is poorly understood. To address this, we generated an FN-induced mutant population from the inbred line ‘BTx623’ and sequenced 40 M1 seedlings to evaluate the mutagenic effects of FNs on sorghum. The results show that each line had an average of 43.7 single-base substitutions (SBSs), 3.7 InDels and 35.15 structural variations (SVs). SBSs accounted for approximately 90.0% of the total number of small mutations. Among the eight treatment groups, FN irradiation at a dose of 19 Gy generated the highest number of mutations. The ratio of transition/transversion ranged from 1.77 to 2.21, and the G/C to A/T transition was the most common substitution in all mutant lines. The distributions of the identified SBSs and InDels were similar and uneven across the genome. An average of 3.63 genes were mutated in each mutant line, indicating that FN irradiation resulted in a suitable density of mutated genes, which can be advantageous for improving elite material for one specific or a few traits. These results provide a basis for the selection of the suitable dose of mutagen and new genetic resources for sorghum breeding.
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(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle
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
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
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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.
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(This article belongs to the Topic Animal Models of Human Disease 2.0)
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Open AccessReview
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
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
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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.
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(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
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
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
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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.
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(This article belongs to the Special Issue Human Genetics: Diseases, Community, and Counseling)
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Open AccessArticle
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
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
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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.
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(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
Exploring the Impact of Genetics in a Large Cohort of Moebius Patients by Trio Whole Exome Sequencing
by
Giada Moresco, Maria Francesca Bedeschi, Marco Venturin, Roberta Villa, Jole Costanza, Alessia Mauri, Carlo Santaniello, Odoardo Picciolini, Laura Messina, Fabio Triulzi, Monica Rosa Miozzo, Ornella Rondinone and Laura Fontana
Genes 2024, 15(8), 971; https://doi.org/10.3390/genes15080971 - 23 Jul 2024
Abstract
Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance/variable expressivity have been described. The genetic etiology of MBS is
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Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance/variable expressivity have been described. The genetic etiology of MBS is still unclear: de novo pathogenic variants in REV3L and PLXND1 are reported in only a minority of cases, suggesting the involvement of additional causative genes. With the aim to uncover the molecular causative defect and identify a potential genetic basis of this condition, we performed trio-WES on a cohort of 37 MBS and MBS-like patients. No de novo variants emerged in REV3L and PLXND1. We then proceeded with a cohort analysis to identify possible common causative genes among all patients and a trio-based analysis using an in silico panel of candidate genes. However, identified variants emerging from both approaches were considered unlikely to be causative of MBS, mainly due to the lack of clinical overlap. In conclusion, despite this large cohort, WES failed to identify mutations possibly associated with MBS, further supporting the heterogeneity of this syndrome, and suggesting the need for integrated omics approaches to identify the molecular causes underlying MBS development.
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(This article belongs to the Special Issue Variations of Rare Genetic Diseases)
Open AccessArticle
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
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
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(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.
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(This article belongs to the Special Issue Advances in Pig Genetics and Breeding)
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