Genes

12 pages, 1476 KiB

Open AccessArticle

Genetic Association Study of Acetylcholinesterase (ACHE) and Butyrylcholinesterase (BCHE) Variants in Sudden Infant Death Syndrome (SIDS)

by Dong Qu, Peter Schürmann, Thomas Rothämel, Thilo Dörk and Michael Klintschar

Genes 2024, 15(12), 1656; https://doi.org/10.3390/genes15121656 - 23 Dec 2024

Viewed by 416

Abstract

Background: Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed [...] Read more.

Background: Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed autonomic function and, together with other risk factors, might trigger SIDS. To explore the contribution of AChE and BChE from a genomic viewpoint, we sought to investigate the association between SIDS and selected single nucleotide polymorphisms (SNPs) in the ACHE and BCHE genes. Methods: In this case-control study, 13 potentially regulatory SNPs were selected from ACHE and BCHE and were genotyped in 201 SIDS cases and 338 controls. The association of SIDS with the 11 successfully genotyped candidate variants was examined using statistical analyses of overall or stratified cases and haplotype analyses. Results: No significant overall associations were observed between SIDS and ACHE and BCHE variants in allele, genotype, and haplotype analyses. In subgroup analyses, eight variants were found to be nominally associated with SIDS, though these associations did not remain statistically significant after correction for multiple comparisons. One haplotype (T-C-G-C-C in rs3495-rs1803274-rs1355538-rs2048493-rs1126680) of BCHE was associated with the female SIDS subgroup (57.3% in controls vs. 46.3% in female SIDS cases, p = 0.010). Conclusions: The selected variants in ACHE and BCHE were not overall associated with SIDS in this study, and thus cannot generally explain the previously reported dysregulation of enzyme activities in SIDS. However, some evidence of association in subgroups and a possible contribution of variants other than those tested here would need to be explored in larger studies. Full article

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

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17 pages, 2616 KiB

Open AccessArticle

Exploring the Role of FICD, a New Potential Gene Involved in Borderline Intellectual Functioning, Psychological and Metabolic Disorders

by Mirella Vinci, Donatella Greco, Maria Grazia Figura, Simone Treccarichi, Antonino Musumeci, Vittoria Greco, Rossella Pettinato, Angelo Gloria, Carla Papa, Salvatore Saccone, Concetta Federico and Francesco Calì

Genes 2024, 15(12), 1655; https://doi.org/10.3390/genes15121655 - 23 Dec 2024

Viewed by 495

Abstract

Background/Objectives: AMPylation is a post-translational modification involving the transfer of adenosine monophosphate (AMP) from adenosine triphosphate (ATP) to target proteins, serving as a critical regulatory mechanism in cellular functions. This study aimed to expand the phenotypic spectrum associated with mutations in the FICD [...] Read more.

Background/Objectives: AMPylation is a post-translational modification involving the transfer of adenosine monophosphate (AMP) from adenosine triphosphate (ATP) to target proteins, serving as a critical regulatory mechanism in cellular functions. This study aimed to expand the phenotypic spectrum associated with mutations in the FICD gene, which encodes an adenyltransferase enzyme involved in both AMPylation and deAMPylation. Methods: A clinical evaluation was conducted on a patient presenting with a complex clinical profile. Whole-exome sequencing (WES) was performed to identify potential genetic variants contributing to the observed phenotype. Results: The patient exhibited borderline intellectual functioning (BIF), acanthosis, abdominal muscle hypotonia, anxiety, depression, obesity, and optic nerve subatrophy. WES revealed a de novo missense variant, c.1295C>T p.Ala432Val, in the FICD gene. This variant, classified as of uncertain significance, is located in the highly conserved region TLLFATTEY (aa 428–436), suggesting a potential impact on protein function. Conclusions: These findings highlight the importance of the FICD gene in diverse clinical manifestations and emphasize the need for further studies to elucidate the genetic mechanisms underlying these phenotypes. Continued research is essential to improve our understanding of FICD-related conditions. Full article

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

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33 pages, 4545 KiB

Open AccessReview

Chemical and Biological Investigations of Antiviral Agents Against Plant Viruses Conducted in China in the 21st Century

by Yuanyou Yang, Lei Hu, Tongtong Chen, Libo Zhang, Delu Wang and Zhuo Chen

Genes 2024, 15(12), 1654; https://doi.org/10.3390/genes15121654 - 23 Dec 2024

Viewed by 730

Abstract

Research into the biology of plant viruses, their mechanisms of pathogenicity, and the induction of host resistance has laid a solid foundation for the discovery of antiviral agents and their targets and the development of effective control technologies. Additionally, recent advancements in fields [...] Read more.

Research into the biology of plant viruses, their mechanisms of pathogenicity, and the induction of host resistance has laid a solid foundation for the discovery of antiviral agents and their targets and the development of effective control technologies. Additionally, recent advancements in fields such as chemical biology, cheminformatics, bioinformatics, and synthetic biology have provided valuable methods and tools for the design of antiviral drugs, the synthesis of drug molecules, assessment of their activity, and investigation of their modes of action. Compared with drug development for human viral diseases, the control of plant viral diseases presents greater challenges, including the cost-benefit of agents, simplification of control technologies, and the effectiveness of treatments. Therefore, in the current context of complex outbreaks and severe damage caused by plant viral diseases, it is crucial to delve deeper into the research and development of antiviral agents. This review provides a detailed overview of the biological characteristics of current targets for antiviral agents, the mode of interaction between plant virus targets and antivirals, and insights for future drug development. We believe this review will not only facilitate the in-depth analysis of the development of antivirals for crops but also offer valuable perspectives for the development of antiviral agents for use in human and veterinary medicine. Full article

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

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25 pages, 779 KiB

Open AccessFeature PaperReview

Epigenetic Regulation and Neurodevelopmental Disorders: From MeCP2 to the TCF20/PHF14 Complex

by Gaea Dominguez, Yongji Wu and Jian Zhou

Genes 2024, 15(12), 1653; https://doi.org/10.3390/genes15121653 - 23 Dec 2024

Viewed by 877

Abstract

Background: Neurodevelopmental disorders (NDDs) affect approximately 15% of children and adolescents worldwide. This group of disorders is often polygenic with varying risk factors, with many associated genes converging on shared molecular pathways, including chromatin regulation and transcriptional control. Understanding how NDD-associated chromatin regulators [...] Read more.

Background: Neurodevelopmental disorders (NDDs) affect approximately 15% of children and adolescents worldwide. This group of disorders is often polygenic with varying risk factors, with many associated genes converging on shared molecular pathways, including chromatin regulation and transcriptional control. Understanding how NDD-associated chromatin regulators and protein complexes orchestrate these regulatory pathways is crucial for elucidating NDD pathogenesis and developing targeted therapeutic strategies. Recently, the TCF20/PHF14 chromatin complex was identified in the mammalian brain, expanding the list of chromatin regulatory remodelers implicated in NDDs. This complex—which includes MeCP2, RAI1, TCF20, PHF14, and HMG20A—plays a vital role in epigenetic and transcriptional regulation. Methods: We review and summarize current research and clinical reports pertaining to the different components of the MeCP2-interacting TCF20/PHF14 complex. We examine the NDDs associated with the TCF20/PHF14 complex, explore the molecular and neuronal functions of its components, and discuss emerging therapeutic strategies targeting this complex to mitigate symptoms, with broader applicability to other NDDs. Results: Mutations in the genes encoding the components of the MeCP2-interacting TCF20/PHF14 complex have been linked to various NDDs, underscoring its critical contribution to brain development and NDD pathogenesis. Conclusions: The MeCP2-interacting TCF20/PHF14 complex and its associated NDDs could serve as a model system to provide insight into the interplay between epigenetic regulation and NDD pathogenesis. Full article

(This article belongs to the Special Issue The Genetic and Epigenetic Basis of Neurodevelopmental Disorders)

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14 pages, 4479 KiB

Open AccessArticle

Genetic Mapping by 55K Single-Nucleotide Polymorphism Array Reveals Candidate Genes for Tillering Trait in Wheat Mutant dmc

by Kemeng Jiao, Guojun Xia, Yuan Zhou, Chenyu Zhao, Huiyuan Yan, Menglei Qi, Pingfan Xie, Yongjing Ni, Jingxue Zhao, Jishan Niu, Zhaofei Chao, Jiangping Ren and Lei Li

Genes 2024, 15(12), 1652; https://doi.org/10.3390/genes15121652 - 22 Dec 2024

Viewed by 791

Abstract

Background: The tiller number is a key agronomic trait for increasing the yield potential of wheat (Triticum aestivum L.). A number of quantitative trait loci (QTLs) and key genes controlling tillering have been identified, but the regulatory mechanisms remain unclear. Methods: In [...] Read more.

Background: The tiller number is a key agronomic trait for increasing the yield potential of wheat (Triticum aestivum L.). A number of quantitative trait loci (QTLs) and key genes controlling tillering have been identified, but the regulatory mechanisms remain unclear. Methods: In this study, we utilized the dwarf-monoculm mutant (dmc) obtained from the ethyl methane sulfonate (EMS)-treated wheat cultivar Guomai 301. The F₂ populations were constructed using the dmc mutant crossed to multiple tiller parents. The F₂ populations were surveyed for tillering traits at the critical fertility stage for genetic analyses. The extreme-tillering-phenotype plants from the F₂ population were used to construct mixing pools that were analyzed by a wheat 55K SNP array. The tillering genes of dmc were mapped using the wheat 55K SNP array combined with transcriptomic data. Results: The results showed that the genetic phenotype of dmc is controlled by two dominant genes. The tillering genes of dmc were mapped on the 60–100 Mb region of chromosome 5B and the 135–160 Mb region of chromosome 7A. A total of sixteen candidate genes associated with the tillering trait of dmc were identified. Two candidate genes, TraesCS5B02G058800 and TraesCS7A02G184200, were predicted to be involved in indole acetic acid (IAA) response and transport, which were considered as potential regulatory genes. Conclusions: This study elucidated the genetic basis of the dmc mutant and provided two valuable reference genes for studying the development and regulatory mechanisms of wheat tillering. Full article

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

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18 pages, 1681 KiB

Open AccessArticle

Complete Genome Assembly of Amycolatopsis bartoniae DSM 45807^T Allows the Characterization of a Novel Glycopeptide Biosynthetic Gene Cluster

by Anastasia Stepanyshyn, Christian Rückert-Reed, Tobias Busche, Bohdan Yaruta, Andres Andreo-Vidal, Flavia Marinelli, Jörn Kalinowski and Oleksandr Yushchuk

Genes 2024, 15(12), 1651; https://doi.org/10.3390/genes15121651 - 22 Dec 2024

Viewed by 591

Abstract

Background: Glycopeptide antibiotics (GPAs) are a very successful class of clinically relevant antibacterials, used to treat severe infections caused by Gram-positive pathogens, e.g., multidrug resistant and methicillin-resistant staphylococci. The biosynthesis of GPAs is coded within large biosynthetic gene clusters (BGCs). In recent years, [...] Read more.

Background: Glycopeptide antibiotics (GPAs) are a very successful class of clinically relevant antibacterials, used to treat severe infections caused by Gram-positive pathogens, e.g., multidrug resistant and methicillin-resistant staphylococci. The biosynthesis of GPAs is coded within large biosynthetic gene clusters (BGCs). In recent years, modern DNA sequencing technologies have allowed the identification and characterization of multiple novel GPA BGCs, leading to the discovery of novel compounds. Our previous research anticipated that the genome of Amycolatopsis bartoniae DSM 45807^T carries a novel GPA BGC, although the genomic sequence quality available at that time did not allow us to characterize its organization properly. Objectives: To address this gap, in the current work we aimed to produce a complete genome assembly of A. bartoniae DSM 45807, and to identify and analyze the corresponding GPA BGC. Methods: Bioinformatic and microbiological methods were utilized in this research. Results: We de novo sequenced and completely assembled the genome of A. bartoniae DSM 45807, and fully characterized the BGC of interest, named aba. This BGC has an unusual gene organization and it contains four genes for sulfotransferases, which are considered to be rare in GPA BGCs. Our pathway prediction indicated that aba encodes the biosynthesis of a putatively novel GPA, although we were not able to detect any GPA production under different cultivation conditions, implying that aba pathway is inactive. Conclusions: Our results indicate aba as a promising source for new GPA tailoring enzymes. Full article

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

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15 pages, 687 KiB

Open AccessReview

Federated Learning: Breaking Down Barriers in Global Genomic Research

by Giulia Calvino, Cristina Peconi, Claudia Strafella, Giulia Trastulli, Domenica Megalizzi, Sarah Andreucci, Raffaella Cascella, Carlo Caltagirone, Stefania Zampatti and Emiliano Giardina

Genes 2024, 15(12), 1650; https://doi.org/10.3390/genes15121650 - 22 Dec 2024

Viewed by 532

Abstract

Recent advancements in Next-Generation Sequencing (NGS) technologies have revolutionized genomic research, presenting unprecedented opportunities for personalized medicine and population genetics. However, issues such as data silos, privacy concerns, and regulatory challenges hinder large-scale data integration and collaboration. Federated Learning (FL) has emerged as [...] Read more.

Recent advancements in Next-Generation Sequencing (NGS) technologies have revolutionized genomic research, presenting unprecedented opportunities for personalized medicine and population genetics. However, issues such as data silos, privacy concerns, and regulatory challenges hinder large-scale data integration and collaboration. Federated Learning (FL) has emerged as a transformative solution, enabling decentralized data analysis while preserving privacy and complying with regulations such as the General Data Protection Regulation (GDPR). This review explores the potential use of FL in genomics, detailing its methodology, including local model training, secure aggregation, and iterative improvement. Key challenges, such as heterogeneous data integration and cybersecurity risks, are examined alongside regulations like GDPR. In conclusion, successful implementations of FL in global and national initiatives demonstrate its scalability and role in supporting collaborative research. Finally, we discuss future directions, including AI integration and the necessity of education and training, to fully harness the potential of FL in advancing precision medicine and global health initiatives. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Genomics)

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16 pages, 3447 KiB

Open AccessArticle

Non-Invasive miRNA Profiling for Differential Diagnosis and Prognostic Stratification of Testicular Germ Cell Tumors

by Panagiotis J. Vlachostergios, Konstantinos Evmorfopoulos, Ioannis Zachos, Konstantinos Dimitropoulos, Eleni Thodou, Maria Samara, Vassilios Tzortzis and Antonis Giakountis

Genes 2024, 15(12), 1649; https://doi.org/10.3390/genes15121649 - 22 Dec 2024

Viewed by 616

Abstract

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. [...] Read more.

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Methods: Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients’ fluids. Results: Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. Conclusions: These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications. Full article

(This article belongs to the Special Issue Genomic Approaches for Disease Diagnosis and Prognosis)

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26 pages, 6347 KiB

Open AccessArticle

The Arabidopsis thaliana Double-Stranded RNA Binding Proteins DRB1 and DRB2 Are Required for miR160-Mediated Responses to Exogenous Auxin

by Kim Zimmerman, Joseph L. Pegler, Jackson M. J. Oultram, David A. Collings, Ming-Bo Wang, Christopher P. L. Grof and Andrew L. Eamens

Genes 2024, 15(12), 1648; https://doi.org/10.3390/genes15121648 - 21 Dec 2024

Viewed by 660

Abstract

DOUBLE-STRANDED RNA BINDING (DRB) proteins DRB1, DRB2, and DRB4 are essential for microRNA (miRNA) production in Arabidopsis thaliana (Arabidopsis) with miR160, and its target genes, AUXIN RESPONSE FACTOR10 (ARF10), ARF16, and ARF17, forming an auxin responsive miRNA [...] Read more.

DOUBLE-STRANDED RNA BINDING (DRB) proteins DRB1, DRB2, and DRB4 are essential for microRNA (miRNA) production in Arabidopsis thaliana (Arabidopsis) with miR160, and its target genes, AUXIN RESPONSE FACTOR10 (ARF10), ARF16, and ARF17, forming an auxin responsive miRNA expression module crucial for root development. Methods: Wild-type Arabidopsis plants (Columbia-0 (Col-0)) and the drb1, drb2, and drb12 mutants were treated with the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D), and the miR160-mediated response of these four Arabidopsis lines was phenotypically and molecularly characterized. Results: In 2,4-D-treated Col-0, drb1 and drb2 plants, altered miR160 abundance and ARF10, ARF16, and ARF17 gene expression were associated with altered root system development. However, miR160-directed molecular responses to treatment with 2,4-D was largely defective in the drb12 double mutant. In addition, via profiling of molecular components of the miR160 expression module in the roots of the drb4, drb14, and drb24 mutants, we uncovered a previously unknown role for DRB4 in regulating miR160 production. Conclusions: The miR160 expression module forms a central component of the molecular and phenotypic response of Arabidopsis plants to exogenous auxin treatment. Furthermore, DRB1, DRB2, and DRB4 are all required in Arabidopsis roots to control miR160 production, and subsequently, to appropriately regulate ARF10, ARF16, and ARF17 target gene expression. Full article

(This article belongs to the Special Issue Plant Genetic Diversity and Omics Research)

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14 pages, 2472 KiB

Open AccessArticle

New Axes of Interaction in Circ_0079593/miR-516b-5p Network in Melanoma Metastasis Cell Lines

by Elisa De Tomi, Elisa Orlandi, Francesca Belpinati, Cristina Patuzzo, Elisabetta Trabetti, Macarena Gomez-Lira and Giovanni Malerba

Genes 2024, 15(12), 1647; https://doi.org/10.3390/genes15121647 - 21 Dec 2024

Viewed by 548

Abstract

Background/Objectives: microRNAs (miRNAs) and circular RNA (circRNAs) show a close interconnection in the control of fundamental functions, such as cell proliferation and tumor development. A full understanding of this complex and interconnected network is essential for better understanding the mechanisms underlying cancer progression. [...] Read more.

Background/Objectives: microRNAs (miRNAs) and circular RNA (circRNAs) show a close interconnection in the control of fundamental functions, such as cell proliferation and tumor development. A full understanding of this complex and interconnected network is essential for better understanding the mechanisms underlying cancer progression. Hsa_circ_0079593 is a circRNA highly expressed in melanoma and is associated with increased metastasis and progression of malignancy, whereas miR516b-5p is a microRNA whose expression is lower in several tumor types, including melanoma; its overexpression inhibits cell proliferation, migration, and invasion. In this study, we tested whether circ_0079593 is involved in the progression of melanoma aggressiveness by regulating CHAF1B and MCAM via the inhibition of miR-516b-5p. Methods: We first verified the expression of the key components in both healthy melanocyte lines and melanoma metastases, subsequently using in vitro assays such as scratch tests, Western blot, qRT-PCR, and dual luciferase report assay; we verified their interconnected regulatory effect. Results: Our results showed that circ_0079593-miR516b-5p interactions are involved in the increase in the migration of metastasis melanoma cells by exploiting their binding to MCAM and CHAF1B mRNAs. Conclusions: This study provides two other regulatory networks in which circ_0079593 may exert its oncogenic function by increasing the speed of movement of metastatic cells through the sponge of miR-516b-5p, which cannot regulate MCAM and CHAF1B expression. Full article

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14 pages, 2696 KiB

Open AccessArticle

Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes

by Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen and Sabika Firasat

Genes 2024, 15(12), 1646; https://doi.org/10.3390/genes15121646 - 21 Dec 2024

Viewed by 925

Abstract

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive [...] Read more.

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next generation sequencing. Methods: This study enrolled 15 consanguineous families, each with multiple affected cases of retinal dystrophy phenotype. DNA was extracted from blood samples. Targeted panel sequencing of 344 known genes for IRDs was performed, followed by Sanger sequencing for segregation analysis. Results: Data analysis revealed a total of eight reported (c.316C>T and c.506G>A in RDH12; c.864dup and c.1012C>T in SPATA7, as well as c.1459T>C, c.1062_1068del, c.1495+1G>A, c.998G>A in the CRB1, LCA5, TULP1, and IFT140 genes, respectively) and four novel homozygous (c.720+1G>T in LCA5, c.196G>C in LRAT, c.620_625del in PRPH2, and c.3411_3414del in CRB1) variants segregating with disease phenotype in each respective family. Furthermore, a novel heterozygous variant of CRB1 gene, i.e., c.1935delC in compound heterozygous condition was found segregating with disease phenotype in one large family with multiple consanguinity loops. Conclusion: Comprehensive molecular diagnosis of 15 consanguineous Pakistani families led to the identification of a total of 5 novel variants contributing to genetic heterogeneity of LCA-associated genes and helped to provide genetic counseling to the affected families. Full article

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

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18 pages, 1226 KiB

Open AccessArticle

House Mice in the Atlantic Region: Genetic Signals of Their Human Transport

by Sofia I. Gabriel, Jonathan J. Hughes, Jeremy S. Herman, John F. Baines, Mabel D. Giménez, Melissa M. Gray, Emilie A. Hardouin, Bret A. Payseur, Peter G. Ryan, Alejandro Sánchez-Chardi, Rainer G. Ulrich, Maria da Luz Mathias and Jeremy B. Searle

Genes 2024, 15(12), 1645; https://doi.org/10.3390/genes15121645 - 21 Dec 2024

Viewed by 656

Abstract

Background/Objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens. Methods: We assembled a dataset [...] Read more.

Background/Objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens. Methods: We assembled a dataset of 758 haplotypes derived from 2765 mice from 47 countries/oceanic archipelagos (a combination of new and published data). Our maximum likelihood phylogeny recovered five previously identified clades, and we used the haplotype affinities within the phylogeny to infer house mouse colonization history, employing statistical tests and indices. From human history, we predefined four European source areas for mice in the Atlantic region (Northern Europe excluding Scandinavia, Southern Europe, Scandinavia, and Macaronesia) and we investigated the colonization from these source areas to different geographic areas in the Atlantic region. Results: Our inferences suggest mouse colonization of Scandinavia itself from Northern Europe, and Macaronesia from both Southern Europe and Scandinavia/Germany (the latter likely representing the transport of mice by Vikings). Mice on North Atlantic islands apparently derive primarily from Scandinavia, while for South Atlantic islands, North America, and Sub-Saharan Africa, the clearest source is Northern Europe, although mice on South Atlantic islands also had genetic inputs from Macaronesia and Southern Europe (for Tristan da Cunha). Macaronesia was a stopover for Atlantic voyages, creating an opportunity for mouse infestation. Mice in Latin America also apparently had multiple colonization sources, with a strong Southern European signal but also input from Northern Europe and/or Macaronesia. Conclusions: D-loop sequences help discern the broad-scale colonization history of house mice and new perspectives on human history. Full article

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

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17 pages, 2764 KiB

Open AccessArticle

Drought Stress Inhibits the Accumulation of Rotenoids and the Biosynthesis of Drought-Responsive Phytohormones in Mirabilis himalaica (Edgew.) Heim Calli

by Shiyi Zhang, Jiaqi Gao, Xiaozhong Lan, Linfan Zhang, Weipeng Lian, Chenglin Wang, Zhanyun Shen, Xiang Li and Juan Liu

Genes 2024, 15(12), 1644; https://doi.org/10.3390/genes15121644 - 21 Dec 2024

Viewed by 610

Abstract

Background: Mirabilis himalaica, distributed in the high-altitude, arid, and semi-arid regions of Xizang, exhibits great tolerance to drought, which is rich in rotenoids and other secondary metabolites. It is still unknown, though, how drought stress influences rotenoid synthesis in M. himalaica [...] Read more.

Background: Mirabilis himalaica, distributed in the high-altitude, arid, and semi-arid regions of Xizang, exhibits great tolerance to drought, which is rich in rotenoids and other secondary metabolites. It is still unknown, though, how drought stress influences rotenoid synthesis in M. himalaica. Methods: In this study, the calli of M. himalaica were subjected to 5% PEG6000 for 0, 20, and 40 h and divided into control group (CK), mild-drought-treated group (M), and high-drought-treated group (H), respectively. We then analyzed the relative content of three main rotenoids in M. himalaica using high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS). Results: Our findings demonstrated that the content of rotenoids was significantly reduced under drought stress. Transcriptome analysis subsequently revealed 14,525 differentially expressed genes (DEGs) between the different treatments. Furthermore, these DEGs exhibited enrichment in pathways associated with isoflavone biosynthesis and hormone signaling pathways. Key genes with decreased expression patterns during drought stress were also found to be involved in rotenoid accumulation and drought-responsive phytohormone signaling, including abscisic acid (ABA), auxin (IAA), and jasmonic acid (JA). Conclusions: These findings elucidate the molecular processes of drought resistance in M. himalaica and shed light on the relationship between rotenoid production and drought stress in M. himalaica. Full article

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

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22 pages, 4014 KiB

Open AccessArticle

Genomic Analysis of Talaromyces verruculosus SJ9: An Efficient Tetracycline-, Enrofloxacin-, and Tylosin-Degrading Fungus

by Jing Fu, Xiaoqing Wu, Chi Zhang, Yuhan Tang, Fangyuan Zhou, Xinjian Zhang and Susu Fan

Genes 2024, 15(12), 1643; https://doi.org/10.3390/genes15121643 - 21 Dec 2024

Viewed by 429

Abstract

Background/Objectives: Many fungi related to Talaromyces verruculosus can degrade a wide range of pollutants and are widely distributed globally. T. verruculosus SJ9 was enriched from fresh strawberry inter-root soil to yield fungi capable of degrading tetracycline, enrofloxacin, and tylosin. Methods: T. verruculosus SJ9 [...] Read more.

Background/Objectives: Many fungi related to Talaromyces verruculosus can degrade a wide range of pollutants and are widely distributed globally. T. verruculosus SJ9 was enriched from fresh strawberry inter-root soil to yield fungi capable of degrading tetracycline, enrofloxacin, and tylosin. Methods: T. verruculosus SJ9 genome was sequenced, assembled, and annotated in this study utilizing bioinformatics software, PacBio, and the Illumina NovaSeq PE150 technology. Results: The genome size is 40.6 Mb, the N50 scaffold size is 4,534,389 bp, and the predicted number of coding genes is 8171. The T. verruculosus TS63-9 genome has the highest resemblance to the T. verruculosus SJ9 genome, according to a comparative genomic analysis of seven species. In addition, we annotated many genes encoding antibiotic-degrading enzymes in T. verruculosus SJ9 through genomic databases, which also provided strong evidence for its ability to degrade antibiotics. Conclusions: Through the correlation analysis of the whole-genome data of T. verruculosus SJ9, we identified a number of genes capable of encoding antibiotic-degrading enzymes in its gene function annotation database. These antibiotic-related enzymes provide some evidence that T. verruculosus SJ9 can degrade fluoroquinolone antibiotics, tetracycline antibiotics, and macrolide antibiotics. In summary, the complete genome sequence of T. verruculosus SJ9 has now been published, and this resource constitutes a significant dataset that will inform forthcoming transcriptomic, proteomic, and metabolic investigations of this fungal species. In addition, genomic studies of other filamentous fungi can utilize it as a reference. Thanks to the discoveries made in this study, the future application of this fungus in industrial production will be more rapid. Full article

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

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14 pages, 2314 KiB

Open AccessArticle

Complete Mitochondrial Genomes of Pluvialis fulva and Charadrius dubius with Phylogenetic Analysis of Charadriiformes

by Kuo Sun, Qingxiong Wang, Kun Bian, Feiran Li, Jie Tang, Lijuan Suo, Xiang Hou and Chao Yang

Genes 2024, 15(12), 1642; https://doi.org/10.3390/genes15121642 - 21 Dec 2024

Viewed by 447

Abstract

Background: Plovers (Charadriidae), within the order of Charadriiformes, a group of modern birds distributed worldwide, are a frequent subject of molecular phylogenetic studies. While research on mitochondrial genome (mitogenome) variation within the family Charadriidae, especially intraspecific variation, is limited. Additionally, the monophyly of [...] Read more.

Background: Plovers (Charadriidae), within the order of Charadriiformes, a group of modern birds distributed worldwide, are a frequent subject of molecular phylogenetic studies. While research on mitochondrial genome (mitogenome) variation within the family Charadriidae, especially intraspecific variation, is limited. Additionally, the monophyly of Charadrius and the phylogenetic placement of Pluvialis remain contentious. Nevertheless, recent studies utilizing complete mitogenomes from available databases to construct phylogenetic trees for Charadriidae and Charadriiformes remain scarce. Methods: This study aims to explore mitogenome variation within Charadrius dubius and clarify the phylogenetic placement of Pluvialis fulva. We sequenced the complete mitogenome of six C. dubius and one P. fulva, and all additional available mitogenomes were integrated within Charadriiformes. The average complete mitogenome length of C. dubius is 16,889 bp, and P. fulva is 16,859 bp. Results: Our results support the suggestion that the monophyly of Charadrius and P. fulva is nested within Charadriidae. The phylogenetic analysis of Charadriiformes based on mitogenomes strongly supports the recognition of three major shorebird clades: Charadrii, Lari and Scolopaci, with Lari and Scolopaci identified as sister clades. Conclusions: Our study reinforces the credibility of the inferred evolutionary relationships within Charadriidae and Charadriiformes. Full article

(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals: 2024–2025)

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17 pages, 7574 KiB

Open AccessArticle

Identification of Retrocopies in Lepidoptera and Impact on Domestication of Silkworm

by Lingzi Bie, Jiahe Sun, Yi Wang and Chunfang Wang

Genes 2024, 15(12), 1641; https://doi.org/10.3390/genes15121641 - 21 Dec 2024

Viewed by 394

Abstract

Background: During the domestication of silkworm, an economic insect, its physiological characteristics have changed greatly. RNA-based gene duplication, known as retrocopy, plays an important role in the formation of new genes and genome evolution, but the retrocopies of lepidopteran insects have not been [...] Read more.

Background: During the domestication of silkworm, an economic insect, its physiological characteristics have changed greatly. RNA-based gene duplication, known as retrocopy, plays an important role in the formation of new genes and genome evolution, but the retrocopies of lepidopteran insects have not been fully identified and analyzed, which not only severely limits researchers from exploring the effects of retrocopies on lepidopteran insects but also affects the studies on the domestication of silkworm. Methods: We compared the genomes and proteomes of eight lepidopteran insects and used a series of screening criteria for auxiliary screening to obtain the retrocopies in lepidopteran insects and explored their characteristics. In addition, based on the silkworm transcriptome data from the SilkDB3.0 website, we explored the functions of the retrocopies on the domestication of the silkworm. Results: A total of 1993 retrocopies and 1208 parental genes in lepidopteran insects were obtained. We revealed that the retrocopies in Lepidoptera do not conform to the “out of X” hypothesis but fit the “out of testis” hypothesis. These retrocopies were subject to strong functional constraints and performed important functions in growth and development. Transcriptome analysis revealed that the expression pattern of the retrocopies and their parental genes were irrelevant. Through the analysis of the retrocopies in silkworm generated after domestication and located in the candidate domestication regions, the possible universal connection between the retrocopies and the domestication of silkworm were found. Conclusions: Our study pioneered the exploration of retrocopies in multiple Lepidoptera species and found the potential association between the retrocopies and the domestication of silkworm. Full article

(This article belongs to the Special Issue Genomics, Transcriptomics, and Proteomics of Insects)

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9 pages, 725 KiB

Open AccessArticle

Impact of Long-Term Cannabidiol (CBD) Treatment on Mouse Kidney Transcriptome

by Mikołaj Rokicki, Jakub Żurowski, Sebastian Sawicki, Ewa Ocłoń, Tomasz Szmatoła, Igor Jasielczuk, Karolina Mizera-Szpilka, Ewelina Semik-Gurgul and Artur Gurgul

Genes 2024, 15(12), 1640; https://doi.org/10.3390/genes15121640 - 21 Dec 2024

Viewed by 603

Abstract

Background: Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions. Objectives: This article investigates the effect of [...] Read more.

Background: Cannabidiol, which is one of the main cannabinoids present in Cannabis sativa plants, has been shown to have therapeutic properties, including anti-inflammatory and antioxidant effects that may be useful for treatment of various kidney conditions. Objectives: This article investigates the effect of long-term cannabidiol (CBD) treatment on changes in the renal transcriptome in a mouse model. The main hypothesis was that systematic CBD treatment would affect gene expression associated with those processes in the kidney. Methods: The study was conducted on male C57BL/6J mice. Mice in the experimental groups received daily intraperitoneal injections of CBD at doses of 10 mg/kg or 20 mg/kg body weight (b.w.) for 28 days. After the experiment, kidney tissues were collected, RNA was isolated, and RNA-Seq sequencing was performed. Results: The results show CBD’s effects on changes in gene expression, including the regulation of genes related to circadian rhythm (e.g., Ciart, Nr1d1, Nr1d2, Per2, and Per3), glucocorticoid receptor function (e.g., Cyp1b1, Ddit4, Foxo3, Gjb2, and Pck1), lipid metabolism (e.g., Cyp2d22, Cyp2d9, Decr2 Hacl1, and Sphk1), and inflammatory response (e.g., Cxcr4 and Ccl28). Conclusions: The obtained results suggest that CBD may be beneficial for therapeutic purposes in treating kidney disease, and its effects should be further analyzed in clinical trials. Full article

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

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11 pages, 570 KiB

Open AccessArticle

Relationship of Interleukin 6 with Hepatic Steatosis and Liver Fibrosis in Rheumatoid Arthritis at a Rheumatology Care Center in Cartagena, Colombia

by Gloria Caterine Pérez-Mingan, Rita Magola Sierra-Merlano, Ismael Yepes, María Judith Palomino Vergara, Miguel Ortiz, Breiner Peña, Eder Cano-Pérez and Doris Gómez-Camargo

Genes 2024, 15(12), 1639; https://doi.org/10.3390/genes15121639 - 21 Dec 2024

Viewed by 533

Abstract

Background/Objectives: This study aimed to investigate the association of IL-6 with steatotic liver disease (SLD) and liver fibrosis (LF) in rheumatoid arthritis (RA) patients at a rheumatology center in Cartagena de Indias, Colombia. Methods: This was a cross-sectional study that included RA and [...] Read more.

Background/Objectives: This study aimed to investigate the association of IL-6 with steatotic liver disease (SLD) and liver fibrosis (LF) in rheumatoid arthritis (RA) patients at a rheumatology center in Cartagena de Indias, Colombia. Methods: This was a cross-sectional study that included RA and non-RA cases. The level of cellular expression of interleukin 6 (IL-6) was evaluated by flow cytometry in peripheral blood leukocytes, and the presence of SLD and LF was detected by elastosonography. The main outcome was to establish the association between the levels of cellular expression of IL-6 and the development of SLD and LF. Results: This study included 47 cases of RA and 34 cases on-RA, with a mean age of 54 and 55 years, respectively. The frequency of SLD was 55.3% in RA and 38.2% in non-RA. The frequency of LF was 12.8% in RA and 14.7% in non-RA, with no statistical difference. The levels of cellular expression of IL-6 were significantly higher in RA compared to non-RA. Cellular expression of IL-6 was associated with the presence of SLD (54% vs. 30.3%; p = 0.002). This association was not maintained in RA cases (49.5% vs. 47.6%; p = 0.571). No association was found between cellular expression of IL-6 and LF in the total population (43.8% vs. 42.7%; p = 0.813) nor in RA cases (59.41% vs. 48.3%; p = 0.526). Conclusions: IL-6 levels were related to SLD in the evaluated sample, and RA was not a risk factor for SLD or LF. The prognostic role of IL-6 for SLD in patients with RA requires further studies. Full article

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

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16 pages, 2450 KiB

Open AccessArticle

Intraspecific Chloroplast Genome Genetic Polymorphism of Pinellia ternata (Xi Junecry) and Its Revelation of a Single Origin in Phylogeny

by Wenlong Xing, Weihan Yu, Yuanyuan Kong, Xian Ren, Liuying Zhu, Qingyang Li, Yujie Yang, Yueqin Cheng and Hongwei Wang

Genes 2024, 15(12), 1638; https://doi.org/10.3390/genes15121638 - 20 Dec 2024

Viewed by 436

Abstract

Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi [...] Read more.

Background: Xi Junecry (Pinellia ternata), a perennial herb of the Araceae family, is indigenous to Xinxian County, Henan Province, China, and is regarded as a premium variety among similar medicinal materials. However, the lack of comprehensive genetic information on Xi Junecry germplasm resources has constrained the cultivation and identification of high-quality varieties. Methods: In this study, six chloroplast genomes of Xi Junecry were assembled and annotated using high-throughput sequencing. Subsequently, comparative analyses were conducted, and a phylogenetic tree was constructed. Results: The six Xi Junecry chloroplast genome lengths ranged from 157,456 to 158,406 bp, and the GC content was between 36.0% and 36.2%. A total of 265 single nucleotide polymorphism sites were identified across the six genomes, with a whole-genome nucleotide diversity (Pi) value of 0.00084. Among the four genomic regions, the small single-copy region exhibited the highest Pi, followed by the large single-copy region, while the inverted repeat region showed the lowest. Nucleotide polymorphism in coding regions was significantly lower than in non-coding regions. Nine hypervariable regions were identified, as follows: ndhE-ndhG, trnN-GUU-ndhF, trnS-GCU-trnG-UCC, atpB-rbcL, psaI, accD-ycf4, psbE-petL, psaC-ndhE, and psbI-trnG-UCC. Positive selection sites were detected in the accD and rbcL genes. Phylogenetic analysis clustered the six Xi Junecry samples into a distinct clade, separating them from other regional Pinellia samples. Conclusions: These findings elucidate the genetic variation levels in Xi Junecry and provide high-variability loci for population history inference, genetic diversity assessment, species domestication studies, and new cultivar development. Full article

(This article belongs to the Special Issue Plant Genetic Resources: Genetic Diversity, Conservation, and Utilization)

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16 pages, 1837 KiB

Open AccessArticle

Genome-Wide Association Analysis of Growth Traits in Hu Sheep

by Tingting Li, Feng Xing, Na Zhang, Jieran Chen, Yuting Zhang, Hengqian Yang, Shiyu Peng, Runlin Ma, Qiuyue Liu, Shangquan Gan and Haitao Wang

Genes 2024, 15(12), 1637; https://doi.org/10.3390/genes15121637 - 20 Dec 2024

Viewed by 473

Abstract

(1) Background: The Hu sheep is a renowned breed characterized by high reproduction, year-round estrus, and resistance to high humidity and temperature conditions. However, the breed exhibits lower growth rates and meat yields, which necessitate improvements through selective breeding. The integration of molecular [...] Read more.

(1) Background: The Hu sheep is a renowned breed characterized by high reproduction, year-round estrus, and resistance to high humidity and temperature conditions. However, the breed exhibits lower growth rates and meat yields, which necessitate improvements through selective breeding. The integration of molecular markers in sheep breeding programs has the potential to enhance growth performance, reduce breeding cycles, and increase meat production. Currently, the applications of SNP chips for genotyping in conjunction with genome-wide association studies (GWAS) have become a prevalent approach for identifying candidate genes associated with economically significant traits in livestock. (2) Methods: To pinpoint candidate genes influencing growth traits in Hu sheep, we recorded the birth weight, weaning weight, and weights at 3, 4, 5, 6, and 7 months for a total of 567 Hu sheep, and genotyping was performed using the Ovine 40K SNP chip. (3) Results: Through GWAS analysis and KEGG pathway enrichment, we identified three candidate genes associated with birth weight (CAMK2B, CACNA2D1, and CACNA1C). Additionally, we found two candidate genes linked to weaning weight (FGF9 and BMPR1B), with CACNA2D1 also serving as a shared gene between birth weight and weaning weight traits. Furthermore, we identified eight candidate genes related to monthly weight (FIGF, WT1, KCNIP4, JAK2, WWP1, PLCL1, GPRIN3, and CCSER1). (4) Conclusion: Our findings revealed a total of 13 candidate genetic markers that can be utilized for molecular marker-assisted selection, aiming to improve meat production in sheep breeding programs. Full article

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

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11 pages, 705 KiB

Open AccessArticle

Novel Intragenic and Genomic Variants Highlight the Phenotypic Variability in HCCS-Related Disease

by Linda M. Reis, Donald Basel, Pierre Bitoun, David S. Walton, Tom Glaser and Elena V. Semina

Genes 2024, 15(12), 1636; https://doi.org/10.3390/genes15121636 - 20 Dec 2024

Viewed by 359

Abstract

Background: Disruption of HCCS results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or [...] Read more.

Background: Disruption of HCCS results in microphthalmia with linear skin lesions (MLS) characterized by microphthalmia/anophthalmia, corneal opacity, aplastic skin lesions, variable central nervous system and cardiac anomalies, intellectual disability, and poor growth in heterozygous females. Structural variants consisting of chromosomal rearrangements or deletions are the most common variant type, but a small number of intragenic variants have been reported. Methods: Exome sequencing identified variants affecting HCCS. Results: Three novel intragenic variants and two genomic deletions of HCCS were found in individuals with primarily ocular features of MLS. X-inactivation was highly skewed in affected individuals with all three intragenic variants. Corneal opacity was the most penetrant feature (100%). In addition, a duplication of uncertain significance including both HCCS and AMELX was identified in a male with corneal anomalies, glaucoma, an atrial septal defect, and enamel hypoplasia along with a family history of developmental ocular disorders consistent with X-linked inheritance. Conclusion: Although variable expressivity is a known feature of MLS, our findings provide additional support for including HCCS in testing for individuals with isolated ocular anomalies and provide further evidence for its association with congenital aphakia, aniridia/other iris defects, and corneal staphyloma/ectasia. Full article

(This article belongs to the Special Issue Genetics of Eye Development and Diseases)

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21 pages, 459 KiB

Open AccessFeature PaperArticle

Neutral Genetic Diversity in Mixed Mating Systems

by Marcy K. Uyenoyama

Genes 2024, 15(12), 1635; https://doi.org/10.3390/genes15121635 - 20 Dec 2024

Viewed by 320

Abstract

Background/Objectives: Systems of reproduction differ with respect to the magnitude of neutral genetic diversity maintained in a population. In particular, the partitioning of reproductive organisms into mating types and regular inbreeding have long been recognized as key factors that influence effective population number. [...] Read more.

Background/Objectives: Systems of reproduction differ with respect to the magnitude of neutral genetic diversity maintained in a population. In particular, the partitioning of reproductive organisms into mating types and regular inbreeding have long been recognized as key factors that influence effective population number. Here, a range of reproductive systems are compared with respect to the maintenance of neutral genetic diversity. This study addresses full gonochorism, full hermaphroditism, androdioecy (male and hermaphroditic reproductives), and gynodioecy (female and hermaphroditic reproductives). Methods: Coalescence theory is used to determine the level of diversity maintained under each mating system considered. Results: For each mating system, the nature of the dependence of the level of neutral diversity on inbreeding depression, sex-specific viability, and other factors is described. In particular, the models account for the effects of sex-specific viability on the evolutionarily stable sex ratio and the collective contribution of each mating type (sex) to the offspring generation. Conclusions: Within the context of conservation biology, population genetic and quantitative genetic theory has addressed the determination of the target minimum effective population size. In contrast, this study proposes and explores a summary statistic (a ratio of effective numbers) as a means of characterizing the context in which evolution occurs. Full article

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

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13 pages, 2860 KiB

Open AccessArticle

The Simultaneous Treatment of PC-3 Cells with the DNA-Demethylating Agent Decitabine and S-Adenosylmethionine Leads to Synergistic Anticancer Effects

by Thomas Schmidt and Carsten Sticht

Genes 2024, 15(12), 1634; https://doi.org/10.3390/genes15121634 - 20 Dec 2024

Viewed by 648

Abstract

Background: Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators. Previous studies have suggested that concordantly [...] Read more.

Background: Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators. Previous studies have suggested that concordantly targeting hypomethylation and hypermethylation is beneficial for suppressing both the oncogenic and pro-metastatic functions of cancer cells. Therefore, we aimed to investigate the effect of a combination of S-adenosylmethionine (SAM) and the demethylating agent decitabine on prostate cancer cells. Materials and Methods: Prostate cancer cells (PC-3) were treated with SAM, decitabine, or a combination of both. Proliferation, migration, invasion, and methylation assays were also performed. A transcriptome study was conducted to detect different gene clusters between the treatment groups, followed by analyses using the Kyoto Encyclopedia of Genes and Genomes pathway and ingenuity pathway analysis. Finally, to gain information on differential gene expression, promoter methylation studies were performed. Results: Groups treated with decitabine, SAM, or their combination showed reduced proliferative capacity. The decitabine-treated group showed a marginal increase in cell migration and invasion, whereas the SAM-treated and combination treatment groups showed reduced invasion and migration potential. Methylation assays demonstrated the restoration of decitabine-induced demethylation in prostate cancer samples, whereas the transcriptome study revealed the upregulation of different gene clusters between the treatment groups. Methylation studies confirmed that SAM could restore the decitabine-induced demethylation of proto-oncogenes, but it did not induce the re-methylation of tumor-suppressor genes. Conclusions: Combination treatment with SAM and decitabine had an additive effect and did not nullify each other. Full article

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

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11 pages, 2480 KiB

Open AccessArticle

Expanding the Genotypic and Phenotypic Spectrum of OFD1-Related Conditions: Three More Cases

by Tatiana Kyian, Artem Borovikov, Inga Anisimova, Oksana Ryzhkova, Maria Bulakh, Elizabeth Bragina, Maria Avakyan, Anna Demchenko, Victoria Zabnenkova, Victor Kovalev, Artem Bukhonin, Elena Kondratyeva and Sergey Kutsev

Genes 2024, 15(12), 1633; https://doi.org/10.3390/genes15121633 - 20 Dec 2024

Viewed by 605

Abstract

Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson–Golabi–Behmel syndrome [...] Read more.

Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson–Golabi–Behmel syndrome type 2, was published once but remains controversial, with many specialists questioning its validity and arguing about its continued listing in the OMIM database. Methods: To investigate the genetic and phenotypic characteristics of the patients, we performed clinical exome sequencing, family-based genetic analysis, X-inactivation studies, electron microscopy, and detailed clinical assessments. Results: Three patients from unrelated families carrying loss-of-function variants in the OFD1 gene were identified, emphasizing the diverse phenotypic spectrum of OFD1-associated disorders. The first patient, a female with a heterozygous frameshift variant p.(Gln398LeufsTer2), was diagnosed with oro-facial-digital syndrome type 1. The second patient, a male with a heterozygous nonsense variant p.(Gln892Ter), presented with features resembling Simpson–Golabi–Behmel syndrome type 2, as previously reported under this diagnosis. The third patient, a male with another heterozygous nonsense variant p.(Glu879Ter), exhibited isolated primary ciliary dyskinesia without any syndromic features. Conclusions: This study contributes to the growing body of evidence on the expanding phenotypic spectrum of OFD1-associated disorders. It underscores the need for further investigation into the molecular mechanisms underlying the diverse presentations and the necessity of re-evaluating diagnostic classifications for conditions such as SGBS2 in the context of variants in the OFD1 gene. Full article

(This article belongs to the Special Issue Genes and Variants in Human Rare Genetic Diseases)

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17 pages, 1804 KiB

Open AccessReview

Zonulopathies as Genetic Disorders of the Extracellular Matrix

by Chimwemwe Chipeta, Jose Aragon-Martin and Aman Chandra

Genes 2024, 15(12), 1632; https://doi.org/10.3390/genes15121632 - 20 Dec 2024

Viewed by 576

Abstract

The zonular fibres are formed primarily of fibrillin-1, a large extracellular matrix (ECM) glycoprotein, and also contain other constituents such as LTBP-2, ADAMTSL6, MFAP-2 and EMILIN-1, amongst others. They are critical for sight, holding the crystalline lens in place and being necessary for [...] Read more.

The zonular fibres are formed primarily of fibrillin-1, a large extracellular matrix (ECM) glycoprotein, and also contain other constituents such as LTBP-2, ADAMTSL6, MFAP-2 and EMILIN-1, amongst others. They are critical for sight, holding the crystalline lens in place and being necessary for accommodation. Zonulopathies refer to conditions in which there is a lack or disruption of zonular support to the lens and may clinically be manifested as ectopia lens (EL)—defined as subluxation of the lens outside of the pupillary plane or frank displacement (dislocation) into the vitreous or anterior segment. Genes implicated in EL include those intimately involved in the formation and function of these glycoproteins as well as other genes involved in the extracellular matrix (ECM). As such, genetic pathogenic variants causing EL are primarily disorders of the ECM, causing zonular weakness by (1) directly affecting the protein components of the zonule, (2) affecting proteins involved in the regulation of zonular formation and (3) causing the dysregulation of ECM components leading to progressive zonular weakness. Herein, we discuss the clinical manifestations of zonulopathy and the underlying pathogenetic mechanisms. Full article

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

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13 pages, 299 KiB

Open AccessReview

Role of the PPARGC1A Gene and Its rs8192678 Polymorphism on Sport Performance, Aerobic Capacity, Muscle Adaptation and Metabolic Diseases: A Narrative Review

by David Varillas-Delgado

Genes 2024, 15(12), 1631; https://doi.org/10.3390/genes15121631 - 20 Dec 2024

Viewed by 818

Abstract

Background/Objectives: The PPARGC1A gene, encoding the PGC-1α protein, is a critical regulator of energy metabolism, influencing mitochondrial biogenesis, fatty acid oxidation, and carbohydrate metabolism. This narrative review aims to evaluate the role of the PPARGC1A gene, with a specific focus on the c.1444G<A [...] Read more.

Background/Objectives: The PPARGC1A gene, encoding the PGC-1α protein, is a critical regulator of energy metabolism, influencing mitochondrial biogenesis, fatty acid oxidation, and carbohydrate metabolism. This narrative review aims to evaluate the role of the PPARGC1A gene, with a specific focus on the c.1444G<A polymorphism (rs8192678), in sports performance, including its impact on aerobic capacity, muscle adaptation, and its potential implications for metabolic health. Methods: A comprehensive literature search was conducted using databases such as PubMed, Scopus, Science Direct, and Web of Science, following PRISMA guidelines. Studies investigating the rs8192678 polymorphism in athletes, its relationship with physical performance, and its broader metabolic effects were included. Data were synthesized qualitatively, and heterogeneity among findings was assessed. The rs8192678 polymorphism influences sports performance differently. Results: the G allele is associated with enhanced mitochondrial efficiency, higher aerobic capacity, and a greater proportion of fatigue-resistant type I muscle fibers, benefiting endurance sports like cycling and triathlon. Conversely, the A allele correlates with reduced mitochondrial biogenesis and oxidative capacity, potentially impairing endurance but showing possible utility in strength-based sports. Furthermore, the A allele is linked to increased risks of metabolic conditions, including type 2 diabetes and obesity. Discrepancies in results highlight the influence of genetic, environmental, and training interactions. Conclusions: the PPARGC1A rs8192678 polymorphism plays a significant role in athletic performance and metabolic regulation. While the G allele confers advantages in endurance sports, the A allele presents mixed implications for strength and metabolic health. These findings support the potential for genetic profiling in personalized training and health interventions but emphasize the need for further research to clarify genotype-environment interactions. Full article

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

17 pages, 3928 KiB

Open AccessFeature PaperArticle

Dynamic Chromatin Accessibility and Gene Expression Regulation During Maize Leaf Development

by Yiduo Wang, Shuai Wang, Yufeng Wu, Jiawen Cheng and Haiyan Wang

Genes 2024, 15(12), 1630; https://doi.org/10.3390/genes15121630 - 20 Dec 2024

Viewed by 563

Abstract

Background/Objectives: Chromatin accessibility is closely associated with transcriptional regulation during maize (Zea mays) leaf development. However, its precise role in controlling gene expression at different developmental stages remains poorly understood. This study aimed to investigate the dynamics of chromatin accessibility and [...] Read more.

Background/Objectives: Chromatin accessibility is closely associated with transcriptional regulation during maize (Zea mays) leaf development. However, its precise role in controlling gene expression at different developmental stages remains poorly understood. This study aimed to investigate the dynamics of chromatin accessibility and its influence on genome-wide gene expression during the BBCH_11, BBCH_13, and BBCH_17 stages of maize leaf development. Methods: Maize leaves were collected at the BBCH_11, BBCH_13, and BBCH_17 developmental stages, and chromatin accessibility was assessed using ATAC-seq. RNA-seq was performed to profile gene expression. Integrated analysis of ATAC-seq and RNA-seq data was conducted to elucidate the relationship between chromatin accessibility and transcriptional regulation. Results: A total of 46,808, 38,242, and 41,084 accessible chromatin regions (ACRs) were identified at the BBCH_11, BBCH_13, and BBCH_17 stages, respectively, with 23.4%, 12.2%, and 21.9% of these regions located near transcription start sites (TSSs). Integrated analyses revealed that both the number and intensity of ACRs significantly influence gene expression levels. Motif analysis identified key transcription factors associated with leaf development and potential transcriptional repressors among genes, showing divergent regulation patterns in ATAC-seq and RNA-seq datasets. Conclusions: These findings demonstrate that chromatin accessibility plays a crucial role in regulating the spatial and temporal expression of key genes during maize leaf development by modulating transcription factor binding. This study provides novel insights into the regulatory mechanisms underlying maize leaf development, contributing to a deeper understanding of chromatin-mediated gene expression. Full article

(This article belongs to the Special Issue Advances in Genetics and Genomics of Plants: 2nd Edition)

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14 pages, 4107 KiB

Open AccessArticle

Polymorphism of Genes Potentially Affecting Growth and Body Size Suggests Genetic Divergence in Wild and Domestic Reindeer (Rangifer tarandus) Populations

by Anna A. Krutikova, Natalia V. Dementieva, Yuri S. Shcherbakov, Vasiliy V. Goncharov, Darren K. Griffin and Michael N. Romanov

Genes 2024, 15(12), 1629; https://doi.org/10.3390/genes15121629 - 20 Dec 2024

Viewed by 730

Abstract

Background/Objectives: A combination of increased human presence in the Arctic zone alongside climate change has led to a decrease in the number of wild reindeer (Rangifer tarandus). Studying the genetic potential of this species will aid in conservation efforts, while [...] Read more.

Background/Objectives: A combination of increased human presence in the Arctic zone alongside climate change has led to a decrease in the number of wild reindeer (Rangifer tarandus). Studying the genetic potential of this species will aid in conservation efforts, while simultaneously promoting improved meat productivity in domestic reindeer. Alongside reducing feed costs, increasing disease resistance, etc., acquiring genetic variation information is a crucial task for domestic reindeer husbandry. This study thus identified highly informative molecular genetic markers usable for assessing genetic diversity and breeding purposes in reindeer. Methods: We analyzed gene polymorphism that may potentially affect animal growth and development in populations of wild (Taimyr Peninsula) and domestic reindeer, including Nenets and Evenk breeds. We screened these populations for polymorphisms by sequencing the GH, GHR, LCORL and BMP2 genes. Results: Following generation of gene sequences, we compared the alleles frequency in the surveyed populations and their genetic divergence. Some loci lacked polymorphism in wild reindeer, unlike domestic breeds. This could suggest a selection-driven microevolutionary divergence in domestic reindeer populations. An isolated domestic population from Kolguyev Island appeared to be genetically remote from continental reindeer. Conclusions: Molecular genetic markers associated with economically important traits in reindeer can be further developed using the data obtained. Monitoring wild reindeer populations and better utilizing the genetic potential of domestic animals will depend on a panel of these marker genes. By using this marker panel, the amount of time spent on selection efforts will be greatly reduced to enhance meat performance during reindeer breeding. Full article

(This article belongs to the Special Issue Wildlife Genetic Diversity and Genomics)

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18 pages, 5689 KiB

Open AccessArticle

Comparative Transcriptome Analysis Reveals Mechanisms of Differential Salinity Tolerance Between Suaeda glauca and Suaeda salsa

by Qidong Yan, Shang Gao, Xianglun Zhang, Guoping Liu, Peitao Chen, Xuanyi Gao, Li Yuan, Yucheng Tian, Dapeng Li, Xuepeng Zhang and Huan Zhang

Genes 2024, 15(12), 1628; https://doi.org/10.3390/genes15121628 - 19 Dec 2024

Viewed by 744

Abstract

Background: Suaeda glauca and Suaeda salsa have obvious morphological features and strongly tolerate saline–alkali environments. However, the mechanisms that lead to the differences in saline–alkali tolerance between them remain unclear. Methods: In this study, we employed comparative transcriptome analysis to investigate S. glauca [...] Read more.

Background: Suaeda glauca and Suaeda salsa have obvious morphological features and strongly tolerate saline–alkali environments. However, the mechanisms that lead to the differences in saline–alkali tolerance between them remain unclear. Methods: In this study, we employed comparative transcriptome analysis to investigate S. glauca and S. salsa under saline–alkali stress. Results: Our sequencing efforts resulted in the identification of 99,868 unigenes. We obtained 12,021 and 6227 differentially expressed genes (DEGs) from the S. glauca and S. salsa under salt stress compared with plants in the control. Notably, 1189 and 1864 were specifically upregulated DEGs in the roots and leaves of S. salsa under saline–alkali conditions, respectively. These genes were enriched in pathways such as “Plant hormone signal transduction”, “Carbon metabolism” and “Starch and sucrose metabolism”. Further analysis of stress-related pathways and gene expression levels revealed that key genes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis, ABA signal transduction, and their downstream transcription factors were upregulated in the roots of S. salsa under saline–alkali conditions. Additionally, 24 DEGs associated with stress response were identified in the roots and leaves of both species. The expression levels of these pathways and related genes were higher in S. salsa than in S. glauca, suggesting that S. salsa enhances its saline–alkali tolerance by elevating the expression of these genes. Conclusions: This study provides a new research perspective for revealing the differences in saline–alkali tolerance mechanisms between S. glauca and S. salsa, bringing forth important candidate genes for studying their saline–alkali tolerance. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants: Molecular Genetics and Genomics—2nd Edition)

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Open AccessArticle

Association Among MCT1 rs1049434 Polymorphism, Athlete Status, and Physiological Parameters in Japanese Long-Distance Runners

by Shotaro Seki, Tetsuro Kobayashi, Kenji Beppu, Manabu Nojo, Kosaku Hoshina, Naoki Kikuchi, Takanobu Okamoto, Koichi Nakazato and Inkwan Hwang

Genes 2024, 15(12), 1627; https://doi.org/10.3390/genes15121627 - 19 Dec 2024

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Abstract

Background/Objectives: Monocarboxylate transporters (MCTs) comprise 14 known isoforms, with MCT1 being particularly important for lactate transport. Variations in lactate metabolism capacity and aerobic performance are associated with the T1470A polymorphism in MCT1. We aimed to investigate the frequency of the T1470A polymorphism [...] Read more.

Background/Objectives: Monocarboxylate transporters (MCTs) comprise 14 known isoforms, with MCT1 being particularly important for lactate transport. Variations in lactate metabolism capacity and aerobic performance are associated with the T1470A polymorphism in MCT1. We aimed to investigate the frequency of the T1470A polymorphism and compare relevant physiological parameters among long-distance runners, wherein these parameters are fundamental to athletic performance. Methods: We included 158 Japanese long-distance runners (LD) and 649 individuals from the general Japanese population (CON). The frequency of the T1470A polymorphism was compared between these groups and across athletic levels using the chi-square test. Additionally, physiological data were collected from 57 long-distance runners, and respiratory gas measurements were obtained using the mixing-chamber method during a graded incremental exercise test. Results: We observed a significant difference between the LD and CON groups in the dominant model and between the sub-28 min group and 28 min or above group in the recessive model. As the competitive level increased, the frequency of the AA genotype also increased. When comparing physiological parameters between the AA genotype and T allele, subjects with the AA genotype showed significantly higher values for oxygen uptake at lactate threshold (p = 0.001), oxygen uptake at onset of blood lactate accumulation (p = 0.01), maximal oxygen uptake (p = 0.005), and maximal blood lactate concentration (p = 0.038). Conclusions: These results suggest that the AA genotype of the T1470A polymorphism of MCT1 is an effective genotype associated with athletic status and aerobic capacity in Japanese long-distance runners. Full article

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

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Genes, Volume 15, Issue 12 (December 2024) – 164 articles

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