Genes

Article

18 pages, 9698 KiB

Open AccessEditor’s ChoiceArticle

Molecular Evolutionary Rate Predicts Intraspecific Genetic Polymorphism and Species-Specific Selection

by Jiaqi Wu, Takahiro Yonezawa and Hirohisa Kishino

Genes 2022, 13(4), 708; https://doi.org/10.3390/genes13040708 - 17 Apr 2022

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It is unknown what determines genetic diversity and how genetic diversity is associated with various biological traits. In this work, we provide insight into these issues. By comparing genetic variation of 14,671 mammalian gene trees with thousands of individual human, chimpanzee, gorilla, mouse, [...] Read more.

It is unknown what determines genetic diversity and how genetic diversity is associated with various biological traits. In this work, we provide insight into these issues. By comparing genetic variation of 14,671 mammalian gene trees with thousands of individual human, chimpanzee, gorilla, mouse, and dog/wolf genomes, we found that intraspecific genetic diversity can be predicted by long-term molecular evolutionary rates rather than de novo mutation rates. This relationship was established during the early stage of mammalian evolution. Moreover, we developed a method to detect fluctuations of species-specific selection on genes based on the deviations of intraspecific genetic diversity predicted from long-term rates. We showed that the evolution of epithelial cells, rather than connective tissue, mainly contributed to morphological evolution of different species. For humans, evolution of the immune system and selective sweeps caused by infectious diseases are the most representative examples of adaptive evolution. Full article

(This article belongs to the Special Issue Genetic Structure of Human Populations)

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27 pages, 19141 KiB

Open AccessEditor’s ChoiceArticle

A Penalization Method for Estimating Heterogeneous Covariate Effects in Cancer Genomic Data

by Ziye Luo, Yuzhao Zhang and Yifan Sun

Genes 2022, 13(4), 702; https://doi.org/10.3390/genes13040702 - 15 Apr 2022

Viewed by 2233

Abstract

In high-throughput profiling studies, extensive efforts have been devoted to searching for the biomarkers associated with the development and progression of complex diseases. The heterogeneity of covariate effects associated with the outcomes across subjects has been noted in the literature. In this paper, [...] Read more.

In high-throughput profiling studies, extensive efforts have been devoted to searching for the biomarkers associated with the development and progression of complex diseases. The heterogeneity of covariate effects associated with the outcomes across subjects has been noted in the literature. In this paper, we consider a scenario where the effects of covariates change smoothly across subjects, which are ordered by a known auxiliary variable. To this end, we develop a penalization-based approach, which applies a penalization technique to simultaneously select important covariates and estimate their unique effects on the outcome variables of each subject. We demonstrate that, under the appropriate conditions, our method shows selection and estimation consistency. Additional simulations demonstrate its superiority compared to several competing methods. Furthermore, applying the proposed approach to two The Cancer Genome Atlas datasets leads to better prediction performance and higher selection stability. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Human Cancers)

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17 pages, 4303 KiB

Open AccessEditor’s ChoiceArticle

hMSH5 Regulates NHEJ and Averts Excessive Nucleotide Alterations at Repair Joints

by Aneesa T. Al-Soodani, Xiling Wu, Nicole C. Kelp, Alexander J. Brown, Steven A. Roberts and Chengtao Her

Genes 2022, 13(4), 673; https://doi.org/10.3390/genes13040673 - 11 Apr 2022

Cited by 1 | Viewed by 3128

Abstract

Inappropriate repair of DNA double-strand breaks (DSBs) leads to genomic instability, cell death, or malignant transformation. Cells minimize these detrimental effects by selectively activating suitable DSB repair pathways in accordance with their underlying cellular context. Here, we report that hMSH5 down-regulates NHEJ and [...] Read more.

Inappropriate repair of DNA double-strand breaks (DSBs) leads to genomic instability, cell death, or malignant transformation. Cells minimize these detrimental effects by selectively activating suitable DSB repair pathways in accordance with their underlying cellular context. Here, we report that hMSH5 down-regulates NHEJ and restricts the extent of DSB end processing before rejoining, thereby reducing “excessive” deletions and insertions at repair joints. RNAi-mediated knockdown of hMSH5 led to large nucleotide deletions and longer insertions at the repair joints, while at the same time reducing the average length of microhomology (MH) at repair joints. Conversely, hMSH5 overexpression reduced end-joining activity and increased RPA foci formation (i.e., more stable ssDNA at DSB ends). Furthermore, silencing of hMSH5 delayed 53BP1 chromatin spreading, leading to increased end resection at DSB ends. Full article

(This article belongs to the Special Issue DNA Damage and Repair in Microorganisms, Plants and Mammalian Systems)

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9 pages, 1052 KiB

Open AccessEditor’s ChoiceArticle

Integrated Quantitative Neuro-Transcriptome Analysis of Several Brain Areas in Human Trisomy 21

by Alejandra Rodríguez-Ortiz, Julio César Montoya-Villegas, Felipe García-Vallejo and Yecid Mina-Paz

Genes 2022, 13(4), 628; https://doi.org/10.3390/genes13040628 - 1 Apr 2022

Viewed by 2370

Abstract

Background: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable. Objective: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS [...] Read more.

Background: Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable. Objective: We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21. Methods: We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes. Results: We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16–22 weeks of gestation and 39–42 years (R² = 0.06) and the highest Z-ratio correlation between the age ranks of 30–39 years and 40–42 years (R² = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole. Conclusions: Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes. Full article

(This article belongs to the Special Issue Epigenetics in Brain Development and Neurodevelopmental Disorders)

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9 pages, 1170 KiB

Open AccessEditor’s ChoiceCommunication

Effectiveness of Two Universal Angiosperm Probe Sets Tested In Silico for Caryophyllids Taxa with Emphasis on Cacti Species

by Delil A. Chincoya and Sofía Solórzano

Genes 2022, 13(4), 570; https://doi.org/10.3390/genes13040570 - 24 Mar 2022

Cited by 1 | Viewed by 2480

Abstract

In angiosperms, huge advances in massive DNA sequencing technologies have impacted phylogenetic studies. Probe sets have been developed with the purpose of recovering hundreds of orthologous loci of targeted DNA sequences (TDS) across different plant lineages. We tested in silico the effectiveness of [...] Read more.

In angiosperms, huge advances in massive DNA sequencing technologies have impacted phylogenetic studies. Probe sets have been developed with the purpose of recovering hundreds of orthologous loci of targeted DNA sequences (TDS) across different plant lineages. We tested in silico the effectiveness of two universal probe sets in the whole available genomes of Caryophyllids, emphasizing phylogenetic issues in cacti species. A total of 870 TDS (517 TDS from Angiosperm v.1 and 353 from Angiosperms353) were individually tested in nine cacti species and Amaranthus hypochondriacus (external group) with ≥17 Gbp of available DNA data. The effectiveness was measured by the total number of orthologous loci recovered and their length, the percentage of loci discarded by paralogy, and the proportion of informative sites (PIS) in the alignments. The results showed that, on average, Angiosperms353 was better than Angiosperm v.1 for cacti species, since the former obtained an average of 275.6 loci that represent 123,687 bp, 2.48% of paralogous loci, and 4.32% of PIS in alignments, whereas the latter recovered 148.4 loci (37,683 bp), 10.38% of paralogous loci, and 3.49% of PIS. We recommend the use of predesigned universal probe sets for Caryophyllids, since these recover a high number of orthologous loci that resolve phylogenetic relationships. Full article

(This article belongs to the Special Issue Cactaceae Genetics and Genomics)

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16 pages, 1480 KiB

Open AccessEditor’s ChoiceArticle

Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

by Abdulnaser Alkhalil, John Clifford, Stacy Ann Miller, Aarti Gautam, Marti Jett, Rasha Hammamieh, Lauren T. Moffatt and Jeffrey W. Shupp

Genes 2022, 13(3), 538; https://doi.org/10.3390/genes13030538 - 18 Mar 2022

Viewed by 2909

Abstract

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using [...] Read more.

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications. Full article

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

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10 pages, 2059 KiB

Open AccessEditor’s ChoiceArticle

Crlz-1 Homozygous Null Knockout Mouse Embryos Are Lethally Stopped in Their Early Development

by Seung-Young Choi, Joo-Hyun Pi, So-Eun Jeong and Chang-Joong Kang

Genes 2022, 13(3), 511; https://doi.org/10.3390/genes13030511 - 14 Mar 2022

Viewed by 2624

Abstract

Although the conditional gene knockout (KO) is a better choice for observing its phenotype in a specific cell, tissue, and/or organ, the simple null gene KO could nevertheless be attempted initially to scan its overall phenotypes at the level of the whole-body system, [...] Read more.

Although the conditional gene knockout (KO) is a better choice for observing its phenotype in a specific cell, tissue, and/or organ, the simple null gene KO could nevertheless be attempted initially to scan its overall phenotypes at the level of the whole-body system, especially for a new gene such as Crlz-1. Therefore, with a hope to glean phenotypic clues for Crlz-1 at the whole-body system, we attempted to generate its null KO mice. Contrary to our original desire, Crlz-1 homozygous null KO mice were not born. However, in the chasing of their homozygous KO embryos, they were found to be lethally impaired from early development, remaining in a state of small globular mass without ever leading to a body shape, indicating the critical role of Crlz-1 as a Wnt target gene for the proliferation and/or differentiation of cells during early mouse embryonic development. Full article

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

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8 pages, 3208 KiB

Open AccessEditor’s ChoiceCommunication

First Description of Inheritance of a Postzygotic OPA1 Mosaic Variant

by Svenja Alter, Navid Farassat, Sebastian Küchlin, Wolf A. Lagrèze and Judith Fischer

Genes 2022, 13(3), 478; https://doi.org/10.3390/genes13030478 - 8 Mar 2022

Viewed by 2314

Abstract

Optic atrophy 1 (MIM #165500) is caused by pathogenic variants in the gene OPA1 (OPA1 MITOCHONDRIAL DYNAMIN-LIKE GTPase, MIM *605290) and is inherited in an autosomal dominant manner. We describe a 6-year-old male patient with severe early onset manifestation of optic [...] Read more.

Optic atrophy 1 (MIM #165500) is caused by pathogenic variants in the gene OPA1 (OPA1 MITOCHONDRIAL DYNAMIN-LIKE GTPase, MIM *605290) and is inherited in an autosomal dominant manner. We describe a 6-year-old male patient with severe early onset manifestation of optic atrophy, whose parents are subjectively asymptomatic. OPA1-sequence analysis revealed the heterozygous missense variant NM_015560.3:c.806C>T, p.(Ser269Phe) in the patient. Segregation analysis of the parents showed that the mother carried a low-grade postzygotic mosaic of this variant, which apparently also involves germline cells. In line with this, ophthalmological investigation of the mother showed subclinical manifestation of optic atrophy 1. This is the first report of an OPA1 postzygotic mosaic that was inherited to offspring. Full article

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

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25 pages, 3377 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

by Chenguang Zhao, Tong Liu and Zheng Wang

Genes 2022, 13(3), 480; https://doi.org/10.3390/genes13030480 - 8 Mar 2022

Cited by 1 | Viewed by 2907

Abstract

Topologically associating domains (TADs) are the structural and functional units of the genome. However, the functions of protein-coding genes existing in the same or different TADs have not been fully investigated. We compared the functional similarities of protein-coding genes existing in the same [...] Read more.

Topologically associating domains (TADs) are the structural and functional units of the genome. However, the functions of protein-coding genes existing in the same or different TADs have not been fully investigated. We compared the functional similarities of protein-coding genes existing in the same TAD and between different TADs, and also in the same gap region (the region between two consecutive TADs) and between different gap regions. We found that the protein-coding genes from the same TAD or gap region are more likely to share similar protein functions, and this trend is more obvious with TADs than the gap regions. We further created two types of gene–gene spatial interaction networks: the first type is based on Hi-C contacts, whereas the second type is based on both Hi-C contacts and the relationship of being in the same TAD. A graph auto-encoder was applied to learn the network topology, reconstruct the two types of networks, and predict the functions of the central genes/nodes based on the functions of the neighboring genes/nodes. It was found that better performance was achieved with the second type of network. Furthermore, we detected long-range spatially-interactive regions based on Hi-C contacts and calculated the functional similarities of the gene pairs from these regions. Full article

(This article belongs to the Special Issue 3D Reconstruction of Genome Structures)

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9 pages, 2880 KiB

Open AccessEditor’s ChoiceArticle

enChIP-Seq Analyzer: A Software Program to Analyze and Interpret enChIP-Seq Data for the Detection of Physical Interactions between Genomic Regions

by Ashita Sarudate, Toshitsugu Fujita, Takahiro Nakayama and Hodaka Fujii

Genes 2022, 13(3), 472; https://doi.org/10.3390/genes13030472 - 7 Mar 2022

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Abstract

Accumulating evidence suggests that the physical interactions between genomic regions play critical roles in the regulation of genome functions, such as transcription and epigenetic regulation. Various methods to detect the physical interactions between genomic regions have been developed. We recently developed a method [...] Read more.

Accumulating evidence suggests that the physical interactions between genomic regions play critical roles in the regulation of genome functions, such as transcription and epigenetic regulation. Various methods to detect the physical interactions between genomic regions have been developed. We recently developed a method to search for genomic regions interacting with a locus of interest in a non-biased manner that combines pull-down of the locus using engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) and next-generation sequencing (NGS) analysis (enChIP-Seq). The clustered regularly interspaced short palindromic repeats (CRISPR) system, consisting of a nuclease-dead form of Cas9 (dCas9) and a guide RNA (gRNA), or transcription activator-like (TAL) proteins, can be used for enChIP. In enChIP-Seq, it is necessary to compare multiple datasets of enChIP-Seq data to unambiguously detect specific interactions. However, it is not always easy to analyze enChIP-Seq datasets to subtract non-specific interactions or identify common interactions. To facilitate such analysis, we developed the enChIP-Seq analyzer software. It enables easy extraction of common signals as well as subtraction of non-specific signals observed in negative control samples, thereby streamlining extraction of specific enChIP-Seq signals. enChIP-Seq analyzer will help users analyze enChIP-Seq data and identify physical interactions between genomic regions. Full article

(This article belongs to the Section Bioinformatics)

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22 pages, 1056 KiB

Open AccessEditor’s ChoiceArticle

Simulation Research on the Methods of Multi-Gene Region Association Analysis Based on a Functional Linear Model

by Shijing Li, Fujie Zhou, Jiayu Shen, Hui Zhang and Yongxian Wen

Genes 2022, 13(3), 455; https://doi.org/10.3390/genes13030455 - 2 Mar 2022

Viewed by 2349

Abstract

Genome-wide association analysis is an important approach to identify genetic variants associated with complex traits. Complex traits are not only affected by single gene loci, but also by the interaction of multiple gene loci. Studies of association between gene regions and quantitative traits [...] Read more.

Genome-wide association analysis is an important approach to identify genetic variants associated with complex traits. Complex traits are not only affected by single gene loci, but also by the interaction of multiple gene loci. Studies of association between gene regions and quantitative traits are of great significance in revealing the genetic mechanism of biological development. There have been a lot of studies on single-gene region association analysis, but the application of functional linear models in multi-gene region association analysis is still less. In this paper, a functional multi-gene region association analysis test method is proposed based on the functional linear model. From the three directions of common multi-gene region method, multi-gene region weighted method and multi-gene region loci weighted method, that test method is studied combined with computer simulation. The following conclusions are obtained through computer simulation: (a) The functional multi-gene region association analysis test method has higher power than the functional single gene region association analysis test method; (b) The functional multi-gene region weighted method performs better than the common functional multi-gene region method; (c) the functional multi-gene region loci weighted method is the best method for association analysis on three directions of the common multi-gene region method; (d) the performance of the Step method and Multi-gene region loci weighted Step for multi-gene regions is the best in general. Functional multi-gene region association analysis test method can theoretically provide a feasible method for the study of complex traits affected by multiple genes. Full article

(This article belongs to the Section Bioinformatics)

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20 pages, 10456 KiB

Open AccessEditor’s ChoiceArticle

Cloning of the Human MORG1 Promoter: Differential Regulation by Hypoxia and Prolyl-Hydroxylase Inhibitors

by Tzvetanka Bondeva and Gunter Wolf

Genes 2022, 13(3), 427; https://doi.org/10.3390/genes13030427 - 25 Feb 2022

Viewed by 2068

Abstract

MAPK-organizer 1 (MORG1) is a molecular scaffold for prolyl-hydroxylase-3 containing a domain (PHD3) protein linking MORG1 to mechanisms of adaptation in hypoxic conditions. In this paper, we report the cloning of the promoter region of the murine and human MORG1 gene. Among other [...] Read more.

MAPK-organizer 1 (MORG1) is a molecular scaffold for prolyl-hydroxylase-3 containing a domain (PHD3) protein linking MORG1 to mechanisms of adaptation in hypoxic conditions. In this paper, we report the cloning of the promoter region of the murine and human MORG1 gene. Among other transcriptional factors binding sites, we identified that both (mouse and human) promoter regions contained several putative hypoxia-inducible factor binding motifs. Analyses of the human MORG1 promoter by reporter assays revealed that hypoxia and pharmacological inhibitors of prolyl-hydroxylases under in vitro conditions in HEK 293 cells differentially regulate the MORG1 promoter reporter activity. The exposure of the cells to 10% hypoxia showed inhibition of MORG1 promotor activity at 6 and 12 h, but stimulation after 24 h while treated with prolyl-hydroxylase inhibitors led to a time-independent MORG1 promoter activation. Mutational analyses of the individual HIF binding sites on human MORG1 promoter suggest that the binding sites work in a complex corporation because single mutations were not sufficient to abolish completely the MORG1 reporter activation by PHD inhibitors. Our data provide the first evidence that not only MORG1 regulate HIF stabilization through a PHD complex, but also that, vice versa, HIFs control MORG1 expression directly or indirectly by a complex regulatory mechanism. Full article

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

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15 pages, 13317 KiB

Open AccessEditor’s ChoiceArticle

Characterization and Functional Study of FAM49B Reveals Its Effect on Cell Proliferation in HEK293T Cells

by Yijian Chen, Yuyan Jiang, Jihui Lao, Yankuan Zhou, Lida Su and Xiao Huang

Genes 2022, 13(2), 388; https://doi.org/10.3390/genes13020388 - 21 Feb 2022

Cited by 2 | Viewed by 3153

Abstract

FAM49B/Fam49b is a member of the Fam49 (Family with sequence similarity 49) gene family, which is characterized by the conserved domain, DUF1394 (Domain of Unknown Function 1394). It has also been named CYRI-B (CYFIP related RAC1 interactor B), implicating its important function of [...] Read more.

FAM49B/Fam49b is a member of the Fam49 (Family with sequence similarity 49) gene family, which is characterized by the conserved domain, DUF1394 (Domain of Unknown Function 1394). It has also been named CYRI-B (CYFIP related RAC1 interactor B), implicating its important function of regulating RAC1-driven cytoskeleton remolding. In this study, to further investigate its functions and mechanisms affecting cell behaviors, HEK293T cells (where FAM49B is highly expressed) were used to establish a FAM49B knockout cell line by CRISPR/Cas9 genome editing technology. Our data have clearly revealed that there are triple alleles of FAM49B in the genome of HEK293T cells. Meanwhile, the proliferation deficiency of the FAM49B KO HEK293T cell line and the significantly changed cell proliferation related gene expression profiles, such as CCND1, have been uncovered. At the same time, the existence of isoform 3 has been confirmed in HEK293T cells. Our studies have suggested that FAM49B may also affect cell proliferation via Cyclins, besides its influence on the cytoskeleton. Full article

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

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15 pages, 679 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Leveraging Gene-Level Prediction as Informative Covariate in Hypothesis Weighting Improves Power for Rare Variant Association Studies

by Ying Ji, Rui Chen, Quan Wang, Qiang Wei, Ran Tao and Bingshan Li

Genes 2022, 13(2), 381; https://doi.org/10.3390/genes13020381 - 19 Feb 2022

Viewed by 2886

Abstract

Gene-based rare variant association studies (RVASs) have low power due to the infrequency of rare variants and the large multiple testing burden. To correct for multiple testing, traditional false discovery rate (FDR) procedures which depend solely on P-values are often used. Recently, Independent [...] Read more.

Gene-based rare variant association studies (RVASs) have low power due to the infrequency of rare variants and the large multiple testing burden. To correct for multiple testing, traditional false discovery rate (FDR) procedures which depend solely on P-values are often used. Recently, Independent Hypothesis Weighting (IHW) was developed to improve the detection power while maintaining FDR control by leveraging prior information for each hypothesis. Here, we present a framework to increase power of gene-based RVASs by incorporating prior information using IHW. We first build supervised machine learning models to assign each gene a prediction score that measures its disease risk, using the input of multiple biological features, fed with high-confidence risk genes and local background genes selected near GWAS significant loci as the training set. Then we use the prediction scores as covariates to prioritize RVAS results via IHW. We demonstrate the effectiveness of this framework through applications to RVASs in schizophrenia and autism spectrum disorder. We found sizeable improvements in the number of significant associations compared to traditional FDR approaches, and independent evidence supporting the relevance of the genes identified by our framework but not traditional FDR, demonstrating the potential of our framework to improve power of gene-based RVASs. Full article

(This article belongs to the Special Issue Statistical Genetics in Human Diseases)

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8 pages, 1609 KiB

Open AccessEditor’s ChoiceArticle

FDDM1 and FDDM2, Two SGS3-like Proteins, Function as a Complex to Affect DNA Methylation in Arabidopsis

by Shengjun Li, Weilong Yang, Yunfeng Liu, Guangyong Li, Xiang Liu, Yaling Liu, James R. Alfano, Chi Zhang and Bin Yu

Genes 2022, 13(2), 339; https://doi.org/10.3390/genes13020339 - 12 Feb 2022

Viewed by 2478

Abstract

DNA methylation is an important epigenetic modification required for the specific regulation of gene expression and the maintenance of genome stability in plants and animals. However, the mechanism of DNA demethylation remains largely unknown. Here, we show that two SGS3-like proteins, FACTOR OF [...] Read more.

DNA methylation is an important epigenetic modification required for the specific regulation of gene expression and the maintenance of genome stability in plants and animals. However, the mechanism of DNA demethylation remains largely unknown. Here, we show that two SGS3-like proteins, FACTOR OF DNA DEMETHYLATION 1 (FDDM1) and FDDM2, negatively affect the DNA methylation levels at ROS1-dependend DNA loci in Arabidopsis. FDDM1 binds dsRNAs with 5′ overhangs through its XS (rice gene X and SGS3) domain and forms a heterodimer with FDDM2 through its XH (rice gene X Homology) domain. A lack of FDDM1 or FDDM2 increased DNA methylation levels at several ROS1-dependent DNA loci. However, FDDM1 and FDDM2 may not have an additive effect on DNA methylation levels. Moreover, the XS and XH domains are required for the function of FDDM1. Taken together, these results suggest that FDDM1 and FDDM2 act as a heterodimer to positively modulate DNA demethylation. Our finding extends the function of plant-specific SGS3-like proteins. Full article

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

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23 pages, 4197 KiB

Open AccessEditor’s ChoiceArticle

Whole Genome DNA Methylation Profiling of D2 Medium Spiny Neurons in Mouse Nucleus Accumbens Using Two Independent Library Preparation Methods

by Yuxiang Li, Haiyang Xu, Javed M. Chitaman and Jian Feng

Genes 2022, 13(2), 306; https://doi.org/10.3390/genes13020306 - 6 Feb 2022

Cited by 2 | Viewed by 3889

Abstract

DNA methylation plays essential roles in various cellular processes. Next-generation sequencing has enabled us to study the functional implication of DNA methylation across the whole genome. However, this approach usually requires a substantial amount of genomic DNA, which limits its application to defined [...] Read more.

DNA methylation plays essential roles in various cellular processes. Next-generation sequencing has enabled us to study the functional implication of DNA methylation across the whole genome. However, this approach usually requires a substantial amount of genomic DNA, which limits its application to defined cell types within a discrete brain region. Here, we applied two separate protocols, Accel-NGS Methyl-Seq (AM-seq) and Enzymatic Methyl-seq (EM-seq), to profile the methylome of D2 dopamine receptor-expressing medium spiny neurons (D2-MSNs) in mouse nucleus accumbens (NAc). Using 40 ng DNA extracted from FACS-isolated D2-MSNs, we found that both methods yielded comparably high-quality methylome data. Additionally, we identified numerous unmethylated regions (UMRs) as cell type-specific regulatory regions. By comparing the NAc D2-MSN methylome with the published methylomes of mouse prefrontal cortex excitatory neurons and neural progenitor cells (NPCs), we identified numerous differentially methylated CpG and non-CpG regions. Our study not only presents a comparison of these two low-input DNA whole genome methylation profiling protocols, but also provides a resource of DNA methylome of mouse accumbal D2-MSNs, a neuron type that has critical roles in addiction and other neuropsychiatric disorders. Full article

(This article belongs to the Special Issue Gene Expression and Chromatin Modification in the Brain)

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25 pages, 3321 KiB

Open AccessEditor’s ChoiceArticle

Balanced Polymorphism at the Pgm-1 Locus of the Pompeii Worm Alvinella pompejana and Its Variant Adaptability Is Only Governed by Two QE Mutations at Linked Sites

by Alexis Bioy, Anne-Sophie Le Port, Emeline Sabourin, Marie Verheye, Patrice Piccino, Baptiste Faure, Stéphane Hourdez, Jean Mary and Didier Jollivet

Genes 2022, 13(2), 206; https://doi.org/10.3390/genes13020206 - 24 Jan 2022

Cited by 2 | Viewed by 3114

Abstract

The polychaete Alvinella pompejana lives exclusively on the walls of deep-sea hydrothermal chimneys along the East Pacific Rise (EPR), and displays specific adaptations to withstand the high temperatures and hypoxia associated with this highly variable habitat. Previous studies have revealed the existence of [...] Read more.

The polychaete Alvinella pompejana lives exclusively on the walls of deep-sea hydrothermal chimneys along the East Pacific Rise (EPR), and displays specific adaptations to withstand the high temperatures and hypoxia associated with this highly variable habitat. Previous studies have revealed the existence of a balanced polymorphism on the enzyme phosphoglucomutase associated with thermal variations, where allozymes 90 and 100 exhibit different optimal activities and thermostabilities. Exploration of the mutational landscape of phosphoglucomutase 1 revealed the maintenance of four highly divergent allelic lineages encoding the three most frequent electromorphs over the geographic range of A. pompejana. This polymorphism is only governed by two linked amino acid replacements, located in exon 3 (E155Q and E190Q). A two-niche model of selection, including ‘cold’ and ‘hot’ conditions, represents the most likely scenario for the long-term persistence of these isoforms. Using directed mutagenesis and the expression of the three recombinant variants allowed us to test the additive effect of these two mutations on the biochemical properties of this enzyme. Our results are coherent with those previously obtained from native proteins, and reveal a thermodynamic trade-off between protein thermostability and catalysis, which is likely to have maintained these functional phenotypes prior to the geographic separation of populations across the Equator about 1.2 million years ago. Full article

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

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12 pages, 851 KiB

Open AccessEditor’s ChoiceArticle

Expanding the Clinical Phenotype of 19q Interstitial Deletions: A New Case with 19q13.32-q13.33 Deletion and Short Review of the Literature

by Elena-Silvia Shelby, Michael Morris, Liliana Pădure, Andrada Mirea, Relu Cocoș, Alexandru Cărămizaru, Simona Șerban-Sosoi, Andrei Pîrvu and Ioana Streață

Genes 2022, 13(2), 212; https://doi.org/10.3390/genes13020212 - 24 Jan 2022

Cited by 2 | Viewed by 4318

Abstract

19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal growth retardation, intellectual disability, expressive language impairment, ectodermal dysplasia, and slender habitus. Since the description of the first case in 1998, less than 30 cases have been reported worldwide. [...] Read more.

19q13 microdeletion syndrome is a very rare genetic disease characterized by pre- and postnatal growth retardation, intellectual disability, expressive language impairment, ectodermal dysplasia, and slender habitus. Since the description of the first case in 1998, less than 30 cases have been reported worldwide. This article aims to review the knowledge gathered so far on this subject and to present the case of a 10-year-old girl admitted to the National University Center for Children Neurorehabilitation “Dr. Nicolae Robanescu” in November of 2018 who presented a slender habitus, growth retardation, facial dysmorphism, skeletal abnormalities, and ectodermal dysplasia. Array-CGH analysis revealed a 1.53 Mb deletion in the 19q13.32-q13.33 region. MLPA for the FKRP gene revealed that the microdeletion was de novo. The patient’s phenotype overlapped with the clinical features of 19q13 microdeletion syndrome. To our knowledge, this is the first case of 19q13 microdeletion syndrome to ever be reported in Romania. We believe our case presents additional features that have never been previously reported in this syndrome, namely, dilatation of the third ventricle and subependymal cyst, left iris coloboma, and tracheomalacia. Moreover, unlike the other 19q13 microdeletion cases that presented with dystonia, our patient also presented dystonia but, interestingly, without having haploinsufficiency of the KMT2B gene. Full article

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

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17 pages, 7896 KiB

Open AccessEditor’s ChoiceArticle

MtWRP1, a Novel Fabacean Specific Gene, Regulates Root Nodulation and Plant Growth in Medicago truncatula

by Wei Chen, Yingjun Chi, Jinglong Zhang, Binqiang Bai, Xiaomin Ji and Yixin Shen

Genes 2022, 13(2), 193; https://doi.org/10.3390/genes13020193 - 22 Jan 2022

Viewed by 2918

Abstract

Fabaceans symbiotically interact with nitrogen-fixing rhizobacteria to form root nodules. Some fabacean specific proteins play important roles in the symbiosis. WRKY-related Protein (WRP) is a novel fabacean specific protein, whose functions have not been well characterized. In this study, MtWRP1 was functionally characterized [...] Read more.

Fabaceans symbiotically interact with nitrogen-fixing rhizobacteria to form root nodules. Some fabacean specific proteins play important roles in the symbiosis. WRKY-related Protein (WRP) is a novel fabacean specific protein, whose functions have not been well characterized. In this study, MtWRP1 was functionally characterized in Medicago truncatula. It contains a WRKY domain at C-terminal and a novel transmembrane (TM) domain at N-terminal, and its WRKY domain was highly similar to the N-terminal WRKY domain of the group I WRKY proteins. The TM domain was highly homologous to the eukaryotic cytochrome b561 (Cytb561) proteins from birds. Subcellular localization revealed that MtWRP1 was targeted to the Golgi apparatus through the novel TM domain. MtWRP1 was highly expressed in roots and nodules, suggesting its possible roles in the regulation of root growth and nodulation. Both MtWRP1-overexpression transgenic M. truncatula and MtWRP1 mutants showed altered root nodulation and plant growth performance. Specifically, the formation of root nodules was significantly reduced in the absence of MtWRP1. These results demonstrated that MtWRP1 plays critical roles in root nodulation and plant growth. Full article

(This article belongs to the Special Issue Mining the Excellent Functional Genes of Forage)

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13 pages, 25329 KiB

Open AccessEditor’s ChoiceArticle

Identification and Functional Analysis of the Regulatory Elements in the pHSPA6 Promoter

by Shuyu Jiao, Chunyan Bai, Chunyun Qi, Heyong Wu, Lanxin Hu, Feng Li, Kang Yang, Chuheng Zhao, Hongsheng Ouyang, Daxin Pang, Xiaochun Tang and Zicong Xie

Genes 2022, 13(2), 189; https://doi.org/10.3390/genes13020189 - 21 Jan 2022

Cited by 2 | Viewed by 3320

Abstract

Functional and expressional research of heat shock protein A6 (HSPA6) suggests that the gene is of great value for neurodegenerative diseases, biosensors, cancer, etc. Based on the important value of pigs in agriculture and biomedicine and to advance knowledge of this little-studied HSPA [...] Read more.

Functional and expressional research of heat shock protein A6 (HSPA6) suggests that the gene is of great value for neurodegenerative diseases, biosensors, cancer, etc. Based on the important value of pigs in agriculture and biomedicine and to advance knowledge of this little-studied HSPA member, the stress-sensitive sites in porcine HSPA6 (pHSPA6) were investigated following different stresses. Here, two heat shock elements (HSEs) and a conserved region (CR) were identified in the pHSPA6 promoter by a CRISPR/Cas9-mediated precise gene editing strategy. Gene expression data showed that sequence disruption of these regions could significantly reduce the expression of pHSPA6 under heat stress. Stimulation studies indicated that these regions responded not only to heat stress but also to copper sulfate, MG132, and curcumin. Further mechanism studies showed that downregulated pHSPA6 could significantly affect some important members of the HSP family that are involved in HSP40, HSP70, and HSP90. Overall, our results provide a new approach for investigating gene expression and regulation that may contribute to gene regulatory mechanisms, drug target selection, and breeding stock selection. Full article

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

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15 pages, 3862 KiB

Open AccessEditor’s ChoiceArticle

Research on Frequent Itemset Mining of Imaging Genetics GWAS in Alzheimer’s Disease

by Hong Liang, Luolong Cao, Yue Gao, Haoran Luo, Xianglian Meng, Ying Wang, Jin Li and Wenjie Liu

Genes 2022, 13(2), 176; https://doi.org/10.3390/genes13020176 - 19 Jan 2022

Cited by 1 | Viewed by 2719

Abstract

As an efficient method, genome-wide association study (GWAS) is used to identify the association between genetic variation and pathological phenotypes, and many significant genetic variations founded by GWAS are closely associated with human diseases. However, it is not enough to mine only a [...] Read more.

As an efficient method, genome-wide association study (GWAS) is used to identify the association between genetic variation and pathological phenotypes, and many significant genetic variations founded by GWAS are closely associated with human diseases. However, it is not enough to mine only a single marker effect variation on complex biological phenotypes. Mining highly correlated single nucleotide polymorphisms (SNP) is more meaningful for the study of Alzheimer's disease (AD). In this paper, we used two frequent pattern mining (FPM) framework, the FP-Growth and Eclat algorithms, to analyze the GWAS results of functional magnetic resonance imaging (fMRI) phenotypes. Moreover, we applied the definition of confidence to FP-Growth and Eclat to enhance the FPM framework. By calculating the conditional probability of identified SNPs, we obtained the corresponding association rules to provide support confidence between these important SNPs. The resulting SNPs showed close correlation with hippocampus, memory, and AD. The experimental results also demonstrate that our framework is effective in identifying SNPs and provide candidate SNPs for further research. Full article

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

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Editorial

5 pages, 141 KiB

Open AccessEditor’s ChoiceEditorial

Genetic and Epigenetic Insights into Pregnancy-Related Complications

by Nihar R. Nayak, Akhilesh Srivastava, Manoj Kumar Jena, Anthony Odibo and Gary Sutkin

Genes 2025, 16(1), 1; https://doi.org/10.3390/genes16010001 - 24 Dec 2024

Cited by 1 | Viewed by 1381

Abstract

Placental dysfunction is a leading cause of numerous pregnancy complications, including preeclampsia, preterm birth, fetal growth restrictions, placental abruption, and late spontaneous abortion [...] Full article

(This article belongs to the Special Issue Genetic and Epigenetic Regulation of Placental Development and Disease)

4 pages, 176 KiB

Open AccessEditor’s ChoiceEditorial

Genetic Research and Plant Breeding 2.0

by Kwon-Kyoo Kang, Yu-Jin Jung and Yong-Gu Cho

Genes 2024, 15(12), 1604; https://doi.org/10.3390/genes15121604 - 15 Dec 2024

Viewed by 960

Abstract

Recent advances in next-generation sequencing technologies have significantly reduced sequencing costs, resulting in the creation of large-scale genomic data that can be utilized for plant breeding [...] Full article

(This article belongs to the Special Issue Genetic Research and Plant Breeding 2.0)

3 pages, 165 KiB

Open AccessEditor’s ChoiceEditorial

Editorial for the Special Issue: Trends in Population Genetics and Identification—Impact on Anthropology

by Verónica Gomes, Luísa Azevedo and Antonio Amorim

Genes 2024, 15(11), 1387; https://doi.org/10.3390/genes15111387 - 29 Oct 2024

Viewed by 1170

Abstract

Technological advances in genetics have revealed many aspects of human ancestry as well as how our genome was shaped by new environments encountered during ancient migrations [...] Full article

(This article belongs to the Special Issue Trends in Population Genetics and Identification—Impact on Anthropology)

4 pages, 171 KiB

Open AccessEditor’s ChoiceEditorial

Editorial: Genetics and Genomics of Polyploid Plants

by Nunzio D’Agostino and Carlo Fasano

Genes 2024, 15(11), 1377; https://doi.org/10.3390/genes15111377 - 25 Oct 2024

Cited by 4 | Viewed by 1395

Abstract

Polyploidy, the condition of having more than two complete sets of chromosomes, is a widespread and influential phenomenon in the plant kingdom [...] Full article

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

4 pages, 163 KiB

Open AccessEditor’s ChoiceEditorial

The Revolution of Genetic Diagnosis: An Example from Rare Disorders

by Stefania Zampatti

Genes 2024, 15(10), 1328; https://doi.org/10.3390/genes15101328 - 15 Oct 2024

Viewed by 1179

Abstract

Since the advent of DNA sequencing, genetic analyses have been increasingly incorporated into clinical practice to support the diagnosis of rare disorders [...] Full article

(This article belongs to the Collection Genetics and Genomics of Rare Disorders)

4 pages, 186 KiB

Open AccessEditor’s ChoiceEditorial

Trends and Prospects in Pig Genomics and Genetics

by Katarzyna Piórkowska and Katarzyna Ropka-Molik

Genes 2024, 15(10), 1292; https://doi.org/10.3390/genes15101292 - 30 Sep 2024

Cited by 1 | Viewed by 1362

Abstract

Pork is one of the most commonly consumed meat in the world [...] Full article

(This article belongs to the Special Issue Trends and Prospects in Pig Genomics and Genetics)

3 pages, 165 KiB

Open AccessEditor’s ChoiceEditorial

Editorial on Genetic Diversity of Plant Tolerance to Environmental Restraints

by Rudy Dolferus and Olive Onyemaobi

Genes 2023, 14(11), 1992; https://doi.org/10.3390/genes14111992 - 25 Oct 2023

Cited by 2 | Viewed by 1035

Abstract

Environmental restraints like cold, drought and heat adversely affect growth and development in different ways and at different plant developmental stages, leading to reduced crop yield [...] Full article

(This article belongs to the Special Issue Genetic Diversity of Plant Tolerance to Environmental Restraints)

3 pages, 185 KiB

Open AccessEditor’s ChoiceEditorial

Coping with Fungal Diseases in Crops: New Advances in Genomics, Breeding and Management

by Elisabetta Mazzucotelli and Anna Maria Mastrangelo

Genes 2023, 14(9), 1758; https://doi.org/10.3390/genes14091758 - 4 Sep 2023

Cited by 1 | Viewed by 1251

Abstract

This Special Issue comprises a collection of eight peer-reviewed articles centered around the plant–pathogen interaction with the aim of proposing strategies that enhance plant resistance to pathogens and limit the damage to crop production, utilizing a multidisciplinary approach [...] Full article

(This article belongs to the Special Issue Coping with Fungal Diseases in Crops: New Advances in Genomics, Breeding and Management)

4 pages, 196 KiB

Open AccessEditor’s ChoiceEditorial

Editorial for the Special Issue “Genetics Studies on Wheat”

by Hongxiang Ma

Genes 2023, 14(9), 1761; https://doi.org/10.3390/genes14091761 - 4 Sep 2023

Cited by 1 | Viewed by 1200

Abstract

Wheat (Triticum aestivum L [...] Full article

(This article belongs to the Special Issue Genetics Studies on Wheat)

2 pages, 182 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue: Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation

by Marek Skrzypski and Paweł A. Kołodziejski

Genes 2023, 14(5), 1121; https://doi.org/10.3390/genes14051121 - 22 May 2023

Cited by 2 | Viewed by 2323

Abstract

Lipid metabolism is pivotal in controlling energy homeostasis [...] Full article

(This article belongs to the Special Issue Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation)

3 pages, 186 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue “DNA Replication/Repair, and the DNA Damage Response in Human Disease”

by Dong Zhang, Kristin A. Eckert and Marietta Y. W. T. Lee

Genes 2023, 14(4), 893; https://doi.org/10.3390/genes14040893 - 11 Apr 2023

Cited by 1 | Viewed by 2315

Abstract

Mutations of numerous genes involved in DNA replication, DNA repair, and DNA damage response (DDR) pathways lead to a variety of human diseases, including aging and cancer [...] Full article

(This article belongs to the Special Issue DNA Replication/Repair, and the DNA Damage Response in Human Disease)

4 pages, 198 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue “Parkinson’s Disease: Genetics and Pathogenesis”

by Suzanne Lesage and Joanne Trinh

Genes 2023, 14(3), 737; https://doi.org/10.3390/genes14030737 - 17 Mar 2023

Cited by 2 | Viewed by 2195

Abstract

Parkinson’s disease (PD) is a common and incurable neurodegenerative disease, affecting 1% of the population over the age of 65 [...] Full article

(This article belongs to the Special Issue Parkinson's Disease: Genetics and Pathogenesis)

4 pages, 194 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue “Feature Papers in Population and Evolutionary Genetics and Genomics”

by Maria-Anna Kyrgiafini and Zissis Mamuris

Genes 2023, 14(1), 38; https://doi.org/10.3390/genes14010038 - 23 Dec 2022

Viewed by 1330

Abstract

Theodosius Dobzhansky famously wrote in 1973 that “nothing in biology makes sense except in the light of evolution” [...] Full article

(This article belongs to the Special Issue Feature Papers in Population and Evolutionary Genetics and Genomics)

3 pages, 185 KiB

Open AccessEditor’s ChoiceEditorial

Special Issue: Genetics of Psychiatric Disease and the Basics of Neurobiology

by Laia Rodriguez-Revenga and Maria Isabel Alvarez-Mora

Genes 2022, 13(11), 2008; https://doi.org/10.3390/genes13112008 - 2 Nov 2022

Viewed by 1480

Abstract

A psychiatric disorder is a mental illness involving significant disturbances in thinking, emotional regulation or behavior [...] Full article

(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)

4 pages, 200 KiB

Open AccessEditor’s ChoiceEditorial

Evolutionary New Genes in a Growing Paradigm

by Esther Betrán and Manyuan Long

Genes 2022, 13(9), 1605; https://doi.org/10.3390/genes13091605 - 8 Sep 2022

Cited by 3 | Viewed by 2104

Abstract

How new genes evolve has become an interesting problem in biology, particularly in evolutionary biology [...] Full article

(This article belongs to the Special Issue How Do New Genes Originate and Evolve?)

3 pages, 191 KiB

Open AccessEditor’s ChoiceEditorial

The Future of Pharmacogenomics Requires New Discoveries and Innovative Education

by Emiliano Giardina and Stefania Zampatti

Genes 2022, 13(9), 1575; https://doi.org/10.3390/genes13091575 - 2 Sep 2022

Cited by 2 | Viewed by 2336

Abstract

Since the beginning of pharmacology, several variations in responses to drugs have been recorded [...] Full article

(This article belongs to the Special Issue Pharmacogenomics: Precision Medicine and Drug Response)

3 pages, 182 KiB

Open AccessEditor’s ChoiceEditorial

Male Reproduction: Regulation, Differentiation and Epigenetics

by Massimo Venditti and Sergio Minucci

Genes 2022, 13(6), 1001; https://doi.org/10.3390/genes13061001 - 2 Jun 2022

Viewed by 1829

Abstract

The production of good-quality spermatozoa (SPZ) is one of the most intricate and far from being completely understood developmental processes during postnatal life [...] Full article

(This article belongs to the Special Issue Male Reproduction: Regulation, Differentiation and Epigenetics)

5 pages, 205 KiB

Open AccessEditor’s ChoiceEditorial

Genetics of Hearing Impairment

by Hannie Kremer and Ignacio del Castillo

Genes 2022, 13(5), 852; https://doi.org/10.3390/genes13050852 - 11 May 2022

Cited by 2 | Viewed by 2355

Abstract

The inner ear is a complex structure at the cellular and molecular levels [...] Full article

(This article belongs to the Special Issue Genetics of Hearing Impairment)

3 pages, 179 KiB

Open AccessEditor’s ChoiceEditorial

Investigations on Nuclear DNA Content and DNA Synthesis in Plants and Fungi Using Flow Cytometry and Fluorescence Microscopy

by Elwira Sliwinska

Genes 2022, 13(3), 417; https://doi.org/10.3390/genes13030417 - 25 Feb 2022

Viewed by 1782

Abstract

The twenty-first century has been an era of extensive genome exploration and modifications, using advanced methods such as genome sequencing and editing [...] Full article

(This article belongs to the Special Issue Investigations on Nuclear DNA Content and DNA Synthesis in Plants and Fungi Using Flow Cytometry and Fluorescence Microscopy)

Review

13 pages, 1592 KiB

Open AccessEditor’s ChoiceReview

Snowflake Data Warehouse for Large-Scale and Diverse Biological Data Management and Analysis

by Tatsuya Koreeda, Hiroshi Honda and Jun-ichi Onami

Genes 2025, 16(1), 34; https://doi.org/10.3390/genes16010034 - 28 Dec 2024

Viewed by 2233

Abstract

With the increasing speed of genomic, transcriptomic, and metagenomic data generation driven by the advancement and widespread adoption of next-generation sequencing technologies, the management and analysis of large-scale, diverse data in the fields of life science and biotechnology have become critical challenges. In [...] Read more.

With the increasing speed of genomic, transcriptomic, and metagenomic data generation driven by the advancement and widespread adoption of next-generation sequencing technologies, the management and analysis of large-scale, diverse data in the fields of life science and biotechnology have become critical challenges. In this paper, we thoroughly discuss the use of cloud data warehouses to address these challenges. Specifically, we propose a data management and analysis framework using Snowflake, a SaaS-based data platform. We further demonstrate its convenience and effectiveness through concrete examples, such as disease variant analysis and in silico drug discovery. By introducing Snowflake, researchers can efficiently manage and analyze a wide array of biological data, enabling the discovery of new biological insights through integrated analysis. Through these specific methodologies and application examples, we aim to accelerate research progress in the field of bioinformatics. Full article

(This article belongs to the Section Bioinformatics)

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18 pages, 2505 KiB

Open AccessEditor’s ChoiceReview

From Species to Varieties: How Modern Sequencing Technologies Are Shaping Medicinal Plant Identification

by Mingcheng Wang, Haifeng Lin, Hongqiang Lin, Panyue Du and Shuqiao Zhang

Genes 2025, 16(1), 16; https://doi.org/10.3390/genes16010016 - 26 Dec 2024

Cited by 19 | Viewed by 1912

Abstract

Background/Objectives: Modern sequencing technologies have transformed the identification of medicinal plant species and varieties, overcoming the limitations of traditional morphological and chemical approaches. This review explores the key DNA-based techniques, including molecular markers, DNA barcoding, and high-throughput sequencing, and their contributions to enhancing [...] Read more.

Background/Objectives: Modern sequencing technologies have transformed the identification of medicinal plant species and varieties, overcoming the limitations of traditional morphological and chemical approaches. This review explores the key DNA-based techniques, including molecular markers, DNA barcoding, and high-throughput sequencing, and their contributions to enhancing the accuracy and reliability of plant identification. Additionally, the integration of multi-omics approaches is examined to provide a comprehensive understanding of medicinal plant identity. Methods: The literature search for this review was conducted across databases such as Google Scholar, Web of Science, and PubMed, using keywords related to plant taxonomy, genomics, and biotechnology. Inclusion criteria focused on peer-reviewed studies closely related to plant identification methods and techniques that contribute significantly to the field. Results: The review highlights that while sequencing technologies offer substantial improvements, challenges such as high costs, technical expertise, and the lack of standardized protocols remain barriers to widespread adoption. Potential solutions, including AI-driven data analysis and portable sequencers, are discussed. Conclusions: This review provides a comprehensive overview of molecular techniques, their transformative impact, and future perspectives for more accurate and efficient medicinal plant identification. Full article

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

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20 pages, 2285 KiB

Open AccessEditor’s ChoiceReview

Advances in the Structure, Function, and Regulatory Mechanism of Plant Plasma Membrane Intrinsic Proteins

by Xueting Li, Yirong Guo, Qiuping Ling, Zhejun Guo, Yawen Lei, Xiaomin Feng, Jiayun Wu and Nannan Zhang

Genes 2025, 16(1), 10; https://doi.org/10.3390/genes16010010 - 25 Dec 2024

Viewed by 1461

Abstract

Plasma membrane intrinsic proteins (PIPs), as members of the aquaporin (AQPs) family, can transport not only water but also urea, CO₂, H₂O₂, metal ions, and trace elements. They are crucial for maintaining water balance, substance transport, and [...] Read more.

Plasma membrane intrinsic proteins (PIPs), as members of the aquaporin (AQPs) family, can transport not only water but also urea, CO₂, H₂O₂, metal ions, and trace elements. They are crucial for maintaining water balance, substance transport, and responding to various stresses. This article delves into the structure, function, response mechanism, molecular mechanism, and regulatory mechanism of PIPs as a result of biological and abiotic stresses. It also summarizes current research trends surrounding PIPs and highlights potential research directions for further exploration. The aim is to assist researchers in related fields in gaining a more comprehensive understanding and precise insight into the advancements in PIP research. Full article

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

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22 pages, 1322 KiB

Open AccessEditor’s ChoiceReview

Genetic Etiology in Pelvic Organ Prolapse: Role of Connective Tissue Homeostasis, Hormone Metabolism, and Oxidative Stress

by Wenxuan Jiang, Rachel Yau Kar Cheung, Cheuk Yan Chung, Symphorosa Shing Chee Chan and Kwong Wai Choy

Genes 2025, 16(1), 5; https://doi.org/10.3390/genes16010005 - 24 Dec 2024

Cited by 2 | Viewed by 1577

Abstract

Background: Pelvic organ prolapse (POP) has become a common health problem among the aging population and affects an increasing number of elderly women worldwide. Studies within family and twin pairs provided strong evidence for the contribution of genetic factors to POP. Given [...] Read more.

Background: Pelvic organ prolapse (POP) has become a common health problem among the aging population and affects an increasing number of elderly women worldwide. Studies within family and twin pairs provided strong evidence for the contribution of genetic factors to POP. Given the incomplete penetrance, polygenic traits, and small effect sizes of each variant in complex diseases, it is not always easy to evaluate the genetic susceptibility and molecular mechanisms involved in POP. Objectives: This review intends to comprehensively summarize the current studies on genetic variants associated with POP. Methods: We performed a comprehensive review to summarize the genetic findings from genome-linkage studies, genome-wide association studies, candidate association studies, and gene expression analyses. Results: We summarized genetic variants associated with connective tissue homeostasis, hormone metabolism, and oxidative stress, which were potentially related to the pathophysiology of POP. We also reviewed the limited polygenic risk score (PRS) studies generated for each individual’s genetic risk stratification and its integration into clinical risk factors for disease prediction. Conclusions: This pooled analysis provides moderate epidemiological credibility for associations of these genetic variants with POP to bridge the gap between genetic research and clinical medicine towards understanding the genetic etiology of POP. It also highlights the potential of PRS as a risk prediction model. Full article

(This article belongs to the Special Issue Genetic Advances and Challenges in Complex Diseases)

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14 pages, 877 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Hypoxia-Inducible Factor in Renal Cell Carcinoma: From Molecular Insights to Targeted Therapies

by Giandomenico Roviello, Irene De Gennaro, Ismaela Vascotto, Giulia Venturi, Alberto D’Angelo, Costanza Winchler, Adriana Guarino, Salvatore Cacioppo, Mikol Modesti, Marinella Micol Mela, Edoardo Francini, Laura Doni, Virginia Rossi, Elisabetta Gambale, Roberta Giorgione, Lorenzo Antonuzzo, Gabriella Nesi and Martina Catalano

Genes 2025, 16(1), 6; https://doi.org/10.3390/genes16010006 - 24 Dec 2024

Cited by 1 | Viewed by 2093

Abstract

Mutations of the von Hippel–Lindau (VHL) tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of VHL lead to impaired degradation of [...] Read more.

Mutations of the von Hippel–Lindau (VHL) tumor suppressor gene occur frequently in clear cell renal cell carcinoma (RCC), the predominant histology of kidney cancer, and have been associated with its pathogenesis and progression. Alterations of VHL lead to impaired degradation of hypoxia-inducible factor 1α (HIF1α) and HIF2α promoting neoangiogenesis, which is pivotal for cancer growth. As such, targeting the VHL-HIF axis holds relevant potential for therapeutic purposes. Belzutifan, an HIF-2α inhibitor, has been recently indicated for metastatic RCC and other antiangiogenic drugs directed against HIF-2α are currently under investigation. Further, clinical and preclinical studies of combination approaches for metastatic RCC including belzutifan with cyclin-dependent kinase 4–6 inhibitors, tyrosine kinase inhibitors, or immune checkpoint inhibitors achieved promising results or are ongoing. This review aims to summarize the existing evidence regarding the VHL/HIF pathway, and the approved and emerging treatment strategies that target this pivotal molecular axis and their mechanisms of resistance. Full article

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

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25 pages, 779 KiB

Open AccessFeature PaperEditor’s ChoiceReview

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

Cited by 1 | Viewed by 2469

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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33 pages, 4545 KiB

Open AccessEditor’s ChoiceReview

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 1711

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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15 pages, 687 KiB

Open AccessEditor’s ChoiceReview

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

Cited by 5 | Viewed by 2345

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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13 pages, 299 KiB

Open AccessEditor’s ChoiceReview

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

Cited by 5 | Viewed by 3100

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)

16 pages, 1584 KiB

Open AccessEditor’s ChoiceReview

Advancements and Challenges in Preimplantation Genetic Testing for Aneuploidies: In the Pathway to Non-Invasive Techniques

by Ana del Arco de la Paz, Carla Giménez-Rodríguez, Aikaterini Selntigia, Marcos Meseguer and Daniela Galliano

Genes 2024, 15(12), 1613; https://doi.org/10.3390/genes15121613 - 17 Dec 2024

Cited by 1 | Viewed by 2937

Abstract

The evolution of preimplantation genetic testing for aneuploidy (PGT-A) techniques has been crucial in assisted reproductive technologies (ARTs), improving embryo selection and increasing success rates in in vitro fertilization (IVF) treatments. Techniques ranging from fluorescence in situ hybridization (FISH) to next-generation sequencing (NGS) [...] Read more.

The evolution of preimplantation genetic testing for aneuploidy (PGT-A) techniques has been crucial in assisted reproductive technologies (ARTs), improving embryo selection and increasing success rates in in vitro fertilization (IVF) treatments. Techniques ranging from fluorescence in situ hybridization (FISH) to next-generation sequencing (NGS) have relied on cellular material extraction through biopsies of blastomeres at the cleavage stage on day three or from trophectoderm (TE) cells of the blastocyst. However, this has raised concerns about its potential impact on embryo development. As a result, there has been growing interest in developing non-invasive techniques for detecting aneuploidies, such as the analysis of blastocoel fluid (BF), spent culture medium (SCM), and artificial intelligence (AI) models. Non-invasive methods represent a promising advancement in PGT-A, offering the ability to detect aneuploidies without compromising embryo viability. This article reviews the evolution and principles of PGT-A, analyzing both traditional techniques and emerging non-invasive approaches, while highlighting the advantages and challenges associated with these methodologies. Furthermore, it explores the transformative potential of these innovations, which could optimize genetic screening and significantly improve clinical outcomes in the field of assisted reproduction. Full article

(This article belongs to the Special Issue Current Advances and Future Perspectives on Preimplantation Genetic Testing)

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