Genes

16 pages, 5017 KiB

Open AccessEditor’s ChoiceArticle

Multi-Omic Analysis Reveals the Molecular Mechanism of UV-B Stress Resistance in Acetylated RcMYB44 in Rhododendron chrysanthum

by Meiqi Liu, Xiaoru Lin, Kun Cao, Liping Yang, Hongwei Xu and Xiaofu Zhou

Genes 2023, 14(11), 2022; https://doi.org/10.3390/genes14112022 - 30 Oct 2023

Cited by 2 | Viewed by 1553

Abstract

Ultraviolet-B (UV-B) radiation is a significant environmental factor influencing the growth and development of plants. MYBs play an essential role in the processes of plant responses to abiotic stresses. In the last few years, the development of transcriptome and acetylated proteome technologies have [...] Read more.

Ultraviolet-B (UV-B) radiation is a significant environmental factor influencing the growth and development of plants. MYBs play an essential role in the processes of plant responses to abiotic stresses. In the last few years, the development of transcriptome and acetylated proteome technologies have resulted in further and more reliable data for understanding the UV-B response mechanism in plants. In this research, the transcriptome and acetylated proteome were used to analyze Rhododendron chrysanthum Pall. (R. chrysanthum) leaves under UV-B stress. In total, 2348 differentially expressed genes (DEGs) and 685 differentially expressed acetylated proteins (DAPs) were found. The transcriptome analysis revealed 232 MYB TFs; we analyzed the transcriptome together with the acetylated proteome, and screened 4 MYB TFs. Among them, only RcMYB44 had a complete MYB structural domain. To investigate the role of RcMYB44 under UV-B stress, a homology tree was constructed between RcMYB44 and Arabidopsis MYBs, and it was determined that RcMYB44 shares the same function with ATMYB44. We further constructed the hormone signaling pathway involved in RcMYB44, revealing the molecular mechanism of resistance to UV-B stress in R. chrysanthum. Finally, by comparing the transcriptome and the proteome, it was found that the expression levels of proteins and genes were inconsistent, which is related to post-translational modifications of proteins. In conclusion, RcMYB44 of R. chrysanthum is involved in mediating the growth hormone, salicylic acid, jasmonic acid, and abscisic acid signaling pathways to resist UV-B stress. Full article

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

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16 pages, 3083 KiB

Open AccessEditor’s ChoiceArticle

Thyroid Transcriptomics Revealed the Reproductive Regulation of miRNA in the Follicular and Luteal Phases in Small-Tail Han Sheep with Different FecB Genotypes

by Cheng Chang, Xiaoyun He, Ran Di, Xiangyu Wang, Miaoceng Han, Chen Liang and Mingxing Chu

Genes 2023, 14(11), 2024; https://doi.org/10.3390/genes14112024 - 30 Oct 2023

Cited by 3 | Viewed by 1755

Abstract

MicroRNA (miRNA) is a type of endogenous short−stranded ncRNA that influences many biological processes such as animal growth, development and metabolism. The thyroid gland is an important endocrine gland in sheep, and an increasing number of studies have shown that the thyroid gland [...] Read more.

MicroRNA (miRNA) is a type of endogenous short−stranded ncRNA that influences many biological processes such as animal growth, development and metabolism. The thyroid gland is an important endocrine gland in sheep, and an increasing number of studies have shown that the thyroid gland plays an important role in animal reproduction, but the molecular mechanisms of the thyroid gland in sheep reproduction are poorly understood. In this study, RNA-seq was used to detect transcriptome expression patterns in the thyroid gland between the follicular phase (FP) and luteal phase (LP) in FecB BB (MM) and FecB ++ (ww) small-tail Han (STH) sheep, respectively, and to identify differentially expressed miRNAs (DEMs) associated with reproduction. Bioinformatic analysis of the target genes of these DEMs revealed that they can be enriched in multiple GO terms associated with the reproductive process in animals and in the KEGG signaling pathway. The miRNA–mRNA coexpression network revealed that oar-miR-133 and oar-miR-370-3p may play an important role in sheep reproduction. The results of the dual-luciferase reporter assay suggest a possible targeting relationship between novel-51 and TARBP2. These results provided a novel resource for elucidating regulatory mechanisms underlying STH sheep prolificacy. Full article

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

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12 pages, 2988 KiB

Open AccessEditor’s ChoiceArticle

Navigating the ALS Genetic Labyrinth: The Role of MAPT Haplotypes

by Ivan Tourtourikov, Kristiyan Dabchev, Tihomir Todorov, Teodor Angelov, Teodora Chamova, Ivailo Tournev, Tanya Kadiyska, Vanyo Mitev and Albena Todorova

Genes 2023, 14(11), 2023; https://doi.org/10.3390/genes14112023 - 30 Oct 2023

Cited by 1 | Viewed by 1792

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the MAPT [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the MAPT (microtubule-associated protein tau) gene, according to their possible effect as a risk factor and as a modifying factor in relation to the age of disease onset. One hundred patients from Bulgaria with sporadic ALS were genotyped for the variants rs1467967, rs242557, rs1800547, rs3785883, rs2471738, and rs7521. Haploview 4.2 and SHEsisPlus were used to reconstruct haplotype frequencies using genotyping data from the 1000 Genomes project as controls. Genotype–phenotype correlation was investigated in the context of age of disease onset and risk of disease development. While the individual variants of the subtypes do not influence the age of onset of the disease, a correlation was found between the specific haplotype GGAGCA (H1b) and the risk of developing sALS, with results showing that individuals harboring this haplotype have a nearly two-fold increased risk of developing sALS compared to other H1 subtypes. The results from this study suggest that fine transcriptional regulation at the MAPT locus can influence the risk of ALS. Full article

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

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33 pages, 2376 KiB

Open AccessEditor’s ChoiceArticle

Three Blind Moles: Molecular Evolutionary Insights on the Tempo and Mode of Convergent Eye Degeneration in Notoryctes typhlops (Southern Marsupial Mole) and Two Chrysochlorids (Golden Moles)

by Mark S. Springer, Christopher A. Emerling and John Gatesy

Genes 2023, 14(11), 2018; https://doi.org/10.3390/genes14112018 - 28 Oct 2023

Cited by 2 | Viewed by 2923

Abstract

Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by [...] Read more.

Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia’s aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis. Full article

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

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21 pages, 9266 KiB

Open AccessEditor’s ChoiceArticle

The Novel Link between Gene Expression Profiles of Adult T-Cell Leukemia/Lymphoma Patients’ Peripheral Blood Lymphocytes and Ferroptosis Susceptibility

by Yu Wang and Hidekatsu Iha

Genes 2023, 14(11), 2005; https://doi.org/10.3390/genes14112005 - 27 Oct 2023

Cited by 3 | Viewed by 2279

Abstract

Ferroptosis, a regulated cell death dependent on iron, has garnered attention as a potential broad-spectrum anticancer approach in leukemia research. However, there has been limited ferroptosis research on ATL, an aggressive T-cell malignancy caused by HTLV-1 infection. Our study employs bioinformatic analysis, utilizing [...] Read more.

Ferroptosis, a regulated cell death dependent on iron, has garnered attention as a potential broad-spectrum anticancer approach in leukemia research. However, there has been limited ferroptosis research on ATL, an aggressive T-cell malignancy caused by HTLV-1 infection. Our study employs bioinformatic analysis, utilizing dataset GSE33615, to identify 46 ferroptosis-related DEGs and 26 autophagy-related DEGs in ATL cells. These DEGs are associated with various cellular responses, chemical stress, and iron-related pathways. Autophagy-related DEGs are linked to autophagy, apoptosis, NOD-like receptor signaling, TNF signaling, and the insulin resistance pathway. PPI network analysis revealed 10 hub genes and related biomolecules. Moreover, we predicted crucial miRNAs, transcription factors, and potential pharmacological compounds. We also screened the top 20 medications based on upregulated DEGs. In summary, our study establishes an innovative link between ATL treatment and ferroptosis, offering promising avenues for novel therapeutic strategies in ATL. Full article

(This article belongs to the Topic Advances in Bioinformatics and Computational Biology of Human Disease)

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16 pages, 2290 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Association Analysis across Endophenotypes in Alzheimer’s Disease: Main Effects and Disease Stage-Specific Interactions

by Thea J. Rosewood, Kwangsik Nho, Shannon L. Risacher, Sujuan Gao, Li Shen, Tatiana Foroud, Andrew J. Saykin and on behalf of the Alzheimer’s Disease Neuroimaging Initiative

Genes 2023, 14(11), 2010; https://doi.org/10.3390/genes14112010 - 27 Oct 2023

Cited by 1 | Viewed by 2313

Abstract

The underlying genetic susceptibility for Alzheimer’s disease (AD) is not yet fully understood. The heterogeneous nature of the disease challenges genetic association studies. Endophenotype approaches can help to address this challenge by more direct interrogation of biological traits related to the disease. AD [...] Read more.

The underlying genetic susceptibility for Alzheimer’s disease (AD) is not yet fully understood. The heterogeneous nature of the disease challenges genetic association studies. Endophenotype approaches can help to address this challenge by more direct interrogation of biological traits related to the disease. AD endophenotypes based on amyloid-β, tau, and neurodegeneration (A/T/N) biomarkers and cognitive performance were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (N = 1565). A genome-wide association study (GWAS) of quantitative phenotypes was performed using an SNP main effect and an SNP by Diagnosis interaction (SNP × DX) model to identify disease stage-specific genetic effects. Nine loci were identified as study-wide significant with one or more A/T/N endophenotypes in the main effect model, as well as additional findings significantly associated with cognitive measures. These nine loci include SNPs in or near the genes APOE, SRSF10, HLA-DQB1, XKR3, and KIAA1671. The SNP × DX model identified three study-wide significant genetic loci (BACH2, EP300, and PACRG-AS1) with a neuroprotective effect in later AD stage endophenotypes. An endophenotype approach identified novel genetic associations and provided insight into the molecular mechanisms underlying the genetic associations that may otherwise be missed using conventional case-control study designs. Full article

(This article belongs to the Special Issue Study on Genotypes and Phenotypes of Neurodegenerative Diseases—2nd Edition)

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27 pages, 1843 KiB

Open AccessEditor’s ChoiceArticle

Current State of Genomics in Nursing: A Scoping Review of Healthcare Provider Oriented (Clinical and Educational) Outcomes (2012–2022)

by Joanne Thomas, Jordan Keels, Kathleen A. Calzone, Laurie Badzek, Sarah Dewell, Christine Patch, Emma T. Tonkin and Andrew A. Dwyer

Genes 2023, 14(11), 2013; https://doi.org/10.3390/genes14112013 - 27 Oct 2023

Cited by 28 | Viewed by 4887

Abstract

In the 20 years since the initial sequencing of the human genome, genomics has become increasingly relevant to nursing. We sought to chart the current state of genomics in nursing by conducting a systematic scoping review of the literature in four databases (2012–2022). [...] Read more.

In the 20 years since the initial sequencing of the human genome, genomics has become increasingly relevant to nursing. We sought to chart the current state of genomics in nursing by conducting a systematic scoping review of the literature in four databases (2012–2022). The included articles were categorized according to the Cochrane Collaboration outcome domains/sub-domains, and thematic analysis was employed to identify key topical areas to summarize the state of the science. Of 8532 retrieved articles, we identified 232 eligible articles. The articles primarily reported descriptive studies from the United States and other high-income countries (191/232, 82%). More than half (126/232, 54.3%) aligned with the “healthcare provider oriented outcomes” outcome domain. Three times as many articles related to the “knowledge and understanding” sub-domain compared to the “consultation process” subdomain (96 vs. 30). Five key areas of focus were identified, including “nursing practice” (50/126, 40%), “genetic counseling and screening” (29/126, 23%), “specialist nursing” (21/126, 17%), “nurse preparatory education” (17/126, 13%), and “pharmacogenomics” (9/126, 7%). Only 42/126 (33%) articles reported interventional studies. To further integrate genomics into nursing, study findings indicate there is a need to move beyond descriptive work on knowledge and understanding to focus on interventional studies and implementation of genomics into nursing practice. Full article

(This article belongs to the Special Issue Advances in Genomic Nursing: Implications for Nursing Education, Practice and Research)

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26 pages, 6863 KiB

Open AccessEditor’s ChoiceArticle

Complete Chloroplast Genomes of Saussurea katochaete, Saussurea superba, and Saussurea stella: Genome Structures and Comparative and Phylogenetic Analyses

by Hui He, Tao Wang, Chuyu Tang, Zhengfei Cao, Xiaojian Pu, Yuling Li and Xiuzhang Li

Genes 2023, 14(11), 2002; https://doi.org/10.3390/genes14112002 - 26 Oct 2023

Cited by 3 | Viewed by 1745

Abstract

Saussurea plants are widely distributed in Asia and Europe; however, their complex phylogenetic relationships have led to many difficulties in phylogenetic studies and interspecific identification. In this study, we assembled, annotated, and analyzed the chloroplast genomes of three Saussurea plants: Saussurea katochaete, [...] Read more.

Saussurea plants are widely distributed in Asia and Europe; however, their complex phylogenetic relationships have led to many difficulties in phylogenetic studies and interspecific identification. In this study, we assembled, annotated, and analyzed the chloroplast genomes of three Saussurea plants: Saussurea katochaete, Saussurea superba, and Saussurea stella. The results showed that the full-length sequences of the three Saussurea plants were 152,561 bp, 151,452 bp, and 152,293 bp, respectively, which represent the typical quadripartite structure, and the genomes were relatively conserved. The gene annotation results showed that the chloroplast genomes of S. katochaete, S. superba, and S. stella were annotated with 128, 124, and 127 unique genes, respectively, which included 83, 80, and 83 protein-coding genes (PCGs), respectively, 37, 36, and 36 tRNA genes, respectively, and 8 rRNA genes. Moreover, 46, 45, and 43 SSR loci, respectively, and nine highly variable regions (rpl32-trnL-UAG, rpl32, ndhF-rpl32, ycf1, trnC-GCA-petN, trnC-GCA, rpcL, psbE-petL, and rpl16-trnG-UUG) were identified and could be used as potential molecular markers for population identification and phylogenetic study of Saussurea plants. Phylogenetic analyses strongly support the sisterhood of S. katochaete with S. superba and S. stella, and are all clustered with S. depsagensis, S. inversa, S. medusa, and S. gossipihora, of which S. gossipiphora is most closely related. Additionally, the phylogenetic results indicate a high frequency of differentiation among different species of Saussurea plants, and many different species or genera are morphologically very different from each other, which may be related to certain genetic material in the chloroplasts. This study provides an important reference for the identification of Saussurea plants and studies their evolution and phylogenetics. Full article

(This article belongs to the Special Issue Plant Plastid Genome)

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10 pages, 2466 KiB

Open AccessEditor’s ChoiceArticle

Distribution of Runs of Homozygosity and Their Relationship with Candidate Genes for Productivity in Kazakh Meat–Wool Sheep Breed

by Makpal Amandykova, Zhanerke Akhatayeva, Altynay Kozhakhmet, Tilek Kapassuly, Zarina Orazymbetova, Kanagat Yergali, Kadyrzhan Khamzin, Kairat Iskakov and Kairat Dossybayev

Genes 2023, 14(11), 1988; https://doi.org/10.3390/genes14111988 - 25 Oct 2023

Cited by 3 | Viewed by 2331

Abstract

Increasing the fertility of sheep remains one of the crucial issues of modern sheep breeding. The Kazakh meat–wool sheep is an excellent breed with high meat and wool productivity and well adapted to harsh conditions. Nowadays, runs of homozygosity (ROHs) are considered a [...] Read more.

Increasing the fertility of sheep remains one of the crucial issues of modern sheep breeding. The Kazakh meat–wool sheep is an excellent breed with high meat and wool productivity and well adapted to harsh conditions. Nowadays, runs of homozygosity (ROHs) are considered a suitable approach for studying the genetic characteristics of farm animals. The aims of the study were to analyze the distribution of ROHs, describe autozygosity, and detect genomic regions with high ROH islands. In this study, we genotyped a total of 281 Kazakh meat–wool sheep using the Illumina iScan^® system (EquipNet, Canton, MA, USA) via Ovine SNP50 BeadChip array. As a results, a total of 15,069 ROHs were found in the three Kazakh meat–wool sheep populations. The mean number of ROH per animal across populations varied from 40.3 (POP1) to 42.2 (POP2) in the category 1+ Mb. Furthermore, the number of ROH per animal in ROH_{1–2 Mb} were much higher than ROH_{2–4 Mb} and ROH_{8–16 Mb} in the three sheep populations. Most of individuals had small number of ROH_{>16 Mb}. The highest and lowest genomic inbreeding coefficient values were observed in POP2 and POP3, respectively. The estimated F_ROH presented the impact that recent inbreeding has had in all sheep populations. Furthermore, a set of interesting candidate genes (BMP2, BMPR2, BMPRIB, CLOCK, KDM2B, TIAM1, TASP1, MYBPC1, MYOM1, and CACNA2D1), which are related to the productive traits, were found. Collectively, these findings will contribute to the breeding and conservation strategies of the Kazakh meat–wool sheep breed. Full article

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

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15 pages, 1216 KiB

Open AccessEditor’s ChoiceArticle

Complete Mitochondrial DNA Genome Variation in the Swedish Population

by Kimberly Sturk-Andreaggi, Martin Bodner, Joseph D. Ring, Adam Ameur, Ulf Gyllensten, Walther Parson, Charla Marshall and Marie Allen

Genes 2023, 14(11), 1989; https://doi.org/10.3390/genes14111989 - 25 Oct 2023

Cited by 1 | Viewed by 2457

Abstract

The development of complete mitochondrial genome (mitogenome) reference data for inclusion in publicly available population databases is currently underway, and the generation of more high-quality mitogenomes will only enhance the statistical power of this forensically useful locus. To characterize mitogenome variation in Sweden, [...] Read more.

The development of complete mitochondrial genome (mitogenome) reference data for inclusion in publicly available population databases is currently underway, and the generation of more high-quality mitogenomes will only enhance the statistical power of this forensically useful locus. To characterize mitogenome variation in Sweden, the mitochondrial DNA (mtDNA) reads from the SweGen whole genome sequencing (WGS) dataset were analyzed. To overcome the interference from low-frequency nuclear mtDNA segments (NUMTs), a 10% variant frequency threshold was applied for the analysis. In total, 934 forensic-quality mitogenome haplotypes were characterized. Almost 45% of the SweGen haplotypes belonged to haplogroup H. Nearly all mitogenome haplotypes (99.1%) were assigned to European haplogroups, which was expected based on previous mtDNA studies of the Swedish population. There were signature northern Swedish and Finnish haplogroups observed in the dataset (e.g., U5b1, W1a), consistent with the nuclear DNA analyses of the SweGen data. The complete mitogenome analysis resulted in high haplotype diversity (0.9996) with a random match probability of 0.15%. Overall, the SweGen mitogenomes provide a large mtDNA reference dataset for the Swedish population and also contribute to the effort to estimate global mitogenome haplotype frequencies. Full article

(This article belongs to the Special Issue Improved Methods in Forensic DNA Analysis)

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15 pages, 1673 KiB

Open AccessEditor’s ChoiceReview

Challenges in the Definitive Diagnosis of Niemann–Pick Type C—Leaky Variants and Alternative Transcripts

by Marisa Encarnação, Isaura Ribeiro, Hugo David, Maria Francisca Coutinho, Dulce Quelhas and Sandra Alves

Genes 2023, 14(11), 1990; https://doi.org/10.3390/genes14111990 - 25 Oct 2023

Cited by 3 | Viewed by 2254

Abstract

Niemann–Pick type C (NPC, ORPHA: 646) is a neuro-visceral, psychiatric disease caused predominantly by pathogenic variants in the NPC1 gene or seldom in NPC2. The rarity of the disease, and its wide range of clinical phenotypes and ages of onset, turn the [...] Read more.

Niemann–Pick type C (NPC, ORPHA: 646) is a neuro-visceral, psychiatric disease caused predominantly by pathogenic variants in the NPC1 gene or seldom in NPC2. The rarity of the disease, and its wide range of clinical phenotypes and ages of onset, turn the diagnosis into a significant challenge. Other than the detailed clinical history, the typical diagnostic work-up for NPC includes the quantification of pathognomonic metabolites. However, the molecular basis diagnosis is still of utmost importance to fully characterize the disorder. Here, the authors provide an overview of splicing variants in the NPC1 and NPC2 genes and propose a new workflow for NPC diagnosis. Splicing variants cover a significant part of the disease-causing variants in NPC. The authors used cDNA analysis to study the impact of such variants, including the collection of data to classify them as leaky or non-leaky pathogenic variants. However, the presence of naturally occurring spliced transcripts can misdiagnose or mask a pathogenic variant and make the analysis even more difficult. Analysis of the NPC1 cDNA in NPC patients in parallel with controls is vital to assess and detect alternatively spliced forms. Moreover, nonsense-mediated mRNA decay (NMD) analysis plays an essential role in evaluating the naturally occurring transcripts during cDNA analysis and distinguishing them from other pathogenic variants’ associated transcripts. Full article

(This article belongs to the Section Genetic Diagnosis)

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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 1012

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)

23 pages, 11195 KiB

Open AccessEditor’s ChoiceArticle

Predicting Prognosis and Immunotherapy Response in Multiple Cancers Based on the Association of PANoptosis-Related Genes with Tumor Heterogeneity

by Yunhan Wang, Boyu Zhang, Zongying Zhang, Jia Ge, Lin Xu, Jiawei Mao, Xiaorong Zhou, Liming Mao, Qiuyun Xu and Mengmeng Sang

Genes 2023, 14(11), 1994; https://doi.org/10.3390/genes14111994 - 25 Oct 2023

Cited by 5 | Viewed by 2693

Abstract

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. [...] Read more.

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients. Full article

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

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14 pages, 481 KiB

Open AccessEditor’s ChoiceReview

The Nutriepigenome

by Mario G. Mirisola

Genes 2023, 14(11), 1997; https://doi.org/10.3390/genes14111997 - 25 Oct 2023

Cited by 3 | Viewed by 2017

Abstract

Unlike genetic changes, epigenetics modulates gene expression without stable modification of the genome. Even though all cells, including sperm and egg, have an epigenome pattern, most of these modifications occur during lifetime and interestingly, some of them, are reversible. Lifestyle and especially nutrients [...] Read more.

Unlike genetic changes, epigenetics modulates gene expression without stable modification of the genome. Even though all cells, including sperm and egg, have an epigenome pattern, most of these modifications occur during lifetime and interestingly, some of them, are reversible. Lifestyle and especially nutrients as well as diet regimens are presently gaining importance due to their ability to affect the epigenome. On the other hand, since the epigenome profoundly affects gene expression profile it can be speculated that the epigenome could modulate individual response to nutrients. Recent years have thus seen growing interest on nutrients, macronutrients ratio and diet regimens capable to affect the epigenetic pattern. In fact, while genetic alterations are mostly detrimental at the individual level, reshaping the epigenome may be a feasible strategy to positively counteract the detrimental effect of aging. Here, I review nutrient consumption and diet regimens as a possible strategy to counteract aging-driven epigenome derangement. Full article

(This article belongs to the Special Issue Nutrigenomics and Cellular Metabolism)

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30 pages, 1414 KiB

Open AccessEditor’s ChoiceReview

Mitochondria, a Key Target in Amyotrophic Lateral Sclerosis Pathogenesis

by Emmanuelle C. Genin, Mélanie Abou-Ali and Véronique Paquis-Flucklinger

Genes 2023, 14(11), 1981; https://doi.org/10.3390/genes14111981 - 24 Oct 2023

Cited by 23 | Viewed by 5537

Abstract

Mitochondrial dysfunction occurs in numerous neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), where it contributes to motor neuron (MN) death. Of all the factors involved in ALS, mitochondria have been considered as a major player, as secondary mitochondrial dysfunction has been found in [...] Read more.

Mitochondrial dysfunction occurs in numerous neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), where it contributes to motor neuron (MN) death. Of all the factors involved in ALS, mitochondria have been considered as a major player, as secondary mitochondrial dysfunction has been found in various models and patients. Abnormal mitochondrial morphology, defects in mitochondrial dynamics, altered activities of respiratory chain enzymes and increased production of reactive oxygen species have been described. Moreover, the identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS. In this review, we focus on the role of mitochondria in ALS and highlight the pathogenic variants of ALS genes associated with impaired mitochondrial functions. The multiple pathways demonstrated in ALS pathogenesis suggest that all converge to a common endpoint leading to MN loss. This may explain the disappointing results obtained with treatments targeting a single pathological process. Fighting against mitochondrial dysfunction appears to be a promising avenue for developing combined therapies in the future. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Mitochondrial Diseases)

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8 pages, 1331 KiB

Open AccessEditor’s ChoiceCase Report

Double Heterozygous Pathogenic Variants in the LOX and PKD1 Genes in a 5-Year-Old Patient with Thoracic Aortic Aneurysm and Polycystic Kidney Disease

by Joanna Kinga Ponińska, Weronika Pelczar-Płachta, Agnieszka Pollak, Katarzyna Jończyk-Potoczna, Grażyna Truszkowska, Ilona Michałowska, Emilia Szafran, Zofia T. Bilińska, Waldemar Bobkowski and Rafał Płoski

Genes 2023, 14(11), 1983; https://doi.org/10.3390/genes14111983 - 24 Oct 2023

Cited by 1 | Viewed by 1679

Abstract

Familial thoracic aortic aneurysms and dissections may occur as an isolated hereditary trait or as part of connective tissue disorders with Mendelian inheritance, but severe cardiovascular disease in pediatric patients is extremely rare. There is growing knowledge on pathogenic variants causing the disease; [...] Read more.

Familial thoracic aortic aneurysms and dissections may occur as an isolated hereditary trait or as part of connective tissue disorders with Mendelian inheritance, but severe cardiovascular disease in pediatric patients is extremely rare. There is growing knowledge on pathogenic variants causing the disease; however, much of the phenotypic variability and gene–gene interactions remain to be discovered. We present a case report of a 5.5-year-old girl with an aortic aneurysm and concomitant polycystic kidney disease. Whole exome sequencing was performed, followed by family screening by amplicon deep sequencing and diagnostic imaging studies. In the proband, two pathogenic variants were identified: p.Tyr257Ter in the LOX gene inherited from her mother, and p.Thr2977Ile in the PKD1 gene inherited from her father. All adult carriers of either of these variants showed symptoms of aortic disease. We conclude that the coexistence of two independent genetic variants in the proband may be the reason for an early onset of disease. Full article

(This article belongs to the Section Genetic Diagnosis)

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11 pages, 2463 KiB

Open AccessEditor’s ChoiceArticle

Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome

by Doriana Misceo, Lokuliyanage Dona Samudita Senaratne, Inger-Lise Mero, Arvind Y. M. Sundaram, Pål Marius Bjørnstad, Krzysztof Szczałuba, Piotr Gasperowicz, Benjamin Kamien, Bård Nedregaard, Asbjørn Holmgren, Petter Strømme and Eirik Frengen

Genes 2023, 14(11), 1985; https://doi.org/10.3390/genes14111985 - 24 Oct 2023

Cited by 2 | Viewed by 2534

Abstract

Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, [...] Read more.

Strømme syndrome is an ultra-rare primary ciliopathy with clinical variability. The syndrome is caused by bi-allelic variants in CENPF, a protein with key roles in both chromosomal segregation and ciliogenesis. We report three unrelated patients with Strømme syndrome and, using high-throughput sequencing approaches, we identified novel pathogenic variants in CENPF, including one structural variant, giving a genetic diagnosis to the patients. Patient 1 was a premature baby who died at 26 days with congenital malformations affecting many organs including the brain, eyes, and intestine. She was homozygous for a donor splice variant in CENPF, NM_016343.3:c.1068+1G>A, causing skipping of exon 7, resulting in a frameshift. Patient 2 was a female with intestinal atresia, microcephaly, and a Peters anomaly. She had normal developmental milestones at the age of 7 years. She is compound heterozygous for CENPF NM_016343.3:c.5920dup and c.8991del, both frameshift. Patient 3 was a male with anomalies of the brain, eye, intestine, and kidneys. He was compound heterozygous for CENPF p.(Glu298Ter), and a 5323 bp deletion covering exon 1. CENPF exon 1 is flanked by repetitive sequences that may represent a site of a recurrent structural variation, which should be a focus in patients with Strømme syndrome of unknown etiology. Full article

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

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11 pages, 4254 KiB

Open AccessEditor’s ChoiceArticle

Amplification Failure of the Amelogenin X Gene Caused by a Rare Mutation in the Primer-Binding Region

by Miwha Chang, Jong Keun Jung, Ji Hwan Park, Ju Yeon Jung, Won-Hae Lee and Joo-Young Kim

Genes 2023, 14(11), 1986; https://doi.org/10.3390/genes14111986 - 24 Oct 2023

Cited by 2 | Viewed by 2095

Abstract

The study of gender markers is essential in forensic genetic analysis. Mutations in the X or Y homologs of the amelogenin gene can be misleading, resulting in serious mistakes in forensic genetic analysis. We recently discovered two male cases of the X homolog [...] Read more.

The study of gender markers is essential in forensic genetic analysis. Mutations in the X or Y homologs of the amelogenin gene can be misleading, resulting in serious mistakes in forensic genetic analysis. We recently discovered two male cases of the X homolog of the amelogenin (AMELX) allelic dropout while analyzing short tandem repeat genotypes obtained from crime scene evidence. Subsequently, we evaluated the molecular characteristics of AMELX allelic dropout in this study. We used two previously reported amelogenin primers to verify a half level of amelogenin gene amplification intensity in the two male cases, which we confirmed was caused by AMELX allelic dropout. We then characterized the point mutation using Sanger sequencing and designed mutation-specific primers that could overcome AMELX allelic dropout. Short tandem repeat genotyping analysis confirmed that the AMELX allelic dropout was recovered by the mutation-specific primer designed specifically for this case. The sequencing of the AMELX allele revealed a single-point variant from A→G at base position 7 downstream from the 3′ end in the amelogenin forward primer-binding region. This point mutation was identically found in two different male cases, resulting in AMELX allelic dropout. To our knowledge, these mutations and the X homolog amplification failure of amelogenin have not been reported in the Korean population. Our study provides a reliable approach to AMELX allelic dropout due to rare case mutations and could enable the better interpretation of gender markers for forensic samples. Full article

(This article belongs to the Special Issue Identification of Human Remains for Forensic and Humanitarian Purposes: From Molecular to Physical Methods)

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13 pages, 2871 KiB

Open AccessEditor’s ChoiceArticle

Impacts of Population Size and Domestication Process on Genetic Diversity and Genetic Load in Genus Ovis

by Dongfeng Wang, Hosein Salehian-Dehkordi, Langda Suo and Fenghua Lv

Genes 2023, 14(10), 1977; https://doi.org/10.3390/genes14101977 - 23 Oct 2023

Cited by 4 | Viewed by 1975

Abstract

In theoretical biology, a prevailing hypothesis posits a profound interconnection between effective population size (N_e), genetic diversity, inbreeding, and genetic load. The domestication and improvement processes are believed to be pivotal in diminishing genetic diversity while elevating levels of inbreeding [...] Read more.

In theoretical biology, a prevailing hypothesis posits a profound interconnection between effective population size (N_e), genetic diversity, inbreeding, and genetic load. The domestication and improvement processes are believed to be pivotal in diminishing genetic diversity while elevating levels of inbreeding and increasing genetic load. In this study, we performed a whole genome analysis to quantity genetic diversity, inbreeding, and genetic load across seven wild Ovis species and five domesticated sheep breeds. Our research demonstrates that the genetic load and diversity of species in the genus Ovis have no discernible impact on recent N_e, and three species within the subgenus Pachyceros tend to carry a higher genetic load and lower genetic diversity patterns. The results coincide with these species’ dramatic decline in population sizes within the subgenus Pachyceros ~80–250 thousand years ago. European mouflon presented with the lowest N_e, lower genetic diversity, and higher individual inbreeding coefficient but a lower genetic load (missense and LoF). This suggests that the small N_e of European mouflon could reduce harmful mutations compared to other species within the genus Ovis. We showed lower genetic diversity in domesticated sheep than in Asiatic mouflon, but counterintuitive patterns of genetic load, i.e., lower weak genetic load (missense mutation) and no significant difference in strong genetic load (LoF mutation) between domestic sheep and Asiatic mouflon. These findings reveal that the “cost of domestication” during domestication and improvement processes reduced genetic diversity and purified weak genetic load more efficiently than wild species. Full article

(This article belongs to the Special Issue Systematic Analysis and Application of Omics Data in Animal Breeding)

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23 pages, 8408 KiB

Open AccessEditor’s ChoiceArticle

Characteristics of the Accessible Chromatin Landscape and Transcriptome under Different Temperature Stresses in Bemisia tabaci

by Xiaona Shen, Xiaodi Wang, Nianwan Yang, Fanghao Wan, Zhichuang Lü, Jianying Guo and Wanxue Liu

Genes 2023, 14(10), 1978; https://doi.org/10.3390/genes14101978 - 23 Oct 2023

Cited by 2 | Viewed by 1653

Abstract

Bemisia tabaci is an important invasive pest with worldwide distribution and strong temperature tolerance. Previous studies have shown that temperature tolerance varies significantly between the different invasive populations. Several key factors involved in epigenetic regulation have been identified and verified in B. tabaci [...] Read more.

Bemisia tabaci is an important invasive pest with worldwide distribution and strong temperature tolerance. Previous studies have shown that temperature tolerance varies significantly between the different invasive populations. Several key factors involved in epigenetic regulation have been identified and verified in B. tabaci; therefore, epigenetic adaptation mechanisms may also exist. This study aimed to detect changes in the chromatin accessibility landscape and genome-wide transcriptome under different temperature stresses in B. tabaci. Assay for transposase-accessible chromatin with high-throughput sequencing and RNA-seq analyses indicated that transcriptional activity of the genes strongly correlates with chromatin accessibility. Chromatin transcription-activated gene expression regulation is dominant during high-temperature stress in B. tabaci, mainly through the transcriptional repression of genes related to low-temperature stress resistance. Furthermore, B. tabaci resists low-temperature stress by regulating enzyme activities and withstands high-temperature stress by regulating metabolism and synthesis of organic substances, both achieved by altering chromatin accessibility. In summary, this study provides a theoretical basis for exploring changes in gene expression and chromatin accessibility under different temperature stresses, offering a new approach to unravelling regulatory mechanisms underlying the onset of molecular regulation in response to various temperature stress conditions. Full article

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

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11 pages, 3010 KiB

Open AccessEditor’s ChoiceArticle

Differentiation of Morphological Traits and Genome-Wide Expression Patterns between Rice Subspecies Indica and Japonica

by Meixia Wang, Lei Huang, Yixuan Kou, Danqi Li, Wan Hu, Dengmei Fan, Shanmei Cheng, Yi Yang and Zhiyong Zhang

Genes 2023, 14(10), 1971; https://doi.org/10.3390/genes14101971 - 21 Oct 2023

Cited by 6 | Viewed by 1979

Abstract

Changes in gene expression patterns can lead to the variation of morphological traits. This phenomenon is particularly evident in recent evolution events such as crop domestication and responses to environmental stress, where alterations in expression levels can efficiently give rise to domesticated syndromes [...] Read more.

Changes in gene expression patterns can lead to the variation of morphological traits. This phenomenon is particularly evident in recent evolution events such as crop domestication and responses to environmental stress, where alterations in expression levels can efficiently give rise to domesticated syndromes and adaptive phenotypes. Rice (Oryza sativa L.), one of the world’s most crucial cereal crops, comprises two morphologically distinct subspecies, Indica and Japonica. To investigate the morphological divergence between these two rice subspecies, this study planted a total of 315 landrace individuals of both Indica and Japonica under identical cultivation conditions. Out of the 16 quantitative traits measured in this study, 12 exhibited significant differences between the subspecies. To determine the genetic divergence between Indica and Japonica at the whole-genome sequence level, we constructed a phylogenetic tree using a resequencing dataset encompassing 95 rice landrace accessions. The samples formed two major groups that neatly corresponded to the two subspecies, Indica and Japonica. Furthermore, neighbor-joining (NJ) trees based on the expression quantity of effectively expressed genes (EEGs) across five different tissues categorized 12 representative samples into two major clades aligning with the two subspecies. These results imply that divergence in genome-wide expression levels undergoes stabilizing selection under non-stressful conditions, with evolutionary trends in expression levels mirroring sequence variation levels. This study further supports the pivotal role of changes in genome-wide expression regulation in the divergence of the two rice subspecies, Indica and Japonica. Full article

(This article belongs to the Special Issue Molecular Phylogenetics and Phylogeography of Seed Plants)

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19 pages, 5219 KiB

Open AccessEditor’s ChoiceArticle

Notch Signaling Regulates Mouse Perivascular Adipose Tissue Function via Mitochondrial Pathways

by Chenhao Yang, Xuehui Yang, Anne Harrington, Christian Potts, Abigail Kaija, Larisa Ryzhova and Lucy Liaw

Genes 2023, 14(10), 1964; https://doi.org/10.3390/genes14101964 - 20 Oct 2023

Cited by 5 | Viewed by 2590

Abstract

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the [...] Read more.

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the Adiponectin-Cre (Adipoq-Cre) strain to activate a ligand-independent Notch1 intracellular domain transgene (N1ICD) to drive constitutive Notch signaling in the adipose tissues (N1ICD;Adipoq-Cre). We previously found that constitutive activation of Notch1 signaling in the PVAT phenocopied the effects of diet-induced obesity. To understand the downstream pathways activated by Notch signaling, we performed a proteomic analysis of the PVAT from control versus N1ICD;Adipoq-Cre mice. This comparison identified prominent changes in the protein signatures related to metabolism, adipocyte homeostasis, mitochondrial function, and ferroptosis. PVAT-derived stromal vascular fraction cells were derived from our mouse strains to study the cellular and molecular phenotypes during adipogenic induction. We found that cells with activated Notch signaling displayed decreased mitochondrial respiration despite similar levels of adipogenesis and mitochondrial number. We observed variable regulation of the proteins related to mitochondrial dynamics and ferroptosis, including PHB3, PINK1, pDRP1, and the phospholipid hydroperoxidase GPX4. Mitochondria regulate some forms of ferroptosis, which is a regulated process of cell death driven by lipid peroxidation. Accordingly, we found that Notch activation promoted lipid peroxidation and ferroptosis in PVAT-derived adipocytes. Because the PVAT phenotype is a regulator of vascular reactivity, we tested the effect of Notch activation in PVAT on vasoreactivity using wire myography. The aortae from the N1ICD;Adipoq-Cre mice had increased vasocontraction and decreased vasorelaxation in a PVAT-dependent and age-dependent manner. Our data provide support for the novel concept that increased Notch signaling in the adipose tissue leads to PVAT whitening, impaired mitochondrial function, increased ferroptosis, and loss of a protective vasodilatory signal. Our study advances our understanding of how Notch signaling in adipocytes affects mitochondrial dynamics, which impacts vascular physiology. Full article

(This article belongs to the Special Issue Cellular and Developmental Biology of Lipid Metabolism)

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11 pages, 257 KiB

Open AccessEditor’s ChoiceArticle

Determination of Carrier Frequency of Actionable Pathogenic Variants in Autosomal Recessive Genetic Diseases in the Turkish Cypriot Population

by Aziz Suat Gunsel, Mahmut Cerkez Ergoren, Hatice Kemal, Haniyeh Rahbar Kafshboran, Levent Cerit, Ayla Turgay and Hamza Duygu

Genes 2023, 14(10), 1967; https://doi.org/10.3390/genes14101967 - 20 Oct 2023

Cited by 1 | Viewed by 2499

Abstract

Whole-exome DNA sequencing is a rich source of clinically useful information for specialists, patients, and their families, as well as elucidating the genetic basis of monogenic and complex diseases in clinical diagnosis. However, interpreting and reporting variants encompassing exome and genome sequence analysis [...] Read more.

Whole-exome DNA sequencing is a rich source of clinically useful information for specialists, patients, and their families, as well as elucidating the genetic basis of monogenic and complex diseases in clinical diagnosis. However, interpreting and reporting variants encompassing exome and genome sequence analysis outcome data are one of the greatest challenges of the genomic era. In this study, we aimed to investigate the frequency and allele frequency spectrum of single nucleotide variants accepted as recessive disease carrier status in Turkish Cypriot exomes. The same sequencing platform and data processing line were used for the analysis of data from 100 Turkish Cypriot whole-exome sequence analysis. Identified variants were classified according to ACMG guidelines, and pathogenic variants were confirmed in other databases such as ClinVar, HGMD, Varsome, etc. Pathogenic variants were detected in 68 genes out of 100 whole-exome sequence data. The carriage rate was the highest in the CYP21A2 gene, causing 21-hydroxylase deficiency (14.70%), 11.76% in the HBB gene causing β-thalassemia, 10.29% in the BTD gene causing biotinidase deficiency, 8.82% in the CFTR gene causing cystic fibrosis, 8.82% in the RBM8A gene causing thrombocytopenia-absent radius syndrome, which is an ultra-rare disease, and 5.88% in the GAA gene causing glycogen storage disease II. The carriage of pathogenic variants in other genes causing the disease (GJB2, PAH, GALC, CYP11B2, COL4A3, HBA1, etc.) was determined as less than 5.00%. Also, the identified variations in the mentioned gene within the examined population were reported. The most prevalent mutation in North Cyprus was a missense variant (c.1360 C>T, p.Pro454Ser) detected in the CYP21A2 gene (rs6445), and the most frequently seen variant in the HBB gene was c.93-21G>A (rs35004220). We investigated reported pathogenic variants by estimating the lower and upper limits of carrier and population frequencies for autosomal recessive diseases, for which exome sequencing may reveal additional medically relevant information. Determining the lower and upper limits of these frequencies will shed light on preventive medicine practices and governmental actions. Full article

(This article belongs to the Section Genetic Diagnosis)

17 pages, 7345 KiB

Open AccessEditor’s ChoiceArticle

Systematic Pan-Cancer Analysis Reveals X-C Motif Chemokine Receptor 1 as a Prognostic and Immunological Biomarker

by Likun Cui, Liye Zhu, Jie Chen, Chunzhen Li, Yizhi Yu and Sheng Xu

Genes 2023, 14(10), 1961; https://doi.org/10.3390/genes14101961 - 19 Oct 2023

Cited by 3 | Viewed by 2292

Abstract

Chemokines and their receptors play an important role in immune monitoring and immune defense during tumor growth and metastasis. However, their prognostic roles in pan-cancer have not been elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered X-C Motif [...] Read more.

Chemokines and their receptors play an important role in immune monitoring and immune defense during tumor growth and metastasis. However, their prognostic roles in pan-cancer have not been elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered X-C Motif Chemokine Receptor 1 (XCR1) as a reliable immunological and prognostic biomarker in pan-cancer using bioinformation. The TCGA database served as the foundation for the primary research database analysis in this work. XCR1 was downregulated in tumors. Patients with reduced XCR1 showed worse prognoses and a concomitant decrease in immune cell infiltration (DCs and CD8⁺ T cells). According to a gene enrichment study, XCR1 enhanced immune system performance by promoting T-cell infiltration through the C-X-C Motif Chemokine Ligand 9 (CXCL9)- C-X-C Motif Chemokine Receptor 3 (CXCR3) axis. In addition, XCR1 is mainly expressed in infiltrated DCs and some malignant cells in tumor tissues. Our data revealed the important role of XCR1 in remodeling the tumor microenvironment and predicting the survival prognosis, which could also be used as a sensitive biomarker for tumor immunotherapy. Full article

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

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13 pages, 1312 KiB

Open AccessEditor’s ChoiceArticle

Multi-Trait Exome-Wide Association Study of Back Pain-Related Phenotypes

by Irina V. Zorkoltseva, Elizaveta E. Elgaeva, Nadezhda M. Belonogova, Anatoliy V. Kirichenko, Gulnara R. Svishcheva, Maxim B. Freidin, Frances M. K. Williams, Pradeep Suri, Yakov A. Tsepilov and Tatiana I. Axenovich

Genes 2023, 14(10), 1962; https://doi.org/10.3390/genes14101962 - 19 Oct 2023

Cited by 3 | Viewed by 2109

Abstract

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40–60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may [...] Read more.

Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40–60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight. This study utilized exome sequencing data from the UK Biobank to perform a multi-trait gene-based association analysis of three BP-related phenotypes: chronic back pain, dorsalgia, and intervertebral disc disorder. We identified the SLC13A1 gene as a contributor to chronic back pain via loss-of-function (LoF) and missense variants. This gene has been previously detected in two studies. A multi-trait approach uncovered the novel FSCN3 gene and its impact on back pain through LoF variants. This gene deserves attention because it is only the second gene shown to have an effect on back pain due to LoF variants and represents a promising drug target for back pain therapy. Full article

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

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13 pages, 8743 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of Lipoxygenase Genes in Rose (Rosa chinensis)

by Wenqi Dong, Bo Jiao, Jiao Wang, Lei Sun, Songshuo Li, Zhiming Wu, Junping Gao and Shuo Zhou

Genes 2023, 14(10), 1957; https://doi.org/10.3390/genes14101957 - 18 Oct 2023

Cited by 3 | Viewed by 1901

Abstract

Lipoxygenases (LOX) play pivotal roles in plant resistance to stresses. However, no study has been conducted on LOX gene identification at the whole genome scale in rose (Rosa chinensis). In this study, a total of 17 RcLOX members were identified in [...] Read more.

Lipoxygenases (LOX) play pivotal roles in plant resistance to stresses. However, no study has been conducted on LOX gene identification at the whole genome scale in rose (Rosa chinensis). In this study, a total of 17 RcLOX members were identified in the rose genome. The members could be classified into three groups: 9-LOX, Type I 13-LOX, and Type II 13-LOX. Similar gene structures and protein domains can be found in RcLOX members. The RcLOX genes were spread among all seven chromosomes, with unbalanced distributions, and several tandem and proximal duplication events were found among RcLOX members. Expressions of the RcLOX genes were tissue-specific, while every RcLOX gene could be detected in at least one tissue. The expression levels of most RcLOX genes could be up-regulated by aphid infestation, suggesting potential roles in aphid resistance. Our study offers a systematic analysis of the RcLOX genes in rose, providing useful information not only for further gene cloning and functional exploration but also for the study of aphid resistance. Full article

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

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8 pages, 707 KiB

Open AccessEditor’s ChoiceCase Report

Identification of a Novel FOXP1 Variant in a Patient with Hypotonia, Intellectual Disability, and Severe Speech Impairment

by Mario Benvenuto, Pietro Palumbo, Ester Di Muro, Concetta Simona Perrotta, Tommaso Mazza, Giuseppa Maria Luana Mandarà, Orazio Palumbo and Massimo Carella

Genes 2023, 14(10), 1958; https://doi.org/10.3390/genes14101958 - 18 Oct 2023

Cited by 2 | Viewed by 2055

Abstract

The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of FOXP1, due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads [...] Read more.

The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of FOXP1, due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads to an emerging disorder known as “FOXP1 syndrome”, mainly characterized by intellectual disability, language impairment, dysmorphic features, and multiple congenital abnormalities with or without autistic features in some affected individuals (MIM 613670). Here we describe a 10-year-old female patient, born to unrelated parents, showing hypotonia, intellectual disability, and severe language delay. Targeted resequencing analysis allowed us to identify a heterozygous de novo FOXP1 variant c.1030C>T, p.(Gln344Ter) classified as likely pathogenetic according to the American College of Medical Genetics and Genomics guidelines. To the best of our knowledge, our patient is the first to date to report carrying this stop mutation, which is, for this reason, useful for broadening the molecular spectrum of FOXP1 clinically relevant variants. In addition, our results highlight the utility of next-generation sequencing in establishing an etiological basis for heterogeneous conditions such as neurodevelopmental disorders and providing additional insight into the phenotypic features of FOXP1-related syndrome. Full article

(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)

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12 pages, 275 KiB

Open AccessEditor’s ChoiceReview

The Role of miRNA Expression Profile in Sudden Cardiac Death Cases

by Alessia Bernini Di Michele, Valerio Onofri, Mauro Pesaresi and Chiara Turchi

Genes 2023, 14(10), 1954; https://doi.org/10.3390/genes14101954 - 17 Oct 2023

Cited by 2 | Viewed by 2227

Abstract

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a [...] Read more.

Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a SCD case and the available methods used for diagnosis cannot always give an exhaustive answer. In addition, the molecular analysis of genes does not lead to a clear conclusion, but it could be interesting to focus attention on the expression level of miRNAs, a class of non-coding RNA of about 22 nucleotides. The role of miRNAs is to regulate the gene expression through complementary binding to 3′-untraslated regions of miRNAs, leading to the inhibition of translation or to mRNA degradation. In recent years, several studies were performed with the aim of exploring the use of these molecules as biomarkers for SCD cases, and to also distinguish the causes that lead to cardiac death. In this review, we summarize experiments, evidence, and results of different studies on the implication of miRNAs in SCD cases. We discuss the different biological starting materials with their respective advantages and disadvantages, studying miRNA expression on tissue (fresh-frozen tissue and FFPE tissue), circulating cell-free miRNAs in blood of patients affected by cardiac disease at high risk of SCD, and exosomal miRNAs analyzed from serum of people who died from SCD. Full article

(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics)

11 pages, 2791 KiB

Open AccessEditor’s ChoiceCommunication

Genomic Scanning of Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs

by Carlos Hervás-Rivero, Houssemeddine Srihi, David López-Carbonell, Joaquim Casellas, Noelia Ibáñez-Escriche, Sara Negro and Luis Varona

Genes 2023, 14(10), 1941; https://doi.org/10.3390/genes14101941 - 15 Oct 2023

Cited by 2 | Viewed by 1953

Abstract

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a [...] Read more.

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a genomic scan of the whole pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto). The datasets consisted of 2069 (338 sows) and 2028 (327 sows) records of litter size (Total Number Born and Number Born Alive) for the Entrepelado and Retinto varieties. All sows were genotyped using the Geneseek GGP PorcineHD 70 K chip. We employed the Unfavorable Haplotype Finder software to extract runs of homozygosity (ROHs) and conducted a mixed-model analysis to identify highly significant differences between homozygous and heterozygous sows for each specific ROH. A total of eight genomic regions located on SSC2, SSC5, SSC7, SSC8, and SSC13 were significantly associated with inbreeding depression, housing some relevant genes such as FSHR, LHCGR, CORIN, AQP6, and CEP120. Full article

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

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11 pages, 1483 KiB

Open AccessEditor’s ChoiceArticle

The Mitochondrial Genome of Linichthys laticeps (Cypriniformes: Cyprinidae): Characterization and Phylogeny

by Renyi Zhang, Tingting Zhu, Hongmei Li and Lei Deng

Genes 2023, 14(10), 1938; https://doi.org/10.3390/genes14101938 - 14 Oct 2023

Cited by 5 | Viewed by 1716

Abstract

Mitochondrial genomes (mitogenomes) have been widely used in phylogenetic analysis and evolutionary biology. The Labeoninae is the largest subfamily of Cypriniformes and has great economic importance and ecological value. In this study, we sequenced, annotated, and characterized the complete mitogenome of Linichthys laticeps [...] Read more.

Mitochondrial genomes (mitogenomes) have been widely used in phylogenetic analysis and evolutionary biology. The Labeoninae is the largest subfamily of Cypriniformes and has great economic importance and ecological value. In this study, we sequenced, annotated, and characterized the complete mitogenome of Linichthys laticeps and then constructed the phylogenetic tree with previously published Labeoninae mitogenomes. The mitogenome of L. laticeps was 16,593 bp in length, with an A + T content of 57.1%. The mitogenome contained a standard set of 37 genes and a control region with the same order and orientation of genes as most fish mitogenomes. Each protein-coding gene (PCG) was initiated by an initial ATG codon, excluding COI, that began with a GTG codon. Furthermore, most of the PCGs were terminated by a conventional stop codon (TAA/TAG), while an incomplete termination codon (TA/T) was detected in 7 of the 13 PCGs. Most tRNA genes in L. laticeps were predicted to fold into the typical cloverleaf secondary structures. The K_a/K_s (ω) values for all PCGs were below one. The phylogenetic relationships of 96 Labeoninae mitogenomes indicated that Labeoninae was not a monophyletic group and L. laticeps was closely related to the genera Discogobio and Discocheilus. Overall, our study provided the first complete annotated mitogenome of L. laticeps, which filled a knowledge gap in Labeoninae and extended the understanding of the taxonomy and mitogenomic phylogeny of the subfamily Labeoninae. Full article

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

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12 pages, 1939 KiB

Open AccessEditor’s ChoiceArticle

Molecular Mechanisms Involved in MAFLD in Cholecystectomized Patients: A Cohort Study

by Shreya C. Pal, Stephany M. Castillo-Castañeda, Luis E. Díaz-Orozco, Mariana M. Ramírez-Mejía, Rita Dorantes-Heredia, Rogelio Alonso-Morales, Mohammed Eslam, Frank Lammert and Nahum Méndez-Sánchez

Genes 2023, 14(10), 1935; https://doi.org/10.3390/genes14101935 - 13 Oct 2023

Cited by 2 | Viewed by 2009

Abstract

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. [...] Read more.

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. This study aimed to investigate the involvement of farnesoid X receptor 1 (FXR1) and fibroblast growth factor receptor 4 (FGFR4) in the progression of fibrosis in cholecystectomized MAFLD patients. A meticulously characterized cohort of 12 patients diagnosed with MAFLD, who had undergone liver biopsies during programmed cholecystectomies, participated in this study. All enrolled patients underwent a follow-up regimen at 1, 3, and 6 months post-cholecystectomy, during which metabolic biochemical markers were assessed, along with elastography, which served as indirect indicators of fibrosis. Additionally, the hepatic expression levels of FGFR4 and FXR1 were quantified using quantitative polymerase chain reaction (qPCR). Our findings revealed a robust correlation between hepatic FGFR4 expression and various histological features, including the steatosis degree (r = 0.779, p = 0.023), ballooning degeneration (r = 0.764, p = 0.027), interphase inflammation (r = 0.756, p = 0.030), and steatosis activity score (SAS) (r = 0.779, p = 0.023). Conversely, hepatic FXR1 expression did not exhibit any significant correlations with these histological features. In conclusion, our study highlights a substantial correlation between FGFR4 expression and histological liver damage, emphasizing its potential role in lipid and glucose metabolism. These findings suggest that FGFR4 may play a crucial role in the progression of fibrosis in cholecystectomized MAFLD patients. Further research is warranted to elucidate the exact mechanisms through which FGFR4 influences metabolic dysfunction and fibrosis in this patient population. Full article

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

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9 pages, 682 KiB

Open AccessEditor’s ChoiceArticle

Effect of Supplementation with Curcuma longa and Rosmarinus officinalis Extract Mixture on Acute Phase Protein, Cathelicidin, Defensin and Cytolytic Protein Gene Expression in the Livers of Young Castrated Polish White Improved Bucks

by Daria M. Urbańska, Marek Pawlik, Agnieszka Korwin-Kossakowska, Michał Czopowicz, Karolina Rutkowska, Ewelina Kawecka-Grochocka, Marcin Mickiewicz, Jarosław Kaba and Emilia Bagnicka

Genes 2023, 14(10), 1932; https://doi.org/10.3390/genes14101932 - 12 Oct 2023

Cited by 2 | Viewed by 1962

Abstract

Goats are an excellent animal model for research on some physiological and pathophysiological processes in humans. The search for supplements that prevent homeostasis disorders and strengthen the immune system is necessary to reduce the risk of many diseases in both humans and animals. [...] Read more.

Goats are an excellent animal model for research on some physiological and pathophysiological processes in humans. The search for supplements that prevent homeostasis disorders and strengthen the immune system is necessary to reduce the risk of many diseases in both humans and animals. The aim of the study was to analyze the effect of supplementation with a mixture of dried extracts of Curcuma longa and Rosmarinus officinalis on the expression of acute-phase protein (SAA, HP, CRP, LALBA, AGP, CP, FGA, FGB, and FGG), cathelicidin (BAC5, BAC7.5, BAC3.4, MAP28, MAP34, and HEPC), beta-defensin-1 (GBD1, DEFB1), and beta-defensin-2, and cytolytic protein (LIZ and LF) genes in the livers of young castrated bucks of the Polish White Improved breed. The higher expression of LF in the control group suggests that it is important for the first line of hepatic immune defense and its expression is downregulated by the mixture of turmeric and rosemary extracts; thus, the spice–herb mixture mutes its activity. The lower expression of FGB and the higher expression of BAC5 genes in the livers of healthy, young castrated bucks who were administered the supplement suggest the silencing effects of the mixture on the acute-phase response and the stimulating effect on the antimicrobial activity of the immune system. Full article

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

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12 pages, 607 KiB

Open AccessEditor’s ChoiceReview

Emerging Opportunities to Study Mobile Element Insertions and Their Source Elements in an Expanding Universe of Sequenced Human Genomes

by Scott E. Devine

Genes 2023, 14(10), 1923; https://doi.org/10.3390/genes14101923 - 10 Oct 2023

Cited by 3 | Viewed by 3067

Abstract

Three mobile element classes, namely Alu, LINE-1 (L1), and SVA elements, remain actively mobile in human genomes and continue to produce new mobile element insertions (MEIs). Historically, MEIs have been discovered and studied using several methods, including: (1) Southern blots, (2) PCR [...] Read more.

Three mobile element classes, namely Alu, LINE-1 (L1), and SVA elements, remain actively mobile in human genomes and continue to produce new mobile element insertions (MEIs). Historically, MEIs have been discovered and studied using several methods, including: (1) Southern blots, (2) PCR (including PCR display), and (3) the detection of MEI copies from young subfamilies. We are now entering a new phase of MEI discovery where these methods are being replaced by whole genome sequencing and bioinformatics analysis to discover novel MEIs. We expect that the universe of sequenced human genomes will continue to expand rapidly over the next several years, both with short-read and long-read technologies. These resources will provide unprecedented opportunities to discover MEIs and study their impact on human traits and diseases. They also will allow the MEI community to discover and study the source elements that produce these new MEIs, which will facilitate our ability to study source element regulation in various tissue contexts and disease states. This, in turn, will allow us to better understand MEI mutagenesis in humans and the impact of this mutagenesis on human biology. Full article

(This article belongs to the Special Issue Mobile-Element-Related Genetic Variation)

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10 pages, 2104 KiB

Open AccessEditor’s ChoiceCommunication

STS and PUDP Deletion Identified by Targeted Panel Sequencing with CNV Analysis in X-Linked Ichthyosis: A Case Report and Literature Review

by Joonhong Park, Yong Gon Cho, Jin Kyu Kim and Hyun Ho Kim

Genes 2023, 14(10), 1925; https://doi.org/10.3390/genes14101925 - 10 Oct 2023

Cited by 2 | Viewed by 2183

Abstract

X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. We describe the identification of STS and PUDP deletions using targeted panel sequencing combined with copy-number variation (CNV) analysis in XLI. A 9-month-old infant was admitted for genetic [...] Read more.

X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. We describe the identification of STS and PUDP deletions using targeted panel sequencing combined with copy-number variation (CNV) analysis in XLI. A 9-month-old infant was admitted for genetic counseling. Since the second day after birth, the infant’s skin tended to be dry and polygonal scales had accumulated over the abdomen and upper extremities. The infant’s maternal uncle and brother (who had also exhibited similar skin symptoms from birth) presented with polygonal scales on their trunks. CNV analysis revealed a hemizygous deletion spanning 719.3 Kb on chromosome Xp22 (chrX:7,108,996–7,828,312), which included a segment of the STS gene and exhibited a Z ratio of −2 in the proband. Multiplex ligation-dependent probe amplification (MLPA) confirmed this interstitial Xp22.31 deletion. Our report underscores the importance of implementing CNV screening techniques, including sequencing data analysis and gene dosage assays such as MLPA, to detect substantial deletions that encompass the STS gene region of Xq22 in individuals suspected of having XLI. Full article

(This article belongs to the Special Issue Genetics of Skin Disorders (2.0 Edition))

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8 pages, 830 KiB

Open AccessEditor’s ChoiceBrief Report

Improving the Completeness of Chromosome-Level Assembly by Recalling Sequences from Lost Contigs

by Junyang Liu, Fang Liu and Weihua Pan

Genes 2023, 14(10), 1926; https://doi.org/10.3390/genes14101926 - 10 Oct 2023

Cited by 1 | Viewed by 1741

Abstract

For a long time, the construction of complete reference genomes for complex eukaryotic genomes has been hindered by the limitations of sequencing technologies. Recently, the Pacific Biosciences (PacBio) HiFi data and Oxford Nanopore Technologies (ONT) Ultra-Long data, leveraging their respective advantages in accuracy [...] Read more.

For a long time, the construction of complete reference genomes for complex eukaryotic genomes has been hindered by the limitations of sequencing technologies. Recently, the Pacific Biosciences (PacBio) HiFi data and Oxford Nanopore Technologies (ONT) Ultra-Long data, leveraging their respective advantages in accuracy and length, have provided an opportunity for generating complete chromosome sequences. Nevertheless, for the majority of genomes, the chromosome-level assemblies generated using existing methods still miss a high proportion of sequences due to losing small contigs in the step of assembly and scaffolding. To address this shortcoming, in this paper, we propose a novel method that is able to identify and fill the gaps in the chromosome-level assembly by recalling the sequences in the lost small contigs. Experimental results on both real and simulated datasets demonstrate that this method is able to improve the completeness of the chromosome-level assembly. Full article

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

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33 pages, 9826 KiB

Open AccessEditor’s ChoiceArticle

Genome-Wide Identification and Expression Analysis of bZIP Family Genes in Stevia rebaudiana

by Mengyang Wu, Jinsong Chen, Weilin Tang, Yijie Jiang, Zhaoyong Hu, Dongbei Xu, Kai Hou, Yinyin Chen and Wei Wu

Genes 2023, 14(10), 1918; https://doi.org/10.3390/genes14101918 - 9 Oct 2023

Cited by 3 | Viewed by 2256

Abstract

The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors widely distributed in eukaryotic organisms. In plants, they are not only involved in growth and development, defense and stress responses and regulation of physiological processes but also play a pivotal role in [...] Read more.

The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors widely distributed in eukaryotic organisms. In plants, they are not only involved in growth and development, defense and stress responses and regulation of physiological processes but also play a pivotal role in regulating secondary metabolism. To explore the function related to the bZIP gene family in Stevia rebaudiana Bertoni, we identified 105 SrbZIP genes at the genome-wide level and classified them into 12 subfamilies using bioinformation methods. Three main classes of cis-acting elements were found in the SrbZIP promoter regions, including development-related elements, defense and stress-responsive elements and phytohormone-responsive elements. Through protein–protein interaction network of 105 SrbZIP proteins, SrbZIP proteins were mainly classified into four major categories: ABF2/ABF4/ABI5 (SrbZIP51/SrbZIP38/SrbZIP7), involved in phytohormone signaling, GBF1/GBF3/GBF4 (SrbZIP29/SrbZIP63/SrbZIP60) involved in environmental signaling, AREB3 (SrbZIP88), PAN (SrbZIP12), TGA1 (SrbZIP69), TGA4 (SrbZIP82), TGA7 (SrbZIP31), TGA9 (SrbZIP95), TGA10 (SrbZIP79) and HY5 (SrbZIP96) involved in cryptochrome signaling, and FD (SrbZIP72) promoted flowering. The transcriptomic data showed that SrbZIP genes were differentially expressed in six S. rebaudiana cultivars (‘023’, ‘110’, ‘B1188’, ‘11-14’, ‘GP’ and ‘GX’). Moreover, the expression levels of selected 15 SrbZIP genes in response to light, abiotic stress (low temperature, salt and drought), phytohormones (methyl jasmonate, gibberellic acid and salicylic acid) treatment and in different tissues were analyzed utilizing qRT-PCR. Some SrbZIP genes were further identified to be highly induced by factors affecting glycoside synthesis. Among them, three SrbZIP genes (SrbZIP54, SrbZIP63 and SrbZIP32) were predicted to be related to stress-responsive terpenoid synthesis in S. rebaudiana. The protein–protein interaction network expanded the potential functions of SrbZIP genes. This study firstly provided the comprehensive genome-wide report of the SrbZIP gene family, laying a foundation for further research on the evolution, function and regulatory role of the bZIP gene family in terpenoid synthesis in S. rebaudiana. Full article

(This article belongs to the Section Bioinformatics)

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13 pages, 2481 KiB

Open AccessEditor’s ChoiceArticle

GIP_HUMAN [22–51] Peptide Encoded by the Glucose-Dependent Insulinotropic Polypeptide (GIP) Gene Suppresses Insulin Expression and Secretion in INS-1E Cells and Rat Pancreatic Islets

by Emily Pusch, Małgorzata Krążek, Tatiana Wojciechowicz, Maciej Sassek, Paweł A. Kołodziejski, Mathias Z. Strowski, Krzysztof W. Nowak and Marek Skrzypski

Genes 2023, 14(10), 1910; https://doi.org/10.3390/genes14101910 - 5 Oct 2023

Cited by 2 | Viewed by 1909

Abstract

GIP_HUMAN [22–51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP_HUMAN [22–51] in ApoE−/− mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the [...] Read more.

GIP_HUMAN [22–51] is a recently discovered peptide that shares the same precursor molecule with glucose-dependent insulinotropic polypeptide (GIP). In vivo, chronic infusion of GIP_HUMAN [22–51] in ApoE−/− mice enhanced the development of aortic atherosclerotic lesions and upregulated inflammatory and proatherogenic proteins. In the present study, we evaluate the effects of GIP_HUMAN [22–51] on insulin mRNA expression and secretion in insulin-producing INS-1E cells and isolated rat pancreatic islets. Furthermore, we characterize the influence of GIP_HUMAN [22–51] on cell proliferation and death and on Nf-kB nuclear translocation. Rat insulin-producing INS-1E cells and pancreatic islets, isolated from male Wistar rats, were used in this study. Gene expression was evaluated using real-time PCR. Cell proliferation was studied using a BrdU incorporation assay. Cell death was quantified by evaluating histone-complexed DNA fragments. Insulin secretion was determined using an ELISA test. Nf-kB nuclear translocation was detected using immunofluorescence. GIP_HUMAN [22–51] suppressed insulin (Ins1 and Ins2) in INS-1E cells and pancreatic islets. Moreover, GIP_HUMAN [22–51] promoted the translocation of NF-κB from cytoplasm to the nucleus. In the presence of a pharmacological inhibitor of NF-κB, GIP_HUMAN [22–51] was unable to suppress Ins2 mRNA expression. Moreover, GIP_HUMAN [22–51] downregulated insulin secretion at low (2.8 mmol/L) but not high (16.7 mmol/L) glucose concentration. By contrast, GIP_HUMAN [22–51] failed to affect cell proliferation and apoptosis. We conclude that GIP_HUMAN [22–51] suppresses insulin expression and secretion in pancreatic β cells without affecting β cell proliferation or apoptosis. Notably, the effects of GIP_HUMAN [22–51] on insulin secretion are glucose-dependent. Full article

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

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18 pages, 6383 KiB

Open AccessEditor’s ChoiceArticle

Sequence Characterization of Extra-Chromosomal Circular DNA Content in Multiple Blackgrass (Alopecurus myosuroides) Populations

by Wangfang Fu, Dana R. MacGregor, David Comont and Christopher A. Saski

Genes 2023, 14(10), 1905; https://doi.org/10.3390/genes14101905 - 4 Oct 2023

Cited by 5 | Viewed by 2674

Abstract

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat, and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance [...] Read more.

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat, and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance is polygenic and evolves from standing genetic variation. Using a CIDER-seq pipeline, we show that herbicide-resistant (HR) and herbicide-sensitive (HS) F3 plants from these F2 seed families as well as the parent populations they were derived from carry extra-chromosomal circular DNA (eccDNA). We identify the similarities and differences in the coding structures within and between resistant and sensitive populations. Although the numbers and size of detected eccDNAs varied between the populations, comparisons between the HR and HS blackgrass populations identified shared and unique coding content, predicted genes, and functional protein domains. These include genes related to herbicide detoxification such as Cytochrome P450s, ATP-binding cassette transporters, and glutathione transferases including AmGSTF1. eccDNA content was mapped to the A. myosuroides reference genome, revealing genomic regions at the distal end of chromosome 5 and the near center of chromosomes 1 and 7 as regions with a high number of mapped eccDNA gene density. Mapping to 15 known herbicide-resistant QTL regions showed that the eccDNA coding sequences matched twelve, with four QTL matching HS coding sequences; only one region contained HR coding sequences. These findings establish that, like other pernicious weeds, blackgrass has eccDNAs that contain homologs of chromosomal genes, and these may contribute genetic heterogeneity and evolutionary innovation to rapidly adapt to abiotic stresses, including herbicide treatment. Full article

(This article belongs to the Special Issue Identification and Innovation of Plant Genes)

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18 pages, 3647 KiB

Open AccessEditor’s ChoiceArticle

Specific Gene Expression in Pseudomonas Putida U Shows New Alternatives for Cadaverine and Putrescine Catabolism

by Luis Getino, Alejandro Chamizo-Ampudia, José Luis Martín, José María Luengo, Carlos Barreiro and Elías R. Olivera

Genes 2023, 14(10), 1897; https://doi.org/10.3390/genes14101897 - 30 Sep 2023

Cited by 4 | Viewed by 2374

Abstract

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism [...] Read more.

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism. Full article

(This article belongs to the Section Genes & Environments)

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19 pages, 2303 KiB

Open AccessEditor’s ChoiceArticle

Enhancing Genetic Gains in Grain Yield and Efficiency of Testing Sites of Early-Maturing Maize Hybrids under Contrasting Environments

by Baffour Badu-Apraku, Adamu Masari Abubakar, Gloria Boakyewaa Adu, Abdoul-Madjidou Yacoubou, Samuel Adewale and Idris Ishola Adejumobi

Genes 2023, 14(10), 1900; https://doi.org/10.3390/genes14101900 - 30 Sep 2023

Cited by 2 | Viewed by 2007

Abstract

The major challenges of maize production and productivity in Sub-Saharan Africa (SSA) include Striga hermonthica infestation, recurrent drought, and low soil nitrogen (low N). This study assessed the following: (i) accelerated genetic advancements in grain yield and other measured traits of early-maturing maize [...] Read more.

The major challenges of maize production and productivity in Sub-Saharan Africa (SSA) include Striga hermonthica infestation, recurrent drought, and low soil nitrogen (low N). This study assessed the following: (i) accelerated genetic advancements in grain yield and other measured traits of early-maturing maize hybrids, (ii) ideal test environments for selecting early-maturing multiple-stress tolerant hybrids, and (iii) high-yielding and stable hybrids across multiple-stress and non-stress environments. Fifty-four hybrids developed during three periods of genetic enhancement (2008–2010, 2011–2013, and 2014–2016) were evaluated in Nigeria, The Republic of Benin, and Ghana under multiple stressors (Striga infestation, managed drought, and Low N) and non-stress environments from 2017 to 2019. Under multiple-stress and non-stress environments, annual genetic gains from selection in grain yield of 84.72 kg ha⁻¹ (4.05%) and 61 kg ha⁻¹ (1.56%), respectively, were recorded. Three mega-environments were identified across 14 stress environments. Abuja was identified as an ideal test environment for selecting superior hybrids. The hybrid TZdEI 352 × TZEI 355 developed during period 3 was the most outstanding under multiple-stress and non-stress environments. On-farm testing of this hybrid is required to verify its superior performance for commercialization in SSA. Considerable progress has been made in the genetic improvement of early-maturing maize hybrids for tolerance of multiple stressors and high yield. The identified core testing sites of this study could be used to enhance the testing and selection of promising hybrids. Full article

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

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11 pages, 1881 KiB

Open AccessEditor’s ChoiceArticle

Uncovering the Molecular Drivers of NHEJ DNA Repair-Implicated Missense Variants and Their Functional Consequences

by Raghad Al-Jarf, Malancha Karmakar, Yoochan Myung and David B. Ascher

Genes 2023, 14(10), 1890; https://doi.org/10.3390/genes14101890 - 29 Sep 2023

Cited by 4 | Viewed by 2212

Abstract

Variants in non-homologous end joining (NHEJ) DNA repair genes are associated with various human syndromes, including microcephaly, growth delay, Fanconi anemia, and different hereditary cancers. However, very little has been done previously to systematically record the underlying molecular consequences of NHEJ variants and [...] Read more.

Variants in non-homologous end joining (NHEJ) DNA repair genes are associated with various human syndromes, including microcephaly, growth delay, Fanconi anemia, and different hereditary cancers. However, very little has been done previously to systematically record the underlying molecular consequences of NHEJ variants and their link to phenotypic outcomes. In this study, a list of over 2983 missense variants of the principal components of the NHEJ system, including DNA Ligase IV, DNA-PKcs, Ku70/80 and XRCC4, reported in the clinical literature, was initially collected. The molecular consequences of variants were evaluated using in silico biophysical tools to quantitatively assess their impact on protein folding, dynamics, stability, and interactions. Cancer-causing and population variants within these NHEJ factors were statistically analyzed to identify molecular drivers. A comprehensive catalog of NHEJ variants from genes known to be mutated in cancer was curated, providing a resource for better understanding their role and molecular mechanisms in diseases. The variant analysis highlighted different molecular drivers among the distinct proteins, where cancer-driving variants in anchor proteins, such as Ku70/80, were more likely to affect key protein–protein interactions, whilst those in the enzymatic components, such as DNA-PKcs, were likely to be found in intolerant regions undergoing purifying selection. We believe that the information acquired in our database will be a powerful resource to better understand the role of non-homologous end-joining DNA repair in genetic disorders, and will serve as a source to inspire other investigations to understand the disease further, vital for the development of improved therapeutic strategies. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology for Cancer Prediction and Prognosis)

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17 pages, 2079 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Antioxidant Defence Systems and Inflammatory Status in Basketball Elite Athletes

by Alessandro Gentile, Carolina Punziano, Mariella Calvanese, Renato De Falco, Luca Gentile, Giovanni D’Alicandro, Ciro Miele, Filomena Capasso, Raffaela Pero, Cristina Mazzaccara, Barbara Lombardo, Giulia Frisso, Paola Borrelli, Cristina Mennitti, Olga Scudiero and Raffaella Faraonio

Genes 2023, 14(10), 1891; https://doi.org/10.3390/genes14101891 - 29 Sep 2023

Cited by 2 | Viewed by 1686

Abstract

Intense physical activity can induce metabolic changes that modify specific biochemical biomarkers. In this scenario, the purpose of our study was to evaluate how intense physical activity can affect oxidative metabolism. Following this, fifteen professional basketball players and fifteen sedentary controls were recruited [...] Read more.

Intense physical activity can induce metabolic changes that modify specific biochemical biomarkers. In this scenario, the purpose of our study was to evaluate how intense physical activity can affect oxidative metabolism. Following this, fifteen professional basketball players and fifteen sedentary controls were recruited and subjected to two samplings of serum and urine in the pre-season (September) and two months after the start of the competitive season (November). Our results have shown an increase in athletes compared to controls in CK and LDH in September (respectively, p-value 0.003 and p-value < 0.001) and in November (both p-value < 0.001), whereas ALT is increased only in November (p-value 0.09). GGT serum levels were decreased in athletes compared to controls in both months (in September p-value 0.001 and in November p-value < 0.001). A gene expression analysis, carried out using RT-PCR, has revealed that IL-2, IL-6, IL-8, xCT and GCLM are increased in athletes in both months (p-value < 0.0001), while IL-10 and CHAC1 are increased only in September if compared to the controls (respectively, p-value 0.040 and p-value < 0.001). In conclusion, physical activity creates an adaptation of the systems involved in oxidative metabolism but without causing damage to the liver or kidney. This information could be of help to sports doctors for the prevention of injuries and illnesses in professional athletes for the construction of the athlete’s passport. Full article

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

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9 pages, 919 KiB

Open AccessEditor’s ChoiceArticle

A Spanish Family with Gordon Syndrome Due to a Variant in the Acidic Motif of WNK1

by Ramón Peces, Carlos Peces, Laura Espinosa, Rocío Mena, Carolina Blanco, Jair Tenorio-Castaño, Pablo Lapunzina and Julián Nevado

Genes 2023, 14(10), 1878; https://doi.org/10.3390/genes14101878 - 27 Sep 2023

Cited by 4 | Viewed by 1856

Abstract

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) [...] Read more.

(1) Background: Gordon syndrome (GS) or familial hyperkalemic hypertension is caused by pathogenic variants in the genes WNK1, WNK4, KLHL3, and CUL3. Patients presented with hypertension, hyperkalemia despite average glomerular filtration rate, hyperchloremic metabolic acidosis, and suppressed plasma renin (PR) activity with normal plasma aldosterone (PA) and sometimes failure to thrive. GS is a heterogeneous genetic syndrome, ranging from severe cases in childhood to mild and sometimes asymptomatic cases in mid-adulthood. (2) Methods: We report here a sizeable Spanish family of six patients (four adults and two children) with GS. (3) Results: They carry a novel heterozygous missense variant in exon 7 of WNK1 (p.Glu630Gly). The clinical presentation in the four adults consisted of hypertension (superimposed pre-eclampsia in two cases), hyperkalemia, short stature with low body weight, and isolated hyperkalemia in both children. All patients also presented mild hyperchloremic metabolic acidosis and low PR activity with normal PA levels. Abnormal laboratory findings and hypertension were normalized by dietary salt restriction and low doses of thiazide or indapamide retard. (4) Conclusions: This is the first Spanish family with GS with a novel heterozygous missense variant in WNK1 (p.Glu630Gly) in the region containing the highly conserved acidic motif, which is showing a relatively mild phenotype, and adults diagnosed in mild adulthood. These data support the importance of missense variants in the WNK1 acidic domain in electrolyte balance/metabolism. In addition, findings in this family also suggest that indapamide retard or thiazide may be an adequate long-standing treatment for GS. Full article

(This article belongs to the Special Issue Identifying the Molecular Basis of Rare Genetic Diseases)

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22 pages, 2244 KiB

Open AccessEditor’s ChoiceReview

Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2

by Mzwanele Ngubo, Fereshteh Moradi, Caryn Y. Ito and William L. Stanford

Genes 2023, 14(10), 1879; https://doi.org/10.3390/genes14101879 - 27 Sep 2023

Cited by 4 | Viewed by 2575

Abstract

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in [...] Read more.

The Polycomb repressive complex 2 (PRC2) is a conserved chromatin-remodelling complex that catalyses the trimethylation of histone H3 lysine 27 (H3K27me3), a mark associated with gene silencing. PRC2 regulates chromatin structure and gene expression during organismal and tissue development and tissue homeostasis in the adult. PRC2 core subunits are associated with various accessory proteins that modulate its function and recruitment to target genes. The multimeric composition of accessory proteins results in two distinct variant complexes of PRC2, PRC2.1 and PRC2.2. Metal response element-binding transcription factor 2 (MTF2) is one of the Polycomb-like proteins (PCLs) that forms the PRC2.1 complex. MTF2 is highly conserved, and as an accessory subunit of PRC2, it has important roles in embryonic stem cell self-renewal and differentiation, development, and cancer progression. Here, we review the impact of MTF2 in PRC2 complex assembly, catalytic activity, and spatiotemporal function. The emerging paradoxical evidence suggesting that MTF2 has divergent roles as either a tumour suppressor or an oncogene in different tissues merits further investigations. Altogether, our review illuminates the context-dependent roles of MTF2 in Polycomb group (PcG) protein-mediated epigenetic regulation. Its impact on disease paves the way for a deeper understanding of epigenetic regulation and novel therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Mechanisms of the Polycomb Repressive Complex 2 (PRC2) and Its Role in Human Cancer)

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13 pages, 3449 KiB

Open AccessEditor’s ChoiceArticle

Association between DNA Methylation in the Core Promoter Region of the CUT-like Homeobox 1 (CUX1) Gene and Lambskin Pattern in Hu Sheep

by Xiaoyang Lv, Yue Li, Weihao Chen, Shanhe Wang, Xiukai Cao, Zehu Yuan, Tesfaye Getachew, Joram Mwacharo, Aynalem Haile, Yutao Li and Wei Sun

Genes 2023, 14(10), 1873; https://doi.org/10.3390/genes14101873 - 26 Sep 2023

Cited by 2 | Viewed by 1677

Abstract

CUT-like homeobox 1 (CUX1) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool [...] Read more.

CUT-like homeobox 1 (CUX1) has been proven to be a key regulator in sheep hair follicle development. In our previous study, CUX1 was identified as a differential expressed gene between Hu sheep lambskin with small wave patterns (SM) and straight wool patterns (ST); however, the exact molecular mechanism of CUX1 expression has been obscure. As DNA methylation can regulate the gene expression, the potential association between CUX1 core promotor region methylation and lambskin pattern in Hu sheep was explored in the present study. The results show that the core promoter region of CUX1 was present at (−1601–(−1) bp) upstream of the transcription start site. A repressive region (−1151–(−751) bp) was also detected, which had a strong inhibitory effect on CUX1 promoter activity. Bisulfite amplicon sequencing revealed that no significant difference was detected between the methylation levels of CUX1 core promoter region in SM tissues and ST tissues. Although the data demonstrated the differential expression of CUX1 between SM and ST probably has no association with DNA methylation, the identification of the core region and a potential repressive region of CUX1 promoter can enrich the role of CUX1 in Hu sheep hair follicle development. Full article

(This article belongs to the Special Issue Genetic Mechanism Analysis and Application of Important Economic Traits in Sheep and Goats)

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22 pages, 1313 KiB

Open AccessEditor’s ChoiceReview

Role of Mitochondrial Dynamics in Heart Diseases

by Takeshi Tokuyama and Shigeru Yanagi

Genes 2023, 14(10), 1876; https://doi.org/10.3390/genes14101876 - 26 Sep 2023

Cited by 29 | Viewed by 6048

Abstract

Mitochondrial dynamics, including fission and fusion processes, are essential for heart health. Mitochondria, the powerhouses of cells, maintain their integrity through continuous cycles of biogenesis, fission, fusion, and degradation. Mitochondria are relatively immobile in the adult heart, but their morphological changes due to [...] Read more.

Mitochondrial dynamics, including fission and fusion processes, are essential for heart health. Mitochondria, the powerhouses of cells, maintain their integrity through continuous cycles of biogenesis, fission, fusion, and degradation. Mitochondria are relatively immobile in the adult heart, but their morphological changes due to mitochondrial morphology factors are critical for cellular functions such as energy production, organelle integrity, and stress response. Mitochondrial fusion proteins, particularly Mfn1/2 and Opa1, play multiple roles beyond their pro-fusion effects, such as endoplasmic reticulum tethering, mitophagy, cristae remodeling, and apoptosis regulation. On the other hand, the fission process, regulated by proteins such as Drp1, Fis1, Mff and MiD49/51, is essential to eliminate damaged mitochondria via mitophagy and to ensure proper cell division. In the cardiac system, dysregulation of mitochondrial dynamics has been shown to cause cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and various cardiac diseases, including metabolic and inherited cardiomyopathies. In addition, mitochondrial dysfunction associated with oxidative stress has been implicated in atherosclerosis, hypertension and pulmonary hypertension. Therefore, understanding and regulating mitochondrial dynamics is a promising therapeutic tool in cardiac diseases. This review summarizes the role of mitochondrial morphology in heart diseases for each mitochondrial morphology regulatory gene, and their potential as therapeutic targets to heart diseases. Full article

(This article belongs to the Special Issue Animals Models in Diseases Genetics)

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15 pages, 2989 KiB

Open AccessEditor’s ChoiceArticle

Transcriptome and Metabolome Analyses Reveal the Mechanism of Corpus Luteum Cyst Formation in Pigs

by Jiage Dai, Jiabao Cai, Taipeng Zhang, Mingyue Pang, Xiaoling Xu, Jiahua Bai, Yan Liu and Yusheng Qin

Genes 2023, 14(10), 1848; https://doi.org/10.3390/genes14101848 - 23 Sep 2023

Cited by 2 | Viewed by 2450

Abstract

Corpus luteum cysts are a serious reproductive disorder that affects the reproductive performance of sows. In this study, transcriptome and metabolome datasets of porcine normal and cyst luteal granulosa cells were generated to explore the molecular mechanism of luteal cyst formation. We obtained [...] Read more.

Corpus luteum cysts are a serious reproductive disorder that affects the reproductive performance of sows. In this study, transcriptome and metabolome datasets of porcine normal and cyst luteal granulosa cells were generated to explore the molecular mechanism of luteal cyst formation. We obtained 28.9 Gb of high−quality transcriptome data from luteum tissue samples and identified 1048 significantly differentially expressed genes between the cyst and normal corpus luteum samples. Most of the differentially expressed genes were involved in cancer and immune signaling pathways. Furthermore, 22,622 information-containing positive and negative ions were obtained through gas chromatography−mass spectrometry, and 1106 metabolites were successfully annotated. Important differentially abundant metabolites and pathways were identified, among which abnormal lipid and choline metabolism were involved in the formation of luteal cysts. The relationships between granulosa cells of luteal cysts and cancer, immune-related signaling pathways, and abnormalities of lipid and choline metabolism were elaborated, providing new entry points for studying the pathogenesis of porcine luteal cysts. Full article

(This article belongs to the Special Issue Genetic Regulation of Animal Reproduction)

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19 pages, 2744 KiB

Open AccessEditor’s ChoiceArticle

Molecular Characterization of Complete Genome Sequence of an Avian Coronavirus Identified in a Backyard Chicken from Tanzania

by Henry M. Kariithi, Jeremy D. Volkening, Gaspar H. Chiwanga, Iryna V. Goraichuk, Peter L. M. Msoffe and David L. Suarez

Genes 2023, 14(10), 1852; https://doi.org/10.3390/genes14101852 - 23 Sep 2023

Cited by 2 | Viewed by 2077

Abstract

A complete genome sequence of an avian coronavirus (AvCoV; 27,663 bp excluding 3′ poly(A) tail) was determined using nontargeted next-generation sequencing (NGS) of an oropharyngeal swab from a backyard chicken in a live bird market in Arusha, Tanzania. The open reading frames (ORFs) [...] Read more.

A complete genome sequence of an avian coronavirus (AvCoV; 27,663 bp excluding 3′ poly(A) tail) was determined using nontargeted next-generation sequencing (NGS) of an oropharyngeal swab from a backyard chicken in a live bird market in Arusha, Tanzania. The open reading frames (ORFs) of the Tanzanian strain TZ/CA127/19 are organized as typical of gammaCoVs (Coronaviridae family): 5′UTR-[ORFs 1a/1b encoding replicase complex (Rep1ab) non-structural peptides nsp2-16]-[spike (S) protein]-[ORFs 3a/3b]-[small envelop (E) protein]-[membrane (M) protein]-[ORFs 4a/4c]-[ORFs 5a/5b]-[nucleocapsid (N) protein]-[ORF6b]-3′UTR. The structural (S, E, M and N) and Rep1ab proteins of TZ/CA127/19 contain features typically conserved in AvCoVs, including the cleavage sites and functional motifs in Rep1ab and S. Its genome backbone (non-spike region) is closest to Asian GI-7 and GI-19 infectious bronchitis viruses (IBVs) with 87.2–89.7% nucleotide (nt) identities, but it has a S gene closest (98.9% nt identity) to the recombinant strain ck/CN/ahysx-1/16. Its 3a, 3b E and 4c sequences are closest to the duck CoV strain DK/GD/27/14 at 99.43%, 100%, 99.65% and 99.38% nt identities, respectively. Whereas its S gene phylogenetically cluster with North American TCoVs and French guineafowl COVs, all other viral genes group monophyletically with Eurasian GI-7/GI-19 IBVs and Chinese recombinant AvCoVs. Detection of a 4445 nt-long recombinant fragment with breakpoints at positions 19,961 and 24,405 (C- and N-terminus of nsp16 and E, respectively) strongly suggested that TZ/CA127/19 acquired its genome backbone from an LX4-type (GI-19) field strain via recombination with an unknown AvCoV. This is the first report of AvCoV in Tanzania and leaves unanswered the questions of its emergence and the biological significance. Full article

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

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13 pages, 2200 KiB

Open AccessEditor’s ChoiceArticle

Identification and Characterization of ABCG15—A Gene Required for Exocarp Color Differentiation in Pear

by Simeng Zhang, Jiayu Xu, Ying Zhang and Yufen Cao

Genes 2023, 14(9), 1827; https://doi.org/10.3390/genes14091827 - 21 Sep 2023

Cited by 1 | Viewed by 1446

Abstract

Exocarp color is a commercially essential quality for pear which can be divided into two types: green and russet. The occurrence of russet color is associated with deficiencies and defects in the cuticular and epidermal layers, which affect the structure of the cell [...] Read more.

Exocarp color is a commercially essential quality for pear which can be divided into two types: green and russet. The occurrence of russet color is associated with deficiencies and defects in the cuticular and epidermal layers, which affect the structure of the cell wall and the deposition of suberin. Until now, the genetic basics triggering this trait have not been well understood, and limited genes have been identified for the trait. To figure out the gene controlling the trait of exocarp color, we perform a comprehensive genome-wide association study, and we describe the candidate genes. One gene encoding the ABCG protein has been verified to be associated with the trait, using an integrative analysis of the metabolomic and transcriptomic data. This review covers a variety of omics resources, which provide a valuable resource for identifying gene-controlled traits of interest. The findings in this study help to elucidate the genetic components responsible for the trait of exocarp color in pear, and the implications of these findings for future pear breeding are evaluated. Full article

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

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9 pages, 235 KiB

Open AccessEditor’s ChoiceArticle

Aromatic L-Amino-Acid Decarboxylase Deficiency Screening by Analysis of 3-O-Methyldopa in Dried Blood Spots: Results of a Multicentric Study in Neurodevelopmental Disorders

by Susanna Rizzi, Carlotta Spagnoli, Melissa Bellini, Carlo Alberto Cesaroni, Elisabetta Spezia, Patrizia Bergonzini, Elisa Caramaschi, Luca Soliani, Emanuela Claudia Turco, Benedetta Piccolo, Laura Demuth, Duccio Maria Cordelli, Giacomo Biasucci, Daniele Frattini and Carlo Fusco

Genes 2023, 14(9), 1828; https://doi.org/10.3390/genes14091828 - 21 Sep 2023

Cited by 2 | Viewed by 1800

Abstract

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The [...] Read more.

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd. Full article

(This article belongs to the Section Neurogenomics)

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