Journal Description
Genes
Genes
is a peer-reviewed, open access journal of genetics and genomics published monthly online by MDPI. The Spanish Society for Biochemistry and Molecular Biology (SEBBM) is affiliated with Genes and their members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, and other databases.
- Journal Rank: JCR - Q2 (Genetics & Heredity) / CiteScore - Q2 (Genetics)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.5 days after submission; acceptance to publication is undertaken in 2.3 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: Reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
3.5 (2022);
5-Year Impact Factor:
3.9 (2022)
Latest Articles
Insights into the Geographical Origins of the Cabo Verde Green Monkey
Genes 2024, 15(4), 504; https://doi.org/10.3390/genes15040504 - 17 Apr 2024
Abstract
The green monkey Chlorocebus sabaeus, L. 1766, native to West Africa, was introduced to the Cabo Verde Archipelago in the 16th century. Historical sources suggest that, due to the importance of Cabo Verde as a commercial entrepôt in the Atlantic slave trade,
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The green monkey Chlorocebus sabaeus, L. 1766, native to West Africa, was introduced to the Cabo Verde Archipelago in the 16th century. Historical sources suggest that, due to the importance of Cabo Verde as a commercial entrepôt in the Atlantic slave trade, establishing the precise place of origin of this introduced species is challenging. Non-invasive fecal samples were collected from feral and captive green monkey individuals in Cabo Verde. Two mitochondrial fragments, HVRI and cyt b, were used to confirm the taxonomic identification of the species and to tentatively determine the geographic origin of introduction to the archipelago from the African continent. By comparing the new sequences of this study to previously published ones, it was shown that Cabo Verde individuals have unique haplotypes in the HVRI, while also showing affinities to several populations from north-western coastal Africa in the cyt b, suggesting probable multiple sources of introduction and an undetermined most probable origin. The latter is consistent with historical information, but may also have resulted from solely using mtDNA as a genetic marker and the dispersal characteristics of the species. The limitations of the methodology are discussed and future directions of research are suggested.
Full article
(This article belongs to the Section Animal Genetics and Genomics)
Open AccessReview
Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus
by
Zeinab Abdelrahman, Alexander Peter Maxwell and Amy Jayne McKnight
Genes 2024, 15(4), 503; https://doi.org/10.3390/genes15040503 - 17 Apr 2024
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance
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Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.
Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
The Impact of Blood Sample Processing on Ribonucleic Acid (RNA) Sequencing
by
Zhiyu Liu, Tinglan Ouyang, Yuwei Yang, Yuqi Sheng, Huajuan Shi, Quanjun Liu, Yunfei Bai and Qinyu Ge
Genes 2024, 15(4), 502; https://doi.org/10.3390/genes15040502 - 17 Apr 2024
Abstract
In gene quantification and expression analysis, issues with sample selection and processing can be serious, as they can easily introduce irrelevant variables and lead to ambiguous results. This study aims to investigate the extent and mechanism of the impact of sample selection and
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In gene quantification and expression analysis, issues with sample selection and processing can be serious, as they can easily introduce irrelevant variables and lead to ambiguous results. This study aims to investigate the extent and mechanism of the impact of sample selection and processing on ribonucleic acid (RNA) sequencing. RNA from PBMCs and blood samples was investigated in this study. The integrity of this RNA was measured under different storage times. All the samples underwent high-throughput sequencing for comprehensive evaluation. The differentially expressed genes and their potential functions were analyzed after the samples were placed at room temperature for 0h, 4h and 8h, and different feature changes in these samples were also revealed. The sequencing results showed that the differences in gene expression were higher with an increased storage time, while the total number of genes detected did not change significantly. There were five genes showing gradient patterns over different storage times, all of which were protein-coding genes that had not been mentioned in previous studies. The effect of different storage times on seemingly the same samples was analyzed in this present study. This research, therefore, provides a theoretical basis for the long-term consideration of whether sample processing should be adequately addressed.
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(This article belongs to the Section RNA)
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Open AccessReview
Principles in the Management of Glioblastoma
by
Domingos Roda, Pedro Veiga, Joana Barbosa Melo, Isabel Marques Carreira and Ilda Patrícia Ribeiro
Genes 2024, 15(4), 501; https://doi.org/10.3390/genes15040501 - 17 Apr 2024
Abstract
Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in
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Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in understanding the pathophysiology of these tumours have not translated into significant achievements in therapies or survival outcomes for patients. Progress in molecular profiling has yielded new omics data for a more refined classification of glioblastoma. Several typical genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signalling, as well as mutation of isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), amplification of epidermal growth factor receptor vIII, and codeletion of 1p/19q. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. Effective treatment options for glioblastoma are limited. Surgery, radiotherapy, and alkylating agent chemotherapy remain the primary pillars of treatment. Only promoter methylation of the gene MGMT predicts the benefit from alkylating chemotherapy with temozolomide and it guides the choice of first-line treatment in elderly patients. Several targeted strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles are under investigation in clinical trials. This review explores the potential genetic and epigenetic biomarkers that could be deployed as analytical tools in the diagnosis and prognostication of glioblastoma. Recent clinical advancements in treating glioblastoma are also discussed, along with the potential of liquid biopsies to advance personalized medicine in the field of glioblastoma, highlighting the challenges and promises for the future.
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(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
Biallelic NDUFA4 Deletion Causes Mitochondrial Complex IV Deficiency in a Patient with Leigh Syndrome
by
Doriana Misceo, Petter Strømme, Fatemeh Bitarafan, Maninder Singh Chawla, Ying Sheng, Sandra Monica Bach de Courtade, Lars Eide and Eirik Frengen
Genes 2024, 15(4), 500; https://doi.org/10.3390/genes15040500 (registering DOI) - 17 Apr 2024
Abstract
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause
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Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause PMDs, which have an estimated birth prevalence of 1:5000. Here, we describe a 4-year-old female presenting from early childhood with psychomotor delay and white matter signal changes affecting several brain regions, including the brainstem, in addition to lactic and phytanic acidosis, compatible with Leigh syndrome, a genetically heterogeneous subgroup of PMDs. Whole genome sequencing of the family trio identified a homozygous 12.9 Kb deletion, entirely overlapping the NDUFA4 gene. Sanger sequencing of the breakpoints revealed that the genomic rearrangement was likely triggered by Alu elements flanking the gene. NDUFA4 encodes for a subunit of the respiratory chain Complex IV, whose activity was significantly reduced in the patient’s fibroblasts. In one family, dysfunction of NDUFA4 was previously documented as causing mitochondrial Complex IV deficiency nuclear type 21 (MC4DN21, OMIM 619065), a relatively mild form of Leigh syndrome. Our finding confirms the loss of NDUFA4 function as an ultra-rare cause of Complex IV defect, clinically presenting as Leigh syndrome.
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(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle
Proteomic Analysis of Lysine Acetylation and Succinylation to Investigate the Pathogenicity of Virulent Pseudomonas syringae pv. tomato DC3000 and Avirulent Line Pseudomonas syringae pv. tomato DC3000 avrRpm1 on Arabidopsis thaliana
by
Yongqiang Ding, Yangxuan Liu, Kexin Yang, Yiran Zhao, Chun Wen, Yi Yang and Wei Zhang
Genes 2024, 15(4), 499; https://doi.org/10.3390/genes15040499 - 16 Apr 2024
Abstract
Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is able to infect many economically important crops and thus causes substantial losses in the global agricultural economy. Pst DC3000 can be divided into virulent lines and avirulent lines. For instance, the pathogen effector avrRPM1
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Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is able to infect many economically important crops and thus causes substantial losses in the global agricultural economy. Pst DC3000 can be divided into virulent lines and avirulent lines. For instance, the pathogen effector avrRPM1 of avirulent line Pst-avrRpm1 (Pst DC3000 avrRpm1) can be recognized and detoxified by the plant. To further compare the pathogenicity mechanisms of virulent and avirulent Pst DC3000, a comprehensive analysis of the acetylome and succinylome in Arabidopsis thaliana was conducted following infection with virulent line Pst DC3000 and avirulent line Pst-avrRpm1. In this study, a total of 1625 acetylated proteins encompassing 3423 distinct acetylation sites were successfully identified. Additionally, 229 succinylated proteins with 527 unique succinylation sites were detected. A comparison of these modification profiles between plants infected with Pst DC3000 and Pst-avrRpm1 revealed significant differences. Specifically, modification sites demonstrated inconsistencies, with a variance of up to 10% compared to the control group. Moreover, lysine acetylation (Kac) and lysine succinylation (Ksu) displayed distinct preferences in their modification patterns. Lysine acetylation is observed to exhibit a tendency towards up-regulation in Arabidopsis infected with Pst-avrRpm1. Conversely, the disparity in the number of Ksu up-regulated and down-regulated sites was not as pronounced. Motif enrichment analysis disclosed that acetylation modification sequences are relatively conserved, and regions rich in polar acidic/basic and non-polar hydrophobic amino acids are hotspots for acetylation modifications. Functional enrichment analysis indicated that the differentially modified proteins are primarily enriched in the photosynthesis pathway, particularly in relation to light-capturing proteins. In conclusion, this study provides an insightful profile of the lysine acetylome and succinylome in A. thaliana infected with virulent and avirulent lines of Pst DC3000. Our findings revealed the potential impact of these post-translational modifications (PTMs) on the physiological functions of the host plant during pathogen infection. This study offers valuable insights into the complex interactions between plant pathogens and their hosts, laying the groundwork for future research on disease resistance and pathogenesis mechanisms.
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(This article belongs to the Special Issue Genetics of Abiotic Stress Tolerance in Plants Volume II)
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Open AccessArticle
Comparison of Fecal MicroRNA Isolation Using Various Total RNA Isolation Kits
by
Theresa Lederer, Noam M. Hipler, Cosima Thon, Juozas Kupcinskas and Alexander Link
Genes 2024, 15(4), 498; https://doi.org/10.3390/genes15040498 - 16 Apr 2024
Abstract
Fecal specimens have long been regarded as promising sources for gastrointestinal cancer screening and have, thus, been extensively investigated in biomarker research. MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating various biological processes. They are commonly dysregulated during tumor development and
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Fecal specimens have long been regarded as promising sources for gastrointestinal cancer screening and have, thus, been extensively investigated in biomarker research. MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in regulating various biological processes. They are commonly dysregulated during tumor development and exhibit differential expression in feces. To assess the preanalytical feasibility of fecal miRNA analysis, we systematically compared the performance of commonly used total RNA extraction methods. Fecal samples from healthy subjects were utilized for this evaluation. Various methods, including miRNeasy, Universal, Trizol, RNeasy, and mirVana kits, were employed to isolate total RNA. MiRNA expression analyses were conducted using TaqMan or SYBR Green qRT-PCR for a subset of miRNAs, with externally spiked-in cel-miR-39 used for normalization. Most methods demonstrated similar performance in terms of the total RNA concentration and purity. Externally spiked cel-miR-39 and endogenous miRNAs (RNU6b, miR-16, and miR-21) exhibited comparable concentrations across the different RNA isolation methods, whereas the RNeasy mini kit consistently yielded lower values. Our findings suggest that various isolation methods produce reproducible and comparable miRNA expression results, supporting the potential comparability and translational applicability of miRNA-based biomarker research in the future.
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(This article belongs to the Special Issue Non-coding RNAs in Human Health and Disease)
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Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant
by
Edith Viridiana Alatorre-Moreno, Ana Miriam Saldaña-Cruz, Edsaúl Emilio Pérez-Guerrero, María Cristina Morán-Moguel, Betsabé Contreras-Haro, David Alejandro López-de La Mora, Ingrid Patricia Dávalos-Rodríguez, Alejandro Marín-Medina, Alicia Rivera-Cameras, Luz-Ma Adriana Balderas-Peña, José Juan Gómez-Ramos, Laura Cortés-Sanabria and Mario Salazar-Páramo
Genes 2024, 15(4), 497; https://doi.org/10.3390/genes15040497 - 16 Apr 2024
Abstract
Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified
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Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. Methods: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. Results: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13–21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54–93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79–88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. Conclusion: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.
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(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessReview
Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis
by
Pashtun Shahim, Gina Norato, Ninet Sinaii, Henrik Zetterberg, Kaj Blennow, Leighton Chan and Christopher Grunseich
Genes 2024, 15(4), 496; https://doi.org/10.3390/genes15040496 - 16 Apr 2024
Abstract
Background: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS. Methods: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science,
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Background: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS. Methods: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939. Results: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival. Discussion: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.
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(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
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Heritability of Gene Expression Measured from Peripheral Blood in Older Adults
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Sri C. Kanchibhotla, Karen A. Mather, Nicola J. Armstrong, Liliana G. Ciobanu, Bernhard T. Baune, Vibeke S. Catts, Peter R. Schofield, Julian N. Trollor, David Ames, Perminder S. Sachdev and Anbupalam Thalamuthu
Genes 2024, 15(4), 495; https://doi.org/10.3390/genes15040495 - 16 Apr 2024
Abstract
The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample
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The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age—75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h2 = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.
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(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessArticle
Identification of Key Genes and Imbalanced SNAREs Assembly in the Comorbidity of Polycystic Ovary Syndrome and Depression
by
Yi Cao, Weijing Wang, Xuxia Song, Qian Wen, Jing Xie and Dongfeng Zhang
Genes 2024, 15(4), 494; https://doi.org/10.3390/genes15040494 - 15 Apr 2024
Abstract
Background: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for
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Background: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. Methods: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein–protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. Results: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. Conclusions: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity.
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(This article belongs to the Section Molecular Genetics and Genomics)
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Open AccessReview
FOXP3: A Player of Immunogenetic Architecture in Lung Cancer
by
Iwona Ziółkowska-Suchanek and Magdalena Żurawek
Genes 2024, 15(4), 493; https://doi.org/10.3390/genes15040493 - 15 Apr 2024
Abstract
The transcription factor forkhead box protein 3 (FOXP3) is considered to be a prominent component of the immune system expressed in regulatory T cells (Tregs). Tregs are immunosuppressive cells that regulate immune homeostasis and self-tolerance. FOXP3 was originally thought to be a Tregs-specific
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The transcription factor forkhead box protein 3 (FOXP3) is considered to be a prominent component of the immune system expressed in regulatory T cells (Tregs). Tregs are immunosuppressive cells that regulate immune homeostasis and self-tolerance. FOXP3 was originally thought to be a Tregs-specific molecule, but recent studies have pinpointed that FOXP3 is expressed in a diversity of benign tumors and carcinomas. The vast majority of the data have shown that FOXP3 is correlated with an unfavorable prognosis, although there are some reports indicating the opposite function of this molecule. Here, we review recent progress in understanding the FOXP3 role in the immunogenetic architecture of lung cancer, which is the leading cause of cancer-related death. We discuss the prognostic significance of tumor FOXP3 expression, tumor-infiltrating FOXP3-lymphocytes, tumor FOXP3 in tumor microenvironments and the potential of FOXP3-targeted therapy.
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(This article belongs to the Special Issue New Advances in Immunogenetics of Disease)
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Shedding a Light on Dark Genes: A Comparative Expression Study of PRR12 Orthologues during Zebrafish Development
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Alessia Muscò, Davide Martini, Matteo Digregorio, Vania Broccoli and Massimiliano Andreazzoli
Genes 2024, 15(4), 492; https://doi.org/10.3390/genes15040492 - 15 Apr 2024
Abstract
Haploinsufficiency of the PRR12 gene is implicated in a human neuro-ocular syndrome. Although identified as a nuclear protein highly expressed in the embryonic mouse brain, PRR12 molecular function remains elusive. This study explores the spatio-temporal expression of zebrafish PRR12 co-orthologs, prr12a and prr12b
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Haploinsufficiency of the PRR12 gene is implicated in a human neuro-ocular syndrome. Although identified as a nuclear protein highly expressed in the embryonic mouse brain, PRR12 molecular function remains elusive. This study explores the spatio-temporal expression of zebrafish PRR12 co-orthologs, prr12a and prr12b, as a first step to elucidate their function. In silico analysis reveals high evolutionary conservation in the DNA-interacting domains for both orthologs, with significant syntenic conservation observed for the prr12b locus. In situ hybridization and RT-qPCR analyses on zebrafish embryos and larvae reveal distinct expression patterns: prr12a is expressed early in zygotic development, mainly in the central nervous system, while prr12b expression initiates during gastrulation, localizing later to dopaminergic telencephalic and diencephalic cell clusters. Both transcripts are enriched in the ganglion cell and inner neural layers of the 72 hpf retina, with prr12b widely distributed in the ciliary marginal zone. In the adult brain, prr12a and prr12b are found in the cerebellum, amygdala and ventral telencephalon, which represent the main areas affected in autistic patients. Overall, this study suggests PRR12’s potential involvement in eye and brain development, laying the groundwork for further investigations into PRR12-related neurobehavioral disorders.
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(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessSystematic Review
Association of Gene Polymorphisms with Normal Tension Glaucoma: A Systematic Review and Meta-Analysis
by
Lijie Pan, Jian Wu and Ningli Wang
Genes 2024, 15(4), 491; https://doi.org/10.3390/genes15040491 - 14 Apr 2024
Abstract
Background: Normal tension glaucoma (NTG) is becoming a more and more serious problem, especially in Asia. But the pathological mechanisms are still not illustrated clearly. We carried out this research to uncover the gene polymorphisms with NTG. Methods: We searched in Web of
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Background: Normal tension glaucoma (NTG) is becoming a more and more serious problem, especially in Asia. But the pathological mechanisms are still not illustrated clearly. We carried out this research to uncover the gene polymorphisms with NTG. Methods: We searched in Web of Science, Embase, Pubmed and Cochrane databases for qualified case-control studies investigating the association between single nucleotide polymorphisms (SNPs) and NTG risk. Odds ratios (ORs) and 95% confidence intervals (CIs) for each SNP were estimated by fixed- or random-effect models. Sensitivity analysis was also performed to strengthen the reliability of the results. Results: Fifty-six studies involving 33 candidate SNPs in 14 genetic loci were verified to be eligible for our meta-analysis. Significant associations were found between 16 SNPs (rs166850 of OPA1; rs10451941 of OPA1; rs735860 of ELOVL5; rs678350 of HK2; c.603T>A/Met98Lys of OPTN; c.412G>A/Thr34Thr of OPTN; rs10759930 of TLR4; rs1927914 of TLR4; rs1927911 of TLR4; c.*70C>G of EDNRA; rs1042522/-Arg72Pro of P53; rs10483727 of SIX1-SIX6; rs33912345 of SIX1-SIX6; rs2033008 of NCK2; rs3213787 of SRBD1 and c.231G>A of EDNRA) with increased or decreased risk of NTG. Conclusions: In this study, we confirmed 16 genetic polymorphisms in 10 genes (OPA1, ELOVL5, HK2, OPTN, TLR4, EDNRA, P53, NCK2, SRBD1 and SIX1-SIX6) were associated with NTG.
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(This article belongs to the Special Issue Molecular Diagnosis and Disease Mechanisms in Eye Disorders)
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Determinants of mer Promoter Activity from Pseudomonas aeruginosa
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Qingyuan Hu, Jue Wang, Chunhong Liu, Yu Feng and Hao Chen
Genes 2024, 15(4), 490; https://doi.org/10.3390/genes15040490 - 13 Apr 2024
Abstract
Since the MerR family is known for its special regulatory mechanism, we aimed to explore which factors determine the expression activity of the mer promoter. The Tn501/Tn21 mer promoter contains an abnormally long spacer (19 bp) between the −35 and −10 elements, which is
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Since the MerR family is known for its special regulatory mechanism, we aimed to explore which factors determine the expression activity of the mer promoter. The Tn501/Tn21 mer promoter contains an abnormally long spacer (19 bp) between the −35 and −10 elements, which is essential for the unique DNA distortion mechanism. To further understand the role of base sequences in the mer promoter spacer, this study systematically engineered a series of mutant derivatives and used luminescent and fluorescent reporter genes to investigate the expression activity of these derivatives. The results reveal that the expression activity of the mer promoter is synergistically modulated by the spacer length (17 bp is optimal) and the region upstream of −10 (especially −13G). The spacing is regulated by MerR transcription factors through symmetrical sequences, and −13G presumably functions through interaction with the RNA polymerase sigma-70 subunit.
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(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle
Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort
by
Naoko Sakuma, Shin-ya Nishio, Shin-ichi Goto, Yohei Honkura, Kiyoshi Oda, Hidehiko Takeda, Marina Kobayashi, Kozo Kumakawa, Satoshi Iwasaki, Masahiro Takahashi, Taku Ito, Yasuhiro Arai, Yasuhiro Isono, Natsuko Obara, Takeshi Matsunobu, Kimihiro Okubo and Shin-ichi Usami
Genes 2024, 15(4), 489; https://doi.org/10.3390/genes15040489 - 12 Apr 2024
Abstract
The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of
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The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.
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(This article belongs to the Special Issue Next Generation Sequencing in Human Disease)
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Combined Analysis of Untargeted Metabolomics and Transcriptomics Revealed Seed Germination and Seedling Establishment in Zelkova schneideriana
by
Fengxia Yan, Tangmei Wei, Chao Yang, Yanbing Yang, Zaiqi Luo and Yunli Jiang
Genes 2024, 15(4), 488; https://doi.org/10.3390/genes15040488 - 12 Apr 2024
Abstract
Zelkova schneideriana Hand.-Mazz is a valuable ornamental tree and timber source, whose seedling breeding and large-scale cultivation are restricted by low seed germination and seedling rates. The regulatory mechanisms underlying seed germination and seedling establishment in Z. schneideriana remain unknown. This study conducted
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Zelkova schneideriana Hand.-Mazz is a valuable ornamental tree and timber source, whose seedling breeding and large-scale cultivation are restricted by low seed germination and seedling rates. The regulatory mechanisms underlying seed germination and seedling establishment in Z. schneideriana remain unknown. This study conducted metabolomic and transcriptomic analyses of seed germination and seedling establishment in Z. schneideriana. Regular expression of genes and metabolite levels has been observed in plant hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, and phenylpropanoid biosynthesis. The reduction in abscisic acid during seed germination may lead to seed release from dormancy. After the seed is released from dormancy, the metabolic levels of auxin, cytokinins, brassinolide, and various sugars are elevated, and they are consumed in large quantities during the seedling establishment stage. Linoleic acid metabolism is gradually activated during seedling establishment. Transcriptome analysis showed that a large number of genes in different metabolic pathways are upregulated during plant establishment, and material metabolism may be accelerated during seedling establishment. Genes regulating carbohydrate metabolism are altered during seed germination and seedling establishment, which may have altered the efficiency of carbohydrate utilization. In addition, the syntheses of lignin monomers and cellulose have different characteristics at different stages. These results provide new insights into the complex mechanisms underlying seed germination and seedling establishment in Z. schneideriana and other woody plants.
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(This article belongs to the Section Plant Genetics and Genomics)
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The Effect of Short-Term Artificial Feed Domestication on the Expression of Oxidative-Stress-Related Genes and Antioxidant Capacity in the Liver and Gill Tissues of Mandarin Fish (Siniperca chuatsi)
by
Zhou Zhang, Xiping Yuan, Hao Wu, Jinwei Gao, Jiayu Wu, Zhenzhen Xiong, Zhifeng Feng, Min Xie, Shaoming Li, Zhonggui Xie and Guoqing Zeng
Genes 2024, 15(4), 487; https://doi.org/10.3390/genes15040487 - 12 Apr 2024
Abstract
To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification,
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To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification, coagulation, and immune regulation, while the gills are important respiratory organs that are sensitive to changes in the water environment. Therefore, we used the liver and gills of Mandarin fish as research materials. The aim of this study was to investigate the effects of short-term artificial feed domestication on the expression of oxidative stress genes and the changes in oxidative-stress-related enzyme activity in the liver and gills of Mandarin fish. We divided the Mandarin fish into two groups for treatment. The control group was fed with live bait continuously for 14 days, while the experimental group was fed with half artificial feed and half live bait from 0 to 7 days (T-7 d), followed by solely artificial feed from 7 to 14 days (T-14 d). The experimental results showed that there was no difference in the body weight, length, and standard growth rate of the Mandarin fish between the two groups of treatments; after two treatments, there were differences in the expression of genes related to oxidative stress in the gills (keap1, kappa, gsta, gstt1, gstk1, SOD, and CAT) and in the liver (GPx, keap1, kappa, gsta, gstt1, gr, and SOD). In the liver, GPx activity and the content of MDA were significantly upregulated after 7 days of domestication, while in the gills, SOD activity was significantly upregulated after 7 days of domestication and GPx activity was significantly downregulated after 14 days of domestication. These results suggest that artificial feed domestication is associated with oxidative stress. Moreover, these results provide experimental basic data for increasing the production of aquaculture feed for Mandarin fish.
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(This article belongs to the Section Animal Genetics and Genomics)
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Screening and Preliminary Identification of Asparagus officinalis Varieties under Low-Temperature Stress
by
Youju Ye, Shuangshuang Wen, Jiali Ying, Yunfei Cai and Renjuan Qian
Genes 2024, 15(4), 486; https://doi.org/10.3390/genes15040486 - 12 Apr 2024
Abstract
To meet the large demand for Asparagus officinalis in the spring market and improve the economic benefits of cultivating asparagus, we explored the molecular mechanism underlying the response of A. officinalis to low temperature. First, “Fengdao No. 1” was screened out under low-temperature
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To meet the large demand for Asparagus officinalis in the spring market and improve the economic benefits of cultivating asparagus, we explored the molecular mechanism underlying the response of A. officinalis to low temperature. First, “Fengdao No. 1” was screened out under low-temperature treatment. Then, the transcriptome sequencing and hormone detection of “Fengdao No. 1” and “Grande” (control) were performed. Transcriptome sequencing resulted in screening out key candidate genes, while hormone analysis indicated that ABA was important for the response to low temperature. The combined analysis indicated that the AoMYB56 gene may regulate ABA in A. officinalis under low temperature. And the phylogenetic tree was constructed, and subcellular localisation was performed. From these results, we speculated that the AoMYB56 gene may regulate ABA in A. officinalis. The results of this research provide a theoretical basis for the further exploration of low-temperature response in A. officinalis.
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(This article belongs to the Special Issue Abiotic Stress in Plants: Genetics and Genomics)
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Recessive GNE Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy
by
Nasrin Tamanna, Byung Kwon Pi, Ah Jin Lee, Sumaira Kanwal, Byung-Ok Choi and Ki Wha Chung
Genes 2024, 15(4), 485; https://doi.org/10.3390/genes15040485 - 11 Apr 2024
Abstract
Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of
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Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find GNE mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES). In silico pathogenic prediction and simulation of 3D structural changes were performed for the mutant GNE proteins. As a result, we identified five pathogenic or likely pathogenic missense variants: c.86T>C (p.Met29Thr), c.527A>T (p.Asp176Val), c.782T>C (p.Met261Thr), c.1714G>C (p.Val572Leu), and c.1771G>A (p.Ala591Thr). Five affected individuals showed compound heterozygous mutations, while only one patient revealed a homozygous mutation. Two patients revealed unreported combinations of combined heterozygous mutations. We observed some specific clinical features, such as complex phenotypes of distal myopathy with distal hereditary peripheral neuropathy, an earlier onset of weakness in legs than that of hands, and clinical heterogeneity between two patients with the same set of compound heterozygous mutations. Our findings on these genetic causes expand the clinical spectrum associated with the GNE mutations and can help prepare therapeutic strategies.
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(This article belongs to the Special Issue Variations of Rare Genetic Diseases)
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