Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.5
2.8
Journals
Genes
Editor’s Choice
share announcement

Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
13 pages, 770 KiB  
Review
Research Progress and Applications of Bovine Genome in the Tribe Bovini
by Xingjie Du, Yu Sun, Tong Fu, Tengyun Gao and Tianliu Zhang
Genes 2024, 15(4), 509; https://doi.org/10.3390/genes15040509 - 18 Apr 2024
Viewed by 2167
Abstract
Various bovine species have been domesticated and bred for thousands of years, and they provide adequate animal-derived products, including meat, milk, and leather, to meet human requirements. Despite the review studies on economic traits in cattle, the genetic basis of traits has only [...] Read more.
Various bovine species have been domesticated and bred for thousands of years, and they provide adequate animal-derived products, including meat, milk, and leather, to meet human requirements. Despite the review studies on economic traits in cattle, the genetic basis of traits has only been partially explained by phenotype and pedigree breeding methods, due to the complexity of genomic regulation during animal development and growth. With the advent of next-generation sequencing technology, genomics projects, such as the 1000 Bull Genomes Project, Functional Annotation of Animal Genomes project, and Bovine Pangenome Consortium, have advanced bovine genomic research. These large-scale genomics projects gave us a comprehensive concept, technology, and public resources. In this review, we summarize the genomics research progress of the main bovine species during the past decade, including cattle (Bos taurus), yak (Bos grunniens), water buffalo (Bubalus bubalis), zebu (Bos indicus), and gayal (Bos frontalis). We mainly discuss the development of genome sequencing and functional annotation, focusing on how genomic analysis reveals genetic variation and its impact on phenotypes in several bovine species. Full article
(This article belongs to the Special Issue Research on Genetics and Genomics of Cattle)
►▼ Show Figures

Figure 1

13 pages, 1907 KiB  
Article
Biogeographical Ancestry Analyses Using the ForenSeqTM DNA Signature Prep Kit and Multiple Prediction Tools
by Nina Mjølsnes Salvo, Gunn-Hege Olsen, Thomas Berg and Kirstin Janssen
Genes 2024, 15(4), 510; https://doi.org/10.3390/genes15040510 - 18 Apr 2024
Cited by 1 | Viewed by 1769
Abstract
The inference of biogeographical ancestry (BGA) can assist in police investigations of serious crime cases and help to identify missing people and victims of mass disasters. In this study, we evaluated the typing performance of 56 ancestry-informative SNPs in 177 samples using the [...] Read more.
The inference of biogeographical ancestry (BGA) can assist in police investigations of serious crime cases and help to identify missing people and victims of mass disasters. In this study, we evaluated the typing performance of 56 ancestry-informative SNPs in 177 samples using the ForenSeq™ DNA Signature Prep Kit on the MiSeq FGx system. Furthermore, we compared the prediction accuracy of the tools Universal Analysis Software v1.2 (UAS), the FROG-kb, and GenoGeographer when inferring the ancestry of 503 Europeans, 22 non-Europeans, and 5 individuals with co-ancestry. The kit was highly sensitive with complete aiSNP profiles in samples with as low as 250pg input DNA. However, in line with others, we observed low read depth and occasional drop-out in some SNPs. Therefore, we suggest not using less than the recommended 1ng of input DNA. FROG-kb and GenoGeographer accurately predicted both Europeans (99.6% and 91.8% correct, respectively) and non-Europeans (95.4% and 90.9% correct, respectively). The UAS was highly accurate when predicting Europeans (96.0% correct) but performed poorer when predicting non-Europeans (40.9% correct). None of the tools were able to correctly predict individuals with co-ancestry. Our study demonstrates that the use of multiple prediction tools will increase the prediction accuracy of BGA inference in forensic casework. Full article
(This article belongs to the Special Issue State-of-the-Art in Forensic Genetics Volume II)
►▼ Show Figures

Figure 1

16 pages, 16398 KiB  
Article
An R2R3-MYB Transcriptional Factor LuMYB314 Associated with the Loss of Petal Pigmentation in Flax (Linum usitatissimum L.)
by Dongliang Guo, Haixia Jiang and Liqiong Xie
Genes 2024, 15(4), 511; https://doi.org/10.3390/genes15040511 - 18 Apr 2024
Cited by 1 | Viewed by 1647
Abstract
The loss of anthocyanin pigments is one of the most common evolutionary transitions in petal color, yet the genetic basis for these changes in flax remains largely unknown. In this study, we used crossing studies, a bulk segregant analysis, genome-wide association studies, a [...] Read more.
The loss of anthocyanin pigments is one of the most common evolutionary transitions in petal color, yet the genetic basis for these changes in flax remains largely unknown. In this study, we used crossing studies, a bulk segregant analysis, genome-wide association studies, a phylogenetic analysis, and transgenic testing to identify genes responsible for the transition from blue to white petals in flax. This study found no correspondence between the petal color and seed color, refuting the conclusion that a locus controlling the seed coat color is associated with the petal color, as reported in previous studies. The locus controlling the petal color was mapped using a BSA-seq analysis based on the F2 population. However, no significantly associated genomic regions were detected. Our genome-wide association study identified a highly significant QTL (BP4.1) on chromosome 4 associated with flax petal color in the natural population. The combination of a local Manhattan plot and an LD heat map identified LuMYB314, an R2R3-MYB transcription factor, as a potential gene responsible for the natural variations in petal color in flax. The overexpression of LuMYB314 in both Arabidopsis thaliana and Nicotiana tabacum resulted in anthocyanin deposition, indicating that LuMYB314 is a credible candidate gene for controlling the petal color in flax. Additionally, our study highlights the limitations of the BSA-seq method in low-linkage genomic regions, while also demonstrating the powerful detection capabilities of GWAS based on high-density genomic variation mapping. This study enhances our genetic insight into petal color variations and has potential breeding value for engineering LuMYB314 to develop colored petals, bast fibers, and seeds for multifunctional use in flax. Full article
(This article belongs to the Special Issue Advances in Genetics and Genomics of Plants)
►▼ Show Figures

Figure 1

10 pages, 1544 KiB  
Article
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 - 17 Apr 2024
Cited by 6 | Viewed by 2533
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 [...] Read more.
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. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

12 pages, 1912 KiB  
Article
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
Viewed by 1781
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 [...] Read more.
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. Full article
(This article belongs to the Section RNA)
►▼ Show Figures

Figure 1

27 pages, 3462 KiB  
Review
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
Cited by 20 | Viewed by 6503
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 [...] Read more.
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. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

20 pages, 2426 KiB  
Review
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
Viewed by 2446
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 [...] Read more.
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)
►▼ Show Figures

Figure 1

12 pages, 2447 KiB  
Article
Insights into the Geographical Origins of the Cabo Verde Green Monkey
by Lara Almeida, Ivo Colmonero-Costeira, Maria J. Ferreira da Silva, Cecilia Veracini and Raquel Vasconcelos
Genes 2024, 15(4), 504; https://doi.org/10.3390/genes15040504 - 17 Apr 2024
Cited by 1 | Viewed by 2871
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, [...] Read more.
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)
►▼ Show Figures

Figure 1

13 pages, 870 KiB  
Article
Heritability of Gene Expression Measured from Peripheral Blood in Older Adults
by 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
Viewed by 1803
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 [...] Read more.
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. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

15 pages, 3832 KiB  
Review
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
Cited by 7 | Viewed by 3746
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Genetics of Motor Neuron Diseases)
►▼ Show Figures

Figure 1

11 pages, 1494 KiB  
Article
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
Cited by 3 | Viewed by 2495
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Non-coding RNAs in Human Health and Disease)
►▼ Show Figures

Figure 1

16 pages, 2601 KiB  
Article
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
Cited by 2 | Viewed by 2041
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Genetics of Abiotic Stress Tolerance in Plants Volume II)
►▼ Show Figures

Figure 1

19 pages, 6311 KiB  
Article
Shedding a Light on Dark Genes: A Comparative Expression Study of PRR12 Orthologues during Zebrafish Development
by 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
Viewed by 2092
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 [...] Read more.
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. Full article
(This article belongs to the Section Animal Genetics and Genomics)
►▼ Show Figures

Figure 1

14 pages, 2245 KiB  
Review
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
Cited by 2 | Viewed by 2616
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue New Advances in Immunogenetics of Disease)
►▼ Show Figures

Figure 1

16 pages, 6524 KiB  
Article
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
Cited by 1 | Viewed by 1720
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 [...] Read more.
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. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

16 pages, 4369 KiB  
Article
Determinants of mer Promoter Activity from Pseudomonas aeruginosa
by 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
Cited by 1 | Viewed by 1942
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 [...] Read more.
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. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
►▼ Show Figures

Figure 1

13 pages, 4693 KiB  
Article
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
Viewed by 1295
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Abiotic Stress in Plants: Genetics and Genomics)
►▼ Show Figures

Figure 1

11 pages, 2470 KiB  
Article
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
Cited by 6 | Viewed by 1822
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, [...] Read more.
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. Full article
(This article belongs to the Section Animal Genetics and Genomics)
►▼ Show Figures

Figure 1

22 pages, 6674 KiB  
Article
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
Cited by 2 | Viewed by 1394
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 [...] Read more.
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. Full article
(This article belongs to the Section Plant Genetics and Genomics)
►▼ Show Figures

Figure 1

13 pages, 1330 KiB  
Article
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
Cited by 1 | Viewed by 2029
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Next Generation Sequencing in Human Disease)
►▼ Show Figures

Figure 1

9 pages, 261 KiB  
Article
Association between the GLP1R A316T Mutation and Adolescent Idiopathic Scoliosis in French Canadian and Italian Cohorts
by Émilie Normand, Anita Franco, Stefan Parent, Giovanni Lombardi, Marco Brayda-Bruno, Alessandra Colombini, Alain Moreau and Valérie Marcil
Genes 2024, 15(4), 481; https://doi.org/10.3390/genes15040481 - 11 Apr 2024
Viewed by 1628
Abstract
Studies have revealed anthropometric discrepancies in girls with adolescent idiopathic scoliosis (AIS) compared to non-scoliotic subjects, such as a higher stature, lower weight, and lower body mass index. While the causes are still unknown, it was proposed that metabolic hormones could play a [...] Read more.
Studies have revealed anthropometric discrepancies in girls with adolescent idiopathic scoliosis (AIS) compared to non-scoliotic subjects, such as a higher stature, lower weight, and lower body mass index. While the causes are still unknown, it was proposed that metabolic hormones could play a role in AIS pathophysiology. Our objectives were to evaluate the association of GLP1R A316T polymorphism in AIS susceptibility and to study its relationship with disease severity and progression. We performed a retrospective case–control association study with controls and AIS patients from an Italian and French Canadian cohort. The GLP1R rs10305492 polymorphism was genotyped in 1025 subjects (313 non-scoliotic controls and 712 AIS patients) using a validated TaqMan allelic discrimination assay. Associations were evaluated by odds ratio and 95% confidence intervals. In the AIS group, there was a higher frequency of the variant genotype A/G (4.2% vs. 1.3%, OR = 3.40, p = 0.016) and allele A (2.1% vs. 0.6%, OR = 3.35, p = 0.017) than controls. When the AIS group was stratified for severity (≤40° vs. >40°), progression of the disease (progressor vs. non-progressor), curve type, or body mass index, there was no statistically significant difference in the distribution of the polymorphism. Our results support that the GLP1R A316T polymorphism is associated with a higher risk of developing AIS, but without being associated with disease severity and progression. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
11 pages, 1574 KiB  
Article
Exploring Adiponectin in Autosomal Dominant Kidney Disease: Insight and Implications
by Ersilia Nigro, Marta Mallardo, Maria Amicone, Daniela D’Arco, Eleonora Riccio, Maurizio Marra, Fabrizio Pasanisi, Antonio Pisani and Aurora Daniele
Genes 2024, 15(4), 484; https://doi.org/10.3390/genes15040484 - 11 Apr 2024
Cited by 2 | Viewed by 1517
Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin [...] Read more.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin is involved in various cellular processes, such as energy and inflammatory and oxidative processes. However, it remains to be determined whether adiponectin is involved in the concomitant metabolic dysfunctions present in PKD. In this scenario, we aimed to analyze: (a) PPARγ, ADIPOQ, ADIPOR1 and ADIPOR2 gene variations in 92 ADPKD patients through PCR-Sanger sequencing; and (b) adiponectin levels and its oligomerization state by ELISA and Western Blot. Our results indicated that: (a) 14 patients carried the PPARγ SNP, 29 patients carried the ADIPOQ SNP rs1501299, and 25 patients carried the analyzed ADIPOR1 SNPs. Finally, 82 patients carried ADIPOR2 SNPs; and (b) Adiponectin is statistically lower in ADPKD patients compared to controls, and further statistically lower in ESRD than in non-ESRD patients. An inverse relationship between adiponectin and albumin and between adiponectin and creatinine and a direct relationship between adiponectin and eGFR were found. Interestingly, significantly lower levels of adiponectin were found in patients bearing the ADIPOQ rs1501299 SNP and associated with low levels of eGFR. In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Graphical abstract

23 pages, 10313 KiB  
Article
LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas
by Ruiting Huang, Ying Kong, Zhiqing Luo and Quhuan Li
Genes 2024, 15(4), 483; https://doi.org/10.3390/genes15040483 - 11 Apr 2024
Cited by 4 | Viewed by 2202
Abstract
Gliomas are the most prevalent primary malignant tumors affecting the brain, with high recurrence and mortality rates. Accurate diagnoses and effective treatment challenges persist, emphasizing the need for identifying new biomarkers to guide clinical decisions. Long noncoding RNAs (lncRNAs) hold potential as diagnostic [...] Read more.
Gliomas are the most prevalent primary malignant tumors affecting the brain, with high recurrence and mortality rates. Accurate diagnoses and effective treatment challenges persist, emphasizing the need for identifying new biomarkers to guide clinical decisions. Long noncoding RNAs (lncRNAs) hold potential as diagnostic and therapeutic biomarkers in cancer. However, only a limited subset of lncRNAs in gliomas have been explored. Therefore, this study aims to identify lncRNA signatures applicable to patients with gliomas across all grades and explore their clinical significance and potential biological mechanisms. Data used in this study were obtained from TCGA, CGGA, and GEO datasets to identify key lncRNA signatures in gliomas through differential and survival analyses and machine learning algorithms. We examined their associations with the clinical characteristics, gene mutations, diagnosis, and prognosis of gliomas. Functional enrichment analysis was employed to elucidate the potential biological mechanisms associated with these significant lncRNA signatures. We explored competing endogenous RNA (ceRNA) regulatory networks. We found that NDUFA6-DT emerged as a significant lncRNA signature in gliomas, with reduced NDUFA6-DT expression associated with a worse prognosis in gliomas. Nomogram analysis incorporating NDUFA6-DT expression levels exhibited excellent prognostic and predictive capabilities. Functional annotation suggested that NDUFA6-DT might influence immunological responses and synaptic transmission, potentially modifying glioma initiation and progression. The associated ceRNA network revealed the possible presence of the NDUFA6-DT-miR-455-3p-YWHAH/YWHAG axis in low-grade glioma (LGG) and glioblastoma multiforme (GBM), regulating the PI3K-AKT signaling pathway and influencing glioma cell survival and apoptosis. We believe that NDUFA6-DT is a novel lncRNA linked to glioma diagnosis and prognosis, potentially becoming a pivotal biomarker for glioma. Full article
(This article belongs to the Special Issue RNAs in Biology)
►▼ Show Figures

Figure 1

14 pages, 1867 KiB  
Article
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
Viewed by 2510
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Variations of Rare Genetic Diseases)
►▼ Show Figures

Figure 1

17 pages, 1307 KiB  
Review
MALAT1: A Long Non-Coding RNA with Multiple Functions and Its Role in Processes Associated with Fat Deposition
by Katarzyna Piórkowska, Karolina Zygmunt, Walter Hunter and Ksenia Wróblewska
Genes 2024, 15(4), 479; https://doi.org/10.3390/genes15040479 - 10 Apr 2024
Cited by 5 | Viewed by 4474
Abstract
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the lncRNA molecules, which are involved in transcriptional and epigenetic regulation and the control of gene expression, including the mechanism of chromatin remodeling. MALAT1 was first discovered during carcinogenesis in lung adenocarcinoma, hence [...] Read more.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) belongs to the lncRNA molecules, which are involved in transcriptional and epigenetic regulation and the control of gene expression, including the mechanism of chromatin remodeling. MALAT1 was first discovered during carcinogenesis in lung adenocarcinoma, hence its name. In humans, 66 of its isoforms have been identified, and in pigs, only 2 are predicted, for which information is available in Ensembl databases (Ensembl Release 111). MALAT1 is expressed in numerous tissues, including adipose, adrenal gland, heart, kidney, liver, ovary, pancreas, sigmoid colon, small intestine, spleen, and testis. MALAT1, as an lncRNA, shows a wide range of functions. It is involved in the regulation of the cell cycle, where it has pro-proliferative effects and high cellular levels during the G1/S and mitotic (M) phases. Moreover, it is involved in invasion, metastasis, and angiogenesis, and it has a crucial function in alternative splicing during carcinogenesis. In addition, MALAT1 plays a significant role in the processes of fat deposition and adipogenesis. The human adipose tissue stem cells, during differentiation into adipocytes, secrete MALAT1 as one the most abundant lncRNAs in the exosomes. MALAT1 expression in fat tissue is positively correlated with adipogenic FABP4 and LPL. This lncRNA is involved in the regulation of PPARγ at the transcription stage, fatty acid metabolism, and insulin signaling. The wide range of MALAT1 functions makes it an interesting target in studies searching for drugs to prevent obesity development in humans. In turn, in farm animals, it can be a source of selection markers to control the fat tissue content. Full article
(This article belongs to the Special Issue Epigenomics, Epigenetics, and Gene Expression Regulation as Determinants of Fat Deposition and Adipogenesis in Mammals)
►▼ Show Figures

Figure 1

19 pages, 7798 KiB  
Article
Effects of Fat and Carnitine on the Expression of Carnitine Acetyltransferase and Enoyl-CoA Hydratase Short-Chain 1 in the Liver of Juvenile GIFT (Oreochromis niloticus)
by Ruijie Guo, Kai Huang, Kai Yu, Jinghua Li, Jiao Huang, Dandan Wang and Yuda Li
Genes 2024, 15(4), 480; https://doi.org/10.3390/genes15040480 - 10 Apr 2024
Viewed by 1383
Abstract
Carnitine acetyltransferase (CAT) and Enoyl-CoA hydratase short-chain 1 (ECHS1) are considered key enzymes that regulate the β-oxidation of fatty acids. However, very few studies have investigated their full length and expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture [...] Read more.
Carnitine acetyltransferase (CAT) and Enoyl-CoA hydratase short-chain 1 (ECHS1) are considered key enzymes that regulate the β-oxidation of fatty acids. However, very few studies have investigated their full length and expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China. Here, we cloned CAT and ECHS1 full-length cDNA via the rapid amplification of cDNA ends, and the expressions of CAT and ECHS1 in the liver of juvenile GIFT were detected in different fat and carnitine diets, as were the changes in the lipometabolic enzymes and serum biochemical indexes of juvenile GIFT in diets with different fat and carnitine levels. CAT cDNA possesses an open reading frame (ORF) of 2167 bp and encodes 461 amino acids, and the ECHS1 cDNA sequence is 1354 bp in full length, the ORF of which encodes a peptide of 391 amino acids. We found that juvenile GIFT had higher lipometabolic enzyme activity and lower blood CHOL, TG, HDL-C, and LDL-C contents when the dietary fat level was 2% or 6% and when the carnitine level was 500 mg/kg. We also found that the expression of ECHS1 and CAT genes in the liver of juvenile GIFT can be promoted by a 500 mg/kg carnitine level and 6% fat level feeding. These results suggested that CAT and ECHS1 may participate in regulating lipid metabolism, and when 2% or 6% fat and 500 mg/kg carnitine are added to the feed, it is the most beneficial to the liver and lipid metabolism of juvenile GIFT. Our results may provide a theoretical basis for GIFT feeding and treating fatty liver disease. Full article
(This article belongs to the Section Animal Genetics and Genomics)
►▼ Show Figures

Figure 1

11 pages, 588 KiB  
Review
Lignin Biosynthesis and Its Diversified Roles in Disease Resistance
by Qing-Hu Ma
Genes 2024, 15(3), 295; https://doi.org/10.3390/genes15030295 - 25 Feb 2024
Cited by 22 | Viewed by 5577
Abstract
Lignin is complex, three-dimensional biopolymer existing in plant cell wall. Lignin biosynthesis is increasingly highlighted because it is closely related to the wide applications in agriculture and industry productions, including in pulping process, forage digestibility, bio-fuel, and carbon sequestration. The functions of lignin [...] Read more.
Lignin is complex, three-dimensional biopolymer existing in plant cell wall. Lignin biosynthesis is increasingly highlighted because it is closely related to the wide applications in agriculture and industry productions, including in pulping process, forage digestibility, bio-fuel, and carbon sequestration. The functions of lignin in planta have also attracted more attentions recently, particularly in plant defense response against different pathogens. In this brief review, the progress in lignin biosynthesis is discussed, and the lignin’s roles in disease resistance are thoroughly elucidated. This issue will help in developing broad-spectrum resistant crops in agriculture. Full article
(This article belongs to the Section Plant Genetics and Genomics)
►▼ Show Figures

Figure 1

29 pages, 676 KiB  
Review
NF-κB: Governing Macrophages in Cancer
by Jessica Cornice, Daniela Verzella, Paola Arboretto, Davide Vecchiotti, Daria Capece, Francesca Zazzeroni and Guido Franzoso
Genes 2024, 15(2), 197; https://doi.org/10.3390/genes15020197 - 31 Jan 2024
Cited by 31 | Viewed by 6972
Abstract
Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumor progression and or-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophage phenotypes: [...] Read more.
Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumor progression and or-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophage phenotypes: M1-like or pro-inflammatory and M2-like or anti-inflammatory. NF-κB transcription factors are central regulators of TAMs in cancers, where they often drive macrophage polarization toward an M2-like phenotype. Therefore, the NF-κB pathway is an attractive therapeutic target for cancer immunotherapy in a wide range of human tumors. Hence, targeting NF-κB pathway in the myeloid compartment is a potential clinical strategy to overcome microenvironment-induced immunosuppression and increase anti-tumor immunity. In this review, we discuss the role of NF-κB as a key driver of macrophage functions in tumors as well as the principal strategies to overcome tumor immunosuppression by targeting the NF-κB pathway. Full article
(This article belongs to the Special Issue Cell Signalling and Inflammation in Cancer)
►▼ Show Figures

Figure 1

13 pages, 457 KiB  
Study Protocol
Autism Spectrum Disorder with Epilepsy: A Research Protocol for a Clinical and Genetic Study
by Roberto Canitano and Yuri Bozzi
Genes 2024, 15(1), 61; https://doi.org/10.3390/genes15010061 - 31 Dec 2023
Cited by 2 | Viewed by 3612
Abstract
Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting ~1% of people worldwide. Core ASD features present with impaired social communication abilities, repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a series of comorbidities. Among these, epilepsy [...] Read more.
Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting ~1% of people worldwide. Core ASD features present with impaired social communication abilities, repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a series of comorbidities. Among these, epilepsy is frequently observed. The co-occurrence of ASD and epilepsy is currently thought to result from common abnormal neurodevelopmental pathways, including an imbalanced excitation/inhibition ratio. However, the pathological mechanisms involved in ASD-epilepsy co-morbidity are still largely unknown. Here, we propose a research protocol aiming to investigate electrophysiological and genetic features in subjects with ASD and epilepsy. This study will include a detailed electroencephalographic (EEG) and blood transcriptomic characterization of subjects with ASD with and without epilepsy. The combined approach of EEG and transcriptomic studies in the same subjects will contribute to a novel stratification paradigm of the heterogeneous ASD population based on quantitative gene expression and neurophysiological biomarkers. In addition, our protocol has the potential to indicate new therapeutic options, thus amending the current condition of absence of data and guidelines for the treatment of ASD with epilepsy. Full article
(This article belongs to the Special Issue Feature Papers in Human Genomics and Genetic Diseases 2023)
►▼ Show Figures

Figure 1

18 pages, 3505 KiB  
Article
Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer’s Disease
by Natalie A. Tan, Angelica M. Alvarado Carpio, H. Craig Heller and Elsa C. Pittaras
Genes 2024, 15(1), 47; https://doi.org/10.3390/genes15010047 - 28 Dec 2023
Cited by 2 | Viewed by 2102
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of brain function. TgSwDI is a well-studied transgenic mouse model of AD, but no longitudinal studies have been performed to characterize cognitive deficits or β-amyloid plaque accumulation for use as a baseline reference in future research. Thus, we use behavioral tests (T-Maze, Novel Object Recognition (NOR), Novel Object Location (NOL)) to study long-term and working memory, and immunostaining to study β-amyloid plaque deposits, as well as brain size, in hippocampal, cerebellum, and cortical slices in TgSwDI and wild-type (WT) mice at 3, 5, 8, and 12 months old. The behavioral results show that TgSwDI mice exhibit deficits in their long-term spatial memory starting at 8 months old and in long-term recognition memory at all ages, but no deficits in their working memory. Immunohistochemistry showed an exponential increase in β-amyloid plaque in the hippocampus and cortex of TgSwDI mice over time, whereas there was no significant accumulation of plaque in WT mice at any age. Staining showed a smaller hippocampus and cerebellum starting at 8 months old for the TgSwDI compared to WT mice. Our data show how TgSwDI mice differ from WT mice in their baseline levels of cognitive function and β-amyloid plaque load throughout their lives. Full article
(This article belongs to the Special Issue Genetics and Genomics of Aging and Dementia)
►▼ Show Figures

Figure 1

18 pages, 14236 KiB  
Article
Comparative Transcriptome Analysis of Gene Expression and Regulatory Characteristics Associated with Different Bolting Periods in Spinacia oleracea
by Hao Wu, Zhilong Zhang, Zhiyuan Liu, Qing Meng, Zhaosheng Xu, Helong Zhang, Wei Qian and Hongbing She
Genes 2024, 15(1), 36; https://doi.org/10.3390/genes15010036 - 26 Dec 2023
Cited by 1 | Viewed by 2014
Abstract
Bolting is a symbol of the transition from vegetative to reproductive growth in plants. Late bolting can effectively prolong the commercial value of spinach and is of great importance for spinach breeding. Bolting has complex regulatory networks, and current research on spinach bolting [...] Read more.
Bolting is a symbol of the transition from vegetative to reproductive growth in plants. Late bolting can effectively prolong the commercial value of spinach and is of great importance for spinach breeding. Bolting has complex regulatory networks, and current research on spinach bolting is relatively weak, with specific regulatory pathways and genes unclear. To clarify the regulatory characteristics and key genes related to bolting in spinach, we conducted a comparative transcriptome analysis. In this study, 18 samples from three periods of bolting-tolerant spinach material 12S3 and bolting-susceptible material 12S4 were analyzed using RNA-seq on, resulting in 10,693 differentially expressed genes (DEGs). Functional enrichment and co-expression trend analysis indicated that most DEGs were enriched in the photoperiod pathway, the hormone signaling pathway, and the cutin, suberin, and wax biosynthetic pathways. According to the weighted gene co-expression network analysis (WGCNA), SpFT (SOV4g003400), SOV4g040250, and SpGASA1 (SOV6g017600) were likely to regulate bolting through the gibberellin and photoperiod pathways, and SpELF4 (SOV1g028600) and SpPAT1 (SOV4g058860) caused differences in early and late bolting among different cultivars. These results provide important insights into the genetic control of bolting in spinach and will help elucidate the molecular mechanisms of bolting in leafy vegetables. Full article
(This article belongs to the Special Issue Vegetable Genetic Breeding)
►▼ Show Figures

Figure 1

24 pages, 1542 KiB  
Review
Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations
by Raafiah Izhar, Margherita Borriello, Antonella La Russa, Rossella Di Paola, Ananya De, Giovambattista Capasso, Diego Ingrosso, Alessandra F. Perna and Mariadelina Simeoni
Genes 2024, 15(1), 37; https://doi.org/10.3390/genes15010037 - 26 Dec 2023
Cited by 35 | Viewed by 6301
Abstract
Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs [...] Read more.
Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as “lyonization”, involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
►▼ Show Figures

Figure 1

16 pages, 4389 KiB  
Review
Unraveling the Epigenetic Tapestry: Decoding the Impact of Epigenetic Modifications in Hidradenitis Suppurativa Pathogenesis
by Elena Maria Nardacchione, Paola Maura Tricarico, Ronald Moura, Adamo Pio d’Adamo, Ayshath Thasneem, Muhammad Suleman, Angelo Valerio Marzano, Sergio Crovella and Chiara Moltrasio
Genes 2024, 15(1), 38; https://doi.org/10.3390/genes15010038 - 26 Dec 2023
Cited by 8 | Viewed by 2764
Abstract
Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, [...] Read more.
Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, severity, and clinical course of this disease, although the exact molecular mechanisms are still being explored. Epigenetics is currently emerging as an interesting field of investigation that could potentially shed light on the molecular intricacies underlying HS, but there is much still to uncover on the subject. The aim of this work is to provide an overview of the epigenetic landscape involved in HS. Specifically, in this in-depth review we provide a comprehensive overview of DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs (such as microRNA—miRNA-132, miRNA-200c, miRNA-30a-3p, miRNA-100-5b, miRNA-155-5p, miRNA-338-5p) dysregulation in HS patients. An interesting element of epigenetic regulation in HS is that the persistent inflammatory milieu observed in HS lesional skin could be exacerbated by an altered methylation profile and histone acetylation pattern associated with key inflammatory genes. Deepening our knowledge on the subject could enable the development of targeted epigenetic therapies to potentially restore normal gene expression patterns, and subsequentially ameliorate, or even reverse, the progression of the disease. By deciphering the epigenetic code governing HS, we strive to usher in a new era of personalized and effective interventions for this enigmatic dermatological condition. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

15 pages, 3680 KiB  
Article
Dynamic Expression Profile of Follicles at Different Stages in High- and Low-Production Laying Hens
by Lan Yang, Xuewei Fan, Kaiyuan Tian, Sensen Yan, Chunhong Xu, Yixiang Tian, Chengpeng Xiao, Xintao Jia, Junlai Shi, Ying Bai and Wenting Li
Genes 2024, 15(1), 40; https://doi.org/10.3390/genes15010040 - 26 Dec 2023
Cited by 9 | Viewed by 2369
Abstract
Improving the efficiency of hens and extending the egg-laying cycle require maintaining high egg production in the later stages. The ovarian follicles, as the primary functional units for ovarian development and oocyte maturation, play a crucial role in regulating the continuous ovulation of [...] Read more.
Improving the efficiency of hens and extending the egg-laying cycle require maintaining high egg production in the later stages. The ovarian follicles, as the primary functional units for ovarian development and oocyte maturation, play a crucial role in regulating the continuous ovulation of hens. The egg production rate of laying hens is mostly affected by proper follicle growth and ovulation in the ovaries. The objective of this study was to identify the key genes and signaling pathways involved in the development of ovarian follicles in Taihang hens through transcriptome screening. In this study, RNA sequencing was used to compare and analyze the transcriptomes of ovarian follicles at four developmental stages: small white follicles (SWF), small yellow follicles (SYF), F5 follicles, and F2 follicles, from two groups: the high continual production group (H-Group) and the low continual production group (L-Group). A total of 24 cDNA libraries were constructed, and significant differential expression of 96, 199, 591, and 314 mRNAs was detected in the SWF, SYF, F5, and F2 follicles of the H and L groups, respectively. Based on the results of GO and KEGG enrichment analyses, each stage of follicle growth possesses distinct molecular genetic features, which have important effects on follicle development and significantly promote the formation of continuous production traits through the biosynthesis of steroid hormones, cytokine–cytokine receptor interaction, and neuroactive ligand–receptor interaction. Additionally, through STEM analysis, we identified 59 DEGs, including ZP4, KCNH1, IGFs, HMGA2, and CDH1, potentially associated with follicular development within four significant modules. This study represents the first transcriptome investigation of follicles in hens with high and low egg-producing characteristics at four crucial developmental stages. These findings provide important molecular evidence for understanding the regulation of follicular development and its variations. Full article
(This article belongs to the Special Issue Poultry Breeding: Genetics and Genomics)
►▼ Show Figures

Figure 1

12 pages, 2629 KiB  
Review
Children with Rare Nager Syndrome—Literature Review, Clinical and Physiotherapeutic Management
by Bożena Anna Marszałek-Kruk, Andrzej Myśliwiec, Anna Lipowicz, Wojciech Wolański, Małgorzata Kulesa-Mrowiecka and Krzysztof Dowgierd
Genes 2024, 15(1), 29; https://doi.org/10.3390/genes15010029 - 24 Dec 2023
Cited by 2 | Viewed by 4230
Abstract
Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare [...] Read more.
Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the SF3B4 gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient’s lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient’s benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures. Full article
(This article belongs to the Special Issue Diagnosis of Rare Genetic Disorders)
►▼ Show Figures

Figure 1

14 pages, 2305 KiB  
Article
Rare Deletions or Large Duplications Contribute to Genetic Variation in Patients with Severe Tinnitus and Meniere Disease
by Alba Escalera-Balsera, Alberto M. Parra-Perez, Alvaro Gallego-Martinez, Lidia Frejo, Juan Martin-Lagos, Victoria Rivero de Jesus, Paz Pérez-Vázquez, Patricia Perez-Carpena and Jose A. Lopez-Escamez
Genes 2024, 15(1), 22; https://doi.org/10.3390/genes15010022 - 22 Dec 2023
Cited by 2 | Viewed by 2090
Abstract
Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare [...] Read more.
Meniere disease (MD) is a debilitating disorder of the inner ear defined by sensorineural hearing loss (SNHL) associated with episodes of vertigo and tinnitus. Severe tinnitus, which occurs in around 1% of patients, is a multiallelic disorder associated with a burden of rare missense single nucleotide variants in synaptic genes. Rare structural variants (SVs) may also contribute to MD and severe tinnitus. In this study, we analyzed exome sequencing data from 310 MD Spanish patients and selected 75 patients with severe tinnitus based on a Tinnitus Handicap Inventory (THI) score > 68. Three rare deletions were identified in two unrelated individuals overlapping the ERBB3 gene in the positions: NC_000012.12:g.56100028_56100172del, NC_000012.12:g.56100243_56101058del, and NC_000012.12:g.56101359_56101526del. Moreover, an ultra-rare large duplication was found covering the AP4M1, COPS6, MCM7, TAF6, MIR106B, MIR25, and MIR93 genes in another two patients in the NC_000007.14:g.100089053_100112257dup region. All the coding genes exhibited expression in brain and inner ear tissues. These results confirm the contribution of large SVs to severe tinnitus in MD and pinpoint new candidate genes to get a better molecular understanding of the disease. Full article
(This article belongs to the Special Issue Molecular and Genetic Diagnosis of Rare Diseases)
►▼ Show Figures

Graphical abstract

19 pages, 3241 KiB  
Article
A Missense Mutation in the Collagen Triple Helix of EDA Is Associated with X-Linked Recessive Hypohidrotic Ectodermal Dysplasia in Fleckvieh Cattle
by Sina Reinartz, Christine Weiß, Maike Heppelmann, Marion Hewicker-Trautwein, Maren Hellige, Laure Willen, Karsten Feige, Pascal Schneider and Ottmar Distl
Genes 2024, 15(1), 8; https://doi.org/10.3390/genes15010008 - 20 Dec 2023
Cited by 1 | Viewed by 1756
Abstract
Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive [...] Read more.
Mutations within the ectodysplasin A (EDA) gene have been associated with congenital hypotrichosis and anodontia (HAD/XHED) in humans, mice, dogs and cattle. We identified a three-generation family of Fleckvieh cattle with male calves exhibiting clinical and histopathological signs consistent with an X-linked recessive HAD (XHED). Whole genome and Sanger sequencing of cDNA showed a perfect association of the missense mutation g.85716041G>A (ss2019497443, rs1114816375) within the EDA gene with all three cases following an X-linked recessive inheritance, but normal EDAR and EDARADD. This mutation causes an exchange of glycine (G) with arginine (R) at amino acid position 227 (p.227G>R) in the second collagen triple helix repeat domain of EDA. The EDA variant was associated with a significant reduction and underdevelopment of hair follicles along with a reduced outgrowth of hairs, a complete loss of seromucous nasolabial and mucous tracheal and bronchial glands and a malformation of and reduction in number of teeth. Thermostability of EDA G227R was reduced, consistent with a relatively mild hair and tooth phenotype. However, incisors and canines were more severely affected in one of the calves, which correlated with the presence of a homozygous missense mutation of RNF111 (g.51306765T>G), a putative candidate gene possibly associated with tooth number in EDA-deficient Fleckvieh calves. Full article
(This article belongs to the Special Issue Genomic View of Cattle Breeding and Domestication)
►▼ Show Figures

Figure 1

16 pages, 5345 KiB  
Article
Whole-Transcriptome Sequencing of Ovary Reveals the ceRNA Regulation Network in Egg Production of Gaoyou Duck
by Lei Zhang, Rui Zhu, Guobo Sun, Jian Wang, Qisheng Zuo and Shanyuan Zhu
Genes 2024, 15(1), 9; https://doi.org/10.3390/genes15010009 - 20 Dec 2023
Cited by 2 | Viewed by 1906
Abstract
To investigate the regulatory mechanism of the competing endogenous RNAs (ceRNAs) on the egg performance of Gaoyou ducks, full transcriptome sequencing was performed to analyze the ovarian tissues in Gaoyou ducks. The ducks were categorized into high- and low-yield groups based on the [...] Read more.
To investigate the regulatory mechanism of the competing endogenous RNAs (ceRNAs) on the egg performance of Gaoyou ducks, full transcriptome sequencing was performed to analyze the ovarian tissues in Gaoyou ducks. The ducks were categorized into high- and low-yield groups based on the individual in-cage egg production records and the hematoxylin–eosin (HE) staining results. The differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) were further processed by GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. In total, 72 DEmRNAs; 23 DElncRNAs; 4 DEcircRNAs; and 5 signaling pathways, including the ovarian steroidogenesis, PI3K-Akt, hedgehog, tryptophan metabolism, and oocyte meiosis signaling pathways, were significantly enriched. These results suggest that they could be associated with the Gaoyou duck’s ovarian function and affect the total egg production or double-yolked egg production. Furthermore, a coregulation network based on the related candidate ceRNAs across the high- and low-yield egg production groups was constructed. Our findings provide new insights into the mechanisms underlying the molecular regulation of related circRNA/lncRNA–miRNA–mRNA in the egg production and double-yolked egg traits of Gaoyou ducks. Full article
(This article belongs to the Section Animal Genetics and Genomics)
►▼ Show Figures

Figure 1

19 pages, 1325 KiB  
Article
The Phylogenetic Relationship of Lamiinae (Coleoptera: Cerambycidae) Using Mitochondrial Genomes
by Ke Li, Sheng-Wu Yu, Hao Hu, Yu-Feng Feng, Kenneth B. Storey, Yue Ma, Jia-Yong Zhang and Dan-Na Yu
Genes 2024, 15(1), 13; https://doi.org/10.3390/genes15010013 - 20 Dec 2023
Cited by 8 | Viewed by 2231
Abstract
Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological [...] Read more.
Lamiinae is the largest subfamily of the Cerambycidae (longhorn beetles), with approximately 21,863 described species. Previous phylogenetic studies of Lamiinae showed that this subfamily was monophyletic, but the relationship between the tribes of Lamiinae is still controversial. Partial molecular data and species morphological characteristics are not sufficient to resolve species phylogenetic studies perfectly. At the same time, the full mitochondrial genome contains more comprehensive genetic data. Benefiting from the development of next-generation sequencing (NGS), mitochondrial genomes can be easily acquired and used as reliable molecular markers to investigate phylogenetic relationships within Cerambycidae. Using NGS technology, we obtained 11 mitochondrial genome sequences of Lamiinae species. Based on this newly generated mitochondrial genome dataset matrix, we reconstructed the phylogeny of Lamiinae. The Bayesian Inference and Maximum Likelihood analyses strongly support the monophyly of four tribes (Lamiini, Batocerini, Mesosini, and Saperdini), whereas the tribe Acanthocinini was identified as paraphyletic. Other mitochondrial structural features were also observed: the start codon in the nad1 gene of all 11 mitochondrial genomes is TTG; 17–22 bp intergenic spacers (IGS) with a ‘TACTA’ motif were found between trnS2 and nad1. Moreover, two long IGS were found in Mesosa myops and Batocera sp. Tandem repeats were found in the IGS of Batocera sp. Full article
(This article belongs to the Special Issue Molecular Evolution, Mitochondrial Genomics and Mitochondrial Genome Expression in Animals—2nd Edition)
►▼ Show Figures

Figure 1

10 pages, 2639 KiB  
Case Report
Novel Homozygous FA2H Variant Causing the Full Spectrum of Fatty Acid Hydroxylase-Associated Neurodegeneration (SPG35)
by Alexander German, Jelena Jukic, Andreas Laner, Philipp Arnold, Eileen Socher, Angelika Mennecke, Manuel A. Schmidt, Jürgen Winkler, Angela Abicht and Martin Regensburger
Genes 2024, 15(1), 14; https://doi.org/10.3390/genes15010014 - 20 Dec 2023
Cited by 5 | Viewed by 2213
Abstract
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, [...] Read more.
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity. Full article
(This article belongs to the Special Issue Human Developmental Disability, Neurogenetics and Rare Diseases: From Basic Science to Genetic Counseling)
►▼ Show Figures

Figure 1

23 pages, 2949 KiB  
Review
The Role of the AT-Rich Interaction Domain 1A Gene (ARID1A) in Human Carcinogenesis
by Jing Jing Li and Cheok Soon Lee
Genes 2024, 15(1), 5; https://doi.org/10.3390/genes15010005 - 19 Dec 2023
Cited by 7 | Viewed by 3308
Abstract
The switch/sucrose non-fermentable (SWI/SNF) (SWI/SNF) complex uses energy from ATP hydrolysis to mobilise nucleosomes on chromatin. Components of SWI/SNF are mutated in 20% of all human cancers, of which mutations in AT-rich binding domain protein 1A (ARID1A) are the most common. [...] Read more.
The switch/sucrose non-fermentable (SWI/SNF) (SWI/SNF) complex uses energy from ATP hydrolysis to mobilise nucleosomes on chromatin. Components of SWI/SNF are mutated in 20% of all human cancers, of which mutations in AT-rich binding domain protein 1A (ARID1A) are the most common. ARID1A is mutated in nearly half of ovarian clear cell carcinoma and around one-third of endometrial and ovarian carcinomas of the endometrioid type. This review will examine in detail the molecular functions of ARID1A, including its role in cell cycle control, enhancer regulation, and the prevention of telomerase activity. ARID1A has key roles in the maintenance of genomic integrity, including DNA double-stranded break repair, DNA decatenation, integrity of the cohesin complex, and reduction in replication stress, and is also involved in mismatch repair. The role of ARID1A loss in the pathogenesis of some of the most common human cancers is discussed, with a particular emphasis on gynaecological cancers. Finally, several promising synthetic lethal strategies, which exploit the specific vulnerabilities of ARID1A-deficient cancer cells, are briefly mentioned. Full article
(This article belongs to the Special Issue Cancer Systems Biology and Genomics)
►▼ Show Figures

Figure 1

16 pages, 4334 KiB  
Article
Integrated Metabolomic and Transcriptomic Analysis of Puerarin Biosynthesis in Pueraria montana var. thomsonii at Different Growth Stages
by Xinyi Hu, Ting Zhu, Xinyi Min, Jianing He, Cong Hou and Xia Liu
Genes 2023, 14(12), 2230; https://doi.org/10.3390/genes14122230 - 18 Dec 2023
Cited by 4 | Viewed by 2002
Abstract
Puerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the [...] Read more.
Puerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the accumulation of metabolites in the puerarin pathway are not detailed, and it is still controversial at the last step of the 8-C-glycosylation reaction. In this study, we conducted a comprehensive analysis of the metabolomic and transcriptomic changes in Pueraria montana var. thomsonii during two growing years, focusing on the vigorous growth and dormant stages, to elucidate the underlying mechanisms governing the changes in metabolite and gene expression within the puerarin biosynthesis pathway. In a comparison of the two growth stages in the two groups, puerarin and daidzin, the main downstream metabolites in the puerarin biosynthesis pathway, were found to accumulate mainly during the vigorous growth stage. We also identified 67 common differentially expressed genes in this pathway based on gene expression differences at different growth stages. Furthermore, we identified four candidate 8-C-GT genes that potentially contribute to the conversion of daidzein into puerarin and eight candidate 7-O-GT genes that may be involved in the conversion of daidzein into daidzin. A co-expression network analysis of important UGTs and HIDs along with daidzein and puerarin was conducted. Overall, our study contributes to the knowledge of puerarin biosynthesis and offers information about the stage at which the 8-C-glycosylation reaction occurs in biosynthesis. These findings provide valuable insights into the cultivation and quality enhancement of Pueraria montana var. thomsonii. Full article
(This article belongs to the Special Issue Medicinal Plant Research from an Omics Perspective)
►▼ Show Figures

Figure 1

15 pages, 4108 KiB  
Article
Transcriptome and Metabolome Analysis of Isoquinoline Alkaloid Biosynthesis of Coptis chinensis in Different Years
by Xinyi Min, Ting Zhu, Xinyi Hu, Cong Hou, Jianing He and Xia Liu
Genes 2023, 14(12), 2232; https://doi.org/10.3390/genes14122232 - 18 Dec 2023
Cited by 7 | Viewed by 2338
Abstract
Coptis chinensis is a perennial herb of the Ranunculaceae family. The isoquinoline alkaloid is the main active component of C. chinensis, mainly exists in its rhizomes and has high clinical application potential. The in vitro synthesis of isoquinoline alkaloids is difficult because [...] Read more.
Coptis chinensis is a perennial herb of the Ranunculaceae family. The isoquinoline alkaloid is the main active component of C. chinensis, mainly exists in its rhizomes and has high clinical application potential. The in vitro synthesis of isoquinoline alkaloids is difficult because their structures are complex; hence, plants are still the main source of them. In this study, two-year and four-year rhizomes of C. chinensis were selected to investigate the effect of growth years on the accumulation of isoquinoline alkaloids. Two-year and four-year C. chinensis were selected for metabolomics detection and transcriptomic analysis. A total of 413 alkaloids were detected by metabolomics analysis, of which 92 were isoquinoline alkaloids. (S)-reticuline was a significantly different accumulated metabolite of the isoquinoline alkaloids biosynthetic pathway in C. chinensis between the two groups. The results of transcriptome analysis showed that a total of 464 differential genes were identified, 36 of which were associated with the isoquinoline alkaloid biosynthesis pathway of C. chinensis. Among them, 18 genes were correlated with the content of important isoquinoline alkaloids. Overall, this study provided a comprehensive metabolomic and transcriptomic analysis of the rapid growth stage of C. chinensis rhizome from the perspective of growth years. It brought new insights into the biosynthetic pathway of isoquinoline alkaloids and provided information for utilizing biotechnology to improve their contents in C. chinensis. Full article
(This article belongs to the Special Issue Medicinal Plant Research from an Omics Perspective)
►▼ Show Figures

Figure 1

10 pages, 636 KiB  
Brief Report
Effects of Platelet Count on Blood Pressure: Evidence from Observational and Genetic Investigations
by Zhen He, Zekai Chen, Martin H. de Borst, Qingying Zhang, Harold Snieder, Chris H. L. Thio and on behalf of the International Consortium of Blood Pressure
Genes 2023, 14(12), 2233; https://doi.org/10.3390/genes14122233 - 18 Dec 2023
Cited by 4 | Viewed by 2799
Abstract
Platelet count has been associated with blood pressure, but whether this association reflects causality remains unclear. To strengthen the evidence, we conducted a traditional observational analysis in the Lifelines Cohort Study (n = 167,785), and performed bi-directional Mendelian randomization (MR) with summary [...] Read more.
Platelet count has been associated with blood pressure, but whether this association reflects causality remains unclear. To strengthen the evidence, we conducted a traditional observational analysis in the Lifelines Cohort Study (n = 167,785), and performed bi-directional Mendelian randomization (MR) with summary GWAS data from the UK Biobank (n = 350,475) and the International Consortium of Blood Pressure (ICBP) (n = 299,024). Observational analyses showed positive associations between platelet count and blood pressure (OR = 1.12 per SD, 95% CI: 1.10 to 1.14 for hypertension; B = 0.07, 95% CI: 0.07 to 0.08 for SBP; B = 0.07 per SD, 95% CI: 0.06 to 0.07 for DBP). In MR, a genetically predicted higher platelet count was associated with higher SBP (B = 0.02 per SD, 95% CI = 0.00 to 0.04) and DBP (B = 0.03 per SD, 95% CI = 0.01 to 0.05). IVW models and sensitivity analyses of the association between platelet count and DBP were consistent, but not all sensitivity analyses were statistically significant for the platelet count-SBP relation. Our findings indicate that platelet count has modest but significant effects on SBP and DBP, suggesting causality and providing further insight into the pathophysiology of hypertension. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

23 pages, 1791 KiB  
Article
Genome-Wide Association Study to Identify Possible Candidate Genes of Snap Bean Leaf and Pod Color
by Burcu Celebioglu, John P. Hart, Timothy Porch, Phillip Griffiths and James R. Myers
Genes 2023, 14(12), 2234; https://doi.org/10.3390/genes14122234 - 18 Dec 2023
Cited by 3 | Viewed by 2046
Abstract
Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral [...] Read more.
Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral nutrition because every nutrient deficiency and many diseases produce symptoms that affect color. In order to identify significant loci related to both leaf and pod color in a snap bean (Phaseolus vulgaris L.) diversity panel, a genome-wide association study (GWAS) was carried out. Leaf color in one and pod traits in multiple environments were characterized using a colorimeter. L*a*b* color data were recorded and used to calculate chroma (C*) and hue angle (H°). Leaves were evaluated at three positions (lower, middle, and upper) in the canopy and both pod exterior and interior colors were obtained. GWAS was conducted using two reference genomes that represent the Andean (G19833) and Middle American (5-593) domestication centers. Narrow sense heritabilities were calculated using the mixed linear model (MLM) method in genome association and prediction integrated tool (GAPIT), and significant single nucleotide polymorphisms (SNPs) for each color parameter were obtained using the Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) GWAS model with two principal components (PCAs). In comparison to pod color traits, narrow sense heritabilities of leaf traits were low and similar for both reference genomes. Generally, narrow sense heritability for all traits was highest in the lower, followed by middle, and then upper leaf positions. Heritability for both pod interior and exterior color traits was higher using the G19833 reference genome compared to 5-593 when evaluated by year and means across years. Forty-five significant SNPs associated with leaf traits and 872 associated with pods, totaling 917 significant SNPs were identified. Only one SNP was found in common for both leaf and pod traits on Pv03 in the 5-593 reference genome. One-hundred thirteen significant SNPs, 30 in leaves and 83 in pods had phenotypic variation explained (PVE) of 10% or greater. Fourteen SNPs (four from G19833 and ten from 5-593) with ≥10 PVE%, large SNP effect, and largest p-value for L* and H° pod exterior was identified on Pv01, Pv02, Pv03, and Pv08. More SNPs were associated with pod traits than with leaf traits. The pod interior did not exhibit colors produced by anthocyanins or flavonols which allowed the differentiation of potential candidate genes associated with chloroplast and photosynthetic activity compared to the pod exterior where candidate genes related to both flavonoids and photosynthesis affected color. Several SNPs were associated with known qualitative genes including the wax pod locus (y), persistent color (pc), purple pods (V), and two genes expressed in seeds but not previously reported to affect other plant tissues (B and J). An evaluation of significant SNPs within annotated genes found a number, within a 200 kb window, involved in both flavonoid and photosynthetic biosynthetic pathways. Full article
(This article belongs to the Topic Vegetable Breeding, Genetics and Genomics)
►▼ Show Figures

Figure 1

10 pages, 1216 KiB  
Article
Influence of Model Structures on Predictors of Protein Stability Changes from Single-Point Mutations
by Cesare Rollo, Corrado Pancotti, Giovanni Birolo, Ivan Rossi, Tiziana Sanavia and Piero Fariselli
Genes 2023, 14(12), 2228; https://doi.org/10.3390/genes14122228 - 17 Dec 2023
Cited by 2 | Viewed by 2254
Abstract
Missense variation in genomes can affect protein structure stability and, in turn, the cell physiology behavior. Predicting the impact of those variations is relevant, and the best-performing computational tools exploit the protein structure information. However, most of the current protein sequence variants are [...] Read more.
Missense variation in genomes can affect protein structure stability and, in turn, the cell physiology behavior. Predicting the impact of those variations is relevant, and the best-performing computational tools exploit the protein structure information. However, most of the current protein sequence variants are unresolved, and comparative or ab initio tools can provide a structure. Here, we evaluate the impact of model structures, compared to experimental structures, on the predictors of protein stability changes upon single-point mutations, where no significant changes are expected between the original and the mutated structures. We show that there are substantial differences among the computational tools. Methods that rely on coarse-grained representation are less sensitive to the underlying protein structures. In contrast, tools that exploit more detailed molecular representations are sensible to structures generated from comparative modeling, even on single-residue substitutions. Full article
(This article belongs to the Special Issue Feature Papers in Technologies and Resources for Genetics 2023)
►▼ Show Figures

Figure 1

26 pages, 3106 KiB  
Review
Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen
by Brian J. Harvey and Harry M. Harvey
Genes 2023, 14(12), 2225; https://doi.org/10.3390/genes14122225 - 16 Dec 2023
Cited by 11 | Viewed by 3674
Abstract
Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive [...] Read more.
Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear oestrogen signalling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of oestrogen in CRC through various genomic and nongenomic signalling pathways involving membrane and nuclear oestrogen receptors. Furthermore, we examine the interplay between oestrogen receptors and other signalling pathways, in particular the Wnt/β-catenin proliferative pathway and hypoxia in shaping biological sex differences and oestrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting oestrogen signalling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon. Full article
(This article belongs to the Special Issue Signaling Pathway of Cancer)
►▼ Show Figures

Graphical abstract

20 pages, 21419 KiB  
Article
Comparison of Single Cell Transcriptome Sequencing Methods: Of Mice and Men
by Bastian V. H. Hornung, Zakia Azmani, Alexander T. den Dekker, Edwin Oole, Zeliha Ozgur, Rutger W. W. Brouwer, Mirjam C. G. N. van den Hout and Wilfred F. J. van IJcken
Genes 2023, 14(12), 2226; https://doi.org/10.3390/genes14122226 - 16 Dec 2023
Cited by 5 | Viewed by 3443
Abstract
Single cell RNAseq has been a big leap in many areas of biology. Rather than investigating gene expression on a whole organism level, this technology enables scientists to get a detailed look at rare single cells or within their cell population of interest. [...] Read more.
Single cell RNAseq has been a big leap in many areas of biology. Rather than investigating gene expression on a whole organism level, this technology enables scientists to get a detailed look at rare single cells or within their cell population of interest. The field is growing, and many new methods appear each year. We compared methods utilized in our core facility: Smart-seq3, PlexWell, FLASH-seq, VASA-seq, SORT-seq, 10X, Evercode, and HIVE. We characterized the equipment requirements for each method. We evaluated the performances of these methods based on detected features, transcriptome diversity, mitochondrial RNA abundance and multiplets, among others and benchmarked them against bulk RNA sequencing. Here, we show that bulk transcriptome detects more unique transcripts than any single cell method. While most methods are comparable in many regards, FLASH-seq and VASA-seq yielded the best metrics, e.g., in number of features. If no equipment for automation is available or many cells are desired, then HIVE or 10X yield good results. In general, more recently developed methods perform better. This also leads to the conclusion that older methods should be phased out, and that the development of single cell RNAseq methods is still progressing considerably. Full article
(This article belongs to the Special Issue Computational Analysis of Single-Cell Transcriptome Data)
►▼ Show Figures

Figure 1

10 pages, 1205 KiB  
Article
Glycogen Storage Disease: Expert Opinion on Clinical Diagnosis Revisited after Molecular Testing
by Rafael de Marchi, Tatiele Nalin, Fernanda Sperb-Ludwig, Franciele Cabral Pinheiro, Ida Vanessa Doederlein Schwartz and Carlos Eduardo Steiner
Genes 2023, 14(12), 2219; https://doi.org/10.3390/genes14122219 - 15 Dec 2023
Cited by 2 | Viewed by 1959
Abstract
This study sought to analyze whether an accurate diagnosis of the type and subtype of hepatic Glycogen Storage Diseases (GSDs) could be performed based on general clinical and biochemical aspects via comparing the proposed diagnostic hypotheses with the molecular results. Twelve physicians with [...] Read more.
This study sought to analyze whether an accurate diagnosis of the type and subtype of hepatic Glycogen Storage Diseases (GSDs) could be performed based on general clinical and biochemical aspects via comparing the proposed diagnostic hypotheses with the molecular results. Twelve physicians with experience in hepatic GSDs reviewed 45 real cases comprising a standardized summary of clinical and laboratory data. There was no relation between the hit rate and the time since graduation, the time of experience in GSD, and the number of patients treated during their careers. The average assertiveness was 47%, with GSD Ia and Ib being the best-identified types, while no expert correctly identified GSD IXc. Underage investigation for later manifestations, incomplete clinical description, and complementary analysis, the overvaluation of a specific clinical finding (“false positive”) or the discarding of the diagnosis in the absence of it (“false negative”), as well as the lack of knowledge of the rarest GSD types, may have impacted the accuracy of the assessment. This study emphasized that characteristics considered as determinants in identifying the specific types or subtypes of GSD are not exclusive, thus becoming factors that may have induced the evaluators to misdiagnose. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
►▼ Show Figures

Figure 1

12 pages, 2481 KiB  
Article
Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds
by Jacklin Sedhom and Lee A. Solomon
Genes 2023, 14(12), 2221; https://doi.org/10.3390/genes14122221 - 15 Dec 2023
Cited by 2 | Viewed by 2258
Abstract
Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for [...] Read more.
Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites. We further revealed direct readout information shared among three evolutionarily related lambdoid phages: λ-phage, Enterobacteria phage VT2-Sakai, and Stx2 converting phage I, suggesting that the λ-CI protein could bind to the operator sites of these other phages. In this study, we show that λ-CI can indeed bind the other two phages’ cognate binding sites as predicted using our algorithm, validating the hypotheses from that paper. We go on to demonstrate the importance of specific hydrogen bond donors and acceptors that are maintained despite changes to the nucleobase itself, and another that has an important role in recognition and binding. This in vitro validation of our algorithm supports its use as a tool to predict alternative binding sites for DNA-binding proteins. Full article
(This article belongs to the Topic Bioinformatics and Intelligent Information Processing)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 601-650 on page 13 of 24.
Back to TopTop