Comprehensive Analysis Of Genes Research Articles

Neuromuscular genetic disorders (NMGDs) are genetically and clinically diverse group of inherited diseases that affect approximately 1 in 1,000 people worldwide with a calculated prevalence of 37 per 10,000 in the general population. These disorders arise from a variety of genetic changes such as insertions, deletions, duplications and expansions of repeats in more than 747 nuclear and mitochondrial genes critical for the function of peripheral nerves, motor neurons, neuromuscular junctions or skeletal muscles, leading to progressive weakness and degeneration of muscles. Major subtypes include muscular dystrophies, congenital myopathies, motor neuron diseases, peripheral neuropathies, and mitochondrial myopathies. Clinical presentation of NMGDs is highly variable in the age of onset, severity and pattern of muscle involvement, often leading to prolonged and complex diagnostic process. Conventional diagnostic methods have relied on clinical history, physical examination and invasive procedures like muscle biopsy. But the development of next-generation sequencing (NGS) has transformed diagnostics by enabling comprehensive analysis of NMGD-related genes. Despite this advancement, interpreting the numerous variants identified by NGS remains challenging. The guidelines of the American College of Medical Genetics and Genomics (ACMG) offer a standardized approach to variant classification as pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign. However, this requires the integration of complex evidence from population data, computational predictions, and functional assays. The major challenge is the robust correlation of genotypic information with the huge phenotypic range of NMGDs which is a task complicated by the unavailability of population-specific genetic databases. To address these issues, we have developed NMPhenogen ( https://gi-lab-tigs.github.io/Homepage/ ), a new database designed to enhance the diagnosis and understanding of NMGDs. NMPhenogen is a centralized repository for data related to NMGD-associated genes and variants along with their clinical presentations. It includes two primary modules: NMPhenoscore, which enhances disease-phenotype correlations, and a Variant classifier, which facilitates standardized variant classification based on published guidelines. This combined resource aims to streamline the diagnostic process, support clinical decision-making, and eventually contribute to improving patient care and genetic counseling.

Lysozyme genes in bivalves: Evolutionary insights and functional roles in host defense against Vibrio infections.

Comprehensive analysis of colony-stimulating factor genes and immunostimulatory effects of CSF3a in rainbow trout (Oncorhynchus mykiss).

Background/Objectives: γ-aminobutyric acid (GABA), a non-protein amino, is synthesized from glutamic acid through the catalytic activity of glutamate decarboxylase (GAD). As a key signaling molecule, GABA plays a vital role in plant responses to abiotic stresses. To explore the potential involvement of the GABA gene family in Juglans regia’s response to environmental stressors, a comprehensive genome-wide identification and analysis of GABA-related genes was performed. Methods: The study examined their protein features, evolutionary relationships, chromosomal locations, and promoter cis-regulatory elements. Additionally, the expression patterns of GABA family genes were analyzed in J. regia seedlings subjected to salt and drought stress. Results: Genome analysis identified three main components of the GABA metabolic pathway in J. regia: glutamate decarboxylases (GADs), GABA transaminases (GABA-Ts), and succinic semialdehyde dehydrogenases (SSADHs). These genes were unevenly distributed across 14 chromosomes, with chromosome 10 containing the highest number. Promoter analysis revealed that about 80% of cis-acting elements were linked to plant hormone regulation, such as abscisic acid (ABA), and stress responses, including drought and high-salinity. Phylogenetic analysis showed that JrGAD1 was distantly related to other JrGAD members, while certain JrGABA-T and JrSSADH genes formed closely related pairs. Under salt and drought stress, JrSSADH23 expression was highly upregulated (2.60-fold and 2.24-fold, respectively), a trend observed for most JrSSADH genes. Conclusions: These findings offer valuable insights into the molecular basis of GABA metabolism in J. regia’s stress adaptation and identify promising genetic targets for developing stress-tolerant varieties.

Comprehensive analysis of mitochondria-associated genes in glioblastoma via single-cell and bulk RNA sequencing

BackgroundDiabetic cardiomyopathy (DCM) represents a distinct myocardial pathology arising from chronic diabetic metabolic disturbances, characterized by progressive structural and functional abnormalities that frequently culminate in heart failure. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, studies are limited on the clinical significance of cuproptosis-related genes (CRGs) in DCM. Therefore, it is helpful to identify CRGs involved in DCM and explore their expression and molecular mechanisms.MethodsWe downloaded three datasets of DCM from the GEO database and a set of cuproptosis-related genes with 176 genes. Following the identification of the differentially expressed cuproptosis-related genes(DECRGs) and hub genes, we performed the functional annotation, protein-protein interaction network, co-expression network analysis, mRNA-miRNA regulatory network.The GSE5606 dataset was then used to verify hub genes. Finally, we validated the expression of hub genes in a high glucose-induced H9C2 cell injury model via RT-qPCR.ResultsWe identified 14 DEFRGs and 7 key genes in the DCM samples compared to the control. Functional enrichment analysis revealed that DECRGs are associated with several pathways, including TCA cycle, respiratory electron transport, oxidative stress, and metabolism pathway. Moreover, Isocitrate dehydrogenase 1(Idh1), Cytochrome P450 Family 1 Subfamily A Member 1(Cyp1a1), 3-Hydroxy-3-Methylglutaryl-CoA Synthase (Hmgcs2) and Hexokinase 2(Hk2) were identified as the hub genes and validated in the GSE5606 datasets with area under the curve(AUC)>0.7. The qRT-PCR results showed that the expression levels of Cyp1a1, Hmgcs2, HK2, and Idh1 in vitro model of DCM and controls were consistent with the bioinformatics analysis results from the mRNA microarray.ConclusionsOverall,we identified hub genes and pathways involved in DCM via bioinformatics analysis and revealed the potential role of cuproptosis, providing useful and novel information to explore the potential candidate genes for DCM diagnostic and therapeutic options.

Disclosure: I. Yamauchi: None. S. Kimura: None. T. Sugawa: None. T. Hakata: None. D. Kosugi: None. K. Okamoto: None. Y. Ueda: None. D. Taura: None. D. Nakajima: None. T. Kubo: None. D. Yabe: None.Objective: Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with normal hormonal functions. The disruption of thyroid hormone (TH) actions by EDCs is gaining attention, as TH activity has been detected in environmental water across multiple countries. This study aims to develop a mouse model to elucidate the mechanisms by which EDCs disrupt TH function. Methods: We administered 3,3',5-triiodo-L-thyronine (LT3) via drinking water to C57BL/6J mice treated with 6-propyl-2-thiouracil (PTU) to induce hypothyroidism and euthyroid controls. TH actions were assessed using growth curves and TH-responsive gene expression profiles. Additionally, we visualized alterations in the hypothalamus-pituitary-thyroid (HPT) axis, including thyroid gland enlargement and follicular dysmorphology, confirmed by thyroid function tests. Results: Euthyroid mice received 0.1 µg/mL or 1 µg/mL of LT3 for 4 weeks. However, only slight phenotypic changes were observed. To enhance sensitivity, hypothyroid mice treated with PTU for 4 weeks were used. Co-administration of 0.1 µg/mL LT3 significantly restored growth retardation, alterations in the HPT axis, and changes in TH-responsive gene expressions. Detailed analyses in these hypothyroid mice enabled us to evaluate TH actions across various organs. Further improvements to the model included the use of sodium iodide combined with PTU for 1 or 2 weeks, which reduced the hypothyroidism induction period. As a result, PTU monotreatment for 2 weeks was sufficient to induce hypothyroidism and significant phenotypic changes. To identify more sensitive TH-responsive genes, RNA sequencing was conducted on the liver, heart, cerebrum, and gastrocnemius muscle of hypothyroid mice generated by PTU monotreatment for 2 weeks. Conclusions: We established a robust in vivo model to evaluate TH actions. This model has provided valuable insights into the endocrine-disrupting potential of 3,3',5-triiodothyroacetic acid (TRIAC). Our previous study identified its disruptive mechanism as cooperation of depletion of circulating endogenous THs via negative feedback and heterogenous distribution of TRIAC among different organs (iScience. 2023; 26: 107135). The improved model and comprehensive analysis of TH-responsive genes offer a promising approach for further research into the effects of EDCs on TH action.Presentation: Saturday, July 12, 2025

BackgroundGlutathione homeostasis, crucial for plant growth and stress adaptation, is regulated by the enzyme γ-glutamylcyclotransferase (GGCT). As the critical component of the glutathione recycling pathway, GGCT plays a vital role in maintaining cellular redox balance under normal and stressful conditions. While the GGCT gene family has been characterized in Arabidopsis thaliana, its diversity, evolution, and functional roles remain unexplored in the U’s triangle Brassica species, which includes important oilseed crops.ResultsWe identified and characterized 154 putative GGCT genes in U’s triangle Brassica species (Brassica nigra, 20; Brassica oleracea, 21; Brassica rapa, 18; Brassica juncea, 35; Brassica napus, 31; Brassica carinata, 29). Phylogenetic analysis grouped these GGCTs into three distinct clades, highlighting their structural and motif diversity. The diversity in cis-regulatory elements highlighted their role in growth and stress responses. Expression profiling of BnaGGCT genes revealed their differential expression patterns across the tissues at different developmental stages, such as BnaGGCT11 and BnaGGCT26, which are specifically expressed during late seed development phases. Furthermore, gene expression analysis under hormones and abiotic stresses indicated their contribution in stress responses as confirmed by eight selected BnaGGCT genes under drought and salt stresses. In addition, SNP analysis of BnaGGCT11 revealed a single-nucleotide variant that is significantly associated with seed weight and yield, potentially influencing gene function or translation efficiency.ConclusionCollectively, this study comprehensively identified GGCTs that enhance our understanding of the functional evolution of the GGCT gene family in U’s triangle Brassica species and lay the groundwork for further research into GGCT-mediated stress responses and seed development. In particular, the seed-specific expression of BnaGGCT11/26 and the SNP in BnaGGCT11 associated with seed weight and yield highlight their potential as candidates for marker-assisted breeding, but future functional validation will be required to substantiate their roles.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12870-025-07422-9.

Comprehensive analysis of MCTP genes in potato reveals StMCTP9 as a critical regulator of tuber development.

Lectins are a diverse class of proteins that play crucial roles in plant defense, stress responses, and various physiological processes. However, comprehensive comparative analyses of lectin gene families across closely related Phaseolus species are lacking, and the evolutionary and stress-responsive dynamics of these genes remain poorly understood. This study provides a comprehensive genome-wide analysis of lectin genes in three Phaseolus species: P. vulgaris, P. lunatus, and P. acutifolius. Using genomic data from the Phytozome database, we identified 132, 132, and 134 putative lectin genes, respectively, across 8 lectin families, with the legume, GNA, and Nictaba families being the most abundant. Domain architecture analysis revealed a broad structural spectrum, from simple merolectins to complex chimerolectins with multiple domains. Expansion analysis indicated that lectin family expansion primarily occurred through tandem and dispersed duplications with similar syntenic profiles across the Phaseolus species. Codon-based evolutionary models revealed that while most lectin genes are purifying selection, several duplicated pairs from specific families (i.e., legume, Pl-Nictaba, and Pa-Hevein) show site-specific and episodic positive selection, suggesting adaptive divergence linked to functional specialization. Expression profiling under abiotic (salinity, cold) and biotic (bacterial, fungal, insect) stress conditions revealed differential regulation of lectin genes, with multiple genes (14) exhibiting pleiotropic effects through upregulation under several stresses. Regulatory analysis identified transcription factors from AP2, B3, Dof, ERF, MYB, and TCP families as potential upstream regulators of these pleiotropic genes, forming complex cis-regulatory networks integrating environmental and developmental signals. This study provides novel insights into the structural diversity, evolutionary dynamics, and stress-responsive roles of lectins in Phaseolus species and identifies promising targets for improving stress resilience in legume crops.

BackgroundBladder cancer, a highly aggressive malignancy, necessitates effective therapeutic strategies due to the significant correlation between muscle invasion and prognosis. Despite advancements in immunotherapy, the mechanisms through which immune-related genes influence bladder cancer remain unclear.MethodsWe conducted a comprehensive causal analysis of immune-related genes using GWAS data from the UK Biobank and FinnGen, and immune gene information from InnateDB. Mendelian Randomization (MR) analysis, supported by sensitivity, colocalization, and reverse causality analyses, was performed using eQTLGen Consortium and proteomics GWAS data. We analyzed protein-protein interaction networks with GeneMANIA and validated findings using mRNA expression and clinical survival data from the TCGA database.ResultsThe expression of the GSTM1 gene demonstrated an inverse correlation with cancer risk, suggesting a protective role in disease progression. Our study also identified OLFM4, NTN1, ITPR3, CLU, and CARD11 as genes significantly associated with immune cell composition and bladder cancer survival. Additionally, we uncovered protein interaction networks and key pathways involving these immune-related genes, providing new insights into bladder cancer intervention and treatment.ConclusionThis study elucidates the immune-related pathways influencing bladder cancer, highlighting GSTM1 and other key immune-related genes as potential biomarkers. These discoveries pave the way for innovative therapeutic approaches, advancing personalized medicine strategies in bladder cancer treatment.

Miscanthus, a perennial grass, is renowned for its remarkable tolerance to abiotic stress. Excessive levels of drought severely impair plant growth and yield. Plant nuclear factor Y (NF-Y) transcription factors (TFs) play pivotal roles in regulating responses to drought stress in species such as Arabidopsis and maize. However, their functional roles in conferring drought tolerance in Miscanthus remain largely unexplored. This study’s genome-wide analysis and gene expression profiling of Miscanthus under dehydration/osmotic stress identified a transcription factors gene, MsNF-YA4, which was significantly upregulated under dehydration/osmotic stress. MsNF-YA4 overexpression in Arabidopsis significantly enhanced drought tolerance, leading to increased transcription of stress- and antioxidant enzyme-related genes. Compared with the wild type (WT), the transgenic lines exhibited markedly higher relative water content (RWC), chlorophyll content, proline level, and antioxidant enzyme activity. Furthermore, the MsNF-YA4/MsNF-YB3/MsNF-YC2 improved the transactivation of the Miscanthus P5CS1, SOD (Cu/Zn) and CAT1 promoters in the transient system. These results offer fresh perspectives on the role of Miscanthus NF-YAs in drought tolerance and offer promising genetic resources for developing drought-tolerant crops through breeding programs.

Fusarium wilt, caused by Fusarium oxysporum f. sp. phaseoli (Fop), is a major constraint to global common bean (Phaseolus vulgaris L.) production. Thiamine (vitamin B1), an essential coenzyme in plant metabolism, has recently emerged as a potential regulatory factor in plant defense. Here, we performed a comprehensive genome-wide analysis of thiamine biosynthesis-related genes in common bean and elucidated their roles in resistance to Fusarium wilt. Five key thiamine biosynthetic genes were identified and characterized, showing conserved functional domains and evolutionary conservation across species. Expression profiling revealed tissue-specific patterns, with PvTHI1-1 and PvTHIC being highly expressed in reproductive and photosynthetic organs, with their relative expression levels 0.28-0.57 higher than other members in the same tissue, while PvTPK maintained a basal expression level in the roots. Upon Fop infection, resistant genotypes exhibited significantly higher expression of thiamine biosynthetic genes and greater accumulation of endogenous thiamine and its derivatives than susceptible ones. Functional analysis using Agrobacterium rhizogenes-mediated transformation demonstrated that overexpression of PvTPK enhanced thiamine metabolism and conferred resistance in susceptible genotypes. Similarly, exogenous application of thiamine upregulated biosynthetic genes and improved disease resistance. Together, these results reveal that thiamine biosynthesis is intricately linked to Fusarium wilt resistance and that both genetic and biochemical manipulation of thiamine pathways can enhance disease tolerance. This study provides new insights into thiamine-mediated plant immunity and establishes a foundation for its application in the control of Fusarium wilt in common bean.

Comprehensive analysis of SDH genes in Populus and functional characterization of SDH4 in xylem and cambium development

Abstract Background Advances in next-generation sequencing (NGS) have significantly enhanced clinical diagnostics by enabling comprehensive analysis of genes associated with various inherited disorders. This study aimed to transfer a previously validated sequencing workflow—originally executed on the NextSeq-500 (Illumina, Inc.)—to the DNBSEQ-G400 platform (MGI Tech Co.). The workflow targets a panel of 4,700 genes with well-established gene-disease associations that span a broad range of clinical phenotypes. Our primary objectives were to evaluate the performance of the DNBSEQ-G400 in terms of data yield, quality, and variant calling accuracy, and to assess its concordance with variants (SNVs and INDELs) detected on the NextSeq-500. Methods An NGS library representing 12 patients—whose saliva-derived DNA was prepared using the xGEN DNA Library Prep kit and enriched with the xGen Inherited Disease Panel V1 (covering 4,700 genes) and Hybridization Capture kit (all from Integrated DNA Technologies, Inc.)—was initially sequenced on the NextSeq-500 platform (paired-end 150-cycle runs) and also on the DNBSEQ-G400 platform (paired-end 300-cycle runs). For the DNBSEQ-G400, an additional step was required: the libraries were processed with the DNBSEQ™ OneStep DNB Make Reagent Kit V4.0 to convert the linear DNA into DNA nanoballs. Data processing, including sequence alignment and variant calling, was performed using the Dragen v.4.2.4 pipeline on the EMEDGENE platform (Illumina, Inc.). For each sample, key performance metrics for the DNBSEQ-G400 were computed—namely, the percentage of bases with a quality score > Q30, total read counts, percentage of mapped reads, average coverage depth, percentage of bases with coverage >20X, and duplication rate. In addition, the study compared the number of single nucleotide variants (SNVs) and insertion/deletion events (INDELs) and calculated the F-measure—a metric integrating precision and recall—between the DNBSEQ-G400 and the NextSeq-500 platforms. Data are presented as medians with the corresponding minimum and maximum ranges. Results The DNBSEQ-G400 generated a median of 54,143,871 reads per sample (range: 31,912,278–72,109,870). A median of 93.06% of bases exceeded a Q30 score (range: 93.03%–93.22%), and 99.1% of reads mapped to the human reference genome (range: 98.02%–99.32%). The median average coverage was 397X (range: 230X–537X), the median percentage of bases with coverage >20X was 99.7% (range: 99.60%–99.80%), and the median duplication rate was 13.52% (range: 12.37%–15.09%). Variant calling identified a median of 7,709 SNVs (range: 7,437–8,028) and 344 INDELs (range: 329–367) per sample. The comparative F-measure was 99% for SNVs (range: 98.5%–99.5%) and 82.3% for INDELs (range: 79.3%–84.6%). Conclusion The results suggest that the workflow can be migrated from the NextSeq-500 to the MGI DNBSEQ-G400 platform. The DNBSEQ-G400 generated high-quality NGS data, as evidenced by robust base quality (median 93.06% of bases > Q30), high mapping rates (median 99.1%), and strong SNV detection (F-measure of 99%). Although the F-measure for INDELs was 82.3%, this is expected given the inherent challenges in indel detection. A limitation of this study is the difference in sequencing cycle numbers (paired-end 150-cycle vs. 300-cycle runs), which may affect direct comparisons. These findings support the adoption of the DNBSEQ-G400 platform in clinical settings.

Comprehensive analysis of calcium-dependent protein kinase genes reveals the potential role of PeCDPK32 in lignin biosynthesis of Phyllostachys edulis

Complement system evolution in Sciaenidae: Insights from c3 and cfh genes.

Comprehensive analysis of MAPK cascade genes in mollusks and their expression patterns in noble scallop Chlamys nobilis under low temperature stress

In the agriculture sector, insects and pests are major constraints to increased global food production. With the advancement in genetic engineering, transgenic crops expressing insecticidal proteins are increasingly prevalent in agriculture having the advantages of being eco-friendly over the non-conventional, synthetic insecticides and pesticides, yet concerns persist regarding their safety, particularly on non-target organisms which necessitate to address thorough investigation before widespread commercialization. The current study was aimed to evaluate the toxicity of Vip3Aa86-expressing transgenic maize in Wistar rats. The presence of Vip3Aa86 gene in maize plants was confirmed through PCR and protein quantification was done through ELISA. Comprehensive histopathological examination, blood chemistry, serum chemistry, urine chemistry and molecular analysis of apoptosis and immunity-related genes were done to evaluate any adverse effects on rats. Results indicated no significant differences in growth, organ weights, hematology, serum, urine chemistry, and gene expression analysis between rats fed with transgenic maize diets and control except for a few variations. PCR amplification of DNA isolated from rats' blood and vital organs did not show transgene amplification in any group. These findings conclude that the consumption of transgenic maize expressing the Vip3Aa86 gene does not pose immediate hazards to rat health under the conditions tested, supporting its regularity approval for commercial use.

Terpene synthases (TPS) facilitate terpenoid production, influencing the flavor, color, and medicinal properties of Crocus sativus (saffron), a triploid geophyte of significant commercial importance. Despite its importance, the CsTPS gene family remains poorly characterized, limiting genetic enhancements in saffron's agronomic features. This research performed a comprehensive genome-wide analysis of CsTPS genes using genomic, transcriptomic, and in silico approaches. BLASTP and PfamScan discovered thirty CsTPS genes, demonstrating conserved TPS domains, varied exon-intron architectures, and chromosomal clustering indicative of tandem duplications. Phylogenetic research categorized these genes into five subfamilies (TPS-a to TPS-e), with the prevalence of TPS-a suggesting a role in sesquiterpene biosynthesis. RNA-seq data (PRJNA976833, PRJNA400472) revealed tissue-specific expression, with CsTPS1 and CsTPS5 expressed in reproductive tissues and CsTPS2 in vegetative tissues. Stress-responsive genes (CsTPS1, CsTPS4) exhibited upregulation in response to cold and pathogen stress, with cis-regulatory elements (e.g., ARE, ABRE) indicating hormone control. The in-silico validation of CsTPS1, chosen for its elevated GMQE score (0.89), included primer design, ePCR, and vector optimization for expression in Arabidopsis thaliana. This study elucidates the contribution of the CsTPS family to saffron terpenoid diversity, providing a foundation for enhancing flavor, yield, and stress tolerance through genetic engineering.