Biochemical Genetics最新文献

The genetic basis of agronomic traits is critical for enhancing yield, quality, and disease resistance in tomato. In this study, genome-wide association study (GWAS) was performed on a diverse panel of 72 tomato accessions to identify genomic regions linked to 18 agronomic, processing, and disease resistance traits. Phenotypic data were collected over two growing seasons, and genotyping was conducted using genotyping-by-sequencing (GBS) on the Illumina platform. A total of 78,828 high-quality single nucleotide polymorphisms (SNPs) were identified, primarily located in intergenic (54.66%), upstream (15.46%), downstream (14.35%), intronic (10.73%), and exonic (2.90%) regions. After stringent filtering, 7751 SNPs were retained for GWAS, leading to the identification of 47 significant quantitative trait loci (QTLs) associated with 13 traits. Fruit length exhibited the highest number of QTLs (23), while chromosomes 1 and 4 contained the most QTLs (9 each). Several candidate genes were identified for key traits, including F-box protein CPR1-like and transcription factor bHLH162-like for fruit weight, F-box protein At5g49610 for fruit length, transcription factor TGA9 for fruit diameter, F-box protein CPR1-like and Beta-D-xylosidase 2 for fruit yield, Cinnamoyl-CoA reductase-like SNL6 and UDP-glucosyltransferase, as well as stress-induced protein KIN2-like and serine/threonine-protein kinase BLUS1 for ToLCV resistance. Population structure and phylogenetic analyses indicated variation among ancestral populations (K = 3). These findings provide valuable genomic resources and identify candidate genes for key traits, supporting genomics-driven breeding in tomato.

The SCN2A gene encodes the alpha subunit of a voltage-gated sodium channel which is necessary for creating and propagating action potentials in neurons. Impairment of the Na_v1.2 function is associated with neurodevelopmental disorders such as Developmental and Epileptic Encephalopathy, Self-limited Neonatal/Infantile Seizures, and Autism Spectrum Disorder. In this study, we used orthologous sequence comparisons, as well as disease associated variants to analyze their location in the structure of Na_v1.2, with the aim of understanding the impact of genetic variants in the structure of this protein at an evolutionary and clinical level. Our analyses reveal different spatial distribution of interspecific variation where different residues locate preferentially in the first cytoplasmic linker, while disease-associated variants tend to cluster in the voltage-sensing segments of the protein domains. Altogether, these discoveries point to structurally important segments in the Na_v1.2 structure that have been conserved through evolution due to their role in maintaining the function of the channel.

Cancer is the second leading cause of death in both developed and developing countries. In cancer cells, hemostasis is disrupted, a process that is maintained under normal conditions in healthy cells. Transcription factors that play a crucial role in preserving this hemostasis have been linked to cancer. In recent years, the involvement of proteins from the FOX transcription factor family in cancer development has been extensively studied, highlighting their potential relevance for therapeutic research. Although one of these proteins, Forkhead Box K2 (FOXK2), was identified in the early 1990s, its biological functions in cellular processes remain incompletely understood. Research has highlighted the roles of FOXK2 in critical molecular processes, including de novo nucleotide synthesis, the expression of metabolic-related enzymes, DNA mismatch repair, cell proliferation, differentiation, apoptosis, and autophagy. Furthermore, it has been shown that FOXK2 mediates the binding of transcription factors that do not directly interact with methylated DNA to methylated regions, and also influences the DNA methylation process. Studies investigating its role in cancer indicate that FOXK2 functions as an oncogenic in certain tissues while acting as a tumor suppressor in others. The role of FOXK2 is particularly controversial, especially in hormone-dependent diseases. In this review, the roles of FOXK2 in various cancer cell types were analysed. Additionally, Gene Ontology (GO) enrichment analyses of miRNAs targeting FOXK2 were conducted, highlighting aspects of FOXK2 that have yet to be explored. GO analysis revealed that miRNAs targeting FOXK2 are particularly involved in regulatory processes. In conclusion, FOXK2 may represent a potential therapeutic target in certain cancer types, although its context-dependent roles require further investigation.

Thoracic aortic aneurysms and dissection are pivotal cardiovascular conditions necessitating accurate diagnostics. DNA methylation, a crucial epigenetic mediator, is implicated in early disease biomarkers. Our analysis of GSE84274 and GSE202047 datasets pinpointed 498 DEGs with promoter DMPs and DMRs. Outliers were detected via DIvisive ANAlysis (DIANA) and Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) (P < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses emphasized vascular and TNF signaling. Utilizing the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) and GATA-Binding Protein 2 (GATA2) were identified as core differentially expressed genes (DEGs). Transcriptomic validation confirmed that promoter methylation modulates transcriptional activity (P < 0.05). Enzyme-Linked Immunosorbent Assay (ELISA) indicated heightened 5-mC levels in β-aminopropionitrile (BAPN)-challenged mice (P < 0.05), and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) confirmed the modulation of DNA Methyltransferase 3 Alpha (DNMT3A), DNMT3B, NR2F2, and GATA2. Methylation-Specific PCR (MSP) and Bisulfite Sequencing PCR (BSP) substantiated the hypermethylation of NR2F2 and GATA2 promoters in TAAD (P < 0.05). Our study correlates heightened promoter methylation of NR2F2 and GATA2 with TAAD, proposing them as novel diagnostic biomarkers.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a survival rate comparable to or worse than that of many cancers. Proper TGF-β signaling is essential for normal lung function, but its disruption plays a key role in pulmonary fibrosis and cancer progression. This study aims to elucidate the role of TGF-β signaling-related genes in the prognosis and treatment of IPF through multi-omics analysis. We obtained datasets from the GEO database and identified differentially expressed genes, followed by enrichment analyses. Core genes were identified using machine learning algorithms. Next, we evaluated the expression of core genes and their predictive ability for IPF, as well as their relationship with lung function and survival time. Then, mendelian randomization revealed core genes causally associated with IPF. Subsequently, pseudotime analysis, cell communication analysis and metabolic analysis were performed using single-cell data. Furthermore, we performed immune infiltration analysis to reveal the immune microenvironment of IPF. Finally, in vivo experiments validated the mRNA expression of the core genes. Two core genes (ACVRL1 and LTBP1) were identified through differential expression analysis and machine learning algorithms. Validation using multiple external datasets confirmed that these core genes exhibit stable expression patterns and have strong predictive ability for IPF patients. Further analysis revealed that the expression of these core genes correlates with lung function and survival time in IPF patients. Mendelian randomization analysis provided evidence of a causal link between ACVRL1 and IPF. Using eQTLGen data, our summary data-based mendelian randomization (SMR) analysis revealed a possible causal link between ACVRL1 and IPF. Similarly, using GTEx eQTL data, our SMR analysis revealed a potential causal link between ACVRL1 and IPF. Furthermore, single-cell data analysis highlighted differences in cell communication and metabolism between ACVRL1 + endothelial cell (EC) and ACVRL1-EC. Finally, RT-qPCR results support the potential role of core genes in IPF. This study provides new perspectives on the development of IPF and may help identify novel therapeutic targets. Further research may reveal how core genes influence cellular function and disease progression, providing novel insights into the intricate mechanisms underlying IPF.

Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by mutations in the arylsulfatase A (ARSA) gene. Few studies have assessed the spectrum of ARSA mutations among Iranian patients. Here, we report eight Iranian patients with clinical features of MLD. Whole exome sequencing led to identification of the underlying mutation in ARSA gene in these patients. Among identified mutations was the recurrent c.938G > C (p.R313P) mutation in exon 5 of this gene, showing its relatively high frequency among Iranians. The results of this study helps in design of population-specific panels for screening purposes in order to decrease the burden of MLD.

Acute myeloid leukemia (AML) with a normal karyotype (CN-AML) constitutes approximately 50% of all AML cases, presenting significant prognostic variability, and highlighting the urgent need for the identification of novel molecular biomarkers. In this study, we systematically assessed GPR183 expression levels using qRT-PCR in our clinical follow-up study which included 283 CN-AML patients. Using Kaplan-Meier analysis, we found that patients with high GPR183 expression levels exhibited significantly worse overall survival (OS) (P = 0.046) and event-free survival (EFS) (P = 0.030) compared to those with low GPR183 expression. Comprehensive univariate and multivariate Cox regression analyses confirmed that GPR183 expression is a prognostic factor for OS and EFS (P < 0.05). To further validate these findings, we analyzed an independent cohort of 104 CN-AML patients from the GSE71014 dataset, corroborating our primary results, and indicating that high GPR183 expression is associated with poorer survival outcomes. Additionally, RNA-seq data from the GSE71014 dataset were analyzed by Gene Set Enrichment Analysis (GSEA). The results suggested that GPR183 may influence disease progression through the activation of the "TNFa Signaling Via NF-κB" pathway. Collectively, these findings suggested that GPR183 could serve as a valuable prognostic biomarker in CN-AML, offering insights into the underlying mechanisms of disease progression.

To investigate the association of polymorphisms in the SOD2 (rs5746136, rs10370, and rs4880) and SOD3 (rs2855262, and rs13306703) genes and dental caries in primary dentition. This cross-sectional study included 753 children aged from 2 to 6 years in primary dentition from 33 public preschools in Nova Friburgo, Rio de Janeiro, Brazil. Covariates such as gender and body mass index were collected. Dental caries experience was evaluated using WHO (2013) criteria. Phenotypes were classified as absence (dmft = 0), presence (dmft ≥ 1) or high caries experience (dmft ≥ 5). Genotyping of the selected polymorphisms was carried out by TaqMan real-time PCR using genomic DNA extracted from buccal cells. Allele and genotype frequencies in recessive, co-dominant and dominant models were compared between phenotype groups. Covariates did not influence on caries experience in any phenotype analyzed. The allele C in rs2855262 (SOD3) presented association with high dental caries experience (dmft ≥ 5) (p = 0.04). The polymorphisms rs5746136 (SOD2) and rs2855262 (SOD3) presented association with caries experience (respectively, dmft ≥ 1 and dmft ≥ 5) in recessive models (p = 0.02). The findings suggest that polymorphisms in SOD2 (rs5746136) and SOD3 (rs2855262) genes are associated with dental caries experience in children with primary dentition. The cross-sectional study design presents known limitations, such as the inability to establish causal relationships. Therefore, the findings of this study should be interpreted with caution, and further is needed to confirm the results and investigate the function of these genes function and their involvement in dental caries and other oral conditions. Altered salivary oxidative stress biomarkers, influenced by genetic variations, play a significant role in the development of dental caries. It emphasizes the importance of genetic screening in oral health assessments. Understanding the SOD2 and SOD3 polymorphisms, could pave the way for personalized preventive strategies and targeted therapeutic interventions in pediatric dentistry.