BMC Medical Genomics最新文献

Background: Chromosomal structural variations (CSVs) that comprise multiple gene mutations are important determinants for multiple diseases. However, the relationship between CSVs, rheumatoid arthritis (RA), and lung cancer is not well understood.

Materials and methods: In this study, we analyzed CSV associations and differences between RA and RA with lung cancer (RA LC) using genome sequencing, with RA-associated interstitial lung disease (RA ILD) as a disease control. First, we analyzed the CSVs of each individual. Then, we identified common CSVs within each disease group and finally analyzed specific CSVs between different diseases. Gene Ontology/KEGG terms, canonical pathways, and feature gene sets were used for the functional annotation and analysis of CSV-related pathways.

Results: Cell size regulation and axon guidance were mutated in all disease groups. Protein deubiquitination was mutated in RA LC, while the negative regulation of extractable stroma and protein catabolism was mutated in RA ILD. Characterization of clinical data also revealed correlations with these specific pathways.

Conclusion: This study identifies common and specific CSVs and associated pathways for RA, LC, and ILD, uncovering key genetic factors that provide new insights into their diagnosis and treatment.

Background: Prostate cancer (PCa) is a prevalent and often aggressive malignancy. While ribosome production is a critical process in numerous cancers, the role of ribosome biogenesis-related genes (RB-RGs) in PCa remains underexplored. Therefore, this study aims to examine the expression characteristics of RB-RGs as potential prognostic markers in PCa.

Methods: Transcriptomic data were obtained from public databases to pinpoint differentially expressed genes (DEGs) associated with PCa. Among these, DEGs that were also identified as regulatory genes were selected as candidate genes and subjected to regression analysis to determine those with prognostic significance. A prognostic risk model was then created and subjected to validation. A standalone prognostic evaluation was performed. Additionally, analyses for enrichment, immune infiltration, and drug prediction were conducted for both high- and low-risk PCa cohorts. Finally, the levels of the prognostic genes were validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western Blot (WB).

Results: SMARCA4, FBLL1, RRS1, and NVL were selected as prognostic genes. A risk model, exhibited considerable precision in evaluating the risk of PCa. The risk score, in conjunction with the prostate-specific antigen (PSA) score and Gleason score, has been recognized as independent prognostic factors for PCa. Analysis of biological pathways indicated notable variations in pathways, especially the cell cycle, when comparing the high- and low-risk groups. The expression of prognostic genes demonstrated a correlation with the presence of 21 distinct types of immune cells, notably including type-17 T helper cells, within PCa samples. Furthermore, notable variations in the levels of target genes (AKT1, CDK1, HIF1A, NFKB1, SRC, and TRIM24) were detected between the high- and low-risk cohorts in relation to different chemotherapeutic agents. PCR analysis showed that NVL and SMARCA4 were significantly upregulated in PCa samples (p < 0.05), with no significant difference in RRS 1. WB analysis showed that SMARCA4, FBLL 1, and RRS1 and NVL were differently expressed in both PCa and Control, with higher upregulation in PCa than in the control group.

Conclusion: Among RB-RGs, SMARCA4, FBLL1, RRS1 and NVL were identified as prognostic genes for PCa, thereby providing a new direction for clinical disease treatment.

Background: β-Thalassemia is a hereditary blood disorder with a highly variable clinical presentation that is partly influenced by genetic modifiers that regulate fetal hemoglobin levels. Elevated HbF can ameliorate the clinical symptoms of β-thalassemia, making the identification of HbF-modifying loci crucial for understanding disease variability and developing potential therapeutic strategies.

Methods: In this study, we evaluated the distribution and effect of known HbF-associated single nucleotide polymorphisms within the BCL11A, HMIP, and XmnI-HBG2 loci in β-thalassemia patients. Our investigation was initiated by a hypothesis based on genomic data from the K562 cell line, which indicated the presence of a specific LRF/ZBTB7A variant. In addition, we explored the role of LRF/ZBTB7A, a transcription factor implicated in globin gene regulation, through Sanger sequencing and in silico analyses. A hypothetical Genetic Modifier Score was devised to quantify the cumulative effect of the five major HbF-associated QTLs.

Results: While we confirmed the previously reported associations of the common SNPs with HbF levels, we also identified novel rare variants in LRF/ZBTB7A (p.Pro241Leu, p.Asp344Asp, p.Glu277del) that may influence HbF expression. XmnI-HBG2 accounted for a small yet significant proportion (7%) of HbF variability. A significant positive correlation was found between the Genetic Modifier Score and HbF levels, yet the model explained only ~ 14% of the variance, highlighting a substantial role for other modifiers such as the novel LRF/ZBTB7A variants identified here.

Conclusions: These results suggest LRF/ZBTB7A is a novel modifier of HbF. The discovery of the variants, against a backdrop of modest QTL effects, underscores its potential and warrants further functional investigation.

Background: Malaria remains a significant public health challenge in Nigeria, accounting for a substantial proportion of global malaria cases and deaths. Although artemisinin-based combination therapies (ACTs) are the recommended first-line treatments, resistance to antimalarial drugs continues to threaten malaria control efforts. This systematic review provides an overview of the molecular surveillance of antimalarial drug resistance in Nigeria, aiming to identify prevalent resistance markers and inform future research and policy directions.

Methods: A systematic search was conducted using databases including PubMed, ScienceDirect, Ovid and Scopus. Studies published from 2010 to 2024 and focused on key resistance markers such as Pfcrt, Pfmdr, Pfdhfr, Pfdhps, and Pfk13 genes were included.

Results: A total of 26 studies met the inclusion criteria, revealing a high overall prevalence of mutations associated with resistance to chloroquine and sulfadoxine-pyrimethamine, particularly in Pfcrt and Pfdhfr genes. Although mutations associated with artemisinin resistance in the Pfk13 gene were less common, their presence warrants attention for future surveillance. Within this overall pattern, regional disparities were evident, with generally lower Pfcrt prevalence in northern Nigeria compared to the south, though levels varied across locations and time periods.

Conclusion: Regional variability in CQ resistance mutations has been observed across Nigeria, with lower prevalence in some northern states but persistence in others. CQ may be reconsidered as an alternative to ACTs only in areas where resistance remains consistently low, contingent upon clinical trials confirming efficacy and safety, and accompanied by molecular surveillance to guide targeted policy decisions.

Background: As a vital endocrine organ, the pancreas exhibits differences in anatomical structure and microenvironment between its head and tail. However, whether there is heterogeneity in miRNA expression within the islet cells of these two regions and what biological significance this heterogeneity may entail remain unclear.

Methods: This study utilized high-throughput sequencing to analyze the miRNA expression profiles in the islet cells from the pancreatic head and tail in rats. The TargetScan and miRDB databases were used to predict target genes of the differentially expressed miRNAs (DEmiRNAs). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analyze the target genes. The key miRNA was verified by qRT-PCR.

Result: A total of 445 miRNAs were detected in the islet cells of the pancreatic head and tail, among which 69 showed significant differences (|log2 fold change|>0.585 and P<0.05). Compared with the pancreatic tail, 28 miRNAs were upregulated and 41 miRNAs were downregulated in the pancreatic head. Bioinformatics analysis revealed that these target genes were significantly enriched in functions such as negative regulation of cellular process, anatomical structure development, intracellular organelle, pancreatic cancer, insulin resistance, MAPK signaling, Wnt signaling, and Hippo signaling. In addition, KEGG analysis of target genes showed that miR-124-3p was in several pathways, such as the insulin signaling pathway, endocrine resistance, small cell lung cancer, and other pathways in cancer. qRT-PCR results showed that miR-124-3p was significantly upregulated in the pancreatic head.

Conclusions: Our findings provide novel insights into the heterogeneity of miRNA expression in the pancreas and the molecular mechanisms underlying pancreatic cancer, offering potential targets for future diagnostic and therapeutic strategies.