Frontiers in Genetics最新文献

Purpose: To highlight the trends and frontiers of RNA methylation in cancer over the past 10 years.

Methods: Research publications on RNA methylation in cancer were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and Bibliometrix were used to conduct bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords relevant to this field.

Results: From 2014 to 2023, research on RNA methylation in cancer has developed rapidly, with an overall increase in the number of publications and citations. China (4320 papers, 115056citations), Sun Yat Sen University (274 papers, 15698 citations), and Zhang, Wei (48 papers, 893 citations) are respectively the countries, institutions, and authors with the highest number of published papers and citations. Frontiers in Oncology (182 papers, 2524 citations) and Molecular Cancer (69 papers, 9224 citations) are the journals with the highest number of published papers and citations in this field, respectively. Co-occurrence analysis of keywords indicates that the research topics can be divided into five clusters: Cluster one: The Role of RNA Methylation in Tumor Heterogeneity, Therapeutic Response, and Prognosis; Cluster two: The Role of Noncoding RNA in RNA Methylation and Tumors; Cluster three: Potential Therapeutic Targets of RNA Methylation in Tumors; Cluster four: The role of RNA methylation in tumor progression and metastasis: A case study of hepatocellular carcinoma and gastric cancer; Cluster five: Regulation mechanisms of m6A methylation in leukemia cell differentiation and tumorigenesis.

Conclusion: This is the first comprehensive study using bibliometrics to analyze the trends and frontiers of RNA methylation in cancer over the past 10 years, pointing out promising research directions for the future and providing valuable references for researchers in this field.

Introduction: Long-read sequencing (LRS) enables accurate structural variant detection and variant phasing. When a molecular diagnosis is suspected, target enrichment can reduce the cost and duration of sequencing.

Methods: LRS was conducted in five inherited retinal dystrophy (IRD) patients harboring a monoallelic variant in RPE65 that remained uncharacterized after clinical exome sequencing (CES). CRISPR-Cas9 guide RNA probes were designed to target a 31 kb region, including the entire RPE65 locus. The DNA was sequenced on a MinION platform. Short-read ×30 whole-genome sequencing (WGS) was performed for five patients to validate nanopore results.

Results: The nanopore sequencing process yielded a median of 271 reads within the targeted region, with a mean depth of 109 and a median read size of 8 kb. All variants identified by CES have been detected using this approach, and no additional RPE65 gene causative variants were found. Nanopore variant detection demonstrated performance akin to short-read WGS at similar coverage levels, although exhibiting increased false positive calls at lower coverage.

Discussion: In this study, we explore the advantages of using a targeted approach together with long-read sequencing to identify variants associated with IRD. The results underscore the utility of targeted long reads for characterizing patients affected by rare diseases when first-tier diagnostic tests are non-conclusive.

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy involving approximately 80 pathogenic genes. Whole-exome sequencing (WES) and confirmatory Sanger sequencing analysis was applied to identify the disease-causing mutations in a Chinese patient with lower limb weakness. We present an 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait. Upon admission, a physical examination revealed hands tremulousness, bilateral calf muscle wasting and weakness, pes cavus, and elevated serum creatine kinase (CK) levels. Electromyography demonstrated axonal neuropathy affecting both upper and lower limbs. A de novo heterozygous missense mutation was identified in the MORC2 gene, NM_001303256.3: c.1199A>G, NP_001290186.1: p.Gln400Arg. Consequently, these clinical and genetic findings suggested a diagnosis of hereditary peripheral neuropathy, CMT type 2Z. Oral mecobalamin and coenzyme Q10 was initiated as subsequent treatment. Our study firstly reports the MORC2 c.1199A>G mutation occurring de novo, highlighting its causal association with CMT2Z, and prompting its reclassification as likely pathogenic. Oral mecobalamin and coenzyme Q10 might be a potential treatment approach for early-stage CMT2Z. We recommend genetic testing for CMT patients to identify the genetic etiology, thereby improving clinical management and facilitating genetic counseling.

Introduction: Cerebral aneurysm (CA) is a common vascular disease. The risk factors of CA include hypertension, smoking, and a family history of genetic predisposition. Although sleep-related problems have been found to have a strong association with cardiovascular disease, there is a lack of research regarding the causal relationship with cerebral aneurysms.

Methods: In this study, we investigated the causal relationship between four sleep-related problems, including snoring, insomnia, narcolepsy, and napping during the day, and CA using a two-sample Mendelian randomization (MR) analysis. Moreover, the potential confounders before sleep problems and CA were further analyzed by multivariate MR (MVMR).

Results: The causal relationship between insomnia and CA was obtained analytically by means of six MR analyses. There was a strong causal effect relationship between insomnia and CA, which suggests this as a potential risk factor [odds ratio (OR) = 8.35, 95% confidence interval (CI) = 2.422-28.791, p = 7.772e-04]. On this basis, hypertension was identified as a mediator between insomnia and CA by MVMR, with a mediating effect of 52.538% (OR = 3.05, 95% CI = 1.549-4.55, p = 0.015).

Conclusion: The causal relationship between insomnia and CA was predicted using genetic variance data, and insomnia was found to be a potential risk factor. Furthermore, hypertension is a mediator between insomnia and CA. Therefore, focusing on sleep problems and improving sleep quality may be an active and effective strategy to prevent CA.

Purpose: The relationship between women's reproductive traits and postpartum depression (PPD) has not been clarified. We reveal the association between genetically predicted modifiable women's reproductive traits and PPD using two-sample Mendelian randomization (MR).

Methods: We used genome-wide association studies (GWASs) to obtain instrumental variables (IVs) of 9 women's reproductive traits. Univariate and multivariate MR analyses were used to examine the association between traits and the risk of PPD (13,657 cases and 236,178 controls). The primary causal effect assessment employed the IVW method. Heterogeneity was assessed using Cochran's Q test. Multiple horizontal effects were assessed using the MR-PRESSO and MR-Egger intercept. Leave-one-out and LASSO regression analyses were used to check the robustness of the UVMR and MVMR results, respectively.

Results: In the UVMR result, genetic prediction showed that age at first sexual intercourse (AFS) (OR = 0.474, 95% CI 0.396-0.567; p = 4.6 × 10-16), age at first birth (AFB) (OR = 0.865, 95% CI 0.805-0.930; p = 8.02 × 10^-5), and age at last live birth (ALLB) (OR = 0.296, 95% CI 0.138-0.636; p = 0.002) were significantly inversely associated with PPD, while a higher lifetime number of sexual partners (LNSP) (OR = 1.431, 95% CI 1.009-2.031; p = 0.045) and a greater number of spontaneous miscarriages (OR = 1.519, 95% CI 1.021-2.262; p = 0.039) are suggested to be associated with an increased risk of PPD. In the MVMR result, only AFB (OR = 0.804, 95% CI 0.661-0.978; p = 0.029) retained a direct causative relationship with PPD.

Conclusion: The study indicates that AFB is a significant risk factor for PPD. Furthermore, the likelihood of developing PPD appears to decrease with increasing gestational age at the time of the first childbirth.

Mungbean plays a significant role in global food and nutritional security. However, the recent drastic rise in atmospheric temperature has posed an imminent threat to mungbean cultivation. Therefore, this study investigates the growth and physiological changes of 87 mungbean germplasm lines under heat stress. Genotypes were examined using parameters including leaf area, chlorophyll content, membrane stability index (MSI), stomatal conductance, pollen viability, number of pods per cluster, number of pods per plant, number of seeds/pod, 100-seed weight and grain yield/plant under heat stress and control environments. A wide range of variation was observed for these traits among genotypes under heat stress and control environments. Genotypes were also identified with variable responses under both environments. The phenotypic expression of selected promising accessions was also validated in control environment conditions at the National Phytotron facility. The selected promising genotypes viz., IC76475, IC418452 and IC489062 validated their heat tolerance behavior for key candidate genes revealed by quantitative real-time PCR (qRT-PCR). These mungbean genotypes can act as potential resources in the mungbean improvement programs for heat stress tolerance. This study also provides a comprehensive understanding of the key mechanisms underlying heat tolerance in mungbean.

Introduction: Genetic evaluation is indicated for individuals with congenital heart disease (CHD), especially if extracardiac anomalies are also present. Timely recognition of genetic diagnoses can facilitate medical management and as well as provide assessment of reproductive risk. At least 20% of the pediatric population with CHD has a syndrome or genetic diagnosis. Further, at least 30% have extracardiac congenital malformations and/or neurodevelopmental differences (NDD), and this is known to increase the likelihood of a genetic/syndromic diagnosis. However, little is known regarding whether these statistics also apply to the current population of adults living with CHD, many of whom were born prior to currently available genetic testing.

Methods: The primary aim of this study was to determine the prevalence of documented genetic and syndromic diagnoses in a cohort of adults with CHD followed by a dedicated adult CHD (ACHD) clinic. The secondary aims were to describe genetic testing and genetic referral patterns in this population and identify the presence of extracardiac comorbidities which are known to be indicative of an underlying genetic diagnosis in the pediatric CHD population. To answer these questions, we performed a retrospective chart review on a sample of adults with CHD (excluding those with isolated bicuspid aortic valve) seen at Cincinnati Children's Hospital in the ACHD clinic between 2010-2021.

Results: Among 233 adult CHD patients, 36 (14%) had a documented genetic or syndromic diagnosis but only 29 (13.7%) had received genetic testing, while 27 (11.6%) had received genetic referrals. Furthermore, of 170 patients without any documented genetics related care (defined as genetic testing, genetic referrals, or genetic diagnosis), 35 (20%) had at least one congenital and/or neurodevelopmental comorbidity. Factors associated with individuals having received genetics related care included younger age (<40), male sex, and presence of extracardiac comorbidities.

Discussion: Our results indicate important gaps in genetics-related care for adults living with CHD. The subset of our cohort with congenital and/or neurodevelopmental comorbidities who received no genetic-related care, represent a population of adults with CHD who may have unrecognized genetic diagnoses.

A gene bank for farm animal genetic resources (FAGR) is an important facility for the diversity conservation of FAGR. The primary purpose of gene banks for FAGR is the reconstruction of those breeds. With the advent of the post-genomic era, gene banks for FAGR have increasingly become an infrastructure for the support of livestock research and animal breeding, and a platform for international research collaboration. China is one of the richest countries in the world in terms of FAGR. Chinese National Gene Banks for FAGR (CNGBFs) have an important legal status and play an important function in the Chinese FAGR protection system. In this paper, we reviewed the current situation of CNGBFs construction, and systematically collected and analyzed legal rules related to CNGBFs. As results, those legal rules were categorized into two types: (a) organization and management, (b) activities. We summarized problems existing in the current legal rules for CNGBFs from three levels: institution, practical operation, and digital development. Improvement directions of legal rules regarding CNGBFs are proposed. They include clarifying the utilization function of CNGBFs and the ownership of FAGR in CNGBFs. Moreover, improving the mechanism of administrative management, rules on domestic and international access and benefit-sharing, and the system of digital sequence information management are also suggested. The improvements in those legal rules will contribute to the appropriate utilization of Chinese FAGR and international collaborations.

Formyl peptide receptor 3 (FPR3) is known to have implications in the progression of various cancer types. Despite this, its biological significance within pan-cancer datasets has yet to be investigated. In this investigation, we scrutinized FPR3's expression profiles, genetic alterations, prognostic significance, immune-related characteristics, methylation status, tumor mutation burden (TMB), and microsatellite instability (MSI) across different types of cancer. We utilized TISCH's single-cell data to identify immune cells closely associated with FPR3. The predictive significance of FPR3 was evaluated independently in gliomas using data from TCGA and CGGA datasets, leading to the development of a prognostic nomogram. Immunohistochemistry and Western blot analysis confirmed FPR3 expression in gliomas. Lastly, the CCK-8 and wound-healing assays were employed to assess the impact of FPR3 on the proliferation and metastasis of GBM cell lines. In numerous cancer types, heightened FPR3 expression correlated with adverse outcomes, immune cell infiltration, immune checkpoints, TMB, and MSI. In glioma, FPR3 emerged as a notable risk factor, with the prognostic model effectively forecasting patient results. The potential biological relevance of FPR3 was confirmed in glioma, and it was shown to have significant involvement in the processes of glioma growth, immune infiltration, and metastasis. Our results imply a potential association of FPR3 with tumor immunity, indicating its viability as a prognostic indicator in glioma.

Background: Arbuscular mycorrhiza (AM) refers to a symbiotic association between plant roots and fungi that enhances the uptake of mineral nutrients from the soil and enables the plant to tolerate abiotic and biotic stresses. Although previously reported RNA-seq analyses have identified large numbers of AM-responsive genes in model plants, such as Solanum lycopersicum L., further studies are underway to comprehensively understand the complex interactions between plant roots and AM, especially in terms of the short- and long-term responses after inoculation.

Results: Herein, we used RNA-seq technology to obtain the transcriptomes of tomato roots inoculated with the fungus Rhizophagus irregularis at 7 and 30 days post inoculation (dpi). Of the 1,019 differentially expressed genes (DEGs) in tomato roots, 635 genes showed differential expressions between mycorrhizal and non-mycorrhizal associations at the two time points. The number of upregulated DEGs far exceeded the number of downregulated ones at 7 dpi, and this difference decreased at 30 dpi. Several notable genes were particularly involved in the plant defense, plant growth and development, ion transport, and biological processes, namely, GABAT, AGP, POD, NQO1, MT4, MTA, and AROGP3. In addition, the Kyoto encyclopedia of genes and genomes pathway enrichment analysis revealed that some of the genes were involved in different pathways, including those of ascorbic acid (AFRR, GME1, and APX), metabolism (CYP, GAPC2, and CAM2), and sterols (CYC1 and HMGR), as well as genes related to cell division and cell cycle (CDKB2 and PCNA).

Conclusion: These findings provide valuable new data on AM-responsive genes in tomato roots at both short- and long-term postinoculation stages, enabling the deciphering of biological interactions between tomato roots and symbiotic fungi.