Genes最新文献

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, dynamic mutations in the receptor-binding domain (RBD) in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have altered the pathogenicity of the variants of the virus circulating in Indonesia. This research analyzes the mutation trend in various RBD samples from Indonesia published in the Global Initiative on Sharing All Influenza Data (GISAID) database using genomic profiling.

Method: Patients in Indonesia infected with SARS-CoV-2, whose samples have been published in genomic databases, were selected for this research. The collected data were processed for analysis following several bioinformatics protocols: visualization into phylogenetic trees, 3D rendering, and the assessment of mutational impact.

Results: In Indonesia, there are 25 unique SARS-CoV-2 clades and 318 unique SARS-CoV-2 RBD mutations from the earliest COVID-19 sample to samples collected in 2022, with T478K being the most prevalent RBD mutation and 22B being the most abundant clade. The Omicron variant has a lower docking score, higher protein destabilization, and higher K_D than the Delta variant and the original virus.

Conclusions: The study findings reveal a decreasing trend in virus pathogenicity as a potential trade-off to increase transmissibility via mutations in RBD over the years.

The evolution of complex multicellularity in land plants represents a pivotal event in the history of life on Earth, characterized by significant increases in biological complexity. This transition, classified as a Major Evolutionary Transition (MET), is best understood through the framework of Evolutionary Transitions in Individuality (ETIs), which focuses on formerly independent entities forming higher-level units that lose their reproductive autonomy. While much of the ETI literature has concentrated on the early stages of multicellularity, such as the formation and maintenance stages, this paper seeks to address the less explored transformation stage. To do so, we apply an approach that we call Transitions in Structural Complexity (TSCs), which focuses on the emergence of new units of organization via the three key evolutionary processes of modularization, subfunctionalization, and integration to the evolution of land plants. To lay the groundwork, we first explore the relationships between sex, individuality, and units of selection to highlight a sexual life cycle-based perspective on ETIs by examining the early stages of the transition to multicellularity (formation) in the sexual life cycle of the unicellular common ancestor of land plants, emphasizing the differences between the transition to multicellularity in eumetazoans and land plants. We then directly apply the TSC approach in this group, identifying key evolutionary events such as the distinct evolutionary innovations like shoot, root, vascular systems, and specialized reproductive structures, arguing that bringing these under the broader rubric of TSCs affords a degree of explanatory unification. By examining these evolutionary processes, this paper provides a new perspective on the evolution of multicellularity in land plants, highlighting both parallels and distinctions with the animal kingdom.

Background: Fanconi syndrome is a disorder of renal proximal tubule transport characterized by metabolic acidosis, amino aciduria, glucosuria, and phosphaturia. There are acquired and hereditary forms of this disorder. A late-onset form of Fanconi syndrome in Basenjis was first described in 1976 and is now recognized as an inherited disease in these dogs. In part because of the late onset of disease signs, the disorder has not been eradicated from the breed by selective mating. A study was therefore undertaken to identify the molecular genetic basis of the disease so that dogs could be screened prior to breeding in order to avoid generating affected offspring. Methods: Linkage analysis within a large family of Basenjis that included both affected and unaffected individuals was performed to localize the causative variant within the genome. Significant linkage was identified between chromosome 3 (CFA3) makers and the disease phenotype. Fine mapping restricted the region to a 2.7 Mb section of CFA3. A whole genome sequence of a Basenji affected with Fanconi syndrome was generated, and the sequence data were examined for the presence of potentially deleterious homozygous variants within the mapped region. Results: A homozygous 317 bp deletion was identified in the last exon of FAN1 of the proband. 78 Basenjis of known disease status were genotyped for the deletion variant. Among these dogs, there was almost complete concordance between genotype and phenotype. The only exception was one dog that was homozygous for the deletion variant but did not exhibit signs of Fanconi syndrome. Conclusions: These data indicate that the disorder is very likely the result of FAN1 deficiency. The mechanism by which this deficiency causes the disease signs remains to be elucidated. FAN1 has endonuclease and exonuclease activity that catalyzes incisions in regions of double-stranded DNA containing interstrand crosslinks. FAN1 inactivation may cause Fanconi syndrome in Basenjis by sensitization of kidney proximal tubule cells to toxin-mediated DNA crosslinking, resulting in the accumulation of genomic and mitochondrial DNA damage in the kidney. Differential exposure to environmental toxins that promote DNA crosslink formation may explain the wide age-at-onset variability for the disorder in Basenjis.

Background: Kidney stone disease (KSD) is characterized by an increasing prevalence worldwide, representing an important clinical issue and a financial burden for healthcare systems. A KSD-causing monogenic variant is traditionally expected in up to 30% of children and 1-5% of adults forming stones, confirmed by a strong connection between a positive family history and KSD. The insufficient use of genetic testing in these patients is associated with a lack of perceived benefit and a scarce awareness of inherited kidney diseases. Genetic testing has important practical implications, such as the possibility of earlier diagnoses, familial counseling, and tailored therapy, based on the evaluation of fine-mapped pathogenic variants. Our aim is to analyze the current evidence on genetic testing in KSD patients to whom genetic tests were applied without strict a priori selection criteria, to provide an overview of its diagnostic yield and factors potentially affecting it (such as the age of KSD onset, a familial history of KSD, consanguinity, and extrarenal features).

Methods: A literature review was performed, selecting original articles published in the last 10 years concerning genetic investigations in patients affected by nephrolithiasis or nephrocalcinosis. Available data were subsequently extracted and analyzed.

Results: In total, 13 studies on 1675 patients (77% pediatric populations) were included; 333 patients were determined to be affected by a monogenic disorder, with an overall yield of about 20%. The likelihood of a positive genetic finding was much higher in pediatric (26%) than adult populations (8%). Cystinuria was the most common diagnosis in both populations. After the removal of conditions that could be identified with a stone composition analysis or urinary chemistry investigation, the diagnostic yield dropped to 19% among pediatric patients and below 5% for adults.

Conclusions: Genetic testing should be considered in KSD pediatric patients and in selected subgroups of adults with suggestive features when a diagnosis is not established after stone examination and blood as well as urine metabolic profiling.

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the CHM gene, which result in a deficiency in Rab-escort protein-1, a key element for intracellular trafficking of vesicles, including those carrying melanin. As choroideremia primarily affects the retinal pigment epithelium, fundus autofluorescence, which focuses on the fluorescent properties of pigments within the retina, is an established imaging modality used for the assessment and monitoring of affected patients.

Methods and results: In this manuscript, we demonstrate the use of both short-wavelength blue and near-infrared autofluorescence and how these imaging modalities reveal distinct disease patterns in choroideremia. In addition, we show how these structural measurements relate to retinal functional measures, namely microperimetry, and discuss the potential role of these retinal imaging modalities in clinical practice and research studies. Moreover, we discuss the mechanisms underlying retinal autofluorescence patterns by imaging with a particular focus on melanin pigment.

Conclusions: This could be of particular significance given the current progress in therapeutic options, including gene replacement therapy.

Background: The caffeoyl-CoA-O methyltransferase (CCoAOMT) family plays essential roles in the methylation of various secondary metabolites, including anthocyanins. Despite the wide identification of the CCoAOMT family in plants, the characterization and function of CCoAOMT protein members in Solanum tuberosum remain poorly understood.

Methods and results: In this study, a total of 12 StCCoAOMT members were identified in the genome of S. tuberosum using the Blastp and HMM search and were unevenly located on eight chromosomes. Collinearity analysis revealed that four tandem duplicated gene pairs and two segmental duplicated gene pairs existed in the S. tuberosum genome, demonstrating that duplication events play a key role in the expansion of the CCoAOMT family. All StCCoAOMTs were clustered into group I and group II based on phylogenetic analysis, which was further verified by the conserved motifs and gene structures analysis. The cis-acting elements analysis illustrated that StCCoAOMTs might be important for photosynthesis, hormone responses, and abiotic stress. Expression analysis demonstrated that StCCoAOMT genes have diverse transcript levels in various tissues and that StCCoAOMT10 was significantly expressed in purple potatoes with abundant anthocyanin content according to RNA-seq data and qRT-PCR assays. In addition, the subcellular localization assay validated that the StCCoAOMT10 protein was mainly localized in the cytoplasm and nucleus.

Conclusions: These results will be of great importance for a better understanding of the features of CCoAOMT family members, especially of the candidate genes involved in the methylation of anthocyanins in S. tuberosum, and also for improving the nutritional quality of S. tuberosum.

Background/objectives: Ulp1 is a vital regulator of the cell cycle, with its absence leading to G2/M phase arrest in Saccharomyces cerevisiae. This study aims to investigate the role of Ulp1 in cell cycle regulation in Pichia pastoris and to elucidate its mechanisms of action, particularly through the modulation of the gene INO1.

Methods: We generated Ulp1 knockout strains in Pichia pastoris using the FLP-FRT system and performed RNA sequencing (RNA-seq) to analyze gene expression changes. We assessed cell proliferation in Ulp1 knockout and INO1 overexpressing strains, as well as the effects of inositol supplementation.

Results: Our findings revealed significant downregulation of INO1 and other genes in Ulp1 knockout strains. Importantly, overexpression of INO1 restored cell proliferation, indicating that Ulp1 regulates this process via INO1. Notably, supplementation with exogenous inositol did not rescue cell proliferation, suggesting that the enzymatic activity of INO1 is not required for Ulp1's regulatory function.

Conclusions: This study demonstrates that Ulp1 modulates cell proliferation in Pichia pastoris through INO1, independent of its enzymatic activity. These insights enhance our understanding of Ulp1's role in cell cycle regulation and open new avenues for exploring the molecular mechanisms governing yeast cell division. Further investigations are warranted to delineate the intricate regulatory pathways involved in this process.

Background: Long non-coding RNAs (lncRNAs) are pivotal mediators during the development of carcinomas; however, it remains to be investigated whether lncRNAs are implicated in oral squamous cell carcinoma (OSCC). Methods: In this study, quantitative real-time PCR was conducted for detecting the expression of LINC01614 in OSCC cell lines. The biological functions of LINC01614 were assessed by loss- and gain-of-function experiments conducted both in vivo and in vitro. Cellular proliferation, migration, and invasion were investigated herein, and dual luciferase reporter assays were additionally performed to explore the relationships among LINC01614, miR-138-5p, and Forkhead box C1 (FOXC1). Results: The research presented herein revealed that OSCC cells express high levels of LINC01614. Functional experiments employing cellular and animal models demonstrated that LINC01614 knockdown repressed the malignant phenotypes of OSCC cells, including their growth, invasiveness, and migration. Further investigation revealed that LINC01614 absorbs miR-138-5p miRNA by functioning as a competing endogenous RNA to downregulate the abundance of FOXC1. Conclusions: The findings revealed that LINC01614 contributes to the progression of OSCC by targeting the FOXC1 signaling pathway. The study provides insights into a novel mechanistic process to regulate the development of OSCC, and established a possible target for the therapeutic management of OSCC.

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. Methods: We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. Results: The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in PTPN11 were most commonly associated with pulmonary valve stenosis (PVS), while RAF1 mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development (p = 0.755), even though the likelihood ratio showed significance in that regard (p = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. Conclusions: The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype-phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies.

Background: Ammopiptanthus mongolicus is a rare temperate evergreen shrub with high tolerance to low temperature, and understanding the related gene expression regulatory network can help advance research on the mechanisms of plant tolerance to abiotic stress. Methods: Here, time-course transcriptome analysis was applied to investigate the gene expression network in A. mongolicus under low temperature stress. Results: A total of 12,606 differentially expressed genes (DEGs) were identified at four time-points during low temperature stress treatment, and multiple pathways, such as plant hormones, secondary metabolism, and cell membranes, were significantly enriched in the DEGs. Trend analysis found that the expression level of genes in cluster 19 continued to upregulate under low temperatures, and the genes in cluster 19 were significantly enriched in plant hormone signaling and secondary metabolic pathways. Based on the transcriptome data, the expression profiles of the genes in abscisic acid, salicylic acid, and flavonoid metabolic pathways were analyzed. It was found that biosynthesis of abscisic acid and flavonoids may play crucial roles in the response to low temperature stress. Furthermore, members of the phenylalanine ammonia-lyase (PAL) family in A. mongolicus were systematically identified and their structures and evolution were characterized. Analysis of cis-acting elements showed that the PAL genes in A. mongolicus were closely related to abiotic stress response. Expression pattern analysis showed that PAL genes responded to various environmental stresses, such as low temperature, supporting their involvement in the low temperature response in A. mongolicus. Conclusions: Our study provides important data for understanding the mechanisms of tolerance to low temperatures in A. mongolicus.