Genes & genomics最新文献

Background and objective: Argininemia (OMIM: 207800), as well as arginase deficiency, a disorder of the urea cycle caused by deficiency of arginase 1 (ARG1, NP_000036.2), is a scarce autosomal recessive genetic disease. The patients who suffered with argininemia often showed spastic paraplegia, epileptic seizures, severe mental retardation, and even the hyperammonemia. In neonatal screening, we found a healthy baby with mild elevated arginine levels. We have demonstrated the genetic etiology of the patient.

Methods: The patient's clinical characteristic and family history were collected. The technologies including Next Generation Sequencing (NGS), Sanger sequencing, Bioinformatics Analysis, RNA extraction, cDNA obtained, Sanger sequencing, Minigene splicing assay, Real-time PCR, Single-molecule real-time (SMRT) sequencing were applied.

Results: One homozygous variant, c.57G > A (p.Q19=), was identified in the proband, which was inherited from the parents. Through different detection methods, we found that the c.57G > A variant causes three different transcriptional versions: normal mRNA (mRNA from blood), mRNA with the exon2 deletion (73bp, mRNA from blood and minigene assay), and mRNA sequence from the SMRT sequencing (parts of exons and introns were detected, including exon 1-4, intron 1 and 4, and part of intron 2, 3, and 5). The expression of ARG1 mRNA and protein also decreased in the blood. The related genes of NMD (Nonsense-mediated mRNA decay), SMG1, UPF1, and UPF3b, were expressed higher than the controls in the blood, which hints the NMD could play a role in the mRNA decay regarding the cDNA with 73bp deletion by c.57G > A variant.

Conclusions: The study is the first study considering a synonymous variant of the ARG1 gene influencing alternative splicing(AS). Otherwise, the variant c.57G > A is relatively frequent in the general population( MAF = 0.0146). Our discovery revealed the variant possesses partial pathogenic potential, which would contribute to the deeper understanding and gold model for the intricate relationship between genetic mutations, arginine metabolism, and physical function.

Background: The family of SQUAMOSA promoter binding protein-like (SPL) transcription factors is essential for regulating plant growth and development. While this SPL gene functional research has been limited in Rhododendron molle (R. molle).

Objective: To preliminarily explore the regulatory mechanism of the SPL gene in flower bud development of R. molle.

Methods: In this study, for R. molle, the flower bud differentiation period was determined by observing the morphological anatomy of the flower bud. The SPL gene family members were identified based on the R. molle genome, Additionally, the expressions of RmSPL genes at five flower bud differentiation stages were analyzed via Quantitative reverse transcription PCR (RT-qPCR).

Results: We first characterized 20 SPL family members in the reference genome of R. molle. The phylogenetic analysis of plant SPL proteins separated them into eight subfamilies (G1-G8) according to conserved gene structures and protein motifs. Cis-elements of promoter region analysis showed that RmSPL genes were regulated by light, phytohormones, stress response, and plant growth and development and may play a critical role in the photoresponse, abasic acid, anaerobic induction, and meristematic expression. Gene expression analysis showed that 18 RmSPL genes were differentially expressed in different developing flower buds. In particular, RmSPL1/7/8/12/13 exhibited significantly different expressions, suggesting that they were likely essential genes for regulating the differentiation of flower buds.

Conclusion: In conclusion, our analysis of RmSPL genes provides a theoretical basis and reference for future functional analysis of RmSPL genes in the flower bud differentiation of R. molle.

Background: The female parental line Jinbuol (JBO, early heading) and two recombinant isogenic lines, JSRIL1 and JSRIL2, have been shown to flower 44, 34 and 16 days earlier, respectively, than the male parental line Samgwang (SG, late heading) in paddy fields.

Objective: To explore how photoperiodicity-related genes are involved in differential heading among these lines.

Methods: Deep sequencing was conducted for these lines, photoperiodicity-related genes (71) were categorized, and qRT-PCR was performed for some key genes.

Results: Deep sequencing revealed a nearly even contribution of parental groups, with 48.5% and 45% of the chromosomes in JSRIL1 and JSRIL2, respectively, inherited from the female parent JBO; however, Chr6 contained the most biased parental contribution, with 99.4% inherited from the female parent. The variation in single-nucleotide polymorphisms (SNPs) among many known flower-inducing genes, including rice GIGANTEA (OsGI); grain number, plant height and heading date 7 (Ghd7); and EARLY HEADING DATE 1 (Ehd1), was minimal. In the JSRILs, HEADING DATE 1 (Hd1) and VERNALIZATION INSENSITIVE 3-LIKE 1 (OsVIL2) originated from JBO, whereas FLAVIN-BINDING, KELCH REPEAT, F BOX 1 (OsFKF1) originated from SG. Interestingly, HEN1 suppressor 1 (OsHESO1) originated from SG in JSRIL1 and JBO in JSRIL2. RNA sequencing and qRT‒PCR analyses of plants at the floral meristem stage revealed that transcriptional regulation through chromosomal restructuring and posttranscriptional regulation might control minute gene regulation, resulting in delayed heading in JSRILs.

Conclusion: Our gene expression and SNP analyses of elite recombinant isogenic lines could be helpful in understanding how photoperiodicity-related genes in rice are modulated.

Background: RNA modifications, a central aspect of epitranscriptomics, add a regulatory layer to gene expression by modifying RNA function without altering nucleotide sequences. These modifications play vital roles across RNA species, influencing RNA stability, translation, and interaction dynamics, and are regulated by specific enzymes that add, remove, and interpret these chemical marks.

Objective: This review examines the role of aberrant RNA modifications in cancer progression, exploring their potential as diagnostic and prognostic biomarkers and as therapeutic targets. We focus on how altered RNA modification patterns impact oncogenes, tumor suppressor genes, and overall tumor behavior.

Methods: We performed an in-depth analysis of recent studies and advances in RNA modification research, highlighting key types and functions of RNA modifications and their roles in cancer biology. Studies involving preclinical models targeting RNA-modifying enzymes were reviewed to assess therapeutic efficacy and potential clinical applications.

Results: Aberrant RNA modifications were found to significantly influence cancer initiation, growth, and metastasis. Dysregulation of RNA-modifying enzymes led to altered gene expression profiles in oncogenes and tumor suppressors, correlating with tumor aggressiveness, patient outcomes, and response to immunotherapy. Notably, inhibitors of these enzymes demonstrated potential in preclinical models by reducing tumor growth and enhancing the efficacy of existing cancer treatments.

Conclusions: RNA modifications present promising avenues for cancer diagnosis, prognosis, and therapy. Understanding the mechanisms of RNA modification dysregulation is essential for developing targeted treatments that improve patient outcomes. Further research will deepen insights into these pathways and support the clinical translation of RNA modification-targeted therapies.

Background: Obesity causes many complex diseases including type 2 diabetes (T2D). Obesity increases the risk of T2D in Europeans, but there are many non-obese (lean) T2D patients in East Asia.

Objective: To discover genetic factors enriched in obese or lean T2D patients, we conducted a genome-wide association (GWA) analysis for T2D stratified by BMI in the Korean population.

Methods: In the discovery stage, 654 and 247 individuals classified as obese (BMI > 25) and lean (BMI < 23) T2D patients, respectively, were compared with 3,842 control subjects for GWA analysis. Several BMI-stratified T2D variants detected in the discovery stage were further tested in the replication stage, which included 402 obese and 220 lean T2D cases, and 3,615 controls.

Results: Meta-analysis combining the discovery and replication stages detected two variants with genome-wide significance: rs2356138 [P = 2.8 × 10^-8, OR = 2.06 (1.59-2.65)] in obese T2D subjects and rs9295478 [P = 2.5 × 10^-9, OR = 1.61 (1.38-1.88)] in lean ones. The SNP rs9295478 is located in CDKAL1, a well-known T2D gene previously identified in several GWA studies. Meanwhile, the SNP rs2356138 is a previously unknown variant located in PKP4.

Conclusion: We discovered genetic loci enriched in obese or lean T2D patients in the Korean population. Our findings should facilitate more effective control of T2D in Koreans.

Proline is a major substrate in collagen biosynthesis and is required for collagen molecule formations. However, detailed explanations of the molecular basis through which proline functions in collagen biosynthesis have yet to be provided. Thus, genome-wide screening was employed to elucidate these in the pre-osteoblastic MC3T3-E1 and human periodontal ligament fibroblast (hPDLF) cell lines. Indeed, both cell lines represent important sources for collagen biosynthesis and tissue regeneration in the dental region, specifically treating extracellular proline during cultivations. The altered gene expression patterns were identified, and the precise expression patterns were confirmed by microarray. Cell viability and osteogenic differentiation patterns were examined using a range of experimental methods, such as the MTS assay, ALP staining, ARS staining, and collagen (COL)-type1A ELISA. Overall, we revealed a cell line-specific function of exogenous proline in collagen biosynthesis during osteogenic differentiation conditions with the candidate signaling pathways. These putative signaling networks could represent plausible answers to understanding collagen biosynthesis for regenerating connective tissues such as skin, muscle, and bone.

Background: The genomes of publicly available electroactive Pseudomonas aeruginosa strains are currently limited to in-silico analyses. This study analyzed the electroactive Pseudomonas aeruginosa PBH03 genome using comparative in-silico studies for biotechnological applications.

Objective: Comparative in-silico and experimental analyses were conducted to identify the novel traits of P. aeruginosa PBH03 by genome sequencing.

Methods: The publicly available genomes of Pseudomonas aeruginosa strains (PA01, PA14, and KRP1) were used for a comparative in-silico study with PBH03. Genome assembly, annotation, phylogenetic analysis, metabolic reconstruction, and comparative functional genes analysis were conducted using bioinformatics tools. The experimental analyses were conducted to validate the heavy metal resistance (Hg and Cu), salinity tolerance levels of PBH03, and acetate assimilation under microaerobic conditions.

Results: Computational analysis showed that the PBH03 genome had a size of 6.8 Mb base pairs with a GC content of 65.7%. Whole genome annotation identified the unique genes absent in the previously sequenced Pseudomonas aeruginosa genomes. These genes were associated with resistance to heavy metals, such as Cu, Hg, As, and a Co-Zn-Cd efflux system. In addition, clustered, regularly interspaced short palindromic repeats, transposable elements, and conjugative transfer proteins were observed in the clustering-based systems. The strain exhibited resistance to Hg (150 mg/L) and Cu (500 mg/L) and showed growth at salinity levels of 40 g/L (typical sea/ocean levels). PBH03 could consume acetate up to 110 mM.

Conclusion: Integrating in-silico and experimental data highlights the intriguing adaptive genomic qualities of PBH03, making it a promising candidate for various biotechnological applications.

Background: Baihu Jia Renshen Decoction (BJRD) is used for diabetes mellitus (DM) management in clinics.

Objective: To elucidate the potential mechanism of BJRD in treating type 1 DM (T1DM).

Methods: T1DM models were established via intraperitoneal injection of streptozotocin (STZ). Rats were subsequently randomly divided into the normal control (NC), model (MOD), insulin (INS), INS + BJRD-medium dose (MID), and INS + BJRD-high dose (HIGH) groups. The rats' body weight was measured. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs) in the muscle and adipose tissues. Quantitative real-time polymerase chain reaction was utilized to verify the DEG levels.

Results: Body weights of MOD, INS, MID, and HIGH groups were significantly reduced as compared to those of NC group. Compared with NC group, MOD group showed significant Hspa1b and Notch3 downregulation and Camkk2 level elevation. Compared with MOD group, INS group showed further downregulation of the Hspa1b level, whereas MID group exhibited an increase. The Camkk2 levels in INS, MID, and HIGH groups were further reduced. The Notch3 levels did not significantly change in INS and MID groups, whereas that of HIGH group increased. Additionally, compared with NC group, MOD group demonstrated upregulation of the Myl1, Mylpf, Acacb, and Pygm levels and downregulation of Fasn level. Compared with MOD group, Myl1, Mylpf, and Pygm levels in INS, MID, and HIGH groups were down-regulated, whereas Fasn and Acacb levels were up-regulated.

Conclusion: BJRD may influence pancreatic β-cell function, thereby enhancing the function of the skeletal muscle and adipose tissues in a T1DM rat model.

Background: The freshwater sculpin Cottus koreanus is endemic to the Korean Peninsula and has a fluvial life history. However, its population has been greatly reduced and it is now listed as an endangered class II species.

Objective: To obtain important information for its conservation, we examine the genetic diversity, population structure, and demographic history of C. koreanus through mitochondrial cytochrome c oxidase subunit I (CO1) gene sequence analysis.

Methods: We analyzed the CO1 gene sequences of 430 individuals of C. koreanus from 23 populations in South Korea.

Results: In all, 32 haplotypes were defined by 124 variable nucleotide sites, of which 28 were unique haplotypes not shared with other regional populations. All sampled populations had high haplotype diversity (H_d = 0.941) and low nucleotide diversity (π = 0.0146). Median-joining network analysis identified two divergent clusters: cluster I that had unique haplotype patterns assigned to each population and cluster II that had a star-like pattern. Each was supported by pairwise F_ST values and hierarchical analysis of molecular variance. The results of the mismatch distribution, goodness-of-fit test, and extended Bayesian skyline plot analysis showed that cluster I has experienced a gradual population expansion since the last glacial maximum, while cluster II experienced a sudden one. The results of neutrality testing supported the results for cluster II but the signal was weak.

Conclusions: C. koreanus inhabits the upper reaches of rivers and has extremely low dispersal ability, resulting in unique genetic structure patterns among populations. Therefore, all populations should be managed and conserved separately.

Background: Propylparaben (PrP) is commonly used as an antimicrobial agent in food, cosmetics, and pharmaceuticals. While recent studies have shown that PrP exposure can cause various disruptions in cellular physiology, the precise mechanisms behind these effects remain unclear.

Objective: In this study, we sought to examine the cytotoxic effects of PrP exposure on human lung cells in a dose- and time-dependent manner. We utilized flow cytometry to analyze the expression of proteins associated with the cell cycle and apoptosis at the single-cell level.

Results: Our results showed that PrP treatment leads to a significant upregulation of genes related to ER stress. The activation of ER stress results in a decrease in cyclin B1 levels, which subsequently causes cell cycle arrest at the G2/M phase. After 48 h of PrP exposure, the unfolded protein response (UPR) triggers an apoptotic signaling pathway, increasing the number of cells undergoing caspase-3-mediated apoptosis. Together, these physiological changes lead to a reduction in cell viability in the presence of PrP.

Conclusion: These findings suggest that PrP exerts harmful effects on human lung cells by activating ER stress, which can lead to apoptosis and cell cycle arrest.