Search Results (394)

The VRTN (vertebrin) gene plays a crucial role in regulating thoracic vertebral number in mammals; however, its function in goats remains largely unexplored. This study aimed to investigate genetic variations in the VRTN gene in Hainan black goats (HNBGs) and evaluate their associations with growth and meat traits. Using whole-genome and Sanger sequencing, we identified four SNPs in the VRTN gene, including three missense mutations (p.Pro615Ser, p.Arg490Lys, p.Thr476Met) and one synonymous mutation (p.Asp688Asp). Tissue expression profiling revealed high VRTN mRNA expression in skeletal muscle and low expression in internal organs, suggesting a potential role in muscle development. Temporal expression analysis indicated dynamic regulation during growth, with higher expression levels observed in early developmental stages. Association analyses revealed significant correlations between specific SNPs and key traits, including body length, chest circumference, carcass weight, and meat quality parameters. Notably, the p.Pro615Ser mutation was associated with a 0.441-fold reduction in VRTN expression and showed strong associations with multiple traits, underscoring its functional importance. These findings demonstrate that VRTN polymorphisms influence growth and muscle development in HNBGs, providing valuable insights for marker-assisted selection in goat breeding. Full article

Fat volume and obesity-related genes (e.g., the FTO gene) are important candidate genes affecting energy metabolism. Single nucleotide polymorphisms (SNPs) in the FTO gene are associated with carcass, growth and meat quality traits of pigs, cattle, sheep, rabbits and ducks. The purpose of this study was to detect the single nucleotide polymorphisms in the chicken FTO gene coding region by DNA sequencing and analyze its association with the carcass and growth traits of Heying black chickens. We detected polymorphisms in exons 5, 7, 8 and 9, respectively, g.57337C>A, g.64757T>G, g.97213G>A and g.220985G>A, which are synonymous mutations. g.57337C>A mutation site CA and AA genotype individuals were significantly higher than CC genotype individuals in live weights, head weights, breast muscle weights and leg muscle weights (p < 0.05), AA genotype individuals were significantly higher than CC genotype individuals in slaughter live weights and liver weights (p < 0.05) and CA and AA genotype individuals were significantly higher than CC genotype individuals in heart weights (p < 0.01). In terms of growth traits, the weights of individuals with genotype CA at 8 weeks were significantly higher than that of individuals with genotype CC (p < 0.05), and the weights of individuals with genotype AA and CA at 10 weeks and 16 weeks were significantly higher than that of individuals with genotype CC (p < 0.05). For the g.64757T > G mutation, individuals with the TT genotype exhibited significantly higher values (p < 0.05) than those with the TG genotype across multiple traits, including slaughter weight, live weight, eviscerated weight and semi-eviscerated weight. Individuals with GG genotypes were significantly higher than individuals with TG genotypes (p < 0.05) in slaughter weights and wing weights. In terms of growth traits, the 16-week-old body weight of individuals with TT genotype was significantly higher than that of individuals with TG genotype (p < 0.01). The GA genotype exhibited significantly higher slaughter weights in the g.97213G>A variant compared to the GG genotype (p < 0.01), and in live weights, eviscerated weights, semi-eviscerated weights, leg muscle weights and wing weights, GA genotype was significantly higher than in GG genotype (p < 0.05). In terms of growth traits, GA genotype was significantly higher in individuals 8 weeks old, 10 weeks old and 16 weeks old than GG genotype (p < 0.05). g.220985G>A was significantly higher in individuals with GG genotype than GA genotype (p < 0.05). In terms of growth traits, the weight of GG genotype was significantly higher than that of GA genotype (p < 0.05). The results showed that the FTO gene may be a candidate gene related to chicken growth and slaughter traits and lays a foundation for Heying black chicken assisted breeding. Full article

Human noroviruses (HuNoVs) stand as the primary cause of acute viral gastroenteritis outbreaks worldwide, particularly impacting children under the age of five. In Russia, reports of norovirus gastroenteritis have surged, especially in the post-COVID-19 era starting in 2022, with elevated infection rates reported into 2024. These viruses exhibit significant mutational variability, leading to the emergence of recombinant strains that can evade immune responses. A comprehensive examination of the complete genome is crucial for understanding the evolution of norovirus genes and for predicting potential outbreaks. This research focuses on analyzing the genotypic composition of HuNoVs circulating in the Sverdlovsk region during 2024, using Sanger sequencing and next-generation sequencing (NGS). Biological samples were collected (n = 384) from patients diagnosed with norovirus infection within the region. Bioinformatics analysis targeted the nucleotide sequences of the ORF1/ORF2 fragment and the assembly of complete genomes for the GII.4 and GII.7 genotypes. In total, 220 HuNoVs were characterized, representing 57.3% of the collected samples. The main capsid variants forming the predominant genotypic profile included GII.4 (n = 88, 40%), GII.7 (n = 86, 39%), and GII.17 (n = 14, 6%). Using NGS, we successfully assembled 8 out of 10 complete genomes for noroviruses GII.4[P16] and GII.7[P7]. Non-synonymous substitutions appeared at amino acid sites corresponding to the subdomains of VP1 in these strains. This molecular–genetic analysis provides contemporary insights into the genotypic composition, circulation patterns, and evolutionary dynamics associated with the dominant genovariants GII.4[P16] and GII.7[P7]. Full article

Background/Objectives: Tumor mutational burden (TMB) has emerged as a potential biomarker of response to immunotherapy across multiple solid tumors. However, its role in cervical cancer remains insufficiently defined. This study aimed to evaluate the genomic landscape and TMB profile in a cohort of patients with cervical cancer treated at a tertiary gynecologic oncology center, with a focus on TMB’s associations with clinical features, HPV infection, and treatment modalities. Methods: A total of 61 patients diagnosed with cervical cancer (82.0% ca. planoepitheliale, 18.0% adenocarcinoma) were retrospectively analyzed. Tumor samples were collected during primary surgery, biopsy, or conization and subjected to targeted next-generation sequencing using the ONCOaccuPanel™ and BRCAaccuTest PLUS™ (NGeneBio). TMB was calculated as non-synonymous mutations per megabase and analyzed using NGeneAnalySys^® software. Variant classification followed ACMG guidelines. Comparative analyses were conducted between TMB-high (≥10 mut/Mb) and TMB-low subgroups, and correlations with clinical and molecular variables were assessed using univariable statistics. Results: High TMB was identified in 36 patients (59.0%), while microsatellite instability was found in only 2 cases (3.3%). No significant associations were observed between TMB status and FIGO stage, histologic subtype, or HPV 16/18 infection. However, higher TMB values were observed in patients with nodal involvement, diabetes, and HPV52 infection. A diverse spectrum of mutations was detected, with PIK3CA and ARID1A being most frequently altered. Several variants of uncertain significance were identified in genes not classically associated with cervical cancer. Conclusions: TMB-high status is relatively frequent in cervical cancer and appears to be independent of FIGO stage or histological subtype. While not predictive of clinical stage, TMB correlates with specific molecular and comorbidity profiles, suggesting its potential relevance for future patient stratification in immunotherapy trials. Full article

As an indigenous goat breed unique to southern China, Leizhou Black Goats (LZBGs) are highly valued for their rapid growth, high reproductive performance, and superior meat quality. However, their offspring frequently exhibit symptoms of muscle atrophy and malnutrition, suggesting potential genetic defects underlying these adverse phenotypes. As a unique extracellular matrix component, collagen Q (COLQ) is specifically enriched within the synaptic basal lamina at vertebrate neuromuscular junctions (NMJs), where it anchors acetylcholinesterase (AChE) to facilitate efficient acetylcholine hydrolysis, ensuring precise neuromuscular signaling. The current investigation sought to characterize the spectrum of genetic polymorphisms within the COLQ gene and assess their correlation with key production traits, including growth performance and meat quality parameters, in the LZBG population. Previously, through whole-genome sequencing and transcriptome sequencing analyses of an LZBG population, we identified four SNPs in the COLQ gene, namely, two missense mutations (SNP1: p.238A/S and SNP3: p.47G/S), one intronic variant (SNP2), and one synonymous mutation (SNP4: p.101P/P). Population genetic analysis revealed strong linkage disequilibrium between SNP1 and SNP2. Computational modeling of protein structures predicted that the identified missense mutations may lead to alterations in protein conformation. Association analyses demonstrated significant correlations of SNP1 and SNP3 with growth and meat quality traits (p < 0.05), where SNP3 reduced COLQ expression by 0.64-fold in homozygotes. Association analysis revealed that both SNP1 and SNP3 showed significant correlations with growth and meat quality traits in LZBGs (p < 0.05). Notably, SNP3 (p.47G/S) was found to regulate COLQ gene expression, reducing its levels by 0.64-fold in homozygous individuals, suggesting its potential as a genetic marker for selecting goats with superior growth performance and muscular development characteristics. The identified genetic variants establish a foundation for marker-assisted selection in LZBG breeding programs with particular relevance to growth performance enhancement, while also advancing the understanding of COLQ’s functional mechanisms in muscle development. Full article

Synonymous codon usage (codon bias) greatly influences not only translation but also mRNA stability. In vertebrates, highly expressed genes preferentially use codons with an optimal tRNA adaptation index (tAI) that mostly end in C or G. Surprisingly, the codon usage of viruses infecting humans often deviates from optimality, showing an enrichment in A/U-ending codons, which are generally associated with slow decoding and reduced mRNA stability. This observation is particularly evident in RNA viruses causing respiratory illnesses in humans. This review analyzes the mutational and selective forces that shape nucleotide composition and codon usage drift in human RNA viruses, as well as their impact on translation, viral fitness, and evolution. It also describes how some viruses overcome suboptimal codon usage to outcompete host mRNA for translation. Finally, the roles of viral tropism and host adaptation in codon usage bias of prototypical viruses are discussed. Full article

The 2022 global mpox outbreak highlighted the risk of sustained human-to-human transmission of monkeypox virus (MPXV) in non-endemic regions, yet genomic surveillance in Asia, particularly in China, remains limited. This study conducted horizontal genomic surveillance of MPXV in Shenzhen from 2023 to 2024 to characterize the phylogenetic structure, mutational patterns, and adaptive evolution of locally circulating strains. Phylogenetic analysis showed 95.2% of strains belonged to the dominant lineage C.1.1, with 4.8% in lineage E.3, forming three distinct genetic clusters that indicate multiple independent introductions and established local transmission chains. Whole-genome mutational analysis identified 146 single-nucleotide polymorphisms (SNPs), 81.5% of which carried APOBEC3-mediated mutation signatures (TC > TT and GA > AA), reflecting host-driven antiviral editing. Notably, dynamic changes in low-complexity regions (LCRs) were observed, implying potential roles in genome plasticity and adaptive evolution. Functional analysis revealed non-synonymous substitution biases in host-interacting proteins OPG064, OPG145, and OPG210, while replication protein OPG105 remained conserved. Structural modeling identified critical substitutions in OPG002 (S54F), OPG016 (R84K), and OPG036 (R48C) that may enhance immune evasion by modulating TNF-α signaling, NKG2D engagement, and Type I interferon antagonism. These findings illuminate unique MPXV evolutionary dynamics in Shenzhen, emphasizing continuous genomic surveillance for non-endemic outbreak preparedness. Full article

Human mitochondrial DNA (mtDNA) is a relevant marker in evolutionary and population genetics, including ancient DNA (aDNA) research, due to inherent characteristics. However, aDNA is prone to damage and sequencing artefacts, potentially confounding evolutionary interpretations. To assess evolutionary patterns in ancient and modern mtDNA, we built a phylogeny comprising 63,965 modern and 3757 ancient public mitogenomes, classified mutations by genomic region and functional effect, and analysed distribution, frequency, and predicted pathogenicity of private and pre-terminal mutations, investigating purifying selection. We compared mutation class ratios (non-synonymous, rRNA, tRNA, nonsense vs. synonymous) across ancient and modern terminal branches and pre-terminal nodes. The predicted pathogenicity of non-synonymous mutations was evaluated across major European haplogroups using three tools. Ancient variants exhibited higher ratios of potentially deleterious mutations and significantly elevated pathogenicity scores compared to modern and pre-terminal branches, highlighting a mutation load likely inflated by damage-related artefacts. Remarkably, nonsense mutations—largely incompatible with life—were over 70 times more frequent in aDNA. The correlation between mutation ratios and predicted deleteriousness across haplogroups suggests a pattern incompatible with biological persistence or relaxed selection alone. These findings highlight the importance of rigorous quality control for ancient data in evolutionary inference, molecular clock calibration, and pathogenic variant identification. Full article

Background/Objectives: The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks and maintenance of genomic stability. Germline loss of FA pathway function in the inherited Fanconi anemia syndrome leads to increased DNA damage and a range of clinical phenotypes, including a heightened risk of head and neck squamous cell carcinoma (HNSCC). Non-synonymous FA gene mutations are also observed in up to 20% of sporadic HNSCCs. The mechanistic target of rapamycin (mTOR) is known to stimulate cell growth, anabolic metabolism including protein synthesis, and survival following genotoxic stress. Methods/Results: Here, we demonstrate that FA− deficient (FA−) HNSCC cells exhibit elevated intracellular amino acid levels, increased total protein content, and an increase in protein synthesis indicative of enhanced translation. These changes are accompanied by hyperactivation of the mTOR effectors translation initiation factor 4E Binding Protein 1 (4E-BP1) and ribosomal protein S6. Treatment with the mTOR inhibitor rapamycin reduced the phosphorylation of these targets and blocked translation specifically in FA− cells but not in their isogenic FA− proficient (FA+) counterparts. Rapamycin-mediated mTOR inhibition sensitized FA− but not FA+ cells to rapamycin under nutrient stress, supporting a therapeutic metabolism-based vulnerability in FA− cancer cells. Conclusions: These findings uncover a novel role for the FA pathway in suppressing mTOR signaling and identify mTOR inhibition as a potential strategy for targeting FA− HNSCCs. Full article

Invasive infections with rare yeasts are increasing worldwide and are associated with higher mortality rates due to their resistance to antifungal drugs. Accurate antifungal susceptibility testing (AFST) is crucial for proper management of rare yeast infections. We performed AFST of 74 Candida kefyr isolates by Etest, EUCAST-based MICRONAUT-AM assay (MCN-AM) and reference Clinical and Laboratory Standards Institute broth microdilution method (CLSI). Essential agreement (EA, ±1 two-fold dilution), categorical agreement (CA), major errors (MEs) and very-major errors (VmEs) were determined using epidemiological cut-off values of ≤1.0 µg/mL, ≤0.03 µg/mL, ≤0.5 µg/mL and ≤1 µg/mL, defining wild-type isolates for fluconazole, voriconazole, micafungin and amphotericin B (AMB), respectively. Results for AMB susceptibility were correlated with ERG2/ERG3 mutations and total-cell sterols. CA of ≥97% was recorded between any two methods while EA varied between 72 and 82%, 87 and 92%, and 49 and 76% for fluconazole, voriconazole and micafungin, respectively. For AMB, CAs between CLSI and Etest; CLSI and MCN-AM; MCN-AM and Etest were 95% (4 ME, 0 VmE), 96% (3 ME, 0 VmE) and 99%, respectively, while EA varied from 32% to 69%. Non-synonymous ERG2/ERG3 mutations and no ergosterol were found in seven of eight isolates of non-wild types for AMB by Etest. Our data show that Etest, CLSI and MCN-AM methods are suitable for AFST of C. kefyr for fluconazole, voriconazole and micafungin. Excellent CAs for AMB between Etest and MCN-AM with concordant sterol profiles but not with CLSI suggest that Etest is also an excellent alternative for the detection of C. kefyr isolates with reduced susceptibility to AMB. Full article

Cowpea (Vigna unguiculata) is a crop of significant socioeconomic importance, particularly in the semi-arid regions of Africa and America. However, its productivity has been adversely affected by viral diseases, including the cowpea aphid-borne mosaic virus (CABMV), a single-stranded RNA virus. It is known that the VPg protein interacts with the host’s translation initiation factor (eIF4E), promoting viral replication. This study aimed to investigate the relationship between mutations in the cowpea eIF4E gene and resistance to CABMV. Twenty-seven cultivars were screened by PCR and bioassays for presence/absence of mutations associated with resistance or susceptibility to Potyviruses. Of the cultivars with mutations previously associated with susceptibility, 88.24% exhibited viral symptoms, while 62.5% associated with resistance remained asymptomatic. The in silico analyses revealed that non-synonymous mutations (Pro68Arg, Gly109Arg) alter the structure of the eIF4E protein, reducing its affinity to VPg. Molecular dynamics simulations also pointed to an enhanced structural stability of eIF4E in resistant cultivars and reinforced, for the first time, key mutations and the functional role of the eIF4E gene in resistance to CABMV in cowpea. Our results offer valuable insights for virus disease management and for genetic improvement programs for this important crop. Full article

Excavating new salt tolerance genes and utilizing them to improve salt-tolerant wheat varieties is an effective way to utilize salinized soil. The NAC gene family plays an important role in plant response to salt stress. In this study, 446 NAC sequences were isolated from the whole genome of common wheat and classified into 118 members based on subgenome homology, named TaNAC1 to TaNAC118. Transcriptome analysis of salt-tolerant wheat breeding line CH7034 roots revealed that 144 of the 446 TaNAC genes showed significant changes in expression levels at least two time points after NaCl treatment. These differentially expressed TaNACs were divided into four groups, and Group 4, containing the largest number of 78 genes, exhibited a successive upregulation trend after salt treatment. Single nucleotide polymorphisms (SNPs) of the TaNAC gene family in 114 wheat germplasms were retrieved from the public database and were subjected to further association analysis with the relative salt-injury rates (RSIRs) of six root phenotypes, and then 20 SNPs distributed on chromosomes 1B, 2B, 2D, 3B, 3D, 5B, 5D, and 7A were correlated with phenotypes involving salt tolerance (p < 0.0001). Combining the results of RT-qPCR and association analysis, we further selected three NAC genes from Group 4 as candidate genes that related to salt tolerance, including TaNAC26-D3.2, TaNAC33-B, and TaNAC40-B. Compared with the wild type, the roots of the tanac26-d3.2 mutant showed shorter length, less volume, and reduced biomass after being subjected to salt stress. Four SNPs of TaNAC26-D3.2 formed two haplotypes, Hap1 and Hap2, and germplasms with Hap2 exhibited better salt tolerance. Snp3, in exon 3 of TaNAC26-D3.2, causing a synonymous mutation, was developed into a Kompetitive Allele-Specific PCR marker, K3, to distinguish the two haplotypes, which can be further used for wheat germplasm screening or marker-assisted breeding. This study provides new genes and molecular markers for improvement of salt tolerance in wheat. Full article

Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims to investigate the genomic determinants associated with cefiderocol resistance in CPE isolates of human origin. Methods: Comparative genomic analyses were conducted between cefiderocol-susceptible and -resistant CPE isolates recovered from human clinical and epidemiological samples at a tertiary care hospital. Whole-genome sequencing, variant annotation, structural modelling, and pangenome analysis were performed to characterize resistance mechanisms. Results: A total of 59 isolates (29 resistant and 30 susceptible) were analyzed, predominantly comprising Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. The most frequent carbapenemase gene among the resistant isolates was bla_NDM, which was also present in a subset of susceptible strains. The resistant isolates exhibited a significantly higher burden of non-synonymous mutations in their siderophore receptor genes, notably within fecR, fecA, fiu, and cirA. Structural modelling predicted deleterious effects for mutations such as fecR:G104S and fecA:A190T. Additionally, porin loss and loop 3 insertions (e.g., GD/TD) in OmpK36, as well as OmpK35 truncations, were more frequent in the resistant isolates, particularly in high-risk clones such as ST395 and ST512. Genes associated with toxin–antitoxin systems (chpB2, pemI) and a hypothetical metalloprotease (group_2577) were uniquely found in the resistant group. Conclusions: Cefiderocol resistance in CPE appears to be multifactorial. NDM-type metallo-β-lactamases and missense mutations in siderophore uptake systems—especially in those encoded by fec, fhu, and cir operons—play a central role. These may be further potentiated by alterations in membrane permeability, such as porin disruption and efflux deregulation. The integration of genomic and structural approaches provides valuable insights into emerging resistance mechanisms and may support the development of diagnostic tools and therapeutic strategies. Full article

Two germplasm collections, comprising 1026 peach accessions located in Italy, were analyzed with 12 simple sequence repeat (SSR) markers. SSR reactions were performed using the multiplex-ready PCR protocol, and 147 alleles were amplified with an average of 12 alleles per locus. BPPCT001 was the most informative marker displaying the highest discrimination power (0.734). The observed heterozygosity showed an average of 0.45 alleles per locus, lower than expected (0.61). The fixation index (F) values were positive in all loci, with an average of 0.27 alleles per locus, suggesting the presence of endogamy. The DNA fingerprinting data allowed the discrimination of 80.95% of the analyzed accessions. If we exclude known sport mutations, known synonymies, and cultivars with the same pedigree, 161 accessions are mislabeled, with an error rate of 16.56% within or between collections. Population structure analysis revealed three subpopulations: modern peach cultivars, modern nectarine cultivars, and a third group mainly comprising traditional peach cultivars. The results obtained in this work will be useful to efficiently manage Genebank, reducing unwanted redundancy, synonyms and homonyms, mislabeling, and spelling errors, as well as identifying parents in controlled crosses. Full article

Echovirus 30 (E-30), a member of the Enterovirus B species, is frequently linked to neurological illnesses such as aseptic meningitis, encephalitis, and hand, foot, and mouth disease. In this study, we present the complete-genome analysis of an Echovirus 30 strain isolated from cerebrospinal fluid (CSF) and stool samples of a pediatric encephalitis case in Kerala, India, during 2023. A comparative genomic investigation was carried out using a dataset of 111 human E-30 isolates, encompassing 116,991 mutation records. This analysis revealed six distinct non-synonymous amino acid substitutions uniquely present in the isolate PQ472410.1, which may be associated with pathogenicity and/or neurotropic behavior. To the best of our knowledge, this represents the first complete-genome sequence report of E-30 from an encephalitis case in India. These findings contribute valuable information to the understanding of E-30’s molecular epidemiology and evolution and offer vital data for enhancing surveillance and response strategies against enteroviral infections. Full article