Search Results (22,202)

Background: Advances in genome-wide DNA-based technologies have fundamentally transformed prenatal genetic diagnostics, enabling detection of clinically significant submicroscopic chromosomal abnormalities that are not identifiable by conventional cytogenetic methods. These developments have important implications for the diagnosis and management of pregnancies complicated by fetal structural abnormalities, as they enable more accurate etiological diagnosis, improved prognostic assessment, and more informed clinical decision-making and reproductive counselling. Methods: This narrative review synthesizes contemporary international evidence on prenatal genetic diagnostic approaches, including conventional karyotyping, chromosomal microarray analysis (CMA), and genome-wide sequencing technologies. The review focuses on diagnostic performance, clinical utility, ethical considerations, and implementation within diverse healthcare systems. Results: Accumulating evidence demonstrates that genome-wide approaches—particularly CMA and sequencing-based methods—provide a higher diagnostic yield in fetuses with structural anomalies, with an incremental yield of approximately 3–5% over conventional karyotyping. This is mainly due to their ability to detect pathogenic copy number variants below the cytogenetic resolution of karyotyping. These technologies improve etiological insight, enhance genotype–phenotype correlation, and support more precise prognostication and reproductive counselling, especially in pregnancies with fetal structural anomalies. Emerging sequencing platforms further expand the diagnostic spectrum by integrating copy number and sequence-level variant detection. Conclusions: Genome-wide Copy Number Variation (CNV) analysis represents a critical component of contemporary prenatal diagnostics and should be integrated into invasive prenatal testing pathways in accordance with international recommendations. Genome-wide approaches need robust counselling frameworks and equitable health policy implementation to spread. The expense, lack of required experience, and variation in healthcare infrastructure across locations make widespread deployment difficult. Full article

Background: Ankylosis of the temporomandibular joint (TMJ) is a rare developmental disorder that involves fibrous or bony fusion within the joint. It is a severe structural and functional disorder. Typically, the phenotype manifests as joint immobilization and results in facial deformity and trismus. To date, ankylosis is rarely diagnosed as congenital and its occurrence mechanism has not been thoroughly understood. We observed a female patient who as a newborn showed slight facial asymmetry and impaired mandibular retraction. In addition, non-uniform occlusal fissures were noted; the lower part of the left earlobe was slightly smaller than the right earlobe. The aim of the work was the identification of pathogenic variants in the genome related to ankylosis. Ankylosis has no known causative gene yet; thus, Whole Exome Sequencing (WES) was performed. Materials and Methods: We observed a female patient with facial asymmetry and impaired mandibular retraction from birth. No phenotypic abnormalities were noted on the head or elsewhere on the body. A diagnostic computed tomography (CT) scan of the head performed at five months of age led to the diagnosis of congenital zygomatic-coronoid ankylosis. Genomic DNA samples were subjected to WES. Library preparation was carried out using the Twist Library Preparation EF Kit 2.0, followed by target enrichment with the Twist Exome 2.0 Plus Comprehensive Exome. Sequencing reads were aligned to the human reference genome (GRCh38), and variant calling was performed using standard bioinformatics workflows. Variants were subsequently filtered, annotated, and interpreted using VariantStudio. Assessment of variant pathogenicity was primarily based on comparisons with public databases, including ClinVar and VarSome, and was supported by in silico prediction tools such as SIFT and PolyPhen-2. Results: In genes responsible for disorders of the I and II pharyngeal arches, three pathogenic variants were identified: in the genes TCOF1 and POLR1B, responsible for the development of Treacher Collins syndrome (TCS), and one in the DHODH gene, responsible for Miller syndrome. Additionally, in genes that have not been linked so far with rare facial disorders, 42 variants were identified, of which 8 are listed as pathogenic. We present the first described patient with congenital ankylosis, who, although showing no phenotypic features of these syndromes, has identified pathogenic variants in genes responsible for craniofacial dysostosis. Conclusions: Variants in TCOF1, POLR1B and DHODH may represent candidate genetic factors associated with susceptibility to ankylosis. WES analysis is an appropriate method in the case of patients with congenital diseases with unknown genetic origin. In this study we provide a comprehensive list of all identified pathogenic variants. This might be useful for scientists searching for the genetic background of skeletal system issues, one of which could be bone and fibrous tissue remodeling. Full article

Mitochondrial succinate dehydrogenase subunits are differentially expressed in multiple tumor types, suggesting their role as a cancer type-dependent metabolic target. However, information on the expression of SDH subunits in breast cancer (BC), particularly in South Asian populations, remains scarce. So, we analyze the expression profile of all four SDH subunits in breast cancer patients from Bangladesh. qRT-PCR was carried out to analyze the mRNA expression of four SDH subunits in Luminal A, Luminal B, Her2+, and triple-negative breast cancer subtypes and the results were compared with The Cancer Genome Atlas (TCGA) database. All four succinate dehydrogenase subunits were significantly upregulated in tumor tissues when compared to controls and showed an alignment with the TCGA except SDHD, which was significantly downregulated in TCGA. Subtype-specific analysis demonstrated differential expression patterns. SDHD upregulation has also been connected to worse outcomes for patients which indicates its role in cancer progression. Furthermore, we found a significant upregulation of METTL3 in our patient cohort. Taken together, the elevated SDHD and METTL3 expression suggests a potential epigenetic mechanism-driven SDHD activation, highlighting its previously unreported role in breast cancer biology and revealing a distinct pattern of SDH dysregulation in the Bangladeshi breast cancer population. Full article

The search for antagonistic microorganisms as alternatives to chemical pesticides is an urgent priority in sustainable agriculture. Previously, we isolated several bacterial isolates from spruce plants, and one of them, identified as Bacillus atrophaeus R7PjV2-12, showed strong antagonistic properties against plant pathogens such as Magnaporthe oryzae, Fusarium avenaceum, and Erwinia billingiae. Given its strong fungicidal properties, we decided to sequence the complete genome of this bacterium to determine how it can inhibit fungal growth. The whole genome size of B. atrophaeus R7PjV2-12 was 4,127,644 bp with 4032 open reading frames. B. atrophaeus R7PjV2-12 genome possessed clusters of secondary metabolites with a complete set of genes with 100% similarity representing clusters of biosynthesis of bacillin, bacillibactin, subtilosin A, and fungicin, which indicates the studied strain’s ability to synthesize these substances. Thus, this paper has shown and discussed the potential importance of B. atrophaeus R7PjV2-12 for biocontrol of pathogenic microorganisms in agriculture. Full article

 Congenital heart disease (CHD) is the most common congenital anomaly worldwide and poses significant diagnostic challenges due to its structural complexity and frequent association with extracardiac anomalies and genetic abnormalities. While conventional tests such as karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), and chromosomal microarray analysis (CMA) are standard first-tier investigations, many cases remain genetically unexplained. Prenatal whole exome sequencing (WES) has emerged as a valuable tool to detect pathogenic single gene variants underlying CHD. This narrative review synthesizes findings from 28 studies involving over 2000 WES-tested fetuses and more than 10,000 CHD cases. The additional diagnostic yield of WES over CMA ranged from 8.0% to 66.7%, with higher yields in syndromic or non-isolated CHD (10–50%) compared to isolated cases (7.1–27.8%). Trio-based WES outperformed proband-only sequencing by improving accuracy, reducing turnaround time, and lowering the rate of variant of uncertain significance (VUS). Prenatal WES not only clarifies genetic etiology but also reveals syndromic diagnoses, allowing CHD to be interpreted within broader multisystem contexts. Integration of phenotypic and genomic data enhances prenatal counseling, prognostication, delivery planning, and postnatal care—advancing precision medicine in fetal cardiology.  Full article

Invasive pneumococcal disease (IPD) results from the dissemination of Streptococcus pneumoniae to normally sterile anatomical sites such as the bloodstream or cerebrospinal fluid. One of the primary roles of pneumococcal conjugate vaccines (PCVs) used in Romania is to reduce the burden of pneumococcal disease. This single-center retrospective study provides an updated overview of IPD epidemiology in a Romanian tertiary hospital. We analyzed 67 IPD cases identified between 2017 and 2023, of which 45 isolates underwent whole-genome sequencing followed by multilocus sequence typing. Results of genome sequence analysis revealed a diverse population of pneumococci, underlining the importance of continuous genomic surveillance. Expanded-valency pneumococcal conjugate vaccines (PCVs), particularly PCV20, showed markedly improved serotype coverage compared to PCV7 and PCV13, while PCV21 showed serotype coverage comparable to that of PCV13. Antimicrobial susceptibility testing revealed sustained resistance to beta-lactams, particularly among meningitis isolates, underscoring the need for targeted antibiotic stewardship and continuous monitoring of local resistance trends. Overall, these findings highlight the evolving epidemiology of invasive pneumococcal disease in Romania, in the post-PCV era, and the need to adapt vaccination and treatment strategies accordingly. Full article

This study systematically measured gross hair weight and hair length traits across five body regions of 759 Tianzhu White Yak individuals. The BSL trait exhibited moderate heritability, while the BL trait demonstrated high heritability (h² = 0.450). All other traits showed low heritability. GWASs were conducted using whole-genome resequencing data comprising 22,566,255 high-quality SNP loci. The MLM model identified 519 genome-wide significant loci and 767 chromosome-wide significant loci. Chromosome 6 harbored the highest number of significant SNP loci, while the remaining significant loci were distributed across multiple autosomes. Strong long-range linkage disequilibrium (r² > 0.7) was observed between numerous significant SNPs on chromosome 6 associated with Gw and HL traits. A total of 73 candidate genes were annotated, including FGF5, CFAP299, and PRDM8. Functional enrichment analysis based on the GO and KEGG databases revealed significant enrichment in cytoplasm and the MAPK signaling pathway. Sanger sequencing results revealed that mutations in the FGF5, CFAP299, PRDM8, ANTXR2, and GPHB5 genes significantly affected the Gw, HL, and BSL traits of Tianzhu White Yak (p < 0.01). Linkage disequilibrium analysis indicated strong linkage disequilibrium (r² > 0.6) among Sanger-sequenced SNP loci on the same chromosome. From a biological perspective, multiple candidate genes such as FGF5 and CFAP299 are involved in hair follicle cycle regulation, cell proliferation, and metabolic control, suggesting its potential role in hair follicle development and hair shaft growth. This study identifies candidate loci and genes for gross hair weight and hair length traits in Tianzhu White Yak, contributing to elucidating the genetic mechanisms underlying hair production performance. Full article

Red pigmentation in apple peel significantly contributes to its commercial value, and bagging treatment contributes to enhancing red coloration in fruits. However, the regulatory mechanisms underlying bagging-induced coloration remain largely unexplored. Through bagging treatment, this study aimed to investigate the role of DNA methylation in anthocyanin biosynthesis in the ‘Nagafu No. 2’ cultivar and its bud mutation variant, which has enhanced red coloration. We compared bagging and unbagging treatments in both the bud mutant (Mt-Bagging and Mt-NoBagging) and the wild type (Control-Bagging and Control-NoBagging). Our results demonstrated that bagging significantly promoted anthocyanin accumulation while reducing chlorophyll content. At 30 days post-bag removal, anthocyanin content was highest in the Mt-Bagging group, followed by the Mt-NoBagging, Control-Bagging, and Control-NoBagging groups, and the highest level of redness (a* values) was detected in the Mt-Bagging group. Genome-wide methylation analysis revealed that differentially methylated regions predominantly targeted structural genes within the anthocyanin biosynthesis pathway, including C4H1, C4H3, C4HL, ANS1, and ANS2. Notably, quantitative PCR analysis confirmed that the upregulation of C4HL, C4H3, and ANS1 in the bagged mutant correlated with its intensified red coloration. These findings offer novel insights into the epigenetic regulation of apple peel pigmentation during bagging cultivation. Full article

Background: Oxidative stress (OS) has been widely implicated in pathophysiology of major psychiatric disorder. However, establishing robust causal links and delineating the specific molecular mechanisms involved continue to pose significant research challenges. Methods: We performed a multi-omics analysis focusing on 817 oxidative stress-related genes (OSGs) in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). We applied summary data-based Mendelian randomization (SMR), integrating large-scale genome-wide association studies for MDD, BD, and SCZ with quantitative trait loci datasets from both blood and brain tissues, including measures of DNA methylation, gene expression, and protein abundance. Results: Multi-omics integration yielded supportive evidence across blood and brain tissues implicating ACE and ACADVL in SCZ, where genetically predicted increases in their methylation, expression, and protein abundance were associated with reduced disease risk. IGF1R was associated with bipolar disorder (BD) risk in blood-specific analyses. Brain-specific analyses further nominated ENDOG as a candidate gene for SCZ. Single-cell SMR indicated that increased ENDOG expression was associated with higher SCZ risk in astrocytes, CD4⁺ naïve T cells, CD8⁺ effector T cells, and natural killer cells, suggesting a potential immune–brain interaction. Conclusions: This study provides multi-level genetic evidence supportive of a potential causal role for specific OSGs in major psychiatric disorders. We identify ACE, ACADVL, IGF1R, and ENDOG as candidate genes for further investigation, offering insights into epigenetic and transcriptional mechanisms that could inform future research on therapeutic targets. Full article

Background/Objectives: Arctic foxes (Vulpes lagopus) exemplify the vulnerability of Arctic species to global warming and anthropogenic impacts, including habitat loss, interspecific competition with temperate species, pollution (chemical and biological), and declining prey abundance. Despite their ecological importance, the evolutionary and demographic history of the species is still incompletely understood, and the colonization history of isolated island populations, such as the one on Iceland, remains unresolved. Methods: We analyzed 80 mitochondrial genomes from across the Holarctic, including 22 Icelandic individuals. We combined phylogenetic reconstruction, coalescence-dating, haplotype network analysis, and diversity metrics to infer matrilineal relationships and colonization history. Results: Seven distinct haplogroups (Hg.1–Hg.7) were identified, which diverged ≥65 thousand years ago (kya). Two haplogroups were broadly distributed across Fennoscandia, Russia, Iceland, and Canada, while others were region-specific: two in eastern Russia (respectively diverging ~171 kya and ~89 kya), one in central Russia (~66 kya), and two in Iceland (~95 kya and ~66 kya). Three haplogroups were detected in Iceland, and at least four unrelated founding females are required to explain the current matrilineal diversity. One haplogroup contained sufficient representatives for molecular dating, yielding a minimum colonization age of ~5600 years, assuming in situ diversification. Observed matrilineal diversity in Iceland does not uniquely identify a single geographic source. Conclusions: Arctic foxes’ distribution and diversity reflect repeated cycles of isolation and expansion as circumpolar environments shifted. Broader sampling across the Nearctic is critical to clarify the timing, sources, and routes of Iceland’s colonization, as Nearctic sampling was limited to a single Canadian mitogenome. Full article

The coatomer complex has been implicated in cancer progression; however, a comprehensive pan-cancer analysis is lacking. Therefore, it is essential to identify the critical roles and essentiality of coatomer genes across pan-cancer. We systematically profiled the genetic alterations, expression patterns, prognostic relevance, and functional dependencies of all coatomer subunits across multiple cancers using more than 10,000 tumor samples from The Cancer Genome Atlas, complemented by functional perturbation data from CRISPR (n = 1178) and RNAi (n = 707) screens in DepMap. Functional validation was also performed to identify the essentiality of selectively essential coatomer genes in hepatocellular carcinoma (HCC). Gene amplification, most notably of COPB2, was the most frequent alteration and was associated with poor survival in bladder and esophageal cancers. Mutations in COPA and SEC31A also demonstrated prognostic significance in endometrial carcinoma. Expression analyses revealed broad upregulation of coatomer genes across cancer types, with COPG1 and COPB1 emerging as strong risk-associated genes (HR > 2). Integrative functional dependency analyses identified COPG1 as selectively essential in multiple cancers, and its loss was associated with increased drug sensitivity. Functional validation in hepatocellular carcinoma revealed that COPG1 knockdown impaired malignant phenotypes and reduced tumorigenicity in vivo. Mechanistically, COPG1 depletion induced Golgi disruption and ER stress, increased ROS production, and suppressed PI3K–AKT signaling, thereby sensitizing cells to sorafenib and doxorubicin. Collectively, this pan-cancer analysis reveals the context-dependent roles of coatomer subunits and identifies COPG1 as a novel oncogenic driver and potential therapeutic target in HCC, mediating chemoresistance through redox modulation and PI3K–AKT pathway inhibition. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, emphasizing the critical need for novel and robust biomarkers to improve prognostication and guide precision oncology. While traditional clinical variables such as tumor stage, age, and sex are routinely used for survival prediction, their prognostic performance is limited. Imaging biomarkers derived from radiomic analysis of advanced medical imaging have emerged as a promising class of noninvasive cancer biomarkers, enabling quantitative characterization of tumor phenotypes. In this study, we investigated the prognostic utility of radiomic imaging biomarkers, with a particular focus on the texture-based feature Busyness, and compared their performance against conventional clinical factors. Survival analyses demonstrated that Busyness achieved significantly stronger discrimination of survival outcomes than stage, age, or sex. Stratified analyses further showed that Busyness consistently remained a dominant predictor of survival across age and sex subgroups, whereas tumor stage alone provided limited prognostic separation. To address class imbalance and enhance model robustness, the Synthetic Minority Over-sampling Technique (SMOTE) was applied, further supporting the stability of the imaging biomarker findings. These results highlight the potential of radiomic imaging biomarkers as powerful prognostic tools in lung cancer and support their integration into clinical workflows. This work contributes to the growing landscape of new cancer biomarkers and provides a foundation for future studies integrating imaging biomarkers with molecular and genomic markers to achieve improved prognostic accuracy. Full article

Pseudomonas syringae pv. syringae (Pss) is an economically significant bacterial pathogen that causes canker in sweet cherry trees. In Chile, sweet cherry (Prunus avium L.) is a key crop whose exponential production growth has increased phytosanitary pressure. However, the genetic diversity and adaptive mechanisms of local Pss populations have remained poorly understood. This study characterized 41 Pss isolates from major Chilean production regions. Their genomes were sequenced and compared with 152 public genomes from the PG2 phylogenetic group. The analysis revealed a predominance of the PG2d subgroup among the Chilean isolates, with a population structure defined by at least 18 genomic clusters, some of which are exclusive to Chile. A characteristic feature of this entire PG2d subgroup is the presence of indole-3-acetic acid (IAA) synthesis genes (iaaM and iaaH). Furthermore, this subgroup displayed a marked increase in ancestral gene gain and loss events, indicating extensive remodeling of the shell genome and supporting a model of lineage-specific adaptive evolution. We also identified lineage-specific orthogroups, structural variants of the T-PAI pathogenicity island, and a differential distribution of Hop-type effector proteins. Furthermore, an extended copper resistance operon (cop and cus systems) was detected in a subset of strains, and a dominant lineage was found to have a dual i1-type of T6SS system. These findings highlight the local diversification of Pss in Chile, likely driven by agro-environmental pressures. This study provides crucial insights into the evolution, adaptation, and pathogenic potential of this important pathogen in a crop of high strategic value. Full article

Xin’anjiang water buffalo (XAJB) is crucial for meat production and agricultural activities in Anhui Province of China. To generate hypotheses regarding how DNA methylation might correlate with transcriptional differences in skeletal muscle, WGBS and RNA-seq were performed on three BF and three BM adult XAJB. The results revealed 31,333 differentially methylated cytosines (DMCs), 1961 differentially methylated regions (DMRs), and 230 differentially expressed genes (DEGs) in skeletal muscle between the two groups. The qRT-PCR results of ten DEGs (COL1A1, THBS1, SLITRK4, VIPR2, IGFBP6, WIF1, MMP16, LMOD3, NPR3 and MYLK4) enriched in protein digestion and absorption pathway, PPAR signaling pathway, ECM-receptor interaction pathway or PI3K-Akt signaling pathway were consistent with the RNA-seq results. Most methylation changes occurred in CG context, and sixteen genes were predicted as dual differential genes in both methylation and transcriptome. Moreover, CG methylation showed a significant negative correlation with gene expression within the 2 kb upstream region (rho = −0.42, p < 0.001). Given the limited number of animals examined, additional investigations with expanded cohorts are essential to verify the association between the methylome and transcriptome signatures underlying skeletal muscle in XAJB. Full article

There is a growing need to understand ciprofloxacin (CIP) resistance in less prevalent Salmonella serovars like Salmonella Dublin, which causes life-threatening conditions in both humans and animals. This study investigated potential factors contributing to CIP-resistance in a Salmonella Dublin isolate. The isolate was detected from an initial screening of 17 biobanked Salmonella isolates using the Kirby-Bauer disk diffusion (KBDF) method. The minimum inhibitory concentration (MIC) values of the identified CIP-resistant Salmonella Dublin isolate and a CIP-susceptible isolate of the same serovar were also obtained using the broth-dilution (BD) method. The two candidates were then challenged in 1/4 of their respective BD MICs for gene expression analysis, focusing on the acrAB efflux genes and the regulator genes marA, ramA, and soxS. Genomes of the isolates were also sequenced using the Oxford Nanopore sequencing platform, and then analyzed for mutations, antimicrobial resistance genes, and plasmids using ABRicate. The SWISS-MODEL server was used for protein modeling and comparison. For our results, the MIC values (KBDF; BD) for the CIP-resistant and CIP-susceptible Salmonella Dublin isolates were (1.5 μg/mL; 1.95 μg/mL) and (<0.125 μg/mL; 0.03 μg/mL), respectively. Both isolates had genes (mdtK, emrR, emrA, and emrB) notable for fluoroquinolone resistance, with the CIP-susceptible isolate also carrying the IncFII(S) plasmid. Expression of the acrA, acrB, ramA, and soxS genes was markedly higher in the CIP-resistant isolate, which also harbored an Asparagine (N) to Serine (S) mutation at position 868 in the GyrA protein. This mutation, however, caused no significant structural change. Despite reporting on a single CIP-resistant Salmonella Dublin isolate, our result highlights the potentially significant role of an efficient efflux system in contributing to CIP resistance in this isolate, even when no impactful mutations were identified. Full article