Search Results (430)

Sternal bursitis is an underexplored lesion in poultry, often overlooked in microbiological diagnostics. In this study, we characterized 36 Escherichia coli isolates recovered from sternal bursitis in broiler chickens, combining phenotypic antimicrobial susceptibility testing, PCR-based screening, and whole genome sequencing (WGS). The genetic analysis revealed a diverse population spanning 15 sequence types, including ST155, ST201, and ST58. Resistance to tetracycline and ciprofloxacin was common, and several isolates carried genes encoding β-lactamases, including blaTEM-1B. Chromosomal mutations associated with quinolone and fosfomycin resistance (e.g., gyrA p.S83L, glpT_E448K) were also identified. WGS revealed a high number of virulence-associated genes per isolate (58–96), notably those linked to adhesion (fim, ecp clusters), secretion systems (T6SS), and iron acquisition (ent, fep, fes), suggesting strong pathogenic potential. Many isolates harbored virulence markers typical of ExPEC/APEC, such as iss, ompT, and traT, even in the absence of multidrug resistance. Our findings suggest that E. coli from sternal bursitis may act as reservoirs of resistance and virulence traits relevant to animal and public health. This highlights the need for including such lesions in genomic surveillance programs and reinforces the importance of integrated One Health approaches. Full article

Pine wilt disease, a devastating disease severely impacting pine ecosystems, is caused by the pinewood nematode Bursaphelenchus xylophilus (Steiner & Bührer, 1934) Nickle, 1970 (Nematoda: Parasitaphelenchidae). Controlling B. xylophilus is crucial for preventing and managing pine wilt disease. Recently discovered novel nematocidal lectins could provide more advantageous materials for utilizing genetically engineered bacteria to control this pathogen. Therefore, this study focuses on identifying novel nematocidal toxins within B. xylophilus lectins. Overall, we obtained twenty-one galectin, one L-type lectin (LTL), and three chitin-binding domain (CBD) genes by screening the B. xylophilus genome database; these genes were successfully expressed proteins. The bioassay results indicated that Bxgalectin2, Bxgalectin3, Bxgalectin4, Bxgalectin9, and BxLTL1 induced mortality rates exceeding 50% in B. xylophilus. Notably, Bxgalectin4 showed the strongest nematocidal activity, causing 88% mortality in the treated nematode population. The enzyme-linked immunosorbent assays further demonstrated that Bxgalectin3 (K_d = 8.992 nM) and Bxgalectin4 (K_d = 9.634 nM) had a higher binding affinity to GPI-anchored proteins from B. xylophilus. Additionally, Bxgalectin2 (K_d = 16.50 nM), Bxgalectin9 (K_d = 16.48 nM), and BxLTL1 (K_d = 24.34 nM) can bind to the GPI-anchored protein. This study reports, for the first time, that lectins endogenous to B. xylophilus exhibit nematocidal activity against their own species. These findings open up the possibility of using nematode lectins as potent control agents in the biological control of B. xylophilus. Full article

Background/Objectives: Value frameworks are useful tools to explicitly define the dimensions and criteria important for decision-making, but no existing frameworks capture the broad value domains of population genomic programs. Using a mixed methods approach, we aimed to develop a novel value framework for evaluating population genomic programs (PGPs). Methods: We first conducted a targeted literature review of published evidence on the value of PGPs and existing frameworks to evaluate and quantify their impact. Value domains and elements were extracted and summarized to develop a preliminary framework. Semi-structured stakeholder interviews on the preliminary framework were conducted from March 2024 to October 2024 with 11 experts representing 9 countries. A thematic analysis of interview transcripts was conducted to map value elements to domains of the final framework. Results: We identified 348 potentially relevant articles from MEDLINE-indexed and the gray literature sources. After title and abstract screening, 23 articles met the inclusion criteria and underwent full-text review, and 8 reported value elements were extracted and mapped to a preliminary framework for testing in interviews. Stakeholder themes were summarized into the value domains and elements of the final framework, which included health as a primary domain, education and research, enterprise and finance, and labor as the core domains, and agriculture and security as extended domains. Domains and elements may be excluded based on stakeholder objectives and program characteristics. Conclusions: This novel framework for assessing the comprehensive value of PGPs provides a foundational step to assess the value of these programs and may promote more efficient and informed allocation of resources. Full article

In November 2024, the fourth annual Symposium focusing on early-age onset cancer (EAOC) was hosted by the Colorectal Cancer Resource & Action Network (CCRAN), assembling clinicians, researchers, and patients virtually to discuss challenges in early detection and diagnosis of individuals afflicted with EAOC across tumour types. The meeting addressed the rising rates of EAOC and identified strategies to overcome barriers to timely detection and diagnosis by closing gaps in public and healthcare provider knowledge on symptoms of cancer in younger adults and reducing inequities in standard screening for younger age groups. Discussions also encompassed the various factors that serve as impediments to accessing diagnostic testing and obtaining results, as well as the critical need for access to diagnostics such as comprehensive genomic profiling (CGP), the results of which could be imperative in helping to guide clinical decisions regarding effective and well-tolerated targeted therapies. The Symposium generated key calls to action regarding increasing EAOC education and awareness among primary care providers and the public, re-evaluation of cancer screening programs’ eligibility criteria to include younger populations, and mechanisms to reduce waiting times for diagnostic testing by addressing technologist shortages and improving access to CGP through national collaborative strategies and increased funding. Full article

Background: Despite remarkable progress in clinical management of patients and intensified screening, colorectal cancer remains the second most common cause of cancer-related death in the United States. The recent surge of next generation sequencing has enabled genomic analysis of colorectal cancer genomes. However, to date, there is little information about leveraging gene expression data and integrating it with somatic mutation information to discover potential biomarkers and therapeutic targets. Here, we integrated gene expression data with somatic mutation information to discover potential diagnostic and prognostic biomarkers and molecular drivers of colorectal cancer. Methods: We used publicly available gene expression and somatic mutation data generated on the same patient populations from The Cancer Genome Atlas. We compared gene expression data between tumors and controls and between dead and alive. Significantly differentially expressed genes were evaluated for the presence of somatic mutations and subjected to functional enrichment analysis to discover molecular networks and signaling pathways enriched for somatic mutations. Results: The investigation revealed a signature of somatic mutated genes transcriptionally associated with colorectal cancer and a signature of significantly differentially expressed somatic mutated genes distinguishing dead from alive. Enrichment analysis revealed molecular networks and signaling pathways enriched for somatic mutations. Conclusions: Integrative bioinformatics analysis combining gene expression with somatic mutation data is a powerful approach for the discovery of potential diagnostic and prognostic biomarkers and potential drivers of colorectal cancer. Full article

Background/Objectives: Prostate cancer (PCa) remains a major contributor to cancer-related morbidity and mortality worldwide. Current diagnostic strategies, largely based on PSA screening, lack specificity and sensitivity, leading to unnecessary invasive procedures and elevated healthcare costs. This real-world study evaluated the EpiSwitch^® PSE assay, a blood-based test analyzing 3D genome conformation signatures, ability to avoid unnecessary biopsies and the resulting clinical and economical benefits. Methods: 187 patients undergoing evaluation for PCa were tested with the EpiSwitch^® PSE assay. Biopsy confirmation was available for 53 patients, while predictive modeling assessed 134 patients using EpiSwitch PSE results and clinical variables. Results: Among the 187 patients evaluated, predictive modeling showed that up to 79.1% (106/134) of patients could safely defer biopsy based on a low-likelihood EpiSwitch PSE result, while an alternative model showed a 66.4% (89/134) biopsy avoidance rate. The PSE result demonstrated strong concordance with biopsy-confirmed diagnoses and was the most influential predictor in multivariate analysis, followed by PI-RADS score. The test achieved a 100% technical success rate, with an average turnaround time of 4.4 days. Conclusions: Incorporating the EpiSwitch PSE assay into clinical workflows enhances decision-making efficiency, reduces unnecessary biopsies, and improves healthcare resource utilization. These findings support the assay’s strong clinical utility and economic value, highlighting its potential for broader adoption as a minimally invasive reflex test and a pre-biopsy triage tool for the early and accurate detection of prostate cancer. Future studies should include prospective, multicenter trials to confirm these results across broader populations and evaluate longitudinal outcomes of patients managed with PSE-guided care. Full article

Potato common scab is one of the major diseases posing a threat to potato production on a global scale. No chemical agents have been found to effectively control the occurrence of this disease, and research on the identification of resistance genes and the development of molecular markers remains relatively limited. In this study, a diploid potato variety H535, which exhibits resistance to the predominant pathogen Streptomyces scabies, was utilized as the male parent, whereas the susceptible diploid potato variety H012 served as the female parent. Building upon the resistance QTL intervals pinpointed through a genome-wide association study, two potential resistance loci were localized on chromosome 2 of the potato genome, spanning the regions between 38–38.6 Mb and 41.3–42.7 Mb. These intervals accounted for 18.03% of the total phenotypic variance and are presumed to be the primary QTLs underlying scab resistance. Building upon this foundation, we expanded the hybrid progeny population, conducted resistance assessments, selected individuals with extreme phenotypes, developed molecular markers, and conducted fine mapping of the resistance gene. A phenotypic evaluation of scab resistance was carried out using a pot-based inoculation test on 175 potato hybrid progenies to characterize the F1 generation population. Twenty lines exhibiting high resistance and thirty lines displaying high susceptibility were selected for investigations. Within the preliminary mapping interval on potato chromosome 2 (spanning 38–43 Mb), a total of 214 SSR (Simple Sequence Repeat) and 133 InDel (Insertion/Deletion) primer pairs were designed. Initial screening with parental lines identified 18 polymorphic markers (8 SSR and 10 InDel) that demonstrated stable segregation patterns. Validation using bulked segregant analysis revealed that 3 SSR markers (with 70–90% linkage) and 6 InDel markers (with 70–90% linkage) exhibited significant co-segregation with the resistance trait. A high-density genetic linkage map spanning 104.59 cm was constructed using 18 polymorphic markers, with an average marker spacing of 5.81 cm. Through linkage analysis, the resistance locus was precisely mapped to a 767 kb interval (41.33–42.09 Mb) on potato chromosome 2, flanked by SSR-2-9 and InDel-3-9. Within this refined interval, four candidate disease resistance genes were identified: RHC02H2G2507, RHC02H2G2515, PGSC0003DMG400030643, and PGSC0003DMG400030661. This study offers novel insights into the genetic architecture underlying scab resistance in potato. The high-resolution mapping results and characterized markers will facilitate marker-assisted selection (MAS) in disease resistance breeding programs, providing an efficient strategy for developing cultivars with enhanced resistance to Streptomyces scabies. Full article

Autosomal trisomy, a genetic disorder characterized by the presence of an extra autosome, is a rare but important chromosomal abnormality in horses, often associated with infertility, developmental abnormalities, and reduced life expectancy. This study represents the largest population-level screening for autosomal trisomy in horses; the analysis used single nucleotide polymorphism (SNP) panel genotype intensity data from 17,078 horses, 6601 of which were juveniles (i.e., ≤12 months of age) when genotyped. Using methodologies adapted from similar screening studies in cattle, the only aneuploidy detected was trisomy 27 in two juvenile male Irish Sport Horses (ISH) (0.03% prevalence among juveniles or 0.01% prevalence in the overall population). One ISH colt was cytogenetically confirmed and displayed no overt external phenotypic abnormalities, while cytogenetics was not undertaken on the other ISH colt, nor was it phenotypically assessed. Parentage analysis revealed that one ISH colt inherited two different copies of chr27 from the sire, demonstrating heterodisomy, likely due to a nondisjunction event during meiosis I in the sire. The other ISH colt inherited two different copies of chr27 from the dam, also indicating heterodisomy; the dam was 23 years of age when the colt was born. Based on the observed prevalence of autosomal trisomy, it can be estimated that at least 3 foals per 10,000 live births are likely to have autosomal trisomy. Though, given that only 74 (i.e., 0.004%) of horses were genotyped within a month of birth, this is likely an underestimate. The economic consequence of undiagnosed trisomy in high-value breeding horses that are potentially infertile could be substantial. As horse genotyping for parentage verification and discovery is transitioning to medium-density single nucleotide polymorphism panels, routine genomic screening for autosomal aneuploidy could be readily undertaken and potentially should form a standard screening prerequisite along with other genetic defects at horse sales. Currently, thoroughbred horses registered for racing are not genotyped, and only a limited number of sport horse studbooks are using SNP genotyping. This highlights an opportunity for those already genotyping to expand their support for breeders through low-cost, high-value chromosomal screening at the time of registration rather than incurring additional costs over the horse’s life cycle to determine the root cause of certain phenotypes owing to the undiagnosed trisomy. Full article

Perkinsiodendron macgregorii, an endangered Chinese endemic tree with high ornamental and ecological value, faces extinction threats due to its poor natural regeneration and habitat degradation. Despite the urgent need for its conservation, the genetic architecture and population differentiation mechanisms of this taxon remain poorly understood, hindering science-based protection strategies. We conducted comprehensive chloroplast genomic analyses of 134 individuals from 13 natural populations to inform science-based conservation. The chloroplast genome (158,538–158,641 bp) exhibited conserved quadripartite organization, with 113 functional genes and elevated GC contents in IR regions (42.99–43.02%). Population-level screening identified 741 SNPs and 678 indels, predominantly in non-coding regions (89.8%), with three distinct phylogeographic clades revealing north-to-south genetic stratification. The northern clade (Clade A) demonstrates the highest haplotype diversity and nucleotide diversity, followed by the southern clade (Clade C), while the central clade (Clade B) exhibits signals of genetic erosion (Tajima’s D > 3.43). Based on the genetic diversity distribution and phylogenetic tree of extant P. macgregorii, we inferred that the northern populations represent ancestral groups, while the Wuyi Mountains region and Nanling Mountains region served as glacial refugia. It is imperative to implement in situ conservation in these two regions. Additionally, ex situ conservation should involve collecting seed from representative populations across all three clades and establishing isolated cultivation lines for each clade. These findings establish a genomic framework for conserving endangered plants. Full article

Background/Objectives: Prostate cancer is the most common cancer among men globally and a leading cause of cancer-related death. Germline genetic evaluation is increasingly recognized as essential for men with high-risk features such as a strong family history or advanced disease. Methods: Comprehensive genetic risk assessment should integrate three components: family history (FH), rare pathogenic mutations (RPMs), and polygenic risk scores (PRS). RPMs in DNA repair genes (e.g., BRCA2, CHEK2, ATM) can inform screening, prognosis, and treatment strategies, particularly for metastatic or aggressive disease. PRS, derived from common genetic variants, provides a personalized and independent measure of prostate cancer risk and may guide decisions on screening intensity and timing. Results: Although PRS cannot yet differentiate between indolent and aggressive cancer, it has the potential to stratify men into low and high-risk categories more effectively than FH or RPMs alone. Knowledge of specific RPMs can influence treatment decisions in clinically advanced prostate cancer. Challenges in clinical implementation include limited provider awareness, underutilization of genetic counseling, and lack of diversity in genomic datasets, which can lead to misdiagnoses. Emerging technologies and digital tools are being developed to streamline genetic testing and counseling. Population-level strategies and tailored screening protocols based on genetic risk are under active investigation. Conclusions: While early evidence suggests high satisfaction with genetic testing among patients, further studies in diverse populations are needed. Integration of germline genetic information into prostate cancer management offers promising avenues for personalized screening, surveillance, and treatment, ultimately aiming to reduce morbidity and mortality. Full article

Dysregulated expression of nuclear receptor superfamily 4 group A member 2 (NR4A2) has recently been associated with autistic spectrum disorder (ASD), speech impairment, and neurodevelopmental delay (NDD); however, its precise role in the prevalence and etiopathogenesis of ASD has not been fully elucidated. Herein, we aimed to explore the role of NR4A2 variants in the genetic underpinnings of ASD among Saudi children of different age ranges and phenotype severities. A total of 338 children with ASD from 315 unrelated families (293 simplex, 2 quads, and 1 quintet) were screened for NR4A2 variants via exome sequencing (ES) of the genomic DNA extracted from peripheral blood mononuclear cells (PBMCs), after which the probands with identified NR4A2 variants were further subjected to trio genetic analyses. ES analysis revealed 10 de novo NR4A2 variants (5 indels/nonsense, 2 missense, and 3 variants affecting splicing) in 8 unrelated probands (2.37%) and 2 affected siblings from 8 unrelated families (6 simplex (2.04%) and 2 quads (8.7%)). Three NR4A2 variants were notably recurrent among both affected and unaffected carriers. All identified indels and two splicing variants met the criteria for pathogenic/loss-of-function (LoF) variants according to the ACMG classification (PVS1), whereas the missense variants were classified as of uncertain significance (VUS). This study is among the first to identify such a high frequency of recurrent variants in an ASD cohort, suggesting their significant contribution to the etiopathogenesis of ASD within this population. Full article

Newborn Bloodspot Screening (NBS) has significantly advanced early disease detection, preventing severe disability and infant mortality. The anticipated integration of genomic technologies into NBS (gNBS) promises earlier diagnosis and targeted treatments. However, it also introduces complexities that necessitate enhanced consent processes. Dynamic Consent Platforms (DCPs), with their layered information and modifiable preferences, may fulfil this rapidly evolving need. This qualitative study explored NBS and genomic interest-holder perspectives on (i) challenges in obtaining informed consent within the current and genomic NBS contexts, and (ii) the acceptability, feasibility, and utility of DCPs for genomics. Sixteen key interest-holders involved in NBS/genomic consent (midwives, genetic counsellors, geneticists, researchers, pathologist, consumer advocate) completed a semi-structured interview. Thematic analysis identified four main themes: (i) looking towards genomic expansions, (ii) systemic issues, (iii) genomic consent information, and (iv) Dynamic Consent Platforms. Participants emphasised revising the timing of consent processes and standardising consent training for clinicians. A nationally standardised DCP was perceived as valuable for addressing consent challenges within gNBS; however, concerns were raised regarding accessibility of online resources for vulnerable populations and integrating DCPs into healthcare systems. Recommendations for future research and clinical implications in this evolving field are discussed. Full article

Background: Adjuvant chemotherapy (ACT) can improve survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC), but its benefit varies significantly across individuals. Identifying patients who are likely to benefit from ACT remains a critical challenge in precision oncology. Methods: We constructed a meta-database from two publicly available NSCLC gene expression datasets (GSE37745 and GSE29013) to address population heterogeneity. Feature selection was performed using Cox-based univariate screening with leave-one-out cross-validation. We then developed and compared three survival modeling frameworks: bagging with elastic net penalized Cox regression, Random Survival Forests (RSF), and DeepSurv neural survival networks. All models incorporated clinical covariates and selected genomic features to predict survival and recommend ACT versus observation (OBS). Results: Across 155 patients, RSF achieved the highest predictive performance, with a test concordance index (C-index) of0.885. Model-based recommendations were associated with improved survival in both training and test datasets, as confirmed by Kaplan–Meier analysis. Key genomic features identified included TTR, MTURN, and ETV3, suggesting their potential relevance in treatment response stratification. DeepSurv demonstrated strong predictive accuracy (C-index = 0.982) but less distinct survival curve separation compared to RSF. Conclusions: Our findings demonstrate that machine learning-driven survival models, particularly RSF, can effectively identify NSCLC patients who may benefit from ACT. This approach supports data-driven, individualized chemotherapy decision-making and contributes to advancing personalized treatment strategies in early-stage NSCLC. Full article

Speed and endurance are the primary goals in racehorse breeding. The Grassland-Thoroughbred is a newly developed breed in northern China that combines speed, endurance, and environmental adaptability. However, current research on the genetic background of this breed and the genes associated with athletic performance remains limited. We conducted whole-genome resequencing on Mongolian (MG), Thoroughbred (TB), Xilingol (XL), and Grassland-Thoroughbred (CY) horses, generating 3813.74 Gb of clean data after quality control. The number of transitions was significantly higher than that of transversions. The SNPs were mainly located in intergenic regions, followed by intronic regions. Principal component analysis, population structure analysis, and phylogenetic tree results indicated that the CYs had a distinct genetic background from MGs, TBs, and XLs, but based on PCA and phylogenetic clustering, they showed greater genetic similarity to Thoroughbreds. Using fixation index (Fst) and nucleotide diversity ratio (π ratio) analyses between CYs and the other three horse populations, 70, 76, and 80 candidate genes were identified from the intersection of the two methods, respectively. A total of 179 candidate genes were obtained from the union of the three groups. Candidate genes associated with athletic performance (ATF2, NDUFS7, PRKG1, IGFN1, MTOR, TTN) and growth and development (MTOR, IGFN1, COL21A1, NEDD4, PIEZO1) were screened. These genes are related to athletic ability and developmental processes in the CY population. Our study reveals genomic information associated with important traits in Grassland-Thoroughbreds and identifies valuable candidate genes, laying a foundation for future breeding and trait association studies. Full article

Copy number variation (CNV) is an important source of genetic variation. However, studies utilizing whole-genome sequencing to investigate CNVs in horse populations and their effects on traits remain relatively limited. This study aims to address the lack of research on the impact of copy number variation (CNV) on racing performance in horse populations, providing new insights for locally bred racing breeds. We analyzed 60 offspring derived from the crossbreeding of Thoroughbred horses and Xilingol horses. These horses were temporarily named “Grassland-Thoroughbred” and were divided into two groups: 30 racing horses and 30 non-racing horses. A total of 89,527 CNVs were identified. After merging overlapping CNVs, 982 copy number variation regions (CNVRs) were recognized, among which the racing horse group (RH) had 29 unique CNVRs, while the non-racing horse group (NR) had 4 unique CNVRs. In addition, a total of 195 genes overlapping with CNVRs were identified. Transcriptomic analysis revealed 120 differentially expressed genes, with MTPN expressed in both CNVR-overlapping genes and mRNA. Both CNVR-overlapping genes and differentially expressed genes were enriched in the MAPK signaling pathway; CNV may affect gene expression through gene dosage effects or regulatory mechanisms. Using Vst statistical analysis, we further screened candidate CNVRs in autosomes that exceeded the 95% differentiation threshold between the RH and NR populations. Several key genes associated with energy metabolism and muscle function were identified, including AGT, IGFN1, IMMPL2, SLC41A3, AOX4, and ACAD11. These findings provide new insights into the genetic structural variation in racing performance and adaptability, fill the gap in CNV studies in the genomics of Grassland-Thoroughbred horses, and offer valuable genomic data for optimizing breeding strategies in native racing horse populations. Full article