Search Results (102)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and neurodegeneration. While its etiology remains unclear, both genetic and environmental factors, including oxidative stress, have been implicated in the development of the disease. The base excision repair (BER) pathway plays a critical role in repairing oxidative DNA damage. This study investigated the association between polymorphisms in BER-related genes and MS susceptibility in a Central European population. Ten SNPs across seven BER genes were genotyped in 102 patients with MS and 118 healthy controls. Six SNPs were significantly associated with MS. Increased risk was observed for rs25478 in XRCC1 (OR = 2.37, 95% CI: 1.44–3.91, p < 0.0001), rs3087404 in SMUG1 (OR = 2.80, 95% CI: 1.49–5.26, p = 0.0012), and rs3219493 in MUTYH (OR = 2.23, 95% CI: 1.35–3.67, p = 0.0018). Conversely, reduced risk was associated with rs2307293 in MBD4 (OR = 0.42, 95% CI: 0.23–0.78, p = 0.006), rs3219489 in MUTYH (OR = 0.55, 95% CI: 0.31–0.97, p = 0.038), and rs4135054 in TDG (OR = 0.52, 95% CI: 0.29–0.94, p = 0.031). Haplotype analysis was performed for SNPs in strong linkage disequilibrium. Only rs3219489 and rs3219472 within the MUTYH gene showed strong LD (r² = 0.90), justifying haplotype-based analysis. Among four inferred haplotypes, the rare G–C haplotype was significantly associated with reduced MS risk (Score = −2.10, p = 0.035), suggesting a protective effect of this allele combination. Other SNPs not in LD were analyzed using a multivariable logistic regression model. Significant associations with decreased MS risk were found for rs1052133 in OGG1 (OR = 0.57, p = 0.043), rs2307293 in MBD4 (OR = 0.16, p = 0.010), and rs4135054 in TDG (OR = 0.38, p < 0.001), while rs3087404 in SMUG1 increased MS risk (OR = 1.98, p = 0.013). These results suggest that genetic variation in BER genes, including both single SNP effects and haplotypes, contributes to MS susceptibility. Further studies are warranted to explore the functional consequences of these variants and validate findings in larger, independent cohorts. Full article

Cutaneous adverse reactions (CARs) are common complications of epidermal growth factor receptor (EGFR) inhibitor therapy, with papulopustular eruptions and paronychia being the most frequent. Growing scientific evidence implies that Staphylococcus aureus is involved in the pathogenesis of these reactions. This observational prospective study characterized 42 S. aureus strains isolated from CARs, analyzing antibiotic resistance, biofilm formation, soluble virulence factors, and virulence/resistance genes using multiplex polymerase chain reaction (PCR). S. aureus was identified in 90% of lesions; in 33% of cases, nasal and skin isolates were genetically identical. High resistance rates were noted for penicillins (85%) and tetracyclines (57%), while all strains remained susceptible to fluoroquinolones, vancomycin, and rifampicin. All isolates formed biofilms, and DNase/esculinase production significantly correlated with CAR severity. An enzymatic score based on these markers was associated with an 18-fold increased risk of severe reactions. Genotypically, clfA and clfB were prevalent (85.7%), while exotoxin genes were less common. These findings support a key role for S. aureus in exacerbating CARs via antibiotic resistance, biofilm production, and the expression of virulence factor. Additionally, we emphasize the role of routine microbial screening—including nasal swabs—and therapy guided by antibiograms. Furthermore, the enzymatic score may further be validated as a predictive biomarker. Full article

Rice is a staple food for over half of the world’s population, and it is grown in over 100 countries. Rice blast disease can cause 10% to 30% crop loss, enough to feed 60 million people. Breeding for resistance can help farmers avoid costly fungicides. This study assessed the relationship between rice blast disease and zinc or anthocyanin content in biofortified rice. Susceptibility to foliar and panicle blast was assessed in a rice panel which differed on grain zinc content and pigmentation. A rice panel (n = 23) was challenged with inoculum of two isolates of Magnaporthe oryzae in a screenhouse-based assay. The zinc content with foliar blast severity was analyzed in the leaves and grain of a subset of non-inoculated rice plants. The effect of foliar zinc supplementation on seedlings was assessed by varying levels of zinc fertilizer solution on four blast susceptible cultivars at 14 days after planting (DAP), followed by inoculation with the blast pathogen at 21 DAP. Foliar blast severity was scored on a 0–9 scale at 7 days after inoculation. The rice panel was scored for anthocyanin content, and the data were correlated with foliar blast severity. The panel was grown in the field, and panicle blast, grain yield and yield-related agronomic traits were measured. Significant differences were observed in foliar blast severity among the rice genotypes, with IRBLK-KA and IR96248-16-2-3-3-B having mean scores greater than 4, as well as BASMATI 370 (a popular aromatic variety), while the rest of the genotypes were resistant. Supplementation with foliar zinc led to a significant decrease in susceptibility. A positive correlation was observed between foliar and panicle blast. The Zn in the leaves was negatively correlated with foliar blast severity, and had a marginally positive correlation with panicle blast. There was no relationship between foliar blast severity and anthocyanin content. Grain yield had a negative correlation with panicle blast, but no correlation was observed between Zn in the grain and grain yield. This study shows that Zn biofortification in the grain may not enhance resistance to foliar and panicle blast. Furthermore, the zinc-biofortified genotypes were not agronomically superior to the contemporary rice varieties. There is a need to apply genomic selection to combine promising alleles into adapted rice genetic backgrounds. Full article

Background: Developmental delay and intellectual disability (DD/ID) are frequently accompanied by epilepsy, and growing evidence implicates variants in voltage-gated calcium channel genes in their pathogenesis. This study aimed to investigate the association of polymorphisms in CACNA1A, CACNA1C, and CACNA1H with DD/ID and epilepsy comorbidity in Korean children. Methods: We retrospectively analyzed 141 pediatric patients diagnosed with DD/ID who underwent whole-exome sequencing (WES) and were not found to have pathogenic monogenic variants. Nine single-nucleotide polymorphisms (SNPs) across CACNA1A, CACNA1C, and CACNA1H were selected based on functional annotation scores and prior literature. Genotype data were extracted from WES variant files, and allele and genotype frequencies were compared with control data from the gnomAD East Asian population and the Korean Reference Genome Database (KRGDB). Subgroup analyses were performed according to epilepsy comorbidity. Results: The CACNA1A rs16023 variant showed a significantly higher B allele frequency in DD/ID patients than in both control datasets and was also associated with epilepsy comorbidity. Genotype distribution analysis revealed that the BB genotype of rs16023 was more frequent in patients with epilepsy. Conclusions: The CACNA1A rs16023 variant may contribute to genetic susceptibility to DD/ID and epilepsy in Korean children, potentially through regulatory mechanisms. These findings support the relevance of calcium channel genes in neurodevelopmental disorders and highlight the importance of integrating functional annotation in variant prioritization. Full article

Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS) that leads to inflammation and demyelination, manifesting in either a relapsing–remitting or progressive form. As a multifactorial disease, MS involves both genetic and environmental factors, with a known significant contribution from human leukocyte antigen (HLA) genes, mainly represented by the HLA-DRB1 and HLA-DQB1 loci, which have been linked to either susceptibility or protection, but variably across populations and ethnic groups. We aimed to study the distribution and polymorphism of HLA-DRB1 and HLA-DQB1 alleles in a population with MS from the southern Moroccan region, in comparison with healthy controls. Materials and Methods: A cross-sectional study was conducted over a period of 2 years (2022–2024) in a MS cohort including 40 patients and 100 healthy controls. DRB1 and DQB1 HLA genotyping was performed using a high-resolution reverse sequence-specific oligonucleotide (SSO) method, based on the Luminex system (xMAP technology, One lambda^®). Data were analyzed using SPSS 26; differences in allele frequencies were evaluated by the Chi-square test and Fisher’s exact test. OR (95% CI) was calculated, and FDR corrections were applied for multiple testing. Results: Among the various HLA-DRB1 and DQB1 alleles studied, including those considered as predisposing to MS, the DQB1*02:01 and DRB1*15:01 alleles were more prevalent in MS patients, with 40% and 8.8% vs. 16% and 4.08% in controls respectively, although these differences were not statistically significant (p = 0.06 and p = 0.12). Likewise, the DRB1*15:01-DQB1*06:02 association was significantly more prevalent in the MS group (9%, p = 0.004). In contrast, the DRB1*07:01 allele, linked to protection against MS in many populations, was significantly predominant in controls (17%, p = 0.004). Similarly, the DRB1*07:01–DQB*02:01 combination was rather more frequent in controls (12%, p = 0.01). Confronted to MS clinical forms, we remarkably noted that the DRB1*13:03 allele was found only among relapsing–remitting MS (RRMS) patients (6%, p = 0.003), while DQB1*02:01 was significantly associated with RRMS (42.1%) and primary progressive MS (41%, p = 0.001), with an intermediate Expanded Disability Status Scale (EDSS) score, which may indicate a possible link with disease progression and severity. Conclusions: The results of our study highlighted particular HLA alleles, DRB1 and DQB1, alone or in combination, as potential immunogenic factors of susceptibility to MS in a population from southern Morocco, while other alleles seem rather to protect against the disease. This HLA polymorphism is also reflected in the clinical forms of the disease, showing a tendency toward severity for certain alleles. However, such preliminary results need to be consolidated and confirmed by studies carried out on a larger population sample, and compared with others on a national scale. Full article

Background: Epidemiological studies suggest lung cancer results from the combined effects of smoking and genetic susceptibility. The clinical application of polygenic risk scores (PRSs), derived from combining the results from multiple germline genetic variants, have not yet been explored in a lung cancer screening cohort. Methods: This was a post hoc analysis of 9191 non-Hispanic white subjects from the National Lung Screening Trial (NLST), a sub-study of high-risk smokers randomised to annual computed tomography (CT) or chest X-ray (CXR) and followed for 6.4 years (mean). This study’s primary aim was to examine the relationship between a composite polygenic risk score (PRS) calculated from 12 validated risk genotypes and developing or dying from lung cancer during screening. Validation was undertaken in the UK Biobank of unscreened ever-smokers (N = 167,796) followed for 10 years (median). Results: In this prospective study, we found our PRS correlated with lung cancer incidence (p < 0.0001) and mortality (p = 0.004). In an adjusted multivariable logistic regression analysis, PRS was independently associated with lung cancer death (p = 0.0027). Screening participants with intermediate and high PRS scores had a higher lung cancer mortality, relative to those with a low PRS score (rate ratios = 1.73 (95%CI 1.14–2.64, p = 0.010) and 1.89 (95%CI 1.28–2.78, p = 0.009), respectively). This was despite comparable baseline demographics (including lung function) and comparable lung cancer characteristics. The PRS’s association with lung cancer mortality was validated in an unscreened cohort from the UK Biobank (p = 0.002). Conclusions: In this biomarker-based cohort study, an elevated PRS was independently associated with dying from lung cancer in both screening and non-screening cohorts. Full article

Black knot (BK) disease, caused by Apiosporina morbosa (Schwein.) v. Arx, significantly afflicts Japanese plums (Prunus salicina L.), resulting in substantial economic losses due to its destructive invasion of branches and trunks. Phenotyping for disease severity is critical to understanding resistance and susceptibility across diverse genotypes. In this study, 200 Japanese plum trees from a mixed lineage breeding program were phenotyped for BK severity using a rating scale from 0 to 5. Trees were rated by two independent raters and repeated on a second day, in early spring 2023, before leaf emergence, for peak visibility. The rating system was designed to capture varying levels of infection, with 0 representing no symptoms and 5 indicating severe infection with major effects to the tree’s overall health. Compared to data from 2015 and 2018, there was a noticeable increase in the number of heavily diseased trees relative to symptom-free trees. In 2023, the proportion of completely resistant trees remained the same as in 2018, suggesting true resistance. Median scores were calculated from four independent ratings per tree, comprised of two individuals on two different days, minimizing individual biases. Additionally, inter-rater reliability was assessed using the weighted Kappa statistic, which yielded a value of 0.903, indicating strong agreement between raters. This phenotypic assessment provides a robust dataset for correlation with genetic markers and supports further breeding efforts aimed at developing BK-resistant cultivars. Full article

Background/Objectives: The resistance to occult mastitis in dairy cows is a multifaceted trait influenced by a variety of genetic and environmental factors, posing significant challenges to its prevention and treatment. Methods: In this study, a cohort of 389 Holstein dairy cows was selected for investigation. The genes NOD2, CXCR1, SPP1 and LF, which are implicated in resistance to occult mastitis, were genotyped utilizing the efficient and cost-effective Kompetitive Allele-Specific PCR (KASP) technology. Additionally, the study analyzed the association between various single nucleotide polymorphisms (SNPs) and the somatic cell score in Holstein dairy cows. Multi-locus penetrance variance analysis (MPVA) analysis was also conducted to assess the resistance of different genotypic combinations to recessive mastitis in dairy cows. A genotyping kit for occult mastitis resistance was developed. Subsequently, 300 Holstein cows were randomly selected to evaluate the accuracy of the kit’s classification and resistance detection. Results: The findings revealed that the most effective genotype combination was SPP1(AA)-CXCR1(CC)-NOD2(CA)-LF(GA). Upon verification, the genotyping kit for recessive mastitis resistance in dairy cows exhibited an accuracy rate of 100% for individual genotyping and 95.90% for resistance detection. Conclusions: From the perspective of disease resistance genetics, this study lays a foundation for the precise management of dairy cow herds. It enables the early identification and removal of individuals susceptible to subclinical mastitis, thereby improving the overall quality of the cattle population. Full article

Developing crop varieties with combined salinity and waterlogging tolerance is essential for sustainable agriculture and food security in regions affected by these stresses. This process requires an efficient method to rapidly and accurately assess the tolerance of multiple genotypes to these stresses. Our study examined the use of a pot trial in combination with the assessment of multiple traits to assess the tolerance of 100 wheat (Triticum aestivum L.) genotypes sourced from around the world to these combined stresses. The stresses were imposed on the plants using 100 mM NaCl and by submerging the root systems of the plants in their bathing solutions. The data gathered were subjected to principal component analysis (PCA), and an integrated score (IS) for each genotype was calculated based on multiple morpho-physiological traits; the score was used to rank the genotypes with respect to tolerance or susceptibility. There were significant differences among the 100 wheat genotypes in terms of the relative reductions in their growth parameters and chlorophyll contents, suggesting a rich, genetic diversity. To assess the accuracy of this methodology and to gain insight into the causes of tolerance or susceptibility, the five most tolerant (Misr4 (W85), Corack (W41), Kzyl-Sark (W94), Hofed (W57), BAW-1157 (W14)), and two least tolerant (Livingstong (W60) and Sunvale (W73)) genotypes were selected based on their IS and PCA analysis. These genotypes were then grown hydroponically with and without salinity stress. The data from this second trial were again subjected to PCA, and their IS were calculated; there was reasonable agreement in the ranking of the genotypes between the two trials. The most tolerant genotype (W85; Misr4 from Egypt) and most susceptible genotype (W73; Sunvale from Australia) were then examined in further detail in a third trial. Plants of Misr4 (W85) had lower Na⁺/K⁺ ratios, higher superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase activities, and higher glutathione concentrations. As a result, plants of Misr4 (W85) had lower concentrations of reactive oxygen species (H₂O₂ and O₂^•−) and malondialdehyde than those of Sunvale (W73). This study offers an efficient methodology for the assessment of multiple sources of germplasm for stress tolerance. It has also identified germplasm that can be used for future breeding work and for further research on the mechanisms of tolerance and susceptibility to combined salinity and waterlogging stresses. Full article

Grape phylloxera, Daktulosphaira vitifoliae (Fitch), is an economically significant pest of grapevines. Identification of phylloxera genotypes is an important aspect of management as genotypes differ in virulence and susceptibility to control using resistant rootstocks. Microsatellite markers developed on polyacrylamide gel systems have been the most widely used molecular method for phylloxera genotype identification, but this approach has been superseded by fluorescent capillary-based genotyping. The current study presents new laboratory methods for amplifying a standard set of eight phylloxera microsatellite markers using PCR-incorporated fluorescently labelled primers, genotyped on an ABI capillary platform. Comparison of allele size data scored on (i) polyacrylamide, (ii) capillary, and (iii) high-throughput sequencing (HTS) platforms revealed that the capillary genotyping most closely matched the HTS allele sizes, while alleles of loci originally scored on a polyacrylamide platform differ in size by up to three base pairs, mostly due to the presence of previously uncharacterised DNA sequence indels. Seven common clonal lineages of phylloxera known from Australia are proposed as reference samples for use in calibrating genotyping systems between platforms and laboratories to ensure universal scoring of allele sizes, providing a critical link for accurately matching previous phylloxera genotype studies with current research. Full article

Asthma is a common complex disease with susceptibility defined through an interplay of genetic and environmental factors. Responsiveness to asthma treatment varies between individuals and is largely determined by genetic variability. The polygenic score (PGS) approach enables an individual risk of asthma and respective response to drug therapy. PGS models could help to predict the individual risk of asthma using 26 SNPs of drug pathway genes involved in the metabolism of glucocorticosteroids (GCS), and beta-2-agonists, antihistamines, and antileukotriene drugs associated with the response to asthma treatment within GWAS were built. For PGS, summary statistics from the Trans-National Asthma Genetic Consortium GWAS meta-analysis, and genotype data for 882 individuals with asthma/controls from the Volga-Ural region, were used. The study group was comprised of Russian, Tatar, Bashkir, and mixed ethnicity individuals with asthma (N = 378) aged 2–18 years. and individuals without features of atopic disease (N = 504) aged 4–67 years from the Volga-Ural region. The DNA samples for the study were collected from 2000 to 2021. The drug pathway genes’ PGS revealed a higher odds for childhood asthma risk (p = 2.41 × 10⁻¹²). The receiver operating characteristic (ROC) analysis showed an Area Under the Curve, AUC = 0.63. The AUC of average significance for moderate-to-severe and severe asthma was observed (p = 5.7 × 10⁻⁹, AUC = 0.64). Asthma drug response pathway gene variant PGS models may contribute to the development of modern approaches to optimise asthma diagnostics and treatment. Full article

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 pol gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27–46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI (p < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients. Full article

Selection for the more efficient production of broilers has resulted in rapid growth rates. The aim was to review the existing knowledge on the effect of growth rate on broiler welfare. Genotypes with faster growth rates consistently demonstrate poorer gait scores and increased prevalence of disorders affecting their legs than slower-growing genotypes. Reduced mobility places faster-growing broilers at an increased risk of developing contact dermatitis, as they spend increased durations sitting in contact with litter. Poor walking ability, heavy body weights, and conformational differences such as proportionally larger breast muscle in genotypes with faster growth can impact a bird’s ability to walk and navigate the environment, making it difficult to access resources and express natural behaviors. Faster growth has also been associated with poor cardiovascular health, increased susceptibility to heat stress, increased prevalence of mortality, ascites, as well as multiple breast muscle myopathies. Feed restriction, a practice associated with hunger and frustration, may be used to control the growth of broiler breeders, with birds having higher growth potential typically experiencing higher restriction levels. Overall, there is strong evidence that fast growth rates negatively impact welfare, and that slower-growing genotypes show significantly improved welfare. Furthermore, some evidence suggests that even minor reductions in growth rate can lead to welfare improvements. Full article

Soil salinity results in reduced productivity in field peas, making soil salinity tolerance a critical breeding objective. In this study, four pot experiments were carried out in semi-controlled environments over four consecutive years to assess the contribution of seedling vigour to salinity tolerance at the seedling stage. Split-plot designs were used to assess the effect of salt stress (sodium chloride solution at 16 dSm⁻¹) and control conditions. Extensive sets of advanced breeding lines were used in 2018–2020 to assess growth differences in relation to the treatment, with elemental analysis used on a subset of 15 lines in 2021. A salt tolerance index (STI) was defined as a proportion of shoot biomass under salt stress (DWstress) relative to the shoot dry weight under control (DWctrl). Visual scores of salt stress were recorded on a 1–10 scale (1 = tolerant, 10 = susceptible) from salt stress treatments. The consistent positive and significant correlations (p < 0.01) between shoot DWctrl and DWstress indicated that vigorous genotypes maintained higher shoot DWstress. Both the shoot DWctrl and shoot DWstress had negative and significant (p < 0.01) correlations with visual scores of salt stress. Shoot DWstress showed strong positive correlations with STI (p < 0.01). Both the shoot DWctrl and Shoot DWstress had negative correlations (p < 0.01) with shoot Na⁺ whereas shoot DWstress had a positive correlation (p < 0.05) with root Na⁺ concentration. The results indicated that seedling vigour (measured as shoot DWctrl) contributed to salinity tolerance by maintaining improved shoot DWstress, limiting Na⁺ deposition in shoot and enduring less tissue damage in field pea seedlings. Additional field evaluations are required to establish the correlations of tolerance at seedling stage with yield under saline conditions. The insights obtained from this study may assist field pea breeders in identifying salt-tolerant parent plants, offspring, and breeding lines during the initial growth phases. Full article

Physical activity increases the risk of non-contact injuries, mainly affecting muscles, tendons, and ligaments. Genetic factors are recognized as contributing to susceptibility to different types of soft tissue injuries, making this broad condition a complicated multifactorial entity. Understanding genetic predisposition seems to offer the potential for personalized injury prevention and improved recovery strategies. The candidate gene analysis approach used so far, has often yielded inconclusive results. This manuscript reviews the most commonly studied genetic variants in genes involved in the musculoskeletal system’s structure and recovery processes (ACTN3, ACE, CKM, MLCK, AMPD1, IGF2, IL6, TNFα, CCL2, COL1A1, COL5A1, MMP3, and TNC). Referring to the literature, it was highlighted that single-gene analyses provide limited insight. On the other hand, novel genetic testing methods identify numerous variants of uncertain physiological relevance. Distinguishing between functionally important variants, modifying variants, and the thousands of irrelevant variants requires advanced bioinformatics methods and basic multiomics research to identify the key biological pathways contributing to injury susceptibility. Tools like the Total Genotype Score (TGS) and Polygenic Risk Score (PRS) offer a more holistic view by assessing the combined effect of multiple variants. However, these methods, while useful in research, lack clinical applicability. In conclusion, it is too early to determine the clinical implications of genetic variability as a tool for improving well-established training and injury prevention methods, as the predictive power of genetic testing for injury predisposition is currently low. Full article