Search Results (13,214)

Disease resistance is one of the most important target traits for sugarcane genetic improvement. Sugarcane brown stripe (SBS) caused by Helminthosporium stenospilum is one of the most destructive foliar diseases, which not only reduces harvest cane yield but also sugar content. This study aimed to identify quantitative trait loci (QTL) and candidate genes associated with SBS resistance. Here, the phenotypic investigation in six field habitats showed a continuous normal distribution, revealing that the SBS resistance trait is a quantitative trait. Two high-density linkage maps based on the single-dose markers calling from the Axiom Sugarcane100K SNP chip were constructed for the dominant sugarcane cultivars YT93-159 (SBS-resistant) and ROC22 (SBS-susceptible) with a density of 2.53 cM and 2.54 cM per SNP marker, and mapped on 87 linkage groups (LGs) and 80 LGs covering 3069.45 cM and 1490.34 cM of genetic distance, respectively. A total of 32 QTL associated with SBS resistance were detected by QTL mapping, which explained 3.73–11.64% of the phenotypic variation, and the total phenotypic variance explained (PVE) in YT93-159 and ROC22 was 107.44% and 79.09%, respectively. Among these QTL, four repeatedly detected QTL (qSBS-Y38-1, qSBS-Y38-2, qSBS-R8, and qSBS-R46) were considered stable QTL. Meanwhile, two major QTL, qSBS-Y38 and qSBS-R46, could account for 11.47% and 11.64% of the PVE, respectively. Twenty-five disease resistance candidate genes were screened by searching these four stable QTL regions in their corresponding intervals, of which Soffic.01G0010840-3C (PR3) and Soffic.09G0017520-1P (DND2) were significantly up-regulated in YT93-159 by qRT-PCR, while Soffic.01G0040620-1P (EDR2) was significantly up-regulated in ROC22. These results will provide valuable insights for future studies on sugarcane breeding in combating this disease. Full article

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article

Background: North Carolina Macular Dystrophy (NCMD) is a non-progressive inherited macular dystrophy characterized by marked phenotypic variability. The genetic etiology of NCMD remains largely unknown, and only a limited number of families have been reported in Europe. Methods: We performed an in-depth investigation of an Italian family affected by NCMD using an integrated approach that combined SNP-array analysis, whole-exome sequencing, and long-read whole-genome sequencing. Additionally, we conducted a comprehensive review of NCMD-related literature. Results: We identified a novel 98 Kb duplication involving both PRDM13 and CCNC genes in a three-generation kindred, where the proband exhibited severe macular alterations, while all other affected family members presented with a milder clinical phenotype. A review of the literature suggests different genotype–phenotype correlations and similar penetrance for duplications and single-nucleotide variants (SNVs) in described families. Specifically, smaller duplications may be associated with more severe phenotypes, while SNVs exhibit high phenotypic variability. Conclusions: In this study, we describe the first NCMD Italian family, in which the integration of second- and third-generation sequencing methods enabled the identification of a novel pathogenic PRDM13 and CCNC duplication, thereby expanding the mutational spectrum of NCMD. Overall, these findings, together with the literature review, highlight the importance of selecting appropriate genetic testing approaches that allow the detection of non-coding variants and CNVs and thus enable accurate diagnosis and effective clinical management of patients and their families. Full article

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

Induced mutation plays an integral part in plant breeding as it introduces new variability among the population. A study was conducted in cowpeas [Vigna unguiculata (L.) Walp] to assess the yield divergence, heritability, genetic advance, and correlation among the M5 Tswana cowpea mutants. The experiment utilized seven genotypes under rainfed and supplementary irrigation during the 2022/23 and 2023/24 cropping seasons. The mutant lines demonstrated significant variations in days to 50% emergence (DE) and days to 50% flowering (DF). Tswana emerged earlier (5–7 days) and flowered in 21–54 days across the two seasons, compared to some of the mutant lines. The yield and yield components varied among some mutant lines and the control. Most importantly, mutants outperformed the Tswana control for some of these traits, indicating potential for genetic improvement. An analysis of genetic parameters revealed minimal environmental influences on some of the observed traits (GH, PN, GY), while others showed little environmental impact. Variation in heritability (H²) and genetic advance (GA%) between the two seasons limited the contribution of genotypic effects in the expression of the studied traits. Correlation analysis revealed strong and significant positive associations between DE and GH, as well as between DF and PW. Most traits, except DF and PW, were positively correlated with grain yield (GY), although the correlations were not significantly different. Cluster analysis grouped the genotypes into four distinct clusters. Principal component analysis (PCA) revealed the superiority of mutant lines (Tswana-300Gy-214, Tswana-400Gy mutant lines, and Tswana-500Gy-31) in their association with improved GY, pod weight (PW), 100-seed weight (100-SW), and seed number per pod (SN/P). Interestingly, the Tswana control formed a separate cluster and diverged from the mutants in PCA, suggesting that induced mutagenesis effectively targeted genes controlling the traits considered in this study. Full article

Background/Objectives: The increased risk of developing tendinopathies in athlete populations has led to investigations of several genes associated with tendon properties, suggesting that some individuals have a greater genetic predisposition for developing tendinopathies. The main purpose of this study was to investigate how the functional polymorphisms within the COL5A1, COL27A1 and TNC genes impact the risk of developing tendinopathies in high-level Croatian athletes. Methods: For this case–control genetic study, we recruited 63 high-level athletes with a diagnosis of tendinopathies and 92 healthy asymptomatic individuals as controls. All individuals were genotyped for three single-nucleotide polymorphisms (SNPs) within the COL5A1, COL27A1 and TNC genes using the pyrosequencing method. Results: TNC rs2104772 TT (p = 0.0089) and the T-T-T haplotype (p = 0.0234), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in cases versus controls, implicating a predisposition for tendinopathies. COL27A1 rs946053 GG (p = 0.0118) and the G-A-C haplotype (p = 0.0424), constructed from rs12722, rs946053 and rs2104772, were significantly overrepresented in controls, implicating a protective role. Conclusions: These results further support associations between functional polymorphisms within the COL27A1 and TNC genes and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in various populations and larger cohorts. Full article

Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead to ambiguity and further delay in diagnosis and medical management. Phenotyping, additional genetic testing, and functional studies can all add valuable information to help reclassify these variants. Here we demonstrate the clinical utility of epigenetic signatures in prioritizing variants of uncertain significance in genes associated with developmental delay (DD) and intellectual disability (ID). Methods: Genome sequencing was performed in a male with developmental delay. He was found to have VUSs in both PHF6 and DDB1 genes, linked with Börjeson–Forssman–Lehmann syndrome (BFLS) and White–Kernohan syndrome (WHIKERS), respectively. These two disorders share a similar phenotype but have distinct inheritance patterns and molecular pathogenic mechanisms. DNA methylation profiling (DNAm) of whole blood was performed using the clinically validated EpiSign assay. Results: The proband’s methylation profile demonstrated a strong correlation with the BFLS methylation signature, supporting the PHF6 variant as a likely cause of his neurodevelopmental disorder. Conclusions: Epigenetic testing for disorders with distinct methylation patterns can provide diagnostic utility when a patient presents with variants of uncertain significance in genes associated with developmental delay. Epigenetic signatures can also guide genetic counselling and family planning. Full article

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) was a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive decline in 604 individuals at risk for Alzheimer’s dementia. Here, we describe the genotyping, imputation, and quality control (QC) procedures for the genetic data of trial participants. Methods: DNA was extracted from either whole blood or serum, and genotyping was performed using the Infinium Global Diversity Array. Established sample and SNP QC procedures were applied to the genotyping data, followed by imputation using the 1000 Genomes Phase 3 v5 reference panel. Results: Significant study-site, specimen type, and batch effects were observed. A total of 494 individuals of inferred European ancestry and 58 individuals of inferred African ancestry were included in the final imputed dataset. Evaluation of the imputed APOE genotype against gold-standard sequencing data showed high concordance (98.2%). We replicated several known genetic associations identified from previous genome-wide association studies, including SNPs previously linked to adiponectin (rs16861209, p = 1.5 × 10⁻⁵), alpha-linolenic acid (rs174547, p = 1.3 × 10⁻⁷), and alpha-tocopherol (rs964184, p = 0.003). Conclusions: This dataset represents the first genetic resource derived from a dietary intervention trial focused on cognitive outcomes. It enables investigation of genetic contributions to variability in cognitive response to the MIND diet and supports integrative analyses with other omics data types to elucidate the biological mechanisms underlying cognitive decline. These efforts may ultimately inform precision nutrition strategies to promote cognitive health. Full article

High-grade serous ovarian cancer (HGSC) is a heterogeneous disease. RNA sequencing (RNAseq) of bulk solid tissue is of limited use in these populations due to heterogeneity. Single-cell RNA-seq (scRNA-seq) allows for the identification of diverse genetic compositions of heterogeneous cell populations. New computational methodologies are now available that use scRNAseq results to estimate cell type proportions in bulk RNAseq data. We performed bulk RNA-seq gene expression analysis on 112 HGSC specimens and 12 benign fallopian tube (FT) controls. We identified several publicly available scRNAseq datasets for use as annotation and reference datasets. Deconvolution was performed with MUlti-Subject SIngle Cell Deconvolution (MuSiC) to estimate cell type proportions in the bulk RNA-seq data. Datasets from the Cancer Genome Atlas (TCGA). HGSC repositories were also evaluated. Clinical variables and percentages of cell types were compared for differences in clinical outcomes and treatment results. Pathway enrichment analysis was also performed. Different annotations for referenced scRNA-seq datasets used for deconvolution of bulk RNA-seq data revealed different cellular proportions that were significantly associated with clinical outcomes; for example, higher proportions of macrophages were associated with a better response to primary chemotherapy. Our deconvolution study of bulk RNAseq HGSC samples identified cell populations within the tumor that may be associated with some of the observed clinical outcomes. Full article

The increasing demand for food to meet the needs of the planet’s growing population requires, among other factors, greater and improved meat production. Meat quality is determined by key consumer-preferred traits, particularly tenderness, juiciness, and flavor. Recently, interest has grown in analyzing the genes associated with these phenotypic characteristics. Single-nucleotide polymorphisms (SNPs) are common genomic variations in cattle and represent the most widely used molecular markers. Research on SNP variation is now a major focus of genomic studies aimed at improving meat quality. Leptin levels reflect the amount of adipose tissue in meat, also known as marbling. Several SNPs in the leptin gene and its receptor have been linked to this meat quality trait. Similarly, SNPs in the calpain/calpastatin system play a significant role in postmortem muscle proteolysis and pork tenderness. This review examines these genetic variants as markers involved in the expression of phenotypic traits in meat products and explores their mechanisms of action. Additionally, it provides insights into the genetic variants associated with production-related characteristics. Full article

Browning significantly impacts the commercial value of luffa (luffa cylindrica) and is primarily driven by the metabolic processes of phenolic acids. Investigating changes in phenolic acids during browning aids in understanding the physiological mechanisms underlying this process and provides a basis for improving storage, processing, variety breeding, and utilization of germplasm resources. This study compared browning-resistant (‘30’) and browning-sensitive (‘256’) luffa varieties using high-throughput sequencing and metabolomics techniques. The results revealed 55 genes involved in the phenylpropanoid biosynthesis pathway, including 8 phenylalanine ammonia-lyase (PAL) genes, 20 peroxidase (POD) genes, 2 polyphenol oxidase (PPO) genes associated with tyrosine metabolism, and 37 peroxisome-related genes. Real-time quantitative (qPCR) was employed to validate 15 browning-related genes, revealing that the expression levels of LcPOD21 and LcPOD6 were 12.5-fold and 25-fold higher in ‘30’ compared to ‘256’, while LcPAL5 and LcPAL4 were upregulated in ‘30’. Enzyme analysis showed that catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were higher in ‘30’ than in ‘256’. Conversely, superoxide dismutase (SOD) and polyphenol oxidase (PPO) activities were reduced in ‘30’, whereas CAT activity was upregulated. The concentrations of cinnamic acid, p-coumaric acid, trans-5-O-(4-coumaroyl)mangiferic acid, and caffealdehyde were lower in browning-resistant luffa ‘30’ than in browning-sensitive luffa ‘256’, suggesting that their levels influence browning in luffa. These findings elucidate the mechanisms underlying browning and inform strategies for the storage, processing, and genetic improvement of luffa. Full article

Background: Inherited thrombophilia is increasingly recognized as a contributing factor to placental vascular pathology and adverse pregnancy outcomes. While the clinical implications are well-established, fewer studies have systematically explored the histopathological changes associated with specific genetic mutations in thrombophilic pregnancies. Materials and Methods: This retrospective observational study included two cohorts of placental samples collected between September 2020 and September 2024 at a tertiary maternity hospital. Group 1 included women diagnosed with hereditary thrombophilia, and Group 2 served as controls without known maternal pathology. Placentas were examined macroscopically and histologically, with pathologists blinded to group allocation. Histological lesions were classified according to the Amsterdam Consensus and quantified using a composite score (0–5) based on five key vascular features. Results: Placental lesions associated with maternal vascular malperfusion—including infarctions, intervillous thrombosis, stromal fibrosis, villous stasis, and acute atherosis—were significantly more frequent in the thrombophilia group (p < 0.05 for most lesions). A combination of well-established thrombophilic mutations (Factor V Leiden, Prothrombin G20210A) and other genetic polymorphisms with uncertain clinical relevance (MTHFR C677T, PAI-1 4G/4G) showed moderate-to-strong correlations with histopathological markers of placental vascular injury. A composite histological score ≥3 was significantly associated with thrombophilia (p < 0.001). Umbilical cord abnormalities, particularly altered coiling and hypertwisting, were also more prevalent in thrombophilic cases. Conclusions: Thrombophilia is associated with distinct and quantifiable placental vascular lesions, even in pregnancies without overt clinical complications. The use of a histological scoring system may aid in the retrospective identification of thrombophilia-related placental pathology and support the integration of genetic and histologic data in perinatal risk assessment. Full article

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Predicting its progression is crucial for preventing late-stage AMD, as it is an irreversible retinal disease. Both genetic factors and retinal images are instrumental in diagnosing and predicting AMD progression. Previous studies have explored automated diagnosis using single fundus images and genetic variants, but they often fail to utilize the valuable longitudinal data from multiple visits. Longitudinal retinal images offer a dynamic view of disease progression, yet standard Long Short-Term Memory (LSTM) models assume consistent time intervals between training and testing, limiting their effectiveness in real-world settings. To address this limitation, we propose time-varied Long Short-Term Memory (TV-LSTM), which accommodates irregular time intervals in longitudinal data. Our innovative approach enables the integration of both longitudinal fundus images and AMD-associated genetic variants for more precise progression prediction. Our TV-LSTM model achieved an AUC-ROC of 0.9479 and an AUC-PR of 0.8591 for predicting late AMD within two years, using data from four visits with varying time intervals. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article