Search Results (1,676)

While a global downward trend in rotavirus diarrhea cases has been observed following vaccine introduction, reassortment, genetic drift, and vaccine-escaping strains remain a concern, particularly in Sub-Saharan Africa. Here, we provide genomic insights into three equine-like G3P[8] rotavirus strains detected in Benin during the post-vaccine era. Whole-genome sequencing was performed using the Illumina MiSeq platform, and genomic analysis was conducted using bioinformatics tools. The G3 of the study strains clustered within the recently described lineage IX, alongside the human-derived equine-like strain D388. The P[8] is grouped within the lineage III, along with cognate strains from the GenBank database. Both the structural and non-structural gene segments of these study strains exhibited genetic diversity, highlighting the ongoing evolution of circulating strains. Notably, we identified a novel NSP2 lineage, designated NSP2-lineage VI. Amino acid comparisons of the G3 gene showed two conservative substitutions at positions 156 (A156V) and 260 (I260V) and one radical substitution at position 250 (K250E) relative to the prototype equine-like strain D388, the equine strain Erv105, and other non-equine-like strains. In the P[8] gene, three conservative (N195G, N195D, N113D) and one radical (D133N) substitutions were observed when compared with vaccine strains Rotarix and RotaTeq. These findings suggest continuous viral evolution, potentially driven by vaccine pressure. Ongoing genomic surveillance is essential to monitor genotype shifts as part of the efforts to evaluate the impact of emerging strains and to assess vaccine effectiveness in Sub-Saharan Africa. Full article

The rugose surface trait in pepper (Capsicum annuum L.), marked by ridges and depressions on the fruit epidermis, is linked to improved fruit texture. To investigate its regulatory basis, histological, textural, and transcriptomic differences, contrasting genotypes were analyzed. Histological analysis revealed that disorganized epidermal cell layers contribute to rugosity, with morphological differences emerging around 10 days post-anthesis (DPA). A computer-aided design (CAD)-based rugosity index (RI) was developed and showed strong correlation with sensory rugosity scores (R² = 0.659, p < 0.001). Texture analysis demonstrated that increasing surface rugosity was associated with reduced rupture force and hardness, as well as elevated pectinase activity. Comparative transcriptome profiling identified 10 differentially expressed genes (DEGs) related to microtubule dynamics (e.g., CA03g18310 and CA09g13510) and phytohormone signaling (e.g., CA03g35180 and CA08g12070), which exhibited distinct spatial and temporal expression patterns. These findings suggest that coordinated cytoskeletal remodeling and hormonal regulation drive epidermal disorganization, leading to surface rugosity and altered fruit texture. The study provides novel insights into the molecular basis of fruit surface morphology and identifies promising targets for breeding high-quality pepper cultivars. Full article

Variants in COL4A3 and COL4A4 cause autosomal dominant and recessive Alport syndrome, yet data on their distribution and clinical expression in different populations remain limited. This study investigated genotype–phenotype correlations and the distribution of COL4A3/COL4A4 variants in a Lithuanian Alport syndrome cohort. A total of 221 individuals from Lithuania were analyzed for COL4A3 and COL4A4 variants using either next-generation sequencing or Sanger sequencing in order to assess variant distribution and associated clinical features. Only individuals with pathogenic, likely pathogenic, or uncertain significance variants were included. Fifty-two individuals (38 index cases) with pathogenic, likely pathogenic, or variants of uncertain significance were identified, as follows: forty-eight were heterozygous, four had autosomal recessive, and four had digenic Alport syndrome. COL4A3 variants were found in 9.5% (21/221) and COL4A4 in 17.6% (39/221). Among the 28 identified variants, 18 were novel. Glycine substitutions (n = 8) were the most frequent and associated with worse kidney outcomes and increased hearing abnormalities. Hematuria was diagnosed significantly earlier than proteinuria (p = 0.05). Most individuals with autosomal dominant Alport syndrome had normal kidney function (eGFR > 90 mL/min/1.73 m²), while those with autosomal recessive Alport syndrome had more severe disease. Kidney failure occurred in 2/4 (50%) autosomal recessive Alport syndrome and 2/48 (4%) autosomal dominant Alport syndrome cases. A significant inverse correlation was found between eGFR and age in proteinuric individuals (r = –0.737; p = 0.013). This study expands knowledge of Alport syndrome in the Lithuanian population and contributes novel variant data to the global Alport syndrome genetic database. Full article

Heat stress is a critical constraint to poultry production in tropical regions, where the temperature–humidity index (THI) frequently exceeds thermoneutral thresholds. Despite growing interest in climate-resilient livestock, limited research has explored the genetic sensitivity of local chicken breeds to increasing THI levels. This study aimed to evaluate the genetic effects of increasing THI on growth performance traits in two tropical chicken breeds. The data included body weight (BW), average daily gain (ADG), and absolute growth rate (AGR) from 4,745 black-boned and 3,001 Thai native synthetic chickens across five generations. Growth data were collected from hatching to 12 weeks of age, whereas temperature and humidity were continuously recorded to calculate daily THI values. A reaction norm model was used to estimate genetic parameters and rate of decline of BW, ADG, and AGR traits under varying THI thresholds (THI70 to THI80). Results indicated that the onset of heat stress occurred at THI72 for black-boned chickens and at THI76 for Thai native synthetic chickens. Heritability estimates for BW, ADG, and AGR decreased as the THI increased in both chicken breeds. However, the Thai native synthetic chickens consistently exhibited higher genetic potential across all THI levels (average heritability: BW = 0.28, ADG = 0.25, AGR = 0.36) compared to the black-boned chickens (average heritability: BW = 0.21, ADG = 0.15, AGR = 0.23). Under mild heat stress (THI72), black-boned chickens showed sharp declines in all traits (average reduction in BW = −10.9 g, ADG = −0.87 g/day, AGR = −3.20 g/week), whereas Thai native synthetic chickens maintained stable performance. At THI76, both breeds experienced significant reductions, particularly in males. Estimated breeding values (EBVs) for AGR decreased linearly with THI, though Thai native synthetic chickens showed greater individual variability, with some birds maintaining stable or positive EBVs up to THI80—suggesting the presence of heat-resilient genotypes. In conclusion, Thai native synthetic chickens demonstrated superior thermotolerance and genetic robustness under increasing THI conditions. The identification of breed-specific THI thresholds and resilient individuals provides novel insights for climate-smart poultry breeding. These findings offer valuable tools for genetic selection, environmental management, and long-term adaptation strategies in response to global climate change. Full article

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Kiwifruit (Actinidia spp.) is a globally important economic fruit with high nutritional value. Fruit peelability, defined as the mechanical ease of separating the peel from the fruit flesh, is a critical quality trait influencing consumer experience and market competitiveness and has emerged as a critical breeding target in fruit crop improvement programs. The present review systematically synthesized existing studies on kiwifruit peelability, and focused on its evolutionary trajectory, genotypic divergence, quantitative evaluation, possible underlying mechanisms, and artificial manipulation strategies. Kiwifruit peelability research has advanced from early exploratory studies in New Zealand (2010s) to systematic investigations in China (2020s), with milestones including the development of evaluation metrics and the identification of genetic resources. Genotypic variation exists among kiwifruit genera. Several Actinidia eriantha accessions and the novel Actinidia longicarpa cultivar ‘Guifei’ exhibit superior peelability, whereas most commercial Actinidia chinensis and Actinidia deliciosa cultivars exhibit poor peelability. Quantitative evaluation highlights the need for standardized metrics, with “skin-flesh adhesion force” and “peel toughness” proposed as robust, instrument-quantifiable indicators to minimize operational variability. Mechanistically, peelability is speculated to be governed by cell wall polysaccharide metabolism and phytohormone signaling networks. Pectin degradation and differential distribution during fruit development form critical “peeling zones”, whereas ethylene, abscisic acid, and indoleacetic acid may regulate cell wall remodeling and softening, collectively influencing skin-flesh adhesion. Owing to the scarcity of easy-to-peel kiwifruit cultivars, artificial manipulation methods, including manual peeling benchmarking, lye treatment, and thermal peeling, can be employed to further optimize kiwifruit peelability. Currently, shortcomings include incomplete genotype-phenotype characterization, limited availability of easy-peeling germplasms, and a fragmented understanding of the underlying mechanisms. Future research should focus on methodological innovation, germplasm development, and the elucidation of relevant mechanisms. Full article

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. 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

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Understanding the alterations to the shoot and root traits of rapeseed (Brassica napus) in response to salt stress is vital for improving its ability to thrive in saline-prone regions. This research aims to evaluate the responses of shoot and root traits of rapeseed at the vegetative stage under salt- and salicylic acid-induced stress in hydroponic culture. Five parents and ten F₃ segregants of rapeseed were subjected to three treatments: T1: control, T2: 8 dSm⁻¹ salt, and T3: 8 dSm⁻¹ salt + 0.1 mM salicylic acid at 21 days of age. Salinity stress significantly reduced the estimated root surface area by 54% compared to control, highlighting the plasticity of roots under stress. The simultaneous application of salt and SA did not alleviate the salinity stress, but rather reinforced the degree of stress and decreased the number of leaves, diameter of the main axis, chlorophyll content, and estimated root surface area by 18.5%, 15.4%, 38.8%, and 23%, respectively, compared to T2. The parental genotype M-245 followed by F₃ genotype M-232×M-223 accounted for the higher overall estimated root surface area. These results provide novel insights into the responses of root traits in rapeseed breeding lines under dual treatment, which hold promising implications for future rapeseed breeding efforts focused on sustainable rapeseed production. Full article

Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. Results: All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the IGHMBP2 gene, consistent with CMT2S. Other variants were identified in the NEFH (CMT2CC), DYNC1H1 (CMT2O), and MPV17 (CMT2EE) genes. Notably, a previously unreported co-occurrence of MPV17 mutation and congenital heart disease was observed in one case. Conclusions: This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel IGHMBP2 variant and unique phenotypic associations provides new insights for future genotype–phenotype correlation studies. Full article

Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article

Porcine Rotavirus (PoRV), a predominant causative agent of neonatal diarrhea in piglets, shares substantial genetic homology with human rotavirus and represents a considerable threat to both public health and the global swine industry in the absence of specific antiviral interventions. The VP6 protein, an internal capsid component, is characterized by exceptional sequence conservation and robust immunogenicity, rendering it an ideal candidate for viral genotyping and vaccine development. In the present study, the recombinant plasmid pET28a(+)-VP6 was engineered to facilitate the high-yield expression and purification of the VP6 antigen. BALB/c mice were immunized to generate monoclonal antibodies (mAbs) through hybridoma technology, and the antigenic specificity of the resulting mAbs was stringently validated. Subsequently, a panel of truncated protein constructs was designed to precisely map linear B-cell epitopes, followed by comparative conservation analysis across diverse PoRV strains. Functional validation demonstrated that all three mAbs exhibited high-affinity binding to VP6, with a peak detection titer of 1:3,000,000 and exclusive specificity toward PoRVA. These antibodies effectively recognized representative genotypes such as G3 and X1, while exhibiting no cross-reactivity with unrelated viral pathogens; however, their reactivity against other PoRV serogroups (e.g., types B and C) remains to be further elucidated. Epitope mapping identified two novel linear B-cell epitopes, ¹²⁸YIKNWNLQNR¹³⁷ and ¹³⁸RQRTGFVFHK¹⁴⁷, both displaying strong sequence conservation among circulating PoRV strains. Collectively, these findings provide a rigorous experimental framework for the functional dissection of VP6 and reinforce its potential as a valuable diagnostic and immunoprophylactic target in PoRV control strategies. Full article

The primary objective of any conservation breeding program is to preserve the genetic diversity of populations. This objective is a persistent challenge, especially in small populations which are prone to loss of heterozygosity. In this study, we proposed a novel parent-selection strategy aimed at the long-term maintenance of high levels of genetic diversity. Our approach is based on estimating the Probability of Offspring Heterozygosity (POH)—the likelihood that a mating will produce heterozygous offspring—using SNP genotype data. This strategy was evaluated through computer simulations, where parental pairs with the highest POH values were preferentially selected to produce the next generation. Simulations explored the effects of varying the number of breeding pairs, and the number of unlinked SNP markers. Selection based on POH resulted in observed heterozygosity (H_OBS) consistently exceeding expected heterozygosity (H_EXP), a trend that was sustained for up to 1000 generations. While further evaluation is needed within more complex population genetic frameworks—accounting for linkage disequilibrium, recombination, optimal contribution, and phenotypic selection—our findings highlight the potential of POH as a valuable tool for enhancing genetic diversity in conservation breeding programs. Full article

Several single-nucleotide polymorphisms (SNPs) across the lipoprotein lipase (LPL) gene have been found to be associated with dyslipidemia and obesity. Several InDels and SNPs in exon 1, intron 2, and intron 7 have been reported; however, their association with lipid parameters and body mass index (BMI) remains unclear. Here, we aimed to investigate the relationship among LPL variants, lipid levels, and BMI in a Kuwaiti population. Sanger sequencing was performed on three targeted regions of the LPL gene. Based on the minor allele frequency, Hardy–Weinberg equilibrium, and linkage disequilibrium, five SNPs were selected and genotyped in a cohort of 688 Kuwaiti samples to investigate their association with lipid levels and BMI. A total of 30 variants (6 InDels and 24 SNPs) were identified; of them, 5 SNPs (rs1800590, rs74377536, rs8176337, rs303, and rs304) were selected for their association with BMI and lipid levels. The G-allele of rs8176337 was found to be associated with increased BMI (β = 1.41; 95% confidence interval = 0.22–2.60; p = 0.02). In addition, an association was observed for rs303 and rs304 with both cholesterol and LDL (p < 0.05). Overall, our results demonstrate an association between LPL variants and lipid levels, and the observed association between rs8176337 and BMI was novel. Full article