Search Results (589)

Northern corn leaf blight is a major fungal disease hindering maize production worldwide. Among the various strategies of disease management, the deployment of host plant resistance is the most economic means to mitigate the yield losses, as it is cost-effective and durable. In this study, we performed the genome-wide association study (GWAS) analysis in a set of 336 maize inbred lines. The experimental material was evaluated for northern corn leaf blight disease response across two seasons during the rainy seasons of 2023 and 2024. The ANOVA results and estimates of genetic variability parameters indicated the existence of a substantial amount of genetic variability. High heritability and high genetic advance as percent mean suggested the presence of additive genetic effects in controlling the disease response. GWAS analysis was performed employing GLM, MLM, CMLM, MLMM, FarmCPU and BLINK. The results from GWAS identified 74 marker associations from GLM and FarmCPU models. The QTN S1_7356398, located on chromosome 1, identified from the GLM model, explained 12.12 percent of phenotypic variation. Another QTN S2_51098833 located on chromosome 2, identified from the FarmCPU model, explained 6.14 percent variation. Remaining associations explained lesser PVE, suggesting the quantitative inheritance of NCLB resistance. Candidate gene identification was performed by keeping B73 as a reference genome. The identified QTNs from the current study were found to be located in annotated genes with functional domains implicated in defence mechanisms in maize and other crops. Many candidate genes, including chitinase, putative serine/threonine protein kinase, and aldehyde oxygenase, were identified and found to play a crucial role in plant defence mechanisms against several biotic and abiotic stresses. Full article

Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy, characterized by marked biological heterogeneity and variable clinical outcomes. Among its rarer genetic subsets is AML with rearrangements of the MDS1 and EVI1 complex locus (MECOM), occurring in fewer than 2% of newly diagnosed cases. This review examines the biology and clinical significance of MECOM-rearranged AML, with a focus on its diverse mechanisms of leukemogenesis, including chromosomal inversion and translocation involving 3q26. We discuss how aberrant EVI1/MECOM activity alters gene expression networks and drives malignant transformation. Current therapeutic approaches—including intensive chemotherapy, hypomethylating agents in combination with venetoclax, and allogeneic stem cell transplantation—are evaluated with particular emphasis on inv(3) and other t(3q26) subtypes. Despite these treatment strategies, outcomes remain poor, underscoring the urgent need for novel, more effective therapies for this high-risk form of AML. Full article

Clostridium perfringens is responsible for various diseases. Foodborne outbreaks (FBOs) result from the in situ production of C. perfringens enterotoxin (CPE) by type F strains during sporulation. The cpe gene can be plasmidic (p-cpe) or chromosomal (c-cpe). Strains (c-cpe) exhibit greater heat resistance and are frequently associated with FBO. Strains cpe-negative are considered heat-sensitive. This study investigates the sporulation abilities and heat resistance of eight C. perfringens strains isolated from French foodborne outbreaks. Whole-genome sequencing classified the strains into two clades: the “chromosomal cpe clade,”, mainly composed of cpe-positive strains with c-cpe and some cpe-negative strains, and the “plasmidic cpe clade,”, primarily containing cpe-negative strains and a few with plasmid-borne cpe. Sporulation assays and thermal inactivation kinetics were performed on FBO strains to evaluate the influence of genetic variability on sporulation abilities and heat resistance. Experimental analyses revealed that strains within the “chromosomal cpe clade” exhibited the highest sporulation abilities, regardless of cpe presence, while those in the “plasmidic cpe clade” had low sporulation ability. Moreover, heat-resistant spores were produced exclusively by strains of the “chromosomal cpe clade,” with c-cpe strains exhibiting the highest heat resistance (δ_{95 °C} ≈ 49 min), followed by cpe-negative strains (δ_{95 °C} ≈ 9.5 min). p-cpe strains exhibited a heat-sensitive phenotype, with δ_{85 °C} values of 12 min. A key finding of this study is the identification of a group with intermediate heat resistance, distinct from the highly heat-resistant (c-cpe) and heat-sensitive (p-cpe) strains. This intermediate heat-resistance phenotype, observed in cpe-negative strains within the “chromosomal cpe clade,” offers a new perspective on C. perfringens stress adaptation, suggesting their potential for persistence in food. Their heat resistance, along with the potential for cpe gene transfer, could make these strains a relevant hazard for cooked, cooled, and re-heated meat products. Full article

Gametogenesis is a fundamental biological process that ensures both genetic recombination and the continuity of successive generations. Interspecific hybrids can reproduce through modified mechanisms, such as hybridogenesis, by transmitting clonal, unrecombined genomes of only one of the parental species via their gametes. Pelophylax grafi (RP) is a natural hybrid frog composed of mixed genomes (subgenomes) of two related species, Pelophylax perezi (P) and Pelophylax ridibundus (R), and coexists in populations with P. perezi. This study tested the involvement of programmed genome elimination in gamete production of P. grafi, providing new insight into reproductive mechanisms of hybrid vertebrates. Using comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH), we examined the genomic constitution of germline cells in tadpoles and adult male and female P. grafi. Controlled crosses between P. perezi and P. grafi produced F1 hybrid tadpoles, whose genotypes confirmed that P. grafi parents transmitted the R subgenome through their gametes. In the early germline cells (gonocytes) of these tadpoles, P chromosomes were selectively eliminated via micronuclei formation during interphase. The occasional presence of the R genome and mixed R/P genome micronuclei suggests variability and imperfect fidelity in the elimination process. In adult hybrids, the majority of diplotene oocytes, spermatogonial stem cells (SSC) and spermatocytes carried R subgenomes. We demonstrated that programmed genome rearrangement in Pelophylax hybrids is an evolutionarily conserved mechanism underlying this unique reproductive strategy. Full article

Background/Objectives: Fabry disease is an X-linked lysosomal storage disorder. It is characterised by impaired metabolism of glycosphingolipids whose accumulation causes irreversible organ damage and life-threatening complications. Genotype–phenotype correlations have a limited scope in Fabry disease as the disorder presents with wide-ranging clinical variability. In other X-linked disorders, epigenetic profiling has identified methylation patterns and disease modifiers that may explain clinical heterogeneity. In this narrative review and thematic analysis, the role of DNA methylation and epigenetics on the clinical phenotype in Fabry disease was investigated. Methods: Embase, PubMed, and PsycINFO were searched to identify literature on DNA methylation and epigenetics in Fabry disease. Based on the eligibility criteria, 20 articles were identified, and a thematic analysis was performed on the extracted data to identify themes. Results: Three themes emerged: (I) genetic modifiers, (II) methylation profiling, and (III) insights into X chromosome inactivation (XCI). The evidence synthesis revealed that telomere length, especially in early disease stages, bidirectional promoter (BDP) methylation by sphingolipids, epigenetic reader proteins, mitochondrial DNA haplogroups, and DNA methylation of the promoter region of the calcitonin receptor gene are potential genetic modifiers in Fabry disease. Methylation patterns also reveal episignatures in Fabry disease evolution and genes implicated in the maintenance of basement membranes. Studies on XCI further emphasise disease heterogeneity and draw attention to methodological issues in the assessment of XCI. Conclusions: This thematic review shows that DNA methylation and genetic modifiers are key factors modifying clinical variability in Fabry disease. More broadly, it underscores a crucial role for epigenetic processes in driving disease onset, progression, and severity in X-linked disorders. Full article

Background/Objectives: X-linked intellectual disability (XLID) is a highly heterogeneous disorder accounting for ~10% of all males with ID. Next-generation sequencing (NGS) has revolutionized the discovery of causal XLID genes and variants; however, many cases remain unresolved. We present a four-generation syndromic XLID family with multiple males exhibiting variable degree of ID, focal dystonia and epilepsy. Methods: Extensive cytogenetic and targeted genetic testing was initially performed, followed by whole-exome sequencing (WES) and short-read whole-genome sequencing (WGS). Apart from the routine NGS analysis pipelines, sequencing data was revisited by focusing on poorly covered/mapped regions on chromosome X (chrX), to potentially reveal unidentified clinically relevant variants. Candidate variant validation and family segregation analysis were performed with Sanger sequencing. Results: All initial diagnostic testing was negative. Subsequently, 300 previously reported “dark” chrX coding DNA sequences, overlapping 97 genes, were cross-checked against 29 chrX genes highly associated (p < 0.05) with ID and focal dystonia, according to Phenomizer. Manual inspection of the existing NGS data in two low-coverage regions, chrX:25013469-25013696 and chrX:111744737-111744820 (hg38), revealed a recurrent pathogenic ARX variant NM_139058.3:c.441_464dup p.(Ala148_Ala155dup) (ARXdup24) associated with non-syndromic or syndromic XLID, including Partington syndrome. Sanger sequencing confirmed ARXdup24 in all affected males, with carrier status in their unaffected mothers, and absence in other unaffected relatives. Conclusions: After several years of diagnostic odyssey, the pathogenic ARXdup24 variant was unmasked, supporting a genotype–phenotype correlation in the first Partington syndrome family in Cyprus. This study highlights that re-examining underrepresented genomic regions and using phenotype-driven tools can provide critical diagnostic insights in unresolved XLID cases. Full article

(1) Background: Water buffaloes (Bubalus bubalis) are important for dairy and meat production. Up to now, genomic analysis has focused on female subjects, leaving the Y chromosome essentially unknown. Advances in third-generation sequencing (TGS) made it possible to improve the study of complex genome sequences, such as buffalo and other mammalian species including humans. (2) Methods: In this study, we applied TGS-based long-read sequencing to generate, in one step, high-quality whole-genome sequences, which can take full advantage of a rapid bioinformatic pipeline, such as that described in the companion paper. (3) Results: Five male buffalo genomes have been fully sequenced at relatively high depth (20–40×) which, combined with the read length typical of TGS, provide the basis for important insights into male-specific genetic traits, including those linked to meat and milk production. (4) Conclusions: With the use of TGS technologies, we offer a complete strategy for fast, one-step genome sequencing which can also be applied to other farm animals with a comparably large genome. This approach can help in revealing genetic features characteristic of an animal individual beyond the simple assessment of a number of SNPs or other known sequence variations, thus supporting improved genetic selection for dairy productivity and future research on genetic variability in buffalo breeds. Full article

Germline mutations in the X-linked cohesin subunit gene SMC1A have been increasingly recognized as a cause of developmental and epileptic encephalopathy (DEE); however, the underlying basis of its marked phenotypic heterogeneity remains elusive. In our narrative review, starting from all literature-reported clinical cases of SMC1A-related DEE, we propose an integrative framework summarizing all the clinical and genetic features, stratified by mutation type, mosaic fraction, and X-chromosome inactivation (XCI) patterns to provide valuable support for genetic diagnosis and variants, found to date. Also, we discuss how somatic mosaicism and epigenetic variability underlie the clinical diversity of SMC1A-associated epilepsy and systematically describe the entire phenotypic spectrum, from early-onset, therapy-resistant seizures to milder intellectual disability profiles. We further examine how SMC1A mutations perturb cohesin’s canonical roles in chromatin loop formation and sister-chromatid cohesion, leading to widespread transcriptional dysregulation of neurodevelopmental gene networks. Evidence that XCI skewing can ameliorate or exacerbate neuronal cohesin deficits and, thus modulate seizure threshold, is presented. Full article

Microbial forensics involves analyzing biological evidence to evaluate weaponized microorganisms or their toxins. This study aimed to detect and type Yersinia pestis from four simulated forensic samples—human plasma diluted in phosphate-buffered saline (#24-2), tomato juice (#24-5), grape juice (#24-8), and a surgical mask (#24-10). Notably, samples #24-10 may have contained live bacteria other than Y. pestis. A real-time polymerase chain reaction confirmed the presence of Y. pestis in all samples; however, whole-genome sequencing (WGS) coverage of the Y. pestis chromosome ranged from 0.46% to 97.1%, largely due to host DNA interference and low abundance. To address these limitations and enable strain-level identification, we designed a hybridization-based target enrichment approach focused on multilocus variable number tandem repeat analysis (MLVA). Next-generation sequencing (NGS) using whole-genome amplification revealed that the accuracy of the 25 MLVA profiles of Y. pestis for samples #24-2, #24-5, #24-8, and #24-10 was 4%, 100%, 52%, and 0%, respectively. However, all samples showed 100% accuracy with target-enriched NGS, confirming they all belong to the same strain. These findings demonstrate that a targeted enrichment strategy for MLVA loci can overcome common obstacles in microbial forensics, particularly when working with trace or degraded samples where conventional WGS proves challenging. Full article

Background and Clinical Significance: Papillon–Lefèvre syndrome (PLS) is an autosomal recessive genetic skin disorder. Genetic studies have demonstrated that mutations in the Cathepsin-C (CTSC) gene, mapped to chromosome 11q14.1–q14.3, are responsible for the pathogenesis of PLS. The hallmark characteristics of this syndrome are palmoplantar keratoderma and severe periodontal disease that leads to premature tooth loss. Palmoplantar keratoderma commonly manifests during early childhood (ages one to four), followed by the onset of severe periodontitis around the age of three to four years. Although periodontitis and premature tooth loss are considered hallmark features, a limited number of cases lacking oral involvement have been reported, underscoring the phenotypic variability in PLS. Case Presentation: This report describes a 6-year-old female patient whose chief presenting complaint was palmoplantar keratoderma, recurrent skin infections, necrotizing granulomatous inflammation of the kidney, and delayed growth; she was genetically confirmed to have a CTSC mutation associated with PLS, yet without any dental manifestations. The lack of oral manifestations and the presence of necrotizing granulomatous inflammation of the kidney in this genetically validated case highlight an atypical presentation. Conclusions: This report discusses an unusual case of PLS of a patient displaying classic skin features without any dental issues. Full article

X chromosome inactivation (XCI) is a fundamental epigenetic process that balances X-linked gene expression between females and males by silencing one X chromosome in female cells. Variability or skewing of XCI can influence the clinical presentation of X-linked disorders. Bain type X-linked intellectual disability syndrome (MRXSB), caused by mutations in the X-linked HNRNPH2 gene, is characterized by intellectual disability, developmental delay, and neurological abnormalities. In female patients, XCI heterogeneity complicates disease modeling and therapeutic development. Induced pluripotent stem cells (iPSCs) offer a unique platform to study patient-specific disease mechanisms, but the dynamics of XCI during iPSC reprogramming, maintenance, and differentiation are not fully understood. In this study, we generated 12 iPSC clones from fibroblasts of a female MRXSB patient heterozygous for the HNRNPH2 c.340C > T mutation. Four clones expressed the mutant HNRNPH2 allele and eight expressed the wild-type allele, indicating X chromosome reactivation (XCR) followed by random XCI during reprogramming. Importantly, these XCI patterns remained stable during long-term iPSC propagation and subsequent differentiation into the three germ layers and neural stem cells. Our findings provide new insights into XCI and XCR dynamics in the context of X-linked neurodevelopmental disorders and emphasize the importance of careful clone selection for accurate disease modeling using iPSC-based approaches. Full article

Polemonium caeruleum L. (Polemoniaceae) is a perennial flowering plant native to Eurasia and North America, which is used as a fodder, medicinal, and ornamental plant. Many issues related to the taxonomy and origin of this valuable species still remain unclear. The intraspecific genetic variability of P. caeruleum and chromosomal organization of its genome are insufficiently studied. For the first time, we analyzed NGS genomic data of P. caeruleum using ReapeatExplorer2/TAREAN/DANTE Pipelines. In its repeatome, we identified 66.08% of Class I retrotransposons; 0.57% of Class II transposons; 0.42% of ribosomal DNA; and 0.87% of satellite DNA (six high-confident and three low-confident putative satellite DNAs). FISH chromosome mapping of seven tandem DNAs was carried out in two P. caeruleum varieties and two wild populations. Our results demonstrated the effectiveness of using satDNAs Pol_C 46 and Pol_C 33 in combination with 45S rDNA and 5S rDNA for precise chromosome identification. This approach allowed us to study intraspecific chromosomal variability and detect chromosomal rearrangements in the studied accessions of P. caeruleum, which could be related to the speciation process. These novel molecular markers are important for chromosome studies within Polemonium to clarify its taxonomy and phylogeny, and also, they expand the potential of different breeding programs. Full article

Wheat germplasm resources are an important material foundation for genetic improvement. In this study, 170 wheat germplasm resources were used from China, the International Maize and Wheat Improvement Center (CIMMYT), Europe (France, Finland, and Sweden), the United States, Canada, and Australia. Seven nutritional quality traits were evaluated for the 2019–2020 and 2020–2021 cropping seasons. The coefficient of variability for seven nutritional quality traits ranged from 6.99% to 30.65%. The average of genetic diversity (Shannon–Wiener diversity index, H′) was 1.87. The results showed that the average frequency of high-throughput competitive allele-specific PCR (KASP) markers was 69.4% on 17 KASP markers related to seven nutritional quality traits, the average of polymorphic information content (PIC) was 0.308, and the genetic effects were from 0.01% to 18.46%. One hundred and seventy wheat germplasm resources were classified into five groups at ΔK = 5 by genetic structure analysis. The first group comprised 62 germplasm resources (36.47%), the second group included 41 germplasm resources (24.11%), the third group contained 20 germplasm resources (11.76%), the fourth group contained 20 germplasm resources (11.76%), and the fifth group had 29 germplasm resources (17.06%). Germplasm resources from CIMMYT and China were found in the first group and the second group, accounting for 56.45% and 65.85%, respectively, while European germplasm resources constituted 50% of those within the fourth group. Five favorable haplotypes were identified, which were located on chromosomes 4A, 6A, 6B, and 7A: G4A1, G4A2, G6A, G6B, and G7A. Their genetic effects were 8.71%, 8.41%, 1.00%, 18.20%, and 1.16%, respectively. In the meantime, we found 12 significant SNPs of seven nutritional quality traits using haplotype analysis. The frequency of favorable haplotypes in the population ranged from 3.53% to 62.35%. Five haplotypes, G4A1, G4A2, G6A, G6B, and G7A, were beneficial, and their genetic effects were positive. Furthermore, the results offered favorable haplotypes and germplasm resources for enhancing nutritional quality. Full article

Lactic acid bacteria (LAB) are central to food fermentation, probiotic delivery, and emerging synthetic biology applications, yet their robust cell envelopes and restriction–modification systems complicate DNA uptake. This review synthesizes practical routes for introducing DNA into LAB—natural competence, electroporation, conjugation, phage-mediated transduction, and biolistics—and outlines vector systems for expression and chromosomal editing, including food-grade strategies. We highlight recent advances that broaden strain tractability while noting strain-to-strain variability and host-specific barriers that still require tailored solutions. These advances directly enable applications in food and probiotic biotechnology, including improving starter robustness, tailoring flavor and texture pathways, and installing food-grade traits without residual selection markers. We close with near-term priorities for standardizing protocols, widening replicon compatibility, and leveraging modern genome-editing platforms to accelerate safe, marker-free engineering of industrial and probiotic LAB. Full article

The increasing demand for novel cut chrysanthemum cultivars has underscored the significance of precision breeding techniques, with particular emphasis on hybridization and molecular tools. This study aimed to assess the cross-compatibility of selected chrysanthemum cultivars and to evaluate the genetic, quantitative, and qualitative diversity among the resulting F₁ progenies. A total of six hybrid combinations were generated using five commercial parental cultivars. Ploidy levels were determined via flow cytometry and chromosome counting, confirming that all parents were allohexaploid (2n = 6x = 54). Pollen viability and germination rates varied significantly among male parents, influencing hybridization success. A total of 30,391 seeds were obtained, with germination rates ranging from 2.69% to 10.73%, depending on the cross combination. F₁ progenies showed considerable phenotypic variability in flowering time, flower stalk length, flower diameter, and branch weight. Molecular characterization using eight iPBS primers revealed a high polymorphism rate (93%) with a mean Polymorphism Information Content (PIC) value of 0.614, confirming substantial genetic diversity among genotypes. Cluster and principal coordinate analyses demonstrated that most F₁ genotypes grouped closely with their maternal parents, although unique genomic variations were also detected. The integration of morphological and molecular data provides valuable insights for selecting superior genotypes and optimizing breeding strategies. This study highlights the importance of evaluating hybridization potential and genetic diversity in the development of commercially viable cut chrysanthemum cultivars. Full article