Journal of Applied Genetics最新文献

This study evaluated the antagonistic capacity of eight Trichoderma isolates against two Fusarium proliferatum isolates that differed in their toxigenic potential. Using co-cultures on solid and liquid media, significant variability in antifungal efficacy was observed among Trichoderma species. T. atroviride and T. viridescens isolates demonstrated the highest antagonistic activity, with markedly stronger inhibition of the less toxigenic F. proliferatum isolate. Quantitative PCR analysis confirmed a reduction in Fusarium biomass, which closely correlated with decreased levels of fumonisins (FB1, FB2, FB3) and beauvericin, as determined by UHPLC-HRMS. Notably, the most effective Trichoderma isolates (AN153, AN215, AN523) consistently suppressed both fungal growth and mycotoxin biosynthesis. Although fumonisin levels were reduced in co-cultures, independent assays in FB1-supplemented liquid media indicated that Trichoderma did not directly degrade mycotoxin. The presence of selected secondary metabolites, including 6-pentyl-2H-pyrone and phenolic acids, was confirmed in co-culture extracts. These findings highlight the isolate-specific nature of Trichoderma-Fusarium interactions and emphasise the potential of selected Trichoderma isolates as biocontrol agents capable of simultaneously limiting pathogen growth and mycotoxin accumulation. Further mechanistic studies are warranted to identify the molecular basis of these antagonistic effects.

In the last decades, the rate of stillbirths in the Icelandic Dairy Cattle population has increased. Some of these stillbirths may be caused by recessive lethal mutations segregating in the population. These alleles can be identified by detecting homozygous haplotype deficiency (HHD) in genotyped animals. The aim of this study was to find genomic regions affecting stillbirth and fertility in the Icelandic Dairy Cattle population. We analysed genotypes from 20,557 animals with 35,481 autosomal markers. We identified HHD segments and estimated their effects on stillbirths and insemination failure, measured as non-return rates. We conducted genome-wide association studies (GWAS) for stillbirth and five fertility traits: interval from first to last inseminations, conception rate, number of inseminations, calving interval and infertility. While no GWAS association reached the genome-wide significance threshold, some of the top signals co-located with HHD haplotypes. A total of 19 haplotypes significantly either decreased fertility, or increased incidence of stillbirths, or both. Two HHD regions on BTA13: 43,577,221-59,026,521 and BTA8: 83,276,598-84,472,391 were associated with both lower fertility and higher incidence of stillbirths. We found no evidence of large structural variations in or around the HHD regions, suggesting that these signals are likely due to single loss-of-function mutation or small structural variations. Further research should focus on exploring these regions using whole genome sequence data.

Leaf rust, caused by Puccinia triticina, is a major wheat disease that impacts yield and quality. This study aimed to identify genetic loci associated with seedling resistance to leaf rust in European winter wheat cultivars. A genome-wide association study was conducted on a panel of 181 wheat genotypes, including 143 modern cultivars and 38 lines with known leaf rust resistance genes. Pathogen evaluation involved 18 P. triticina isolates, which revealed diverse virulence levels and allowed resistant cultivars to be identified. The study identified 88 marker-trait associations clustered into 23 quantitative trait loci (QTL) across 13 chromosomes. Three QTL-QLr.ihar-1B.1, QLr.ihar-3D.1, and QLr.ihar-4 A.1-correspond to the major resistance genes Lr26, Lr24, and Lr28. Several QTL appear novel, with six (QLr.ihar-2B.2, QLr.ihar-3 A.1, QLr.ihar-3B.2, QLr.ihar-7 A.1, QLr.ihar-7D.1, and QLr.ihar-7D.2) explaining over 20% of phenotypic variance that could be considered for breeding purposes. Among 113 resistant cultivars, only 23 QTL were present in 51 genotypes, suggesting that resistance in the remaining 62 cultivars is under control of unidentified loci. The findings highlight the complex and diverse resistance patterns in European wheat, offering significant insights for breeding programs targeting enhanced leaf rust resistance.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 is a powerful tool for gene editing and the regulation of gene expression. It enables the introduction of targeted mutations, thereby facilitating functional studies of specific genes in various cellular processes. In this study, we aimed to generate a deletion in the promoter region of the CEBPB gene, which encodes a transcription factor involved in adipogenesis, and to evaluate the impact of this modification on the adipogenic differentiation potential of porcine mesenchymal stem cells (MSCs). A 575-bp deletion was introduced in the target region, resulting in the generation of both homozygous and heterozygous mutant cells. Adipogenic differentiation was assessed by quantifying transcript levels of adipocyte marker genes (GATA2, CEBPA, PPARG, and FABP4) at days 0, 4, 6, 8, and 10 of the differentiation process. Disruption of CEBPB expression led to the downregulation of these adipogenic markers, indicating impaired adipocyte differentiation. Additionally, to assess the proliferative capacity of the edited cells, the expression levels of proliferation-associated genes (CCND1, MCM2, and PCNA) were measured. A reduction in their transcript levels was observed in both homozygous and heterozygous mutant cells. These findings indicate that both homozygous and heterozygous deletions in the CEBPB promoter completely block adipogenesis and alter MSC proliferation, highlighting the pivotal role of CEBPB not only in adipogenic differentiation but also in the regulation of cell proliferation in porcine mesenchymal stem cells. These results provide new insights into the molecular mechanisms underlying adipose tissue development and have implications for pig breeding strategies aimed at optimizing carcass composition, as well as for biomedical research focused on adipose tissue biology.

Buckwheat is an underutilized crop with high nutritional values and antioxidant properties. The study was conducted with an aim to assess the genetic variability of 37 Fagopyrum esculentum Moench. and 67 Fagopyrum tataricum Gaertn. accessions using agro-morphological, biochemical, and microsatellite markers. For yield per plant, accessions, namely, IC24297, IC26591, and IC13413, with superior performances were identified. Based on correlations and regression-based path analysis, the key component traits, namely, number of seeds per plant, 100-seed weight, leaf blade width, seed width, and cyme length, were identified. Among F. esculentum group, EC18771, IC107238, and IC107265 had the highest carbohydrate, protein, and the lowest phytic acid, respectively. Likewise, IC24297, EC18769, and IC26596, with the highest carbohydrate, protein, and lowest phytic acid content, respectively, were identified under the F. tataricum group. By analyzing 65 SSR markers, an average of 2.63 alleles per locus was detected, with an average PIC value of 0.431. The observed heterozygosity for the polymorphic markers varied from 0.019 (Fagopyrum tataricum) to 0.462 (Fagopyrum esculentum), with an average of 0.099, showing the lower level of expected heterozygosity in tartary buckwheat accessions. Based on Nei's genetic distances, the buckwheat accessions were grouped into three clusters. Clusters I and III included the tartary accessions, while Cluster II encompassed both species. The AMOVA, conducted by categorizing the accessions into 25 subpopulations, indicated that 80% of the observed variation was due to differences among individuals, whereas 19% was due to within individuals. Based on additive main effects and multiplicative interaction (AMMI) and multi-trait stability index (MTSI) analyses, accessions, namely, IC13141, IC49667, IC26587, IC107983, and IC107981, have been identified as the best accessions, exhibiting high mean yield and stability across all three environments, and could be utilized in augmenting the buckwheat cultivation.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling regulates immune responses and tumorigenesis. Variations in NF-κB pathway genes may alter susceptibility to acute lymphoblastic leukemia (ALL). To evaluate associations between selected NFKB1 and NFKBIA polymorphisms and ALL risk in a Saudi population. We genotyped NFKB1 (rs93059, rs1287, rs1801) and NFKBIA (rs1050851, rs1957106, rs3138054) in 150 ALL patients and 115 matched controls using TaqMan® assays. Associations were assessed under multiple genetic models, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The NFKB1 rs93059 A allele was associated with reduced ALL risk (OR = 0.68; 95% CI: 0.48-0.97; p = 0.03), with the AA genotype showing protection in codominant (p = 0.03) and recessive (p = 0.02) models. For NFKB1 rs1287, the AA genotype increased risk (OR = 2.75; 95% CI: 1.14-6.62; p = 0.02) in the codominant model. The NFKB1 rs1801 C allele was enriched in patients (OR = 1.54; 95% CI: 1.04-2.23; p = 0.01). No significant associations were observed for NFKBIA variants after multiple-testing correction. NFKB1 rs93059 and rs1801 may influence ALL susceptibility in the Saudi population, underscoring the potential contribution of NF-κB pathway variants to leukemia risk. Functional analyses are warranted to clarify underlying mechanisms.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. COPD, within its context of disease etiology, is characterized by chronic inflammation of the lungs. It is distinguished by the aberrant production of oxidants, inflammatory cytokines, dysregulated immune cell activity, and remodeling of the airways. In this study, we analyzed the polymorphic association of antioxidants (GSTM1/T1) and inflammation-related genes (CXCL8, IL-33, and IL-6) with COPD. A case-control study was conducted with 227 subjects (116 healthy controls and 111 COPD cases). GSTM1/T1 genes were amplified by multiplex PCR' and inflammatory genes (CXCL8, IL-33, and IL-6) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. GSTM1/T1 gene deletion rates in the COPD group were significantly higher than those in the control group (GSTM1: OR = 11.85, CI = 4.033-34.79, P < 0.0001; GSTT1: OR = 2.303, CI = 1.206-4.399, P = 0.0113). In addition, our research revealed a significant association between the combined GSTM1/T1 null genotype and increased susceptibility to COPD (OR = 18.66, CI = 2.345-148.5, P = 0.0003). A significantly increased frequency of the "CC" genotype of the CXCL8 (rs2227532) gene variant (OR = 7.50, CI = 2.429-23.16, P < 0.0001) was observed in COPD patients compared to the control group. However, there was no significant association of the IL-33 (rs7044343) polymorphism between healthy controls and COPD patients. The IL-6 (rs2069860) gene variant was found to be monomorphic. As a result of the investigation, it was concluded that individuals with the null genotype of GSTM1/T1 combined and the presence of the CXCL8 (rs2227532) gene variant have a higher likelihood of developing COPD.

Hyponatremia can occur in endocrinological diseases, neoplasms, kidney diseases, and acquired or genetically conditioned disorders of antidiuretic hormone levels. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by a point mutation of the type 2 vasopressin receptor (AVPR2) gene. This mutation results in constitutive activation of the AVPR2 and a low sodium level.We reported the first familial NSIAD in Poland in siblings with hyponatremia. Case 1. A 2.5-year-old boy, during a respiratory tract infection, showed the following laboratory test results: Na 125 mmol/L, serumosmolality 260 mOsm/kg H2O, low uric acid level, and increased fractional sodium and uric acid excretions. Thyroid, adrenal, and renal function were normal. Copeptin level was low. Case 2. A 7-month-old brother presented with reduced activity and muscle tone, a sodium level of 117 mmol/L, and a serum osmolality of 249 mOsm/kg H2O. They were both confirmed to be hemizygous for the R137C mutation on the AVPR2 gene. The boys were advised to restrict their oral fluid intake and supplement sodium orally, aiming for sodium levels of 133-140 mmol/L. Conclusions: Genetic testing for an AVPR2 mutation is crucial in patients with hyponatremia, normovolemia, hypoosmolality, and low copeptin level.

Despite the growing recognition of microRNAs (miRNAs) as critical biomarkers in cancer, current approaches to their analysis remain fragmented, disjointed, and poorly integrated with emerging computational advances. This lack of cohesion limits progress toward reproducible and clinically actionable biomarker discovery. To address this unmet need, we present a review that unifies the latest findings and tools in bioinformatics, machine learning (ML), and large language models (LLMs) for miRNA analysis in oncology, thereby bridging a significant methodological gap in the field. We begin by critically synthesizing, benchmarking, and evaluating algorithms, including miRDeep2 and DIANA-miRPath, within a functional pipeline that spans next-generation sequencing (NGS) data processing to multi-omics integration. Building on this foundation, we review ML-augmented layers incorporating supervised and deep learning (DL) algorithms, specifically support vector machines (SVMs), convolutional neural networks (CNNs), and recurrent neural networks (RNNs), to enable robust miRNA signature identification, classification, and target prediction. Furthermore, we explore the integration of generative models and LLMs to support hypothesis generation and enhance reproducibility in biomarker discovery workflows. This comprehensive framework enhanced with artificial intelligence (AI) is contextualized through cancer-specific datasets, with particular emphasis on translational applications for early detection, prognosis, and therapy selection. By systematically organizing fragmented methodologies into a scalable and reproducible pipeline, our work provides a strategic roadmap to accelerate the development of miRNA-based precision cancer.

This study aimed to evaluate the effects of selection for post-weaning weight on reproductive traits in Nellore cattle by (i) estimating genetic parameters and trends for birth weight (BIW), body weight at selection (BW), days to calving (DC), and pregnancy rate (PR); and (ii) performing a genome-wide association study (GWAS), gene annotation, and functional enrichment analyses to uncover genomic regions, candidate genes, biological processes, and metabolic pathways underlying DC and PR. The dataset contained 12,865 Nellore animals from the experimental breeding program of the Institute of Animal Science (IZ, Sertãozinho, Brazil), including three selection lines: Nellore Control (NeC, stablishing selection for post-weaning weight), Nellore Selection (NeS, selected for higher post-weaning weight), and Nellore Traditional (NeT, selected for higher post-weaning weight and lower residual feed intake). Genomic data were available for 2,326 animals and 384,521 autosomal SNP markers after quality control. Genetic parameters were estimated using Bayesian inference under the ssGBLUP framework. Genetic trends from 1981 to 2021 were derived from linear regressions considering genomic estimated breeding values (GEBVs). The weighted single-step GWAS (WssGWAS) was used to identify genomic regions that explained more than 1.0% of the additive genetic variance for DC and PR, which were further analyzed for gene annotation and functional enrichment. Heritability estimates were high for BIW (0.46 ± 0.02) and BW (0.41 ± 0.02), and low for DC and PR (0.10 ± 0.02 for both). Moderate genetic correlations were observed between BIW and DC, especially in lines selected for higher growth (NeS: 0.38 ± 0.12; NeT: 0.56 ± 0.09), in contrast, BW showed weak genetic correlations with reproductive traits, with estimates for DC of - 0.11 ± 0.18 (NeC), 0.15 ± 0.15 (NeS), and 0.36 ± 0.14 (NeT), and for PR of 0.25 ± 0.22 (NeC), - 0.12 ± 0.17 (NeS), and - 0.44 ± 0.16 (NeT). Genetic trends indicated consistent increases in BW and BIW in NeS and NeT, while NeC showed more favorable trends for DC and PR. The GWAS identified 13 and 9 genomic windows associated with DC and PR, respectively, with pleiotropic regions on chromosome 14 influencing both traits. Key candidate genes annotated included PLAG1, MOS, MAPK13, MAPK14, and FKBP5. Functional enrichment revealed biological processes related to hormone metabolism, immune modulation, and oocyte development. Selection for increased growth does not directly impair reproductive traits; however, it indirectly influences fertility due to correlated response in BIW, which is genetically associated with DC.