Journal of Applied Genetics最新文献

Meeting the projected 70% rise in agricultural output by 2050 to sustain a global population of 9.6 billion poses a formidable challenge amid intensifying biotic and abiotic stresses. Traditional breeding methods, although foundational, are limited in their ability to improve complex polygenic traits such as yield, stress tolerance, and disease resistance. Genomic selection (GS) has emerged as a transformative approach that leverages genome-wide markers to predict breeding values with higher accuracy and efficiency. Unlike marker-assisted selection (MAS) and genome-wide association studies (GWAS), which emphasize major-effect loci, GS captures the cumulative contribution of numerous small-effect loci, enabling faster genetic gains for complex traits. This review outlines the conceptual framework, evolution, and integration of GS with cutting-edge technologies such as high-throughput genotyping, phenomics, multi-omics, and machine learning. It also discusses key achievements, implementation strategies, and the potential of GS to enhance selection accuracy, shorten breeding cycles, and develop climate-resilient, high-yielding cultivars. The integration of GS within modern breeding pipelines represents a paradigm shift toward sustainable crop improvement and global food security in an era of climatic uncertainty.

Non-small-cell lung cancer treatment relies greatly on immunotherapy, especially in individuals without targetable mutations enabling the use of molecularly targeted therapies. Negative immune checkpoint inhibitors significantly contribute to improving patients' survival and quality of life. Both programmed death ligand 1 expression on tumour cells and tumour mutational burden are used to predict the response to such treatment and qualify patients for therapy; however, in some cases, these biomarkers do not perform sufficiently well. Discovering new markers indicating resistance or response to immunotherapy would therefore enable clinicians to tailor the therapy course to the patient's benefit. This paper aims to describe the genetic and immunological background of immunotherapy courses and identify factors potentially related to clinical benefit or lack of response to immunotherapy, using next-generation sequencing of tumour tissue and flow cytometry analysis of lymphocyte subpopulations in the peripheral blood of non-small cell lung cancer patients in a preliminary study.

The aim of this study was to apply DArTseq technology to analyze T. spelta L. (spelt wheat) genotypes in order to eliminate duplicates in the gene bank and ensure the high quality and purity of the stored material. The research included the analysis of genetic similarity, the construction of dendrograms, and association mapping, which enabled the identification of specific molecular diagnostic markers for spelt wheat. Spelt is an ancient cereal species gaining popularity, especially in organic farming. It is characterized by natural resistance to biotic factors and tolerance to environmental stress. Spelt is a valuable material in plant resistance breeding aimed at developing varieties resistant to diseases and well adapted to unfavourable environmental conditions. In this study, molecular characterization of 27 spelt genotypes was carried out using high-throughput DArTseq technology, enabling simultaneous analysis of SilicoDArT and SNP markers. A total of 96,136 markers were identified, of which 16,712 met the quality criteria and were used for genetic similarity and association mapping. Based on similarity coefficients, a dendrogram was created, distinguishing four main genotype groups. Association mapping revealed over 2,600 markers significantly associated with the virulence level of the B. graminis f. sp. tritici pathogen. Particular attention was paid to SilicoDArT 7,492,586 and SNP 1,126,088 markers, showing significant associations with plant response to three of the five analyzed isolates. Chromosomal regions (1D, 3D, 5B, 6 A) associated with resistance were also identified, confirming the polygenic nature of this trait. Results indicate high genetic variability of the analyzed material and the usefulness of DArTseq technology in identifying markers for resistance breeding. The presented markers can be used in marker-assisted breeding programs, especially considering the growing interest in spelt as a cereal for organic farming. These findings provide a valuable basis for further improvement of spelt resistance and sustainable cereal breeding.

Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in regulating endothelial permeability and maintaining blood-brain barrier (BBB) integrity. As a cellular receptor for the Japanese Encephalitis Virus (JEV) envelope protein, PLVAP significantly influences viral neuroinvasion and central nervous system entry. This study employed computational approaches to investigate the functional impact of non-synonymous single-nucleotide polymorphisms (nsSNPs) in the PLVAP gene and their potential effects on JEV-host interactions. We retrieved 11,883 SNPs from the NCBI dbSNP database and identified 403 unique nsSNPs for comprehensive analysis. Approximately 50% of these variants resulted in alterations to amino acid charge or polarity, indicating potential functional consequences. Stability analysis revealed 43 nsSNPs that significantly destabilized PLVAP structure (ΔΔG ≤ -1 kcal/mol), with several variants also affecting local protein disorder. Conservation analysis identified 29 deleterious nsSNPs, emphasizing their evolutionary importance and functional relevance. Five critical variants (R26H, I35T, E175G, V44G, and I39S) were prioritized based on their pronounced destabilizing effects on PLVAP structure and function. Molecular docking studies demonstrated that these mutations substantially altered PLVAP-JEV envelope protein binding interactions, potentially modifying viral entry efficiency and host susceptibility. These findings suggest clinical applications, including the use of PLVAP variants as biomarkers for risk stratification and guiding vaccination strategies in endemic regions. Moreover, insights into PLVAP-JEV interactions open avenues for therapeutic interventions, such as small-molecule inhibitors targeting viral entry. This computational framework may be extended to other flavivirus-host interactions, advancing antiviral drug discovery and personalized medicine approaches for JEV prevention.

Undifferentiated pleomorphic sarcoma (UPS) is a diagnosis of exclusion; given limited effective treatments and marked heterogeneity, there is a need to identify therapeutic targets, a task facilitated by next-generation sequencing (NGS) in clinical practice. We report 2 STS pts with the diagnosis of UPS, G3 - each treated in a clinical trial (NCT03651374) with UNRESARC protocol consisting of neoadjuvant chemotherapy (CHT), radiotherapy, and surgical resection. Biopsy samples from each patient were subjected to NGS with the TruSight™ Oncology 500 assay (Illumina) and analysed in PierianDX (commercial software). 5 pathogenic alterations were identified: Case A: CCNE1 (6 copies) and MYC (3 copies) amplifications; Case B: CCND1 (3 copies), EGFR (3 copies) and FGFR1 (4 copies) amplifications. Amplifications of cell-cycle associated (CCNE1, CCND1) and apoptosis-related (MYC) genes contribute to uncontrolled proliferation and resistance to apoptosis, while amplifications in receptor tyrosine kinases (EGFR and FGFR1) activate pathways (RAS/MAPK and PI3K/AKT), involved in tumour growth and metastasis. In both patients, a poor pathological response, early local recurrence (LRFS of 9 months in both patients) and progressive disease (PD) when treated with first-line palliative CHT (PFS of 5 months in A and 4 months in B) were noted. All tumours demonstrated a low tumour mutation burden (TMB) (1.6-3.9 mut/Mb) and no microsatellite instability (MSI), explaining no sensitivity to immune checkpoint inhibitors. NGS assays may enable accurate diagnosis and identify predictive biomarkers and novel therapeutic targets - of particular importance in poor-prognosis entities such as UPS. Our report is consistent with the literature classifying UPS as malignancy with a high frequency of CNAs and low TBM.

Background: Colorectal cancer (CRC) is a major global health concern with increasing incidence. Current treatments, though improved, require novel biomarkers for better diagnosis and management. Disulfidptosis, a recently characterized form of cell death, may play a critical role in CRC progression.

Methods: Utilizing summary-data-based Mendelian randomization (SMR), we identified RNH1 as a gene linked to CRC and disulfidptosis. The expression and intercellular communication of RNH1 in CRC were analyzed using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (stRNA-seq). A prognostic model was built using a Deep Learning Survival Neural Network (DeepSurv). Additionally, we performed RNA sequencing (RNA-seq) analysis to analyze the function of RNH1. Validation was performed through qPCR on CRC and normal tissue samples.

Results: RNH1 was identified as a gene linked to disulfidptosis and positively correlated with CRC risk. scRNA-seq analysis revealed that RNH1 + malignant cells showed distinct metabolic pathways and greater cell interactions. stRNA-seq analysis confirmed these interactions, especially with endothelial cells. DeepSurv analysis produced a prognostic model, showing different survival outcomes between high-risk and low-risk groups. RNA-seq analysis showed that the RNH1 + high expression group had higher immune cell abundance scores and tumor microenvironment scores, and RNH1 was positively correlated with most immune checkpoints. Drug sensitivity analysis suggested that CRC patients with high RNH1 expression were more sensitive to certain therapeutic agents. qPCR showed that the expression level of RNH1 in cancer tissues of CRC patients was significantly higher than that in normal tissues.

Conclusion: RNH1 acts as a biomarker for CRC, influencing tumor growth via disulfidptosis, tumor microenvironment alterations, and metabolic pathways. Its high expression correlates with immune escape. This study suggests RNH1 as a potential therapeutic target for CRC, warranting further exploration of its mechanistic roles and treatment potential.

Cohen syndrome (CS) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the VPS13B gene. It is characterized by early-onset multisystemic symptoms, including chorioretinal dystrophy, progressive high myopia, developmental delay, hypotonia, abnormal fat distribution, short stature, microcephaly, facial dysmorphism, and leukopenia. However, the condition exhibits extensive phenotypic and allelic heterogeneity. Here, we report a 24-year-old male presenting with atypical retinitis pigmentosa, myopia, leukopenia, abnormal fat distribution, and minor facial dysmorphic features. The patient showed neither neurologic symptoms nor other commonly observed CS traits. Multigene next-generation sequencing (NGS) panel testing revealed two novel VPS13B variants - an intragenic deletion encompassing exon 5 and a donor splice site variant c.11392 + 2dup in a compound heterozygous state. Furthermore, we conducted a literature review and summarized the phenotypic and genetic heterogeneity of CS, with an additional emphasis on individuals exhibiting mild manifestations. The present study introduces two novel VPS13B variants associated with mild CS and highlights the possibility that biallelic VPS13B mutations may lead to a less severe clinical presentation without developmental delay, which is widely considered an inherent part of the syndrome clinical picture.

15q26 deletion syndrome is a rare genetic condition caused by the deletion of terminal end of the long arm of chromosome 15 (Drayer's syndrome). Clinical presentation usually implies intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance, brachydactyly and diaphragmatic hernia. Lymphangioleiomiomatosis (LAM) is a rare genetic disease affecting multiple organs, which almost exclusively afflicts women. Typical presentation of LAM disease is pulmonary LAM, characterized by cyst-like destruction of pulmonary tissue, which leads to loss of pulmonary function, and if progresses further can lead to recurring pneumothoraxes. Co-existence of these two rare diseases hasn't been reported so far. Here we report a case of the simultaneous presence of 15q26 deletion syndrome and LAM disease in a 38-year-old female. She presented with short statue, brachydactyly, pes equinovarus, microcephaly and signs of intellectual disability manifesting from birth and early childhood. At the age of 23 she starts to suffer of recurring pneumothoraxes with gradual loss of pulmonary function. CT and pathohistological findings revealed the presence of pulmonary LAM and genetic testing revealed 15q26.2 microdeletion characteristic for 15q26 deletion syndrome. Successful treatment of LAM using mTOR inhibitor Sirolimus resulted in clinical and functional improvement.

Gilles de la Tourette syndrome (GTS) and other tic disorders (TDs) have a substantial genetic component with their heritability estimated at between 60 and 80%. Here we propose an oligogenic risk score of TDs using whole-genome sequencing (WGS) data from a group of Polish GTS patients, their families, and control samples (n = 278). In this study, we first reviewed the literature to obtain a preliminary list of 84 GTS/TD candidate genes. From this list, 10 final risk score genes were selected based on single-gene burden tests (SKAT p < 0.05) between unrelated GTS cases (n = 37) and synthetic control samples based on a database of local allele frequencies. These 10 genes were CHADL, DRD2, MAOA, PCDH10, HTR2A, SLITRK5, SORCS3, KCNQ5, CDH9, and CHD8. Variants in and in the vicinity (± 20 kbp) of the ten risk genes (n = 7654) with a median minor allele frequency in the non-Finnish European population of 0.02 were integrated into an additive classifier. This risk score was then applied to healthy and GTS-affected individuals from 23 families and 100 unrelated healthy samples from the Polish population (AUC-ROC = 0.62, p = 0.02). Application of the algorithm to a group of patients with other tic disorders revealed a continuous increase of the oligogenic score with healthy individuals with the lowest mean, then patients with other tic disorders, then GTS patients, and finally with severe GTS cases with the highest oligogenic score. We have further compared our WGS results with the summary statistics of the Psychiatric Genomics Consortium genome-wide association study (PGC GWAS) of TDs and found no signal overlap except for the CHADL gene locus. Polygenic risk scores from common variants of GTS GWAS show no difference between patient and control groups, except for the comparison between patients with non-GTS TDs and patients with severe GTS. Overall, we leveraged WGS data to construct a GTS/TD risk score based on variants that may cooperatively contribute to the aetiology of these disorders. This study provides evidence that typical and severe adult GTS as well as other tic disorders may exist on a single spectrum in terms of their genetic background.