Journal Of Applied Genetics[JOURNAL]
Sun
200 papers
Genomic characterization of resistant and relapsed adult B-cell acute lymphoblastic leukemia.
Płotka A, Marcinkowska-Swojak M, Rakoczy M … +7 more , Zeńczak M, Litowczenko W, Koralewska N, Kanduła Z, Gil L, Handschuh L, Lewandowski K
J Appl Genet · 2026 Mar · PMID 41882472 · Publisher ↗
Here, we implemented WGS to characterize the genomic landscape of B-cell acute lymphoblastic leukemia (B-ALL), with emphasis on resistant/relapsed (R/R) cases. The study group contained 64 adult patients with B-ALL diagn...
Here, we implemented WGS to characterize the genomic landscape of B-cell acute lymphoblastic leukemia (B-ALL), with emphasis on resistant/relapsed (R/R) cases. The study group contained 64 adult patients with B-ALL diagnosed and treated between 2008 and 2023, including 29 R/R cases. WGS-based mutation analysis was conducted in reference to the immunological and cytogenetic subtypes of the disease and response to therapy. In total, we identified 2,237 variants across 1,267 genes, including 248 pathogenic and 126 likely pathogenic genetic lesions. The numerous associations between the mutation profiles and B-ALL subtypes were found. Notably, 517 genes harbored variants exclusive to the R/R group. Mutated genes were significantly enriched in pathways related to DNA repair (e.g., BRCA2, FANCM), kinase signaling (JAK2, NF1), and chromatin remodeling (CREBBP, BARD1), as well as the gene ontology term “regulation of phosphorylation” (GO:0042325). The results of our study suggest an association between the presence of mutations in genes encoding proteins involved in phosphorylation processes and the R/R B-ALL. Furthermore, R/R patients also exhibited an increased mutational burden compared to those who responded to therapy. This highlights the need for precise evaluation of the nature of molecular changes in individual patients to determine the risk of therapy failure.
Evaluation of pedigree structure, inbreeding levels, and inbreeding depression in reproduction traits in two Polish Złotnicka native pig breeds.
Pycińska N, Szulc K, Sell-Kubiak E
J Appl Genet · 2026 May · PMID 41857340 · Full text
This study aimed to assess the pedigree structure, estimate the level of inbreeding, and determine its impact on reproductive traits in two native Polish pig breeds covered by genetic resource conservation programs: Złot...
This study aimed to assess the pedigree structure, estimate the level of inbreeding, and determine its impact on reproductive traits in two native Polish pig breeds covered by genetic resource conservation programs: Złotnicka White (ZW) and Złotnicka Spotted (ZS). The inbreeding coefficient was estimated using the classical Wright’s method and, for the first time, in those breeds, the modified VanRaden’s method, which accounts for incomplete pedigree information. The analysis included pedigree data collected between 1953 and 2021 for 6,126 ZW and 5,934 ZS individuals. The average inbreeding coefficients for the ZW breed were 9.97% (Wright) and 26.34% (VanRaden), whereas those for the ZS breed were 9.38% and 21.3%, respectively. In the ZS population, a substantial increase in inbreeding per generation was observed, exceeding the recommended threshold of 1%; i.e. 1.47% using Wright’s method and 1.25% using VanRaden’s method. Effective population size estimates indicated a risk of reduced genetic diversity, particularly according to VanRaden’s method. Further analysis of reproductive traits did not confirm clear or consistent effects of inbreeding depression. In ZW sows, statistically significant but irregular differences were found between inbreeding classes, whereas in ZS pigs, no significant effects were found. Those results should be interpreted with caution, given the incomplete pedigree information available for part of the population. Overall, the effect of inbreeding on the number of piglets born alive and surviving to 21 days was weak and of limited biological relevance. The results emphasise the need for intensified measures to control the increase in inbreeding and to maintain genetic diversity in these native pig populations.
Multi-year evaluation of genetic variability and population structure in bell pepper using integrated phenotypic traits and SSR marker data.
Sood S, Sood T, Sood VK … +4 more , Kaur J, Anuradha, Aakriti, Sharma M
J Appl Genet · 2026 Mar · PMID 41792537 · Publisher ↗
Bell pepper (Capsicum annuum L. var. grossum Sendt.) is a nutritionally rich and economically important crop of the Solanaceae family, valued for its therapeutic properties and export potential. However, its cultivation...
Bell pepper (Capsicum annuum L. var. grossum Sendt.) is a nutritionally rich and economically important crop of the Solanaceae family, valued for its therapeutic properties and export potential. However, its cultivation under diverse agro-climatic conditions exposes it to several biotic and abiotic stresses, highlighting the need to exploit genetic variability for crop improvement. In this study, 26 bell pepper genotypes were analysed to explore genetic diversity and population differentiation. Evaluation was performed based on 24 traits, including 9 DUS descriptors, 12 quantitative traits, and 3 quality-related traits, along with 75 SSR markers. Among the DUS descriptors, eight were polymorphic, with “Fruit: Shape in longitudinal section” exhibiting the highest variability (1.54). Mahalanobis D² statistic grouped the genotypes into six distinct clusters. Out of the 75 SSR markers, 31 were polymorphic and generated 130 alleles, with a mean of 4.19 alleles per locus. The polymorphism information content (PIC) varied from 0.29 to 0.78 (mean: 0.58), indicating moderate to high genetic diversity. Cluster analysis using UPGMA separated the genotypes into two main groups, while Neighbor-Joining and STRUCTURE analyses identified three subgroups. Fourteen genotypes consistently grouped across both phenotypic and molecular analyses and exhibited resistance to bacterial wilt. A strong correlation between phenotypic and molecular datasets (Mantel test: R = 0.7689) confirms the utility of an integrated approach for identifying genetically diverse and disease-resistant parental lines for bell pepper breeding programmes.
Efficacy of menthol on cell viability of lung cancer cell line (A549): bioinformatics study and effect on the expression of the tumor suppressor gene p53.
Jaliseh SA, Kulus D, Kaviani B
J Appl Genet · 2026 Mar · PMID 41787049 · Publisher ↗
Lung cancer is among the most common cancers in the world and is currently considered an epidemic on a global scale. Its rate is steadily increasing among men and women. The p53 gene is the most recognized tumor suppress...
Lung cancer is among the most common cancers in the world and is currently considered an epidemic on a global scale. Its rate is steadily increasing among men and women. The p53 gene is the most recognized tumor suppressor gene that is mutated in over 50% of human cancers. One of the methods to prevent cancer is the use of plant-based antioxidants. Menthol is a ten-carbon alcohol that is extracted from the pure essential oil of some plants, such as mint, oregano, and eucalyptus, and has food and medicinal uses. The present study aimed to investigate the effect of menthol on lung cancer cells, A549. In order to investigate the cytotoxicity of menthol on cancer cells and determine its half-maximal inhibitory concentration (IC50), the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test was performed. To investigate the effect of menthol on the expression of the p53 tumor suppressor gene, RNA extraction and cDNA synthesis were performed, and the change of gene expression in the concentration of IC50 was evaluated using the quantitative Real-Time PCR method. The binding of menthol to the P53 protein was investigated by the molecular docking method. According to the results of this research, the cytotoxic effect of menthol on the A549 cell line was proven, and the IC50 of menthol was determined at a concentration of 9.65 mg·mL− 1. Moreover, it was found that menthol upregulated p53 gene expression. The result of the bioinformatics analysis revealed that the amino acids asparagine and serine of the P53 mutant protein establish a hydrogen bond with menthol, resulting in the reduction of protein function and improved resistance against cancer. The interaction energy between menthol and P53 protein was determined to be -12.5 kJ·mol− 1. In conclusion, the menthol active ingredient increases the expression of the p53 tumor suppressor gene in lung cancer cell lines; therefore, it can be considered a possible alternative for lung cancer treatment after additional clinical studies.
Alpha-methylacyl-CoA racemase (AMACR) deficiency: report on novel patient and literature review.
Lipiński P, Rusecka J, Sobczyńska-Tomaszewska A … +3 more , Vaz FM, Stradomska T, Tylki-Szymańska A
J Appl Genet · 2026 Mar · PMID 41766008 · Publisher ↗
Alpha-methylacyl-CoA racemase (AMACR) deficiency is an autosomal recessive disorder of peroxisomal β-oxidation of branched-chain fatty acids and C27-bile acids. Since its first report in 2000, several children were diagn...
Alpha-methylacyl-CoA racemase (AMACR) deficiency is an autosomal recessive disorder of peroxisomal β-oxidation of branched-chain fatty acids and C27-bile acids. Since its first report in 2000, several children were diagnosed via molecular analyses, mostly due to elevated liver enzymes. Here we present an early-onset form of AMACR deficiency in clinically asymptomatic child who was diagnosed upon incidental findings of elevated liver enzymes and glucosuria. This case expands the phenotypic (biochemical) spectrum of AMACR deficiency. The manuscript was enriched by the literature review on patients with AMACR deficiency diagnosed in childhood. We recommend to perform serum/plasma peroxisomal metabolites, including VLCFA, bile acids intermediates and phitanic and pristanic acid, in every children with persistently elevated liver enzymes, especially with coagulopathy and with or without cholestatic jaundice.
The methylation of LHX2, RAPGEFL1, RARB and RYR2 has prognostic significance in head and neck squamous cell carcinoma patients.
Skalski M, Kowal-Wiśniewska E, Jaskiewicz-Rajewicz K … +8 more , Kiwerska K, Bartochowska A, Ustaszewski A, Górecki T, Majchrzak-Celińska A, Wierzbicka M, Jarmuż-Szymczak M, Paluszczak J
J Appl Genet · 2026 Mar · PMID 41766007 · Publisher ↗
Head and neck squamous cell carcinomas (HNSCC) are a group of frequently occurring tumors with a high rate of relapse and 5-year survival of approximately 60%. Novel diagnostic and prognostic biomarkers analyzed in liqui...
Head and neck squamous cell carcinomas (HNSCC) are a group of frequently occurring tumors with a high rate of relapse and 5-year survival of approximately 60%. Novel diagnostic and prognostic biomarkers analyzed in liquid biopsy could improve clinical management of patients and prolong their survival. Thus, the aim of this study was to evaluate the utility of DNA methylation analysis in the clinical management of HNSCC patients. Based on our previous studies and the analysis of TCGA data, we selected six epigenetically regulated genes, which differentiated HNSCC patients from healthy controls. Next, we used a two-step nested MethyLight assay to analyze the DNA methylation of DAPK1, LHX2, MGMT, RAPGEFL1, RARB, and RYR2 in HNSCC tumor samples, which was followed by confirmatory analysis of cfDNA from plasma samples in another cohort of HNSCC patients. We provided evidence for the relevance of DAPK1, LHX2, MGMT, RAPGEFL1, RARB, and RYR2 methylation analysis in HNSCC diagnosis. Importantly, the methylation of RAPGEFL1, RARB, and RYR2 in tumor samples was found to be associated with HNSCC recurrence. The presence of methylation of RARB and LHX2 in cfDNA distinguished HNSCC patients from healthy controls. Overall, we report that LHX2, RAPGEFL1, RARB, and RYR2 are promising candidates for a methylation-based diagnostic tool in HNSCC patients.
Genetic mapping of fertility restoration (Rf) genes and development-validation of linked SNPs for A cytoplasm of sorghum (Sorghum bicolor (L.) Moench).
Wasudeo NG, Rayaprolu L, Kns UK … +4 more , Mehtre SP, Kalpande H, Deshpande SP, Wani SH
J Appl Genet · 2026 Feb · PMID 41761040 · Publisher ↗
Sorghum (Sorghum bicolor L. Moench) is one of the most important cereal crops in which cytoplasmic genetic male sterility (CGMS) is widely exploited for hybrid breeding. Commercial sorghum hybrids globally are predominan...
Sorghum (Sorghum bicolor L. Moench) is one of the most important cereal crops in which cytoplasmic genetic male sterility (CGMS) is widely exploited for hybrid breeding. Commercial sorghum hybrids globally are predominantly based on the A1 cytoplasmic genetic male sterility (CGMS) system because of its operational ease and cytoplasmic stability. To map fertility restoration (Rf) loci, hybrids were developed by crossing the CMS line 296 A with a recombinant inbred line (RIL) population derived from the cross 296B × IS18551, which segregates for fertility restoration genes. The RIL population consisted of advanced-generation lines (F₆:₇), ensuring high homozygosity suitable for genetic mapping. In addition, F₂ and BC₁F₁ populations were developed from selected fertile RIL-derived hybrids to validate fertility restoration loci.The RIL population was genotyped using a genotyping-by-sequencing (GBS) approach and employed for genome-wide genetic mapping of fertility restoration genes. Based on significant associations, a set of 19 single nucleotide polymorphism (SNP) markers associated with fertility restoration was selected and converted into Kompetitive Allele-Specific PCR (KASP) assays. These 19 KASP markers were first validated in the RIL population and subsequently evaluated using a diverse panel of 150 sorghum lines, comprising 72 maintainer (B) lines and 78 restorer (R) lines.Of the 19 validated KASP markers, six markers were associated with the major fertility restoration locus Rf1 on chromosome SBI-08, while the remaining markers were linked to loci located on chromosomes SBI-01, SBI-03, SBI-07, SBI-09, and SBI-10. The results clearly demonstrate the ability of specific SNP markers to discriminate fertility restoration responses between B- and R-lines. The identified polymorphic SNP markers provide robust molecular tools for fast-tracking line conversion and marker-assisted selection in sorghum hybrid breeding programs. Overall, this study enhances the current understanding of fertility restoration genetics in sorghum by identifying key Rf loci, improving hybrid breeding efficiency, and providing new insights into cytoplasm–nuclear interactions governing male fertility restoration.
Correction to: Dynamics of accumulation of lysine and tryptophan, and kernel modification in opaque2, opaque16, and double mutant (opaque2/opaque16) genotypes during kernel development in maize.
Chand G, Muthusamy V, Allen T … +9 more , Gain N, Singh B, Dutta S, Prakash NR, Singh S, Sarika K, Chawla G, Zunjare RU, Hossain F
J Appl Genet · 2026 May · PMID 41653384 · Publisher ↗
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Advancements in somatic mutation detection through loop-mediated isothermal amplification (LAMP) in human tumors.
Nazarizadeh-Ravari F, Salehinezhad-Yazdi MM, Shahbazi S
J Appl Genet · 2026 Feb · PMID 41644930 · Publisher ↗
Loop-mediated isothermal amplification (LAMP) is a robust and specific isothermal nucleic acid assessment technique. Due to its practicality and diverse detection strategies, LAMP has gained new insights in the analysis...
Loop-mediated isothermal amplification (LAMP) is a robust and specific isothermal nucleic acid assessment technique. Due to its practicality and diverse detection strategies, LAMP has gained new insights in the analysis of somatic mutations in various tumor types, where the proportion of mutated DNA is often markedly low compared to wild-type DNA. We conducted an evaluation of articles from PubMed and Google Scholar published up to May 2025, focusing on somatic mutation detection in human cancers using LAMP. In addition to reviewing the articles found using specific keywords, we also examined and evaluated the references cited in those articles. By employing various primer design strategies specific to single base substitutions such as mismatch and loop primers, the researchers addressed the challenge of distinguishing between wild-type and mutant alleles. Furthermore, the specificity and sensitivity of the LAMP assay were enhanced by incorporating Locked Nucleic Acid (LNA) and Peptide Nucleic Acid (PNA) probes. The use of additives and adjustments in reaction conditions has also been discussed as strategies to improve reactions efficiency. LAMP demonstrates the capability to detect mutations present at levels as low as 0.1% in tumor tissues, indicating its potential for high-sensitivity mutation detection. The studies contribute to refining LAMP as a reliable, rapid, and cost-effective method for somatic mutation detection. The versatile detection approaches further enhance the utility and accessibility of the LAMP technique in various research and clinical settings. This paves the way for its broader application in clinical diagnostics and personalized medicine.
Epstein-barr virus and multiple sclerosis: from pathogenesis and diagnosis to EBV-specific T cell therapy and gene-targeted therapeutics.
Pushkarna M, Zwamel A, Verma S … +6 more , Malathi H, Mustafayeva M, Kaur H, Al-Nuaimi AMA, Husseen B, Dahghani M
J Appl Genet · 2026 Jan · PMID 41504999 · Publisher ↗
Multiple sclerosis (MS) is a central nervous system (CNS) disorder defined by inflammation, demyelination, and neuronal damage. Several independent studies have confirmed the prevalence of EBV infection in MS and the pre...
Multiple sclerosis (MS) is a central nervous system (CNS) disorder defined by inflammation, demyelination, and neuronal damage. Several independent studies have confirmed the prevalence of EBV infection in MS and the presence of elevated anti-EBV antibody titers in serum prior to and throughout the clinical period of MS. EBV stands out from other human-infecting viruses in that it can activate, infect, and clone the B cells and remain a latent infection inside them. The prevalence of EBV-positive B cell lymphoproliferative diseases in immunocompromised individuals demonstrates the critical significance of immune surveillance in managing EBV infection. It has also been postulated that a deficiency in EBV-specific CD8 T cell regulation predisposes to MS by allowing EBV-infected autoreactive B cells and plasma cells to concentrate in the CNS. Thus, EBV-specific T-cell therapy might have the potential to eradicate B lymphocytes infected by EBV in the CNS, preventing disease development and leading to enhanced clinical outcomes. One of the effective approaches for treating MS patients is application of EBV-specific T cells. In this method, peripheral blood mononuclear cells (PBMCs) are isolated from patients and expanded with EBV-specific antigens, resulting in antiviral cytotoxic response. This review discusses the significance of EBV in the pathogenesis of MS, the impact of disease-modifying T-cell treatments targeting EBV, therapeutic implications to target EBV in MS pathogenesis, and several novel EBV-targeting gene therapies.
Genetic architecture of the sieve element occlusion (SEO) family underlying potential regulatory mechanisms in citrus stress response.
Dos Santos LN, Cavalcante LDN, Dutt M … +1 more , de Souza AA
J Appl Genet · 2026 Jan · PMID 41504998 · Publisher ↗
The Sieve Element Occlusion (SEO) proteins are subunits that assemble into structural filamentous phloem proteins, commonly referred to as P-proteins. These proteins in Arabidopsis play a structural role and contribute t...
The Sieve Element Occlusion (SEO) proteins are subunits that assemble into structural filamentous phloem proteins, commonly referred to as P-proteins. These proteins in Arabidopsis play a structural role and contribute to plant defense by reversible sieve plate (SP) sealing. This mechanism could be particularly important also in Citrus trees affected by Huanglongbing (HLB), as SEO genes are highly induced in susceptible species C. sinensis upon Candidatus Liberibacter asiaticus (CLas) colonization. Given the limited information on this gene family in Citrus, we analyzed 27 SEO genes within the Rutaceae family, with a focus on genera closely related to Citrus, to better understand their potential roles in HLB tolerance. Genomic sequences revealed conserved exon-intron structures similar to Arabidopsis thaliana, while promoter regions contained a higher number of light-responsive Cis-elements, along with elements associated with growth, development, stress responses, and phloem-specific gene expression. Subcellular localization identified the cytoplasm as the primary site, with additional predictions for the plasma membrane and mitochondria. Phylogenetic analysis categorized SEO proteins into five subgroups, refining their classification in Citrus. Lately, protein interaction networks indicated strong connections with proteins involved in coordinated immune responses. These findings improve the understanding of SEO protein dynamics and evolutionary conservation, highlighting their role in phloem biology. Further investigation of these SEO genes and their promoters in the plant response to HLB could help identify specific targets for developing disease-tolerant Citrus varieties through genetic engineering.
Updated sequence of ramoplanin biosynthetic gene cluster from Actinoplanes ramoplaninifer ATCC 33,076.
Yushchuk O, Rückert-Reed C, Busche T … +2 more , Marinelli F, Kalinowski J
J Appl Genet · 2026 May · PMID 41499035 · Publisher ↗
Actinoplanes ramoplaninifer ATCC 33,076 is the only known producer of the glycolipodepsipeptide antibiotic ramoplanin. Ramoplanin (Rmp) interferes with peptidoglycan biosynthesis by binding to lipid II and consequently i...
Actinoplanes ramoplaninifer ATCC 33,076 is the only known producer of the glycolipodepsipeptide antibiotic ramoplanin. Ramoplanin (Rmp) interferes with peptidoglycan biosynthesis by binding to lipid II and consequently impeding the transglycosylation reactions. Rmp exhibits excellent antimicrobial properties against Gram-positive bacteria, including methicillin- and vancomycin-resistant strains of staphylococci and enterococci, as well as Clostridioides difficile, showing no cross-resistance with glycopeptides and β-lactams. Rmp is poorly absorbed in the gastrointestinal tract when administered orally, exhibits poor local tolerability after intravenous injections and scarce tissue penetrability upon intramuscular injection. Moreover, Rmp is reported to be rather instable in the bloodstream. Consequently, Rmp oral capsule has reached phase II and III clinical trials for the eradication of vancomycin-resistant Enterococcus faecium and Clostridioides difficile in the gastrointestinal tract, respectively. The modification of Rmp through combinatorial biosynthesis might open new perspectives for this antibiotic, enhancing and/or modifying its pharmacokinetics. To understand the genetics underlying Rmp biosynthesis, its biosynthetic gene cluster (BGC) was sequenced two decades ago, revealing a 16-modular non-ribosomal peptide synthetase (NRPS) machinery, which is unusual considering that ramoplanin is a 17 amino acid peptide. Bearing in mind that older sequencing approaches often produced errors when facing iterative DNA segments (as is the case with NRPS genes), we aimed to resequence the ramoplanin BGC using new sequencing approaches. Thus, in the current paper, we present a new sequence of the ramoplanin BGC (ramo), revealing a conventional 17-modular NRPS machinery. Additionally, we reannotated the ramo genes, providing new insights into Rmp biosynthesis.
Accelerating genetic gain through integrated genomic selection in crop plants.
Edukondalu B, Aswini N, Amaresh … +7 more , Krishnappa G, Soundharya B, Nikhitha G, Pathy TL, Krishna K, Hari Y, Vinayaka
J Appl Genet · 2026 May · PMID 41483119 · Publisher ↗
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, althou...
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.
When genetics meets immunology: the assessment of genetic and immunological backgrounds in advanced NSCLC patients treated with immunotherapy - preliminary study.
Krzyżanowska N, Nicoś M, Wojas-Krawczyk K … +8 more , Krawczyk P, Chmielewska I, Jankowski T, Kucharczyk T, Wójcik-Superczyńska M, Sroka-Bartnicka A, Stokowy T, Milanowski J
J Appl Genet · 2026 Jan · PMID 41483118 · Publisher ↗
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 signi...
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.
Characterization of spelt wheat (Triticum spelta L.) genotypes using DArTseq technology.
Pietrusińska-Radzio A, Bilska-Kos A, Bocianowski J
J Appl Genet · 2026 May · PMID 41455027 · Full text
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 r...
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.
Polymorphism of the HMGA2 gene in Polish children and adolescents with short stature and diverse growth hormone secretion.
Majewska KA, Kaczmarek-Ryś M, Hoppe-Gołębiewska J … +6 more , Nowacka-Woszuk J, Prauzińska M, Szydłowski J, Naskręcka M, Kędzia A, Pławski A
J Appl Genet · 2025 Dec · PMID 41432898 · Publisher ↗
HMGA2 is one of the common genes strongly associated with adult and childhood height. Some studies have also linked this gene to growth hormone deficiency (GHD). This study aimed to investigate polymorphic variants of th...
HMGA2 is one of the common genes strongly associated with adult and childhood height. Some studies have also linked this gene to growth hormone deficiency (GHD). This study aimed to investigate polymorphic variants of the HMGA2 gene in Polish children and adolescents with short stature and GHD. Study cohort consisted of 157 children with short stature, including 111 with GHD and 46 with normal growth hormone (GH) secretion. The control group consisted of 142 healthy children of normal height. High-resolution melting (HRM) was used to screen for sequence variants and Sanger sequencing was performed to identify the detected changes. No variants were identified in the coding sequence of the HMGA2 gene. However, two known polymorphisms were observed in intron 3: the G insertion (rs3834468) and the T > A substitution (rs73115423). The statistical analysis of these allele frequencies comparing all short stature children versus controls revealed no significant differences for both polymorphisms studied. However, for rs73115423 within the short stature group, children with GHD had over 3 times lower. A allele frequency than those with normal GH secretion, and the difference was statistically significant (p = 0.042). For rs3834468 no differences were identified within the short stature group. Our findings do not support a definitive role of HMGA2 in the pathogenesis of short stature in Polish children and adolescents. However, they highlight a potential involvement of this gene in the complex mechanisms regulating the somatotropic axis, particularly in relation to GH secretion.
Computational analysis of Non-synonymous SNP effects on human PLVAP gene structure and function.
Khatoon M, Sekar YS, Rani S … +10 more , Ramesh V, Shijili M, Jangid V, Archana CA, Palavesam A, Jacob SS, Hiremath J, Patil SS, Gulati BR, Suresh KP
J Appl Genet · 2025 Dec · PMID 41428257 · Publisher ↗
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 (...
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.
Clinicopathological and genomic profiling in undifferentiated pleomorphic sarcoma: Small series, clear message.
Remiszewski P, Tysarowski A, Seliga KA … +8 more , Bobak K, Piątkowski J, Golik P, Spałek MJ, Szumera-Ciećkiewicz A, Wągrodzki M, Rutkowski P, Czarnecka AM
J Appl Genet · 2025 Dec · PMID 41413689 · Publisher ↗
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...
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.
Exploring the pathogenic mechanism of RNH1 in colorectal cancer based on eQTL, Multi-omics and deep learning.
Chen C, Chen X, Yang Y … +4 more , Cai Y, Chen N, Jiang D, Weng Y
J Appl Genet · 2025 Dec · PMID 41366589 · Publisher ↗
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 recentl...
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.
Further evidence for a wide phenotypic and mutational spectrum of Cohen syndrome: case report and literature review.
Futyma A, Biel K, Krawczyński MR
J Appl Genet · 2025 Dec · PMID 41361689 · Publisher ↗
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, progres...
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.
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