Journal of Applied Genetics最新文献

{"title":"Beyond the complex: inosine drives the antiviral and epigenetic effects of inosine pranobex.","authors":"Dariusz Wawrzyniak, Mariola Dutkiewicz, Dawid Dorna, Michał Kątny, Mirosława Naskręt-Barciszewska, Paweł Głodowicz, Jarosław Pieczuro, Katarzyna Rolle, Łukasz Idczak, Szymon Romankiewicz, Jan Barciszewski","doi":"10.1007/s13353-026-01066-7","DOIUrl":"https://doi.org/10.1007/s13353-026-01066-7","url":null,"abstract":"<p><p>Inosine pranobex (IP) is a long-used antiviral drug whose mechanism of action remains incompletely understood. However, molecular efficacy has been attributed mainly to immunomodulatory effects. There are data which suggest that the cellular activity of IP stems from its major constituent compound, inosine, known for its pleiotropic roles in purine metabolism, RNA modification, and translation regulation. We investigated whether IP acts as a stable complex or a mixture of its components and compared the biological effects of inosine itself and IP in vitro. The structural composition of IP was analyzed using compositional and microscopic methods. Cytotoxicity, antiviral activity against coxsackievirus B3 (CVB-3), and global DNA methylation changes were evaluated in A549 and HeLa cell lines using MTT, colony formation, plaque reduction, and post-labeling methods, respectively. We found that IP is physically heterogeneous and function as a mixture of components rather than a stable complex. In cell-based assays, inosine exhibited higher antiviral activity than IP, particularly under pre-treatment conditions, where it provided stronger protection against CVB-3-induced cytopathic effects. Neither compound showed significant cytotoxicity within the tested concentration ranges. Both inosine and IP influenced global DNA methylation levels, but inosine induced more pronounced and concentration-dependent changes. The superior antiviral and epigenetic activity of inosine compared with IP suggests that inosine is the main principal active component responsible for IP's biological effects. While IP's immunomodulatory functions were not evaluated here, our findings strongly suggest that inosine contributes substantially to its antiviral efficacy. Further studies, including in vivo models, are warranted to clarify the epigenetic mechanism underlying these observations.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Molecular interplay of lncRNAs, miRNAs, and mRNAs axes in triple-negative breast cancer: implications for metastatic progression.","authors":"Deepshikha Rathore, Ishita Agarwal, Smit Patel, Nishita Adnani, Nandani Dharwal, Nirali Shukla, Heena V Dave","doi":"10.1007/s13353-026-01068-5","DOIUrl":"https://doi.org/10.1007/s13353-026-01068-5","url":null,"abstract":"","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel SCN5A variant associated with flecainide-responsive multifocal ventricular arrhythmia and recovered cardiomyopathy.","authors":"Elżbieta Katarzyna Biernacka, Joanna Ponińska, Krzysztof Smarż, Andrzej Budaj","doi":"10.1007/s13353-026-01067-6","DOIUrl":"https://doi.org/10.1007/s13353-026-01067-6","url":null,"abstract":"<p><p>Multifocal Ectopic Purkinje-related Premature Contractions (MEPPC) is a rare genetic arrhythmogenic syndrome caused by gain-of-function mutations in the SCN5A gene, leading to frequent multifocal premature ventricular contractions and risk of cardiomyopathy. We report a case highlighting the diagnostic and therapeutic challenges associated with unrecognized MEPPC. A 27-year-old woman presented with highly symptomatic ventricular and supraventricular arrhythmias and severe left ventricular dysfunction, refractory to conventional therapy and ablation. Initiation of flecainide resulted in immediate arrhythmia suppression and full recovery of cardiac function. Genetic testing revealed two SCN5A variants: a novel likely pathogenic p.(Val215Ala) located in a known MEPPC hotspot, and p.(Phe1570Cys), a variant with known loss-of-function properties, unlikely to be causative in MEPPC but potentially modulating the phenotype. This report underscores the importance of early recognition of MEPPC based on arrhythmic patterns and the critical role of targeted genetic testing in optimizing treatment strategies.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformative Applications and Innovations in Next-Generation Sequencing Data Analysis.","authors":"Abhijit Beura, Tikam Chand Dakal, Mangesh Sudhakar Rajguru, Gowrang K Manjunath, Shweta Mahalingam, Abhishek Kumar","doi":"10.1007/s13353-026-01064-9","DOIUrl":"https://doi.org/10.1007/s13353-026-01064-9","url":null,"abstract":"<p><p>Next-generation sequencing (NGS) has revolutionized the field of genomics by providing rapid, high-throughput, and cost-effective platforms for analyzing genomes, transcriptomes, and epigenomes. Its application spans cancer genomics, infectious disease research, rare disease diagnostics, and precision medicine, enabling comprehensive detection of genetic variants and their functional implications. The advent of advanced methods such as single-cell sequencing, long-read technologies, and multi-omics integration has further expanded the scope of NGS, allowing unprecedented insights into cellular heterogeneity, structural variations, and systems-level interactions. These innovations have facilitated the identification of actionable mutations, supported biomarker discovery, and enhanced our understanding of complex biological processes in both research and clinical contexts. Despite these advancements, several challenges remain. The vast volume of sequencing data necessitates robust computational infrastructures for storage, processing, and interpretation. Sequencing error rates, though improving, continue to impact variant detection and clinical reliability. Ethical concerns regarding privacy, data sharing, and equitable access are also critical barriers that must be addressed, particularly in resource-limited settings. Moreover, translating genomic findings into clinically actionable outcomes requires standardized frameworks and interdisciplinary collaboration among clinicians, geneticists, and bioinformaticians. Looking ahead, the integration of artificial intelligence, machine learning, and automation into NGS data pipelines promises to significantly enhance accuracy, scalability, and clinical utility. These emerging innovations, coupled with global efforts to ensure accessibility and ethical implementation, position NGS as a cornerstone of precision medicine, paving the way for individualized treatment strategies and transformative improvements in healthcare delivery.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating genetic gain through integrated genomic selection in crop plants.","authors":"Bandela Edukondalu, Nunavath Aswini, Amaresh, Gopalareddy Krishnappa, Buruka Soundharya, Gottimukkala Nikhitha, T Lakshmi Pathy, Kasanaboina Krishna, Yadla Hari, Vinayaka","doi":"10.1007/s13353-025-01034-7","DOIUrl":"10.1007/s13353-025-01034-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"249-269"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare T-box variants in adult pulmonary arterial hypertension with congenital heart disease.","authors":"Li Li, Guoliang Chen, Nating Qiao, Jianwei Li, Zhixin Wang, Yaxuan Lyu, Yanqing Guo","doi":"10.1007/s13353-025-00958-4","DOIUrl":"10.1007/s13353-025-00958-4","url":null,"abstract":"<p><p>We report the clinical and genetic features of three adult patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) carrying rare T-box variants. All three patients had weakness and cyanosis. Two patients had chest tightness, dry cough, and hemoptysis, and one patient had lower limb edema. Besides meeting the diagnostic criteria of CHD-PAH, three patients respectively presented the clinical features of specific syndromes. Specifically, patient 1 presented with clinical features consistent with tetralogy of Fallot, patient 2 presented with characteristics associated with small patella syndrome, and the patient 3 exhibited features consistent with Holt-Oram syndrome. Exome sequencing revealed that the TBX1 (c.820 T > C) variant was identified in patient 1, the TBX4 (c.251del) variant was detected in patient 2 and the TBX5 (c.486del) variant was found in patient 3. Our study for the first time found that CHD-PAH patients carry T-box gene variants, which has added new clues to understanding the pathogenesis of CHD-PAH and is expected to provide new targets and ideas for the diagnosis and treatment of CHD-PAH.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"365-371"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium-sensing receptor genetic variants and their association with CKD-MBD in South Indian Tamils.","authors":"G Priyadarshini, A Dhinesh, Sreejith Parameswaran, Jayaprakash Sahoo, Sandhiya Selvarajan, Medha Rajappa","doi":"10.1007/s13353-025-00955-7","DOIUrl":"10.1007/s13353-025-00955-7","url":null,"abstract":"<p><p>The progressive degradation of the renal parenchyma and reduction of functional nephrons characterise chronic kidney disease (CKD). Disorders of bone mineral metabolism is one of the leading causes of morbidity and mortality in CKD. Calcium-sensing receptor (CASR) allows cells to detect changes in blood calcium levels and regulate its concentration. Hence, we aim to study the relationship between genetic variants of CASR and CKD and their relation with mineral bone disease (MBD). A total of 180 CKD patients and 180 controls were recruited. Bone mineral density of the lumbar spine, hip, and forearm was measured using a dual X-ray absorptiometry (DEXA) scan. Circulating levels of parathyroid hormone (PTH) were measured by ELISA. Genotyping was done by real-time quantitative PCR. A significant difference in the distribution of the GAG haplotype (rs7652589, rs1501899, rs1801725) was observed between CKD patients and controls. Participants with the GT genotype of rs1801725 had lower BMD in the forearm. The TT genotype of rs1801725 was associated with decreased serum calcium levels. A regression model indicated that the GT genotype of rs1801725 and AG and GG genotypes of rs7652589 were significant predictors of forearm BMD. GAG haplotype of CASR SNPs is linked to CKD risk in South Indian Tamils. GT genotype of rs1801725 and AG and GG genotype of rs7652589 are independent predictors of MBD in patients with CKD.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"395-402"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of selection for growth on reproductive traits in Nellore females: Genetic parameters and genome-wide association studies.","authors":"Isabela Meirelles Cardoso Garcia, Viviane Andrade Ligori, Jessica Moraes Malheiros, Gustavo Roberto Dias Rodrigues, Pablo Dominguez-Castaño, Josineudson Augusto Ii Vasconcelos Silva, Fábio Morato Monteiro, Joslaine Noely Dos Santos Gonçalves Cyrillo, Maria Eugênia Zerlotti Mercadante","doi":"10.1007/s13353-025-01026-7","DOIUrl":"10.1007/s13353-025-01026-7","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"459-476"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Riboflavin treatment in L-2-hydroxyglutaric aciduria: report on a pediatric patient and literature review.","authors":"Patryk Lipiński, Elżbieta Ciara, Anna Bogdańska, Elżbieta Jurkiewicz, Anna Tylki-Szymańska","doi":"10.1007/s13353-025-00974-4","DOIUrl":"10.1007/s13353-025-00974-4","url":null,"abstract":"<p><p>L-2-hydroxyglutaric aciduria (L-2-HGA, #236,792) is an autosomal recessive neurodegenerative disorder caused by the deficiency of L-2-hydroxyglutarate dehydrogenase, a flavin adenine dinucleotide (FAD)-dependent enzyme, due to biallelic pathogenic variants in the L2HGDH gene. The present study described the patient with L2HGA presenting with a slight psychomotor delay, epilepsy from 5 years of age, non-progressive cerebellar ataxia, and mild to moderate intellectual disability during 10 years of follow-up. Two different heterozygous variants in the L2HGDH gene were identified in the patient: a known substitution c.829C > T(p.Arg277*) and a novel substitution c.1196 + 1G > A corresponding with significantly increased urinary L-2-hydroxyglutarate (L2HG) excretion. A 6-month period of treatment with riboflavin (100 mg/day) was implemented with no clinical nor biochemical effect.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"443-449"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-trait stability index in the selection of high-yielding and stable barley genotypes.","authors":"Alireza Pour-Aboughadareh, Bita Jamshidi, Omid Jadidi, Jan Bocianowski, Janetta Niemann","doi":"10.1007/s13353-025-00998-w","DOIUrl":"10.1007/s13353-025-00998-w","url":null,"abstract":"<p><p>The analysis of genotype-by-environment interaction (GEI) in multi-environmental trials (METs) represents a crucial component of breeding programs prior to the release of new commercial cultivars tailored for specific regions or diverse environmental conditions. Moreover, emphasizing individual traits during selection can yield misleading conclusions. Consequently, the implementation of robust selection models is essential for identifying superior genotypes based on multiple traits. The present dataset demonstrates the utility of the multi-trait stability index (MTSI) in identifying high-yielding and stable barley genotypes across ten diverse environments. The evaluated phenological and agronomic traits included days to heading, days to physiological maturity, grain-filling period, plant height, thousand-kernel weight, and grain yield. A combined analysis of variance (ANOVA) revealed significant effects attributable to environments (E), genotypes (G), and their interaction (GEI) across all assessed traits. Correlation analysis further indicated positive associations between all measured traits and grain yield. In the MTSI model, three first factors accounted for 75% of the total phenotypic variation observed across the test environments. The highest selection gain percentages were recorded for thousand-kernel weight and grain yield. Among the genotypes evaluated, G3, G10, and G14, characterized by the lowest values of the MTSI index, were identified as superior in terms of grain yield, stability, and desirable agronomic attributes. In conclusion, the findings highlight the efficacy of the MTSI in reliably identifying superior genotypes in METs. The results demonstrate that the MTSI index not only enhances the efficiency of the selection process but also improves the accuracy of genotype evaluation and ranking across heterogeneous environmental conditions. This underscores the potential of the MTSI index to support informed breeding decisions, ultimately facilitating the development of high-performing plant varieties that exhibit both yield stability and adaptability across diverse environments.</p>","PeriodicalId":14891,"journal":{"name":"Journal of Applied Genetics","volume":" ","pages":"317-323"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}