Genetic variations are considered important for athletic performance. In this regard, α-actinin-3 (ACTN3) and angiotensin I-converting enzyme (ACE) gene polymorphisms are widely studied for their association with elite athlete status. The ACE gene regulates circulatory homeostasis, with the I variant of the ACE insertion/deletion (ACE I/D) gene polymorphism being associated with endurance performance, while the R allele of the R577X polymorphism of the ACTN3 gene, crucial for fast glycolytic muscle fibers, has been associated with speed and power performances. The present study investigated the association of these genetic variants with elite boxer (N = 57) status and compared with elite power/speed athletes (N = 40), endurance athletes (N = 44) and nonathletes (N = 98) in the Indian population. The R allele frequency was significantly higher in boxers than the nonathletes (p < 0.05). The allele and genotype frequencies of boxers, endurance and power/speed athletes did not differ significantly (p > 0.05). After analyzing the overall athletic cohort on the basis of their level of performance, the frequency of RR genotype (24.1 %) and R allele (47.7 %) in national level athletes was found significantly higher than in nonathletes (8.7 % and 34.2 %, respectively), with a significant difference (p < 0.05) between national level endurance athletes and nonathletes only. The ACE I/D gene polymorphism was not associated with any of the athletic cohorts (p > 0.05). Taken altogether, our study showed that the R allele of ACTN3 gene polymorphism is associated with elite boxer status as compared to the nonathletes.
{"title":"Association of ACTN3 and ACE gene polymorphisms with Indian elite boxer status","authors":"Vijmendra Kumar Grover , Jai Prakash Verma , Ashish Kumar , Nivedita Sharma , Pramod Kumar Tiwari","doi":"10.1016/j.genrep.2025.102357","DOIUrl":"10.1016/j.genrep.2025.102357","url":null,"abstract":"<div><div>Genetic variations are considered important for athletic performance. In this regard, α-actinin-3 (ACTN3) and angiotensin I-converting enzyme (ACE) gene polymorphisms are widely studied for their association with elite athlete status. The ACE gene regulates circulatory homeostasis, with the I variant of the ACE insertion/deletion (ACE I/D) gene polymorphism being associated with endurance performance, while the R allele of the R577X polymorphism of the ACTN3 gene, crucial for fast glycolytic muscle fibers, has been associated with speed and power performances. The present study investigated the association of these genetic variants with elite boxer (<em>N</em> = 57) status and compared with elite power/speed athletes (<em>N</em> = 40), endurance athletes (<em>N</em> = 44) and nonathletes (<em>N</em> = 98) in the Indian population. The R allele frequency was significantly higher in boxers than the nonathletes (<em>p</em> < 0.05). The allele and genotype frequencies of boxers, endurance and power/speed athletes did not differ significantly (<em>p</em> > 0.05). After analyzing the overall athletic cohort on the basis of their level of performance, the frequency of RR genotype (24.1 %) and R allele (47.7 %) in national level athletes was found significantly higher than in nonathletes (8.7 % and 34.2 %, respectively), with a significant difference (<em>p</em> < 0.05) between national level endurance athletes and nonathletes only. The ACE I/D gene polymorphism was not associated with any of the athletic cohorts (<em>p</em> > 0.05). Taken altogether, our study showed that the R allele of ACTN3 gene polymorphism is associated with elite boxer status as compared to the nonathletes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102357"},"PeriodicalIF":0.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-08DOI: 10.1016/j.genrep.2025.102353
Mohammad Salimi Asl , Yousef Jafari Abarghan , Narjes Bakhtari , Sepideh Shohani , Mina Mohammadi Sarband , Sorayya Ghasemi
Background
Aniridia is a congenital eye disorder characterized by a partially or completely missing iris, frequently accompanied by other eye abnormalities. Communication difficulties, social interaction issues, and repetitive behaviors are hallmarks of autism spectrum disorder (ASD), a neurodevelopmental disorder. Identifying a causal gene(s) that is involved in aniridia and ASD in a patient is the goal of this research.
Methods
Genetic counseling, pedigree analysis, and a thorough clinical evaluation were performed on a 9-year-old female patient who presented with congenital aniridia and ASD. Karyotyping, Comparative Genomic Hybridization (CGH)-array, Whole-Exome Sequencing (WES), Sanger sequencing, and STR-based paternity testing were performed. In silico structural modeling was done using I-TASSER, and PyMOL 3.1.1 was used to find putative genetic variants.
Results
WES identified a novel de novo heterozygous point mutation, c.194G>A (p.Gly65Glu), in the PAX6 gene. Sanger sequencing confirmed this mutation, which was not discovered in population databases. STR-based paternity testing verified its de novo mutation. In silico tools (PolyPhen-2: 0.998; SIFT: 0.01; CADD: 35.0) predicted a deleterious effect.
Conclusions
This study provides the first report of a novel de novo PAX6:c.194G>A (p.Gly65Glu) mutation associated with aniridia and ASD. The findings highlight the pleiotropic role of PAX6 and support the utility of WES in detecting rare variants in complex phenotypes. Functional studies are necessary to confirm the pathogenic mechanism.
虹膜缺失是一种先天性眼部疾病，其特征是虹膜部分或完全缺失，通常伴有其他眼部异常。沟通困难、社会互动问题和重复行为是自闭症谱系障碍（ASD）的特征，这是一种神经发育障碍。本研究的目标是确定与患者无虹膜和ASD有关的致病基因。方法对1例9岁女性先天性无虹膜伴ASD患者进行遗传咨询、家系分析和全面临床评估。进行核型分析、比较基因组杂交（CGH）阵列、全外显子组测序（WES）、Sanger测序和基于str的亲子鉴定。使用I-TASSER进行硅结构建模，使用PyMOL 3.1.1寻找假定的遗传变异。结果在PAX6基因中发现了一个新的从头杂合点突变c.194G> a （p.Gly65Glu）。Sanger测序证实了这种在人口数据库中未发现的突变。基于str的亲子鉴定证实了其从头突变。在硅工具（polyphen2: 0.998; SIFT: 0.01; CADD: 35.0）预测有害影响。结论本研究首次报道了一种新的PAX6:c.194G> a （p.Gly65Glu）突变与无视网膜和ASD相关。这些发现强调了PAX6的多效性作用，并支持WES在检测复杂表型中的罕见变异方面的应用。功能研究是确认致病机制的必要条件。
{"title":"Comprehensive genomic analysis of the novel PAX6:c.194G>A (p.Gly65Glu) mutation: Highlighting a potential association with aniridia and autism spectrum disorder","authors":"Mohammad Salimi Asl , Yousef Jafari Abarghan , Narjes Bakhtari , Sepideh Shohani , Mina Mohammadi Sarband , Sorayya Ghasemi","doi":"10.1016/j.genrep.2025.102353","DOIUrl":"10.1016/j.genrep.2025.102353","url":null,"abstract":"<div><h3>Background</h3><div>Aniridia is a congenital eye disorder characterized by a partially or completely missing iris, frequently accompanied by other eye abnormalities. Communication difficulties, social interaction issues, and repetitive behaviors are hallmarks of autism spectrum disorder (ASD), a neurodevelopmental disorder. Identifying a causal gene(s) that is involved in aniridia and ASD in a patient is the goal of this research.</div></div><div><h3>Methods</h3><div>Genetic counseling, pedigree analysis, and a thorough clinical evaluation were performed on a 9-year-old female patient who presented with congenital aniridia and ASD. Karyotyping, Comparative Genomic Hybridization (CGH)-array, Whole-Exome Sequencing (WES), Sanger sequencing, and STR-based paternity testing were performed. In silico structural modeling was done using I-TASSER, and PyMOL 3.1.1 was used to find putative genetic variants.</div></div><div><h3>Results</h3><div>WES identified a novel de novo heterozygous point mutation, c.194G>A (p.Gly65Glu), in the <em>PAX6</em> gene. Sanger sequencing confirmed this mutation, which was not discovered in population databases. STR-based paternity testing verified its de novo mutation. In silico tools (PolyPhen-2: 0.998; SIFT: 0.01; CADD: 35.0) predicted a deleterious effect.</div></div><div><h3>Conclusions</h3><div>This study provides the first report of a novel de novo <em>PAX6</em>:c.194G>A (p.Gly65Glu) mutation associated with aniridia and ASD. The findings highlight the pleiotropic role of <em>PAX6</em> and support the utility of WES in detecting rare variants in complex phenotypes. Functional studies are necessary to confirm the pathogenic mechanism.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102353"},"PeriodicalIF":0.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-07DOI: 10.1016/j.genrep.2025.102352
Nikola Vintrlikova , Marek Dvorak , Martina Kolackova , Monika Damyanov , Andrea Ridoskova , Martin Brtnicky , Tomas Vaculovic , Dalibor Huska
The application of zinc oxide nanoparticles (ZnO NPs) in agriculture and plant research is a topic of significant debate. In this study, we explored the molecular responses of Arabidopsis thaliana (Columbia (Col-0) ecotype) to ZnO NP exposure, with a primary focus on miRNA expression and metabolite profiles, providing new insights into the mechanisms underlying plant responses. ZnO NPs were applied at three concentrations (8, 40, 80 mg·kg−1) in peat tablets (Jiffy®). Our results reveal dose-dependent negative effects on plant phenotypic traits, particularly reductions in growth and chlorophyll content. Notably, ZnO NPs caused significant disruptions in metal homeostasis, with elevated zinc accumulation and altered uptake of manganese, iron, and calcium. Gene expression analysis of antioxidant defense responses demonstrated concentration-specific regulation, indicating a shift towards more specialized antioxidants under ZnO NP stress. Specifically, the lower concentrations (8 and 40 mg·kg−1) led to the overexpression of genes related to H2O2 scavenging and glutathione synthesis, while the 80 mg·kg−1 concentration induced the upregulation of genes associated with superoxide scavenging, highlighting a dose-dependent shift in oxidative stress response mechanisms. These molecular changes were accompanied by significant alterations in miRNA expression and metabolite profiles, in a non-linear and dose-dependent manner. A significant role was observed for the miR156-SPL regulatory module at the 40 and 80 mg·kg−1 concentrations. Furthermore, proline (approx. 20 % increase, 8, 80 mg·kg−1), taurine (16 %, 80 mg·kg−1), fumaric acid (31 %, 40 mg·kg−1), and glutamic acid (50 %, 8 mg·kg−1) were implicated in the plant's adaptive response to ZnO NPs, contributing to antioxidant defense and metal-binding mechanisms. Together, these results highlight that ZnO NP exposure elicits complex and multi-layered adaptive mechanisms involving the interplay of elemental stress, antioxidant responses, miRNA regulation, and metabolic adjustments.
{"title":"ZnO nanoparticle effects on Arabidopsis thaliana: Insights into miRNA and metabolite profiles","authors":"Nikola Vintrlikova , Marek Dvorak , Martina Kolackova , Monika Damyanov , Andrea Ridoskova , Martin Brtnicky , Tomas Vaculovic , Dalibor Huska","doi":"10.1016/j.genrep.2025.102352","DOIUrl":"10.1016/j.genrep.2025.102352","url":null,"abstract":"<div><div>The application of zinc oxide nanoparticles (ZnO NPs) in agriculture and plant research is a topic of significant debate. In this study, we explored the molecular responses of <em>Arabidopsis thaliana</em> (Columbia (Col-0) ecotype) to ZnO NP exposure, with a primary focus on miRNA expression and metabolite profiles, providing new insights into the mechanisms underlying plant responses. ZnO NPs were applied at three concentrations (8, 40, 80 mg·kg<sup>−1</sup>) in peat tablets (Jiffy®). Our results reveal dose-dependent negative effects on plant phenotypic traits, particularly reductions in growth and chlorophyll content. Notably, ZnO NPs caused significant disruptions in metal homeostasis, with elevated zinc accumulation and altered uptake of manganese, iron, and calcium. Gene expression analysis of antioxidant defense responses demonstrated concentration-specific regulation, indicating a shift towards more specialized antioxidants under ZnO NP stress. Specifically, the lower concentrations (8 and 40 mg·kg<sup>−1</sup>) led to the overexpression of genes related to H<sub>2</sub>O<sub>2</sub> scavenging and glutathione synthesis, while the 80 mg·kg<sup>−1</sup> concentration induced the upregulation of genes associated with superoxide scavenging, highlighting a dose-dependent shift in oxidative stress response mechanisms. These molecular changes were accompanied by significant alterations in miRNA expression and metabolite profiles, in a non-linear and dose-dependent manner. A significant role was observed for the miR156-SPL regulatory module at the 40 and 80 mg·kg<sup>−1</sup> concentrations. Furthermore, proline (approx. 20 % increase, 8, 80 mg·kg<sup>−1</sup>), taurine (16 %, 80 mg·kg<sup>−1</sup>), fumaric acid (31 %, 40 mg·kg<sup>−1</sup>), and glutamic acid (50 %, 8 mg·kg<sup>−1</sup>) were implicated in the plant's adaptive response to ZnO NPs, contributing to antioxidant defense and metal-binding mechanisms. Together, these results highlight that ZnO NP exposure elicits complex and multi-layered adaptive mechanisms involving the interplay of elemental stress, antioxidant responses, miRNA regulation, and metabolic adjustments.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102352"},"PeriodicalIF":0.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-06DOI: 10.1016/j.genrep.2025.102351
Yulin Li , Yanli Liu , Yunyang Song , Yifeng Yin , Rui Bai , Fanghui Wu , Yanfang Wang
Background
Botulinum toxin type A (BoNT/A) has been growing applications in the medical field, yet concerns regarding its biosafety persist. Currently, recombinant vaccines targeting the Hc structural domain is the predominant focus of research. However, their large molecular weight and tendency to form inclusion bodies during expression reduces vaccine activity. Therefore, in this study, cutting-edge bioinformatics and immunoinformatics tools were utilized to develop a low-cost, highly active and safe BONT/A-Hc multi-epitope vaccine.
Methods
The complete sequence of BONT/A was obtained from the NCBI database, and the IEDB platform was used to screen B and T cell antigenic epitopes, and construct a multi-epitope vaccine, and conduct predictive analyses of its antigenicity, allergenicity, and toxicity. The designed multi-epitope vaccine genes were cloned into vectors and expressed using a prokaryotic system to determine their expression forms and activities. Finally, the accuracy of the predicted results was verified by SDS-PAGE and Western blot.
Results
The constructed multi-epitope vaccine contains six dominant epitopes, exhibits strong antigenicity, non-sensitization and non-toxicity. Computer simulations indicate it can effectively elicit the desired immune response. The multi-epitope vaccine was successfully cloned into vectors and expressed in soluble form with detectable activity.
Conclusion
The multi-epitope vaccine constructed based on bioinformatics and immunoinformatics screening was predicted to have good immune effects. This study not only provides new ideas for solving the technical challenges in the design and production of multi-epitope vaccines, but also provides important guidance for the efficient development of a vaccine effective against BoNT/A poisoning.
A型肉毒毒素（BoNT/A）在医学领域的应用越来越广泛，但对其生物安全性的担忧仍然存在。目前，针对Hc结构域的重组疫苗是研究的主要焦点。然而，它们的大分子量和在表达过程中形成包涵体的倾向降低了疫苗的活性。因此，本研究利用尖端的生物信息学和免疫信息学工具，开发了一种低成本、高活性、安全的BONT/ a - hc多表位疫苗。方法从NCBI数据库获取BONT/A的完整序列，利用IEDB平台筛选B细胞和T细胞抗原表位，构建多表位疫苗，并对其抗原性、致敏性和毒性进行预测分析。将设计的多表位疫苗基因克隆到载体中，利用原核系统进行表达，以确定其表达形式和活性。最后通过SDS-PAGE和Western blot验证预测结果的准确性。结果构建的多表位疫苗含有6个优势表位，具有较强的抗原性、无致敏性和无毒性。计算机模拟表明，该方法可以有效地引发所需的免疫反应。该多表位疫苗成功克隆到载体中，并以可溶性形式表达，具有可检测的活性。结论基于生物信息学和免疫信息学筛选构建的多表位疫苗具有良好的免疫效果。本研究不仅为解决多表位疫苗设计和生产中的技术难题提供了新思路，也为高效研制有效抗BoNT/ a中毒的疫苗提供了重要指导。
{"title":"Bioinformatics and immunoinformatics-assisted design studies of a heavy chain multi-epitope vaccine for botulinum toxin type A","authors":"Yulin Li , Yanli Liu , Yunyang Song , Yifeng Yin , Rui Bai , Fanghui Wu , Yanfang Wang","doi":"10.1016/j.genrep.2025.102351","DOIUrl":"10.1016/j.genrep.2025.102351","url":null,"abstract":"<div><h3>Background</h3><div><em>Botulinum toxin</em> type A (BoNT/A) has been growing applications in the medical field, yet concerns regarding its biosafety persist. Currently, recombinant vaccines targeting the Hc structural domain is the predominant focus of research. However, their large molecular weight and tendency to form inclusion bodies during expression reduces vaccine activity. Therefore, in this study, cutting-edge bioinformatics and immunoinformatics tools were utilized to develop a low-cost, highly active and safe BONT/A-Hc multi-epitope vaccine.</div></div><div><h3>Methods</h3><div>The complete sequence of BONT/A was obtained from the NCBI database, and the IEDB platform was used to screen B and T cell antigenic epitopes, and construct a multi-epitope vaccine, and conduct predictive analyses of its antigenicity, allergenicity, and toxicity. The designed multi-epitope vaccine genes were cloned into vectors and expressed using a prokaryotic system to determine their expression forms and activities. Finally, the accuracy of the predicted results was verified by SDS-PAGE and Western blot.</div></div><div><h3>Results</h3><div>The constructed multi-epitope vaccine contains six dominant epitopes, exhibits strong antigenicity, non-sensitization and non-toxicity. Computer simulations indicate it can effectively elicit the desired immune response. The multi-epitope vaccine was successfully cloned into vectors and expressed in soluble form with detectable activity.</div></div><div><h3>Conclusion</h3><div>The multi-epitope vaccine constructed based on bioinformatics and immunoinformatics screening was predicted to have good immune effects. This study not only provides new ideas for solving the technical challenges in the design and production of multi-epitope vaccines, but also provides important guidance for the efficient development of a vaccine effective against BoNT/A poisoning.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102351"},"PeriodicalIF":0.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-04DOI: 10.1016/j.genrep.2025.102354
Xin Zhang , Nanfang Li , Qing Zhu , Wen Jiang , Ting Wu , Mei Yang , Di Shen , Wenbo Yang , Mengru Wang , Jing Hong
The GAS6/AXL signalling pathway has been implicated in inflammation and tissue injury, but its role in aldosterone-induced renal damage remains unclear. This study investigated whether aldosterone regulates the expression of growth arrest-specific 6 (GAS6) and its receptor AXL in the kidney, and whether this regulation is dependent on mineralocorticoid receptor (MR) activation. Male C57BL/6J mice were treated with aldosterone, with or without the MR antagonists spironolactone or finerenone. Immunohistochemical analysis showed significantly increased expression of GAS6 and AXL in kidneys from aldosterone-treated mice compared with controls (P < 0.01). AXL expression was positively correlated with MR, interleukin-1β, and CCL2 levels (P < 0.05). Both spironolactone and finerenone treatment reduced the expression of GAS6 and AXL to near-control levels (P < 0.05). These findings suggest that aldosterone stimulates renal GAS6/AXL expression via MR activation and that this pathway may contribute to renal inflammation.
{"title":"Expression and significance of GAS6 and AXL in C57BL/6J mice with aldosterone-induced renal injury","authors":"Xin Zhang , Nanfang Li , Qing Zhu , Wen Jiang , Ting Wu , Mei Yang , Di Shen , Wenbo Yang , Mengru Wang , Jing Hong","doi":"10.1016/j.genrep.2025.102354","DOIUrl":"10.1016/j.genrep.2025.102354","url":null,"abstract":"<div><div>The GAS6/AXL signalling pathway has been implicated in inflammation and tissue injury, but its role in aldosterone-induced renal damage remains unclear. This study investigated whether aldosterone regulates the expression of growth arrest-specific 6 (GAS6) and its receptor AXL in the kidney, and whether this regulation is dependent on mineralocorticoid receptor (MR) activation. Male C57BL/6J mice were treated with aldosterone, with or without the MR antagonists spironolactone or finerenone. Immunohistochemical analysis showed significantly increased expression of GAS6 and AXL in kidneys from aldosterone-treated mice compared with controls (<em>P</em> < 0.01). AXL expression was positively correlated with MR, interleukin-1β, and CCL2 levels (<em>P</em> < 0.05). Both spironolactone and finerenone treatment reduced the expression of GAS6 and AXL to near-control levels (<em>P</em> < 0.05). These findings suggest that aldosterone stimulates renal GAS6/AXL expression via MR activation and that this pathway may contribute to renal inflammation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102354"},"PeriodicalIF":0.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MHC class I molecules are expressed on the surface of all nucleated cells and play a significant role in graft rejection. B2m, the non-polymorphic constituent of the MHC class I molecule, is crucial to the structural integrity of the MHC class I. Targeting B2m using gene editing technologies to generate cells with minimal or no surface MHC class I expression is a promising strategy for addressing graft rejection. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is among the most effective approaches to editing genes, in vitro and in vivo, in a wide range of cell lines and species. However, delivery methods to transfer the CRISPR/Cas9 system to the cells can bring up challenges. In this study, we have deployed FolicPolySpermine nanoparticles based on spermine, polyethylene glycol, and folic acid for the transfection of two gRNAs targeting B2m and Cas9 into the HEK293T cell line. These nanoparticles were effectively transferred to the HEK293T cells, and we validated the expression and functionality of the CRISPR/Cas9 system within the cells. Moreover, we compared the efficiency of lipofectamine 2000 and FolicPolySpermine as delivery systems. FolicPolySpermine nanoparticle, as a biocompatible, safe, and efficient strategy, is useful in the transfection of CRISPR plasmids with high efficacy and precision into the target cells. Additionally, our study demonstrated that the use of dual gRNAs is a suitable approach for directly targeting and inducing predicted deletions at specific loci, which can be utilized for gene knockout purposes. All in all, our findings highlight the potential of FolicPolySpermine as a promising gene delivery method for the CRISPR/Cas9 system.
{"title":"Optimized delivery of dual-gRNA CRISPR/Cas9 via FolicPolySpermine nanoparticles for MHC class I elimination through B2M gene knockout","authors":"Hossein Jafari Khamirani , Maryam Aghasipour , Somayeh Khoddam , Amirmasoud Shiri , Hossein Heli , Maryam Ranjbar , Mahsa Jafari Khamirani , Sina Zoghi , Mehdi Dianatpour , Seyed Alireza Dastgheib","doi":"10.1016/j.genrep.2025.102350","DOIUrl":"10.1016/j.genrep.2025.102350","url":null,"abstract":"<div><div>MHC class I molecules are expressed on the surface of all nucleated cells and play a significant role in graft rejection. <em>B2m</em>, the non-polymorphic constituent of the MHC class I molecule, is crucial to the structural integrity of the MHC class I. Targeting B2m using gene editing technologies to generate cells with minimal or no surface MHC class I expression is a promising strategy for addressing graft rejection. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is among the most effective approaches to editing genes, in vitro and in vivo, in a wide range of cell lines and species. However, delivery methods to transfer the CRISPR/Cas9 system to the cells can bring up challenges. In this study, we have deployed FolicPolySpermine nanoparticles based on spermine, polyethylene glycol, and folic acid for the transfection of two gRNAs targeting <em>B2m</em> and Cas9 into the HEK293T cell line. These nanoparticles were effectively transferred to the HEK293T cells, and we validated the expression and functionality of the CRISPR/Cas9 system within the cells. Moreover, we compared the efficiency of lipofectamine 2000 and FolicPolySpermine as delivery systems. FolicPolySpermine nanoparticle, as a biocompatible, safe, and efficient strategy, is useful in the transfection of CRISPR plasmids with high efficacy and precision into the target cells. Additionally, our study demonstrated that the use of dual gRNAs is a suitable approach for directly targeting and inducing predicted deletions at specific loci, which can be utilized for gene knockout purposes. All in all, our findings highlight the potential of FolicPolySpermine as a promising gene delivery method for the CRISPR/Cas9 system.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102350"},"PeriodicalIF":0.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With a length of 331 nucleotides, Rn7SK small nuclear RNA (snRNA) is an extremely plentiful noncoding RNA (ncRNA). Multiple lines of evidence propose that Rn7SK snRNA controls RNA polymerase II transcription by regulating the positive transcription elongation factor b (P-TEFb) function. Previous researches has shown that Rn7SK is downregulated in some tumor cells. This investigation aimed to analyze the impact of the downregulation of Rn7SK expression via transfection of Rn7SK-siRNA on proliferation, migration, and spheroid formation in human gastric adenocarcinoma cells AGS. Also, the expression level of genes engaged in cancer cell proliferation and apoptosis was assessed.
Results
The obtained findings demonstrated that transfection of AGS cells with Rn7SK-siRNA increased their migration, proliferation, and spheroid formation. Besides, qPCR analysis revealed higher and lower expression levels of genes involved in proliferation and apoptosis, respectively, in Rn7SK-siRNA-transfected AGS cells.
Conclusions
Our result suggests that Rn7SK has a crucial role in the progression of human gastric cancer AGS cells, and applying effective strategies to overexpress Rn7SK might help with the efficient treatment of gastric cancer.
{"title":"Targeted inhibition of 7SK long non-coding RNA using Rn7SK-siRNA promotes gastric cancer cell proliferation and migration","authors":"Maryam Valizadeh-Otagsara , Hassan Dariushnejad , Vahideh Tarhriz , Roya Fattahi , Mozhgan Abasi","doi":"10.1016/j.genrep.2025.102349","DOIUrl":"10.1016/j.genrep.2025.102349","url":null,"abstract":"<div><h3>Background</h3><div>With a length of 331 nucleotides, Rn7SK small nuclear RNA (snRNA) is an extremely plentiful noncoding RNA (ncRNA). Multiple lines of evidence propose that Rn7SK snRNA controls RNA polymerase II transcription by regulating the positive transcription elongation factor b (P-TEFb) function. Previous researches has shown that Rn7SK is downregulated in some tumor cells. This investigation aimed to analyze the impact of the downregulation of Rn7SK expression via transfection of Rn7SK-siRNA on proliferation, migration, and spheroid formation in human gastric adenocarcinoma cells AGS. Also, the expression level of genes engaged in cancer cell proliferation and apoptosis was assessed.</div></div><div><h3>Results</h3><div>The obtained findings demonstrated that transfection of AGS cells with Rn7SK-siRNA increased their migration, proliferation, and spheroid formation. Besides, qPCR analysis revealed higher and lower expression levels of genes involved in proliferation and apoptosis, respectively, in Rn7SK-siRNA-transfected AGS cells.</div></div><div><h3>Conclusions</h3><div>Our result suggests that Rn7SK has a crucial role in the progression of human gastric cancer AGS cells, and applying effective strategies to overexpress Rn7SK might help with the efficient treatment of gastric cancer.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102349"},"PeriodicalIF":0.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.genrep.2025.102348
Loick P. Kojom Foko , Joseph Hawadak , Vineeta Singh
Background
Antimalarial immunity is greatly modulated by the genetic structure of Plasmodium populations, which is an important hurdle to successful vaccine development.
Methods
Dried blood spots were collected from hospital patients living in four towns (Douala, Maroua, Mayo-Oulo, and Pette). Genomic DNA was extracted and used to genotype the merozoite surface protein 1 and 2 genes (msp1 and msp2).
Results
K1 (76.3 %) and IC/3D7 (83.3 %) were the most frequently found msp1 and msp2 allelic types, respectively. The total number of genotypes was 24 msp1 (11 K1; 8 Mad20; 5 RO33) and 43 msp2 (29 IC/3D7; 14 FC27). Monoclonal infections were predominant: 68.4 % for msp1 [K1 (46.1 %), Mad20 (18.4 %), and RO33 (3.9 %)], and 67.1 % for msp2 [IC/3D7 (50.0 %), and FC27 (17.1 %)]. Individuals living in Pette had fewer chances to get msp1-related monoclonal infections than those living in Douala (OR = 0.22, p = 0.01). Regarding msp2, IC/3D7 and FC27 genotypes found in MI accounted for 58.6 % and 100 % of total IC/3D7 and FC27 genotypes found. No statistically significant association was found between MOI, age, parasite density, and geographical area.
Conclusion
This study reveals a high genetic diversity of P. falciparum infections, with a predominance of monoclonal infections.
{"title":"Investigating polymorphism of Plasmodium falciparum msp1 and msp2 vaccine candidates reveals a high proportion of genetically diverse monoclonal infections in Cameroon","authors":"Loick P. Kojom Foko , Joseph Hawadak , Vineeta Singh","doi":"10.1016/j.genrep.2025.102348","DOIUrl":"10.1016/j.genrep.2025.102348","url":null,"abstract":"<div><h3>Background</h3><div>Antimalarial immunity is greatly modulated by the genetic structure of <em>Plasmodium</em> populations, which is an important hurdle to successful vaccine development.</div></div><div><h3>Methods</h3><div>Dried blood spots were collected from hospital patients living in four towns (Douala, Maroua, Mayo-Oulo, and Pette). Genomic DNA was extracted and used to genotype the merozoite surface protein 1 and 2 genes (<em>msp1</em> and <em>msp2</em>).</div></div><div><h3>Results</h3><div>K1 (76.3 %) and IC/3D7 (83.3 %) were the most frequently found <em>msp1</em> and <em>msp2</em> allelic types, respectively. The total number of genotypes was 24 <em>msp1</em> (11 K1; 8 Mad20; 5 RO33) and 43 <em>msp2</em> (29 IC/3D7; 14 FC27). Monoclonal infections were predominant: 68.4 % for <em>msp1</em> [K1 (46.1 %), Mad20 (18.4 %), and RO33 (3.9 %)], and 67.1 % for <em>msp2</em> [IC/3D7 (50.0 %), and FC27 (17.1 %)]. Individuals living in Pette had fewer chances to get <em>msp1</em>-related monoclonal infections than those living in Douala (OR = 0.22, <em>p</em> = 0.01). Regarding <em>msp2</em>, IC/3D7 and FC27 genotypes found in MI accounted for 58.6 % and 100 % of total IC/3D7 and FC27 genotypes found. No statistically significant association was found between MOI, age, parasite density, and geographical area.</div></div><div><h3>Conclusion</h3><div>This study reveals a high genetic diversity of <em>P. falciparum</em> infections, with a predominance of monoclonal infections.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102348"},"PeriodicalIF":0.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-30DOI: 10.1016/j.genrep.2025.102347
Katarzyna Chojnacka , Marcin Mikulewicz
Background
Genetic variants, particularly single-nucleotide polymorphisms (SNPs), have been linked to craniofacial growth, dentoalveolar development, and skeletal remodeling through core pathways that govern morphogenesis (e.g., FGF/FGFR, WNT/β-catenin, TGF-β/BMP, and the GH/IGF axis). Interethnic differences in allele frequencies and effect sizes indicate ancestry-specific architecture. Multiple candidate genes and loci related to skeletal Class II/III malocclusion have been reported across genome-wide association studies (GWAS) and candidate-gene analyses, including signals at GHR/IGF1, FGFR2, RUNX2, WNT3A, MSX1, and GLI2.
Aim
To collate and critically appraise current genetic evidence on skeletal malocclusions and to identify a functionally supported subset of SNPs relevant to precision orthodontic care. Given cohort heterogeneity and ancestry-specific effects, loci labeled as higher-confidence were prioritized when replication (where available), biological plausibility, and clinical association converged. Here, a functional SNP denotes a variant with experimental or expression evidence for a biological effect on gene regulation, protein function, or development.
Methods
Narrative review with a structured search of PubMed/Scopus (last search May 5, 2025). Two complementary approaches were applied: (i) an annotation table linking genotype, phenotype, putative mechanism, zygosity, and references; and (ii) an allele-phenotype matrix stratified by ancestry (Asian, European, admixed).
Results
Of approximately 95 reported SNPs screened, 38 met the predefined criteria (including replication where available, functional relevance to craniofacial development, and clinical association with prognathism and/or maxillary deficiency). Replication remains limited for several loci. The resulting set provides a pragmatic basis for risk stratification, not deterministic prediction. From this 38-SNP higher-confidence set, we selected an illustrative 11-SNP subset to prototype PRS-Ortho v1.
Conclusions
This narrative review synthesizes evidence from over 70 peer-reviewed studies and presents 38 functionally supported SNPs currently most relevant to craniofacial growth. These data support the personalization of diagnosis, treatment planning, and prognosis in precision orthodontics, while underscoring the need for multi-ethnic replication and prospective evaluation before routine clinical testing. An 11-SNP subset (PRS-Ortho v1) is provided as a prototype for illustrative, unweighted scoring.
{"title":"Genomic architecture of skeletal malocclusions: Implications for precision orthodontics - Narrative review","authors":"Katarzyna Chojnacka , Marcin Mikulewicz","doi":"10.1016/j.genrep.2025.102347","DOIUrl":"10.1016/j.genrep.2025.102347","url":null,"abstract":"<div><h3>Background</h3><div>Genetic variants, particularly single-nucleotide polymorphisms (SNPs), have been linked to craniofacial growth, dentoalveolar development, and skeletal remodeling through core pathways that govern morphogenesis (e.g., FGF/FGFR, WNT/β-catenin, TGF-β/BMP, and the GH/IGF axis). Interethnic differences in allele frequencies and effect sizes indicate ancestry-specific architecture. Multiple candidate genes and loci related to skeletal Class II/III malocclusion have been reported across genome-wide association studies (GWAS) and candidate-gene analyses, including signals at GHR/IGF1, FGFR2, RUNX2, WNT3A, MSX1, and GLI2.</div></div><div><h3>Aim</h3><div>To collate and critically appraise current genetic evidence on skeletal malocclusions and to identify a functionally supported subset of SNPs relevant to precision orthodontic care. Given cohort heterogeneity and ancestry-specific effects, loci labeled as higher-confidence were prioritized when replication (where available), biological plausibility, and clinical association converged. Here, a functional SNP denotes a variant with experimental or expression evidence for a biological effect on gene regulation, protein function, or development.</div></div><div><h3>Methods</h3><div>Narrative review with a structured search of PubMed/Scopus (last search May 5, 2025). Two complementary approaches were applied: (i) an annotation table linking genotype, phenotype, putative mechanism, zygosity, and references; and (ii) an allele-phenotype matrix stratified by ancestry (Asian, European, admixed).</div></div><div><h3>Results</h3><div>Of approximately 95 reported SNPs screened, 38 met the predefined criteria (including replication where available, functional relevance to craniofacial development, and clinical association with prognathism and/or maxillary deficiency). Replication remains limited for several loci. The resulting set provides a pragmatic basis for risk stratification, not deterministic prediction. From this 38-SNP higher-confidence set, we selected an illustrative 11-SNP subset to prototype PRS-Ortho v1.</div></div><div><h3>Conclusions</h3><div>This narrative review synthesizes evidence from over 70 peer-reviewed studies and presents 38 functionally supported SNPs currently most relevant to craniofacial growth. These data support the personalization of diagnosis, treatment planning, and prognosis in precision orthodontics, while underscoring the need for multi-ethnic replication and prospective evaluation before routine clinical testing. An 11-SNP subset (PRS-Ortho v1) is provided as a prototype for illustrative, unweighted scoring.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102347"},"PeriodicalIF":0.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ARHGAP31 is a GTPase activating protein that inactivates Rac1 and Cdc42 by promoting their conversion from the GTP to GDP bound state. Pathologic variants in ARHGAP31 are primarily associated with Adams-Oliver syndrome (AOS), a congenital disorder characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLDs), attributed to disrupted Rho GTPase signaling. In this study, exome sequencing and bioinformatic analysis were employed to investigate a 6-year-old male presenting with craniofacial anomalies (high palate, dental malalignment), developmental delay (motor and speech), and gastrointestinal dysmotility (feeding difficulties, constipation) notably without ACC or TTLDs. Trio exome sequencing revealed a heterozygous de novo frameshift variant in ARHGAP31 (NM_020754.4:c.732del, p.(Met245Ter)), absent from population databases (gnomAD, dbSNP) and both parental genomes. In silico predictions (MutationTaster, SWISS-MODEL) suggested a pathogenic effect (probability: 0.99), with nonsense-mediated decay (NMD) and truncation of the RhoGAP domain critical for cytoskeletal regulation. The variant's proximal truncation site likely disrupts autoinhibitory regulation, enhancing RhoGAP activity and impairing Cdc42/Rac1 signaling. Despite parental consanguinity, the de novo variant highlights the diagnostic value of trio sequencing in consanguineous families. Moreover, until now only gain-of-function mutation of ARHGAP31 was found to be associated with AOS, while this article reports a brand-new loss-of-function mutation. Overall, these findings support the existence of a novel ARHGAP31-related neurodevelopmental disorder distinct from AOS, expanding the allelic and phenotypic spectrum associated with this gene.
{"title":"Exome sequencing reveals a novel de novo ARHGAP31 frameshift variant in a neurodevelopmental disorder: Structural and functional insights into RhoGAP domain loss","authors":"Jalal Gharesouran , Mohammad Reza Asadi , Samira Behroozi , Maryam Rezazadeh , Soudeh Ghafouri-Fard","doi":"10.1016/j.genrep.2025.102345","DOIUrl":"10.1016/j.genrep.2025.102345","url":null,"abstract":"<div><div>ARHGAP31 is a GTPase activating protein that inactivates Rac1 and Cdc42 by promoting their conversion from the GTP to GDP bound state. Pathologic variants in <em>ARHGAP31</em> are primarily associated with Adams-Oliver syndrome (AOS), a congenital disorder characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLDs), attributed to disrupted Rho GTPase signaling. In this study, exome sequencing and bioinformatic analysis were employed to investigate a 6-year-old male presenting with craniofacial anomalies (high palate, dental malalignment), developmental delay (motor and speech), and gastrointestinal dysmotility (feeding difficulties, constipation) notably without ACC or TTLDs. Trio exome sequencing revealed a heterozygous de novo frameshift variant in <em>ARHGAP31</em> (NM_020754.4:c.732del, p.(Met245Ter)), absent from population databases (gnomAD, dbSNP) and both parental genomes. In silico predictions (MutationTaster, SWISS-MODEL) suggested a pathogenic effect (probability: 0.99), with nonsense-mediated decay (NMD) and truncation of the RhoGAP domain critical for cytoskeletal regulation. The variant's proximal truncation site likely disrupts autoinhibitory regulation, enhancing RhoGAP activity and impairing Cdc42/Rac1 signaling. Despite parental consanguinity, the de novo variant highlights the diagnostic value of trio sequencing in consanguineous families. Moreover, until now only gain-of-function mutation of <em>ARHGAP31</em> was found to be associated with AOS, while this article reports a brand-new loss-of-function mutation. Overall, these findings support the existence of a novel ARHGAP31-related neurodevelopmental disorder distinct from AOS, expanding the allelic and phenotypic spectrum associated with this gene.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102345"},"PeriodicalIF":0.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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