Gene Reports最新文献_第9页

Optimized delivery of dual-gRNA CRISPR/Cas9 via FolicPolySpermine nanoparticles for MHC class I elimination through B2M gene knockout 优化双grna CRISPR/Cas9通过FolicPolySpermine纳米颗粒通过敲除B2M基因消除MHC I类

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-10-03 DOI: 10.1016/j.genrep.2025.102350

Hossein Jafari Khamirani , Maryam Aghasipour , Somayeh Khoddam , Amirmasoud Shiri , Hossein Heli , Maryam Ranjbar , Mahsa Jafari Khamirani , Sina Zoghi , Mehdi Dianatpour , Seyed Alireza Dastgheib

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.

MHC I类分子在所有有核细胞表面表达，在移植物排斥反应中起重要作用。B2m是MHC I类分子的非多态性成分，对MHC I类的结构完整性至关重要。利用基因编辑技术靶向B2m，生成表面MHC I类表达很少或没有表达的细胞，是解决移植物排斥反应的一种很有前景的策略。集群规则间隔短回文重复序列（CRISPR）技术是最有效的基因编辑方法之一，在体外和体内，在广泛的细胞系和物种中。然而，将CRISPR/Cas9系统转移到细胞中的递送方法可能会带来挑战。在这项研究中，我们部署了基于精胺、聚乙二醇和叶酸的FolicPolySpermine纳米颗粒，将靶向B2m和Cas9的两种grna转染到HEK293T细胞系中。这些纳米颗粒被有效地转移到HEK293T细胞中，我们验证了细胞内CRISPR/Cas9系统的表达和功能。此外，我们比较了lipofectamine 2000和FolicPolySpermine作为递送系统的效率。FolicPolySpermine纳米颗粒作为一种具有生物相容性、安全、高效的策略，在将CRISPR质粒转染到靶细胞中具有较高的效率和精度。此外，我们的研究表明，使用双grna是直接靶向和诱导特定位点预测缺失的合适方法，可用于基因敲除目的。总而言之，我们的发现突出了FolicPolySpermine作为CRISPR/Cas9系统的一种有前途的基因传递方法的潜力。

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引用次数: 0

Genome analysis of Pseudomonas spp. CPA-7, a strain with potential as a biocontrol agent 具有生物防治潜力的假单胞菌CPA-7的基因组分析

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI: 10.1016/j.genrep.2025.102326

Cyrelys Collazo , Jose Francisco Sanchez-Herrero , Rui Alves , Julio Rozas , Isabel Alegre , Abdelrhaman Eleiwa , Inmaculada Viñas

We report the whole genome sequence of CPA-7, a strain isolated from apple surface and classified as Pseudomonas graminis, that has shown antagonistic activity against pathogenic bacteria in several food matrices. Its genome comprises 5,786,948 bp, with 60.5 % average of C + G content. From the 5122 predicted protein coding sequences (CDSs), 4703 (91.8 %) were functionally annotated. Comparative genomic analyses using 366 fully sequenced Pseudomonas strains placed CPA-7 within the P. lutea group, more related to P. graminis UASWS1507. However, ANI values in respect to the other fully sequenced P. graminis (91–92 %), including the type strain DSM11363, were below the intraspecific bacterial threshold (95 %). Whole genomic digital DNA-DNA hybridization in the Type Strain Genome Server also gave a below threshold score for P. graminis (47.7 %), suggesting the need for revision of this taxon. BLAST analyses of 16S rRNA showed >99 % identity with other Pseudomonas spp. while the rpoD amplified sequence revealed a 100 % similarity with Pseudomonas sp. Irchel 1A17. Single orthologs analysis unraveled 341 CDSs unique to CPA-7 compared to the rest of P. graminis strains including genes involved in transport, adherence, and adaptability. Genome mining uncovered genes potentially involved in biological control, and plant growth promoting activities which corresponded to in vitro activities such as the production of siderophores, 1-aminocyclopropane-1-carboxylate deaminase, and Indole-3-acetic acid as well as Phosphorous solubilization. Furthermore, multiple genes associated with chemotaxis, colonization, and metabolic plasticity, unravel the genetic basis for the potentialities of CPA-7 as a biocontrol agent, opening several lines for further investigation.

我们报道了从苹果表面分离的一株被归类为谷草假单胞菌的CPA-7的全基因组序列，该菌株对几种食物基质中的致病菌具有拮抗活性。其基因组全长5,786,948 bp， C + G含量平均为60.5%。在5122个预测的蛋白编码序列（CDSs）中，4703个（91.8%）被功能注释。利用366个全测序假单胞菌菌株进行比较基因组分析，发现CPA-7属于P. lutea组，与P. graminis UASWS1507更相关。然而，对于其他完全测序的禾草假单胞菌（91 - 92%），包括型菌株DSM11363， ANI值低于种内细菌阈值（95%）。全基因组数字DNA-DNA杂交在型菌株基因组服务器上也给出了低于阈值的评分（47.7%），表明该分类单元需要修订。BLAST分析显示，16S rRNA与其他假单胞菌属的同源性为99%，而rpoD扩增序列与假单胞菌属Irchel 1A17的同源性为100%。单一同源物分析揭示了CPA-7与其他禾草假单胞菌菌株相比所特有的341个CDSs，包括参与运输、粘附和适应性的基因。基因组挖掘发现了可能参与生物控制和植物生长促进活性的基因，这些活性与铁载体的产生、1-氨基环丙烷-1-羧酸脱氨酶、吲哚-3-乙酸以及磷的溶解等体外活性相对应。此外，与趋化性、定植和代谢可塑性相关的多个基因揭示了CPA-7作为生物防治剂潜力的遗传基础，为进一步研究开辟了几个领域。

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引用次数: 0

Kinase regulation of DNA polymerase alpha - primase (polα-primase) complex: Inference from decade-long global phosphoproteomes DNA聚合酶α-引物酶复合物的激酶调控：来自十年来全球磷酸化蛋白质组学的推断

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1016/j.genrep.2025.102312

Aromal Monipillil Ajayakumar , Athira Perunelly Gopalakrishnan , Amal Fahma , Althaf Mahin , Suhail Subair , Prathik Basthikoppa Shivamurthy , Poornima Ramesh , Rajesh Raju

DNA polymerase alpha - primase (polα-primase) complex is crucial for DNA replication, which is an association of catalytic (POLA1), regulatory (POLA2) and primase (PRIM1 and PRIM2) subunits. POLA1 extends the primers synthesized by the primase subunits, while POLA2 interacts with the replication factors including AND-1 and contributes to the assembly of replication machinery. This review presents a characterization of the kinase-mediated phosphoregulatory network regulating the polα-primase complex, with a specific focus on phosphorylation sites identified on POLA1. In addition, patterns of co-differential regulation among polα-primase subunits are discussed based on mass spectrometry-based phosphoproteomics data integration. The candidate upstream kinases potentially responsible for phosphorylating polα-primase complex are highlighted, drawing on current phosphorylation site–kinase mapping resources. These kinases modulate polα-primase complex activity in a site-specific manner, integrating its function into key cellular processes such as the DNA damage response, immune signaling, and oncogenic transformation. While substantial knowledge exists, particularly on global phosphoregulation, critical gaps remain especially in experimentally validated, site-specific functional studies of polα-primase complex phosphorylation. This review not only highlights key regulatory mechanisms but also paves the way for targeted investigations in the future, some of which are now actively being explored.

DNA聚合酶α-引物酶（polα-primase）复合体是DNA复制的关键，它是催化（POLA1）、调控（POLA2）和引物酶（PRIM1和PRIM2）亚基的结合产物。POLA1扩展引物酶亚基合成的引物，而POLA2与包括and -1在内的复制因子相互作用，并参与复制机制的组装。这篇综述介绍了调节polα-引物酶复合物的激酶介导的磷酸化调控网络的特征，并特别关注在POLA1上鉴定的磷酸化位点。此外，基于质谱的磷酸化蛋白质组学数据整合，讨论了polα-引物酶亚基之间的共差异调控模式。利用当前磷酸化位点激酶定位资源，强调了可能负责磷酸化polα-引物酶复合物的候选上游激酶。这些激酶以位点特异性的方式调节polα-引物酶复合物的活性，将其功能整合到关键的细胞过程中，如DNA损伤反应、免疫信号传导和致癌转化。虽然存在大量的知识，特别是在全局磷酸化调控方面，但关键的空白仍然存在，特别是在实验验证的，位点特异性的polα-引物酶复合物磷酸化的功能研究中。这篇综述不仅强调了关键的监管机制，而且为未来的有针对性的调查铺平了道路，其中一些正在积极探索中。

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引用次数: 0

LncRNA RASGRF2-AS1 regulates proliferation, apoptosis, and angiogenesis of HUVECs LncRNA RASGRF2-AS1调控HUVECs的增殖、凋亡和血管生成

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI: 10.1016/j.genrep.2025.102319

Cairong Liu , Yunyan Liu , Yijie Li , Lin Huang

Background

Oxidized low-density lipoprotein (oxLDL) is a key contributor to the development of atherosclerosis and plays a crucial role as a proinflammatory mediator in the onset and progression of vascular endothelial dysfunction. According to a previous study, RASGRF2-AS1 was found to be one of the most notably downregulated long noncoding RNAs in human umbilical vein endothelial cells (HUVECs) following oxLDL stimulation. To date, the biological roles of RASGRF2-AS1 have not been reported. Therefore, we set out to explore the function of RASGRF2-AS1 in HUVECs.

Methods

RASGRF2-AS1 expression in HUVECs was measured using quantitative real-time PCR (qRT-PCR). To silence RASGRF2-AS1, both siRNA and lentivirus-mediated shRNA were utilized. The Cell Counting Kit-8 (CCK-8) assay was employed to evaluate cell proliferation. Then, we used annexin V/PI staining to determine cell apoptosis and cell cycle distribution after RASGRF2-AS1 knockdown. Microtubule-associated protein 1 light chain 3 β (MAP1LC3B) and sequestosome 1 (SQSTM1/p62) expression levels were also measured by western blot. Furthermore, candidate proteins predicted to interact with RASGRF2-AS1 were determined by RNA pull-down assays and mass spectrometry.

Results

RASGRF2-AS1 was highly expressed in HUVECs. After RASGRF2-AS1 expression was downregulated with siRNA and shRNA, G0/G1 cell cycle arrest increased, inhibiting HUVEC proliferation. Downregulating RASGRF2-AS1 also promoted apoptosis and suppressed tube formation in HUVECs. In addition, the western blot results indicated that RASGRF2-AS1 knockdown decreased p62 expression and increased MAP1LC3B expression. Furthermore, RNA pull-down assays identified several co-precipitating proteins as potential interactors of RASGRF2-AS1. These candidates included S100-A9, ZN598, NRROS, ZMYM5, IF4A1, PDIP3, and PLCB4.

Conclusions

RASGRF2-AS1 is a novel key lncRNA involved in regulating HUVECs proliferation, apoptosis, and angiogenic ability. Consequently, RASGRF2-AS1 could be a promising target for treating arteriosclerosis obliterans.

氧化低密度脂蛋白（oxLDL）是动脉粥样硬化发展的关键因素，在血管内皮功能障碍的发生和发展中起着促炎介质的重要作用。根据先前的一项研究，RASGRF2-AS1被发现是oxLDL刺激后人脐静脉内皮细胞（HUVECs）中最明显下调的长链非编码rna之一。迄今为止，RASGRF2-AS1的生物学作用尚未报道。因此，我们开始探索RASGRF2-AS1在huvec中的功能。方法采用实时荧光定量PCR （qRT-PCR）检测HUVECs中srasgrf2 - as1的表达。为了沉默RASGRF2-AS1，使用了siRNA和慢病毒介导的shRNA。细胞计数试剂盒-8 （CCK-8）检测细胞增殖情况。然后，我们用annexin V/PI染色检测RASGRF2-AS1敲低后的细胞凋亡和细胞周期分布。western blot检测微管相关蛋白1轻链3 β (MAP1LC3B)和sequestosome 1 （SQSTM1/p62）表达水平。此外，预测与RASGRF2-AS1相互作用的候选蛋白通过RNA下拉试验和质谱测定。结果rasgrf2 - as1在huvec中高表达。用siRNA和shRNA下调RASGRF2-AS1表达后，G0/G1细胞周期阻滞增加，抑制HUVEC增殖。下调RASGRF2-AS1也可促进huvec细胞凋亡，抑制小管形成。此外，western blot结果显示，RASGRF2-AS1敲低可降低p62表达，增加MAP1LC3B表达。此外，RNA pull-down实验确定了几种共沉淀蛋白作为RASGRF2-AS1的潜在相互作用物。这些候选物包括S100-A9、ZN598、NRROS、ZMYM5、IF4A1、PDIP3和PLCB4。结论srasgrf2 - as1是参与调节HUVECs增殖、凋亡和血管生成能力的新型关键lncRNA。因此，RASGRF2-AS1可能是治疗动脉硬化闭塞症的一个有希望的靶点。

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引用次数: 0

Genetic variation of white spot syndrome virus (WSSV) envelope protein VP28 influences its adaptivity in shrimps 白斑综合征病毒（WSSV）包膜蛋白VP28的遗传变异影响其在对虾中的适应性

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-08-07 DOI: 10.1016/j.genrep.2025.102310

SiouNing Aileen See , Subha Bhassu , Swee Seong Tang , Khatijah Yusoff

White spot syndrome virus (WSSV) is a significant viral pathogen in aquaculture leading to substantial economic loss. A comprehensive understanding of WSSV transmission, adaptation, and the mechanisms underlying shrimp survival and resistance is crucial. In this study, VP28 envelope protein gene from Malaysian WSSV isolates was sequenced and analysed using phylogenetic methods. The analysis revealed that VP28 gene shared over 87 % identity with other known WSSV isolates, as determined by NCBI BLAST. Phylogenetic analysis highlighted amino acid (aa) substitution at positions 42nd, 136th, and 180th to 183rd between Malaysia strains and those from other countries, potentially impacting the structure of VP28 and contributing to viral adaptability. Comparative studies of the VP28 gene's nucleotide composition and codon usage bias shed light on the molecular evolution of WSSV and its adaptation to hosts. Notably, comparisons between the VP28 sequences of Malaysian isolates from 2020 and 2022 revealed contrasting patterns: the 2020 strain exhibited higher nucleotide identity, whereas the 2022 strain had greater peptide identity compared to published VP28 sequences. These differences suggest that genetic variation and virulence of VP28 in global outbreaks may be influenced by host-pathogen interactions, environmental factors and selective pressures. This study offers insights into the evolutionary forces shaping the WSSV genome.

白斑综合征病毒（White spot syndrome virus， WSSV）是水产养殖中一种重要的病毒性病原体，造成了巨大的经济损失。全面了解WSSV的传播、适应以及虾的生存和抗性机制至关重要。本研究对马来西亚WSSV分离株的VP28包膜蛋白基因进行了测序和系统发育分析。通过NCBI BLAST分析发现，VP28基因与其他已知WSSV分离株的同源性超过87%。系统发育分析显示，马来西亚病毒与其他国家病毒在42、136、180 ~ 183位点发生了氨基酸（aa）取代，这可能会影响VP28的结构，有助于病毒的适应性。VP28基因的核苷酸组成和密码子使用偏向性的比较研究有助于了解WSSV的分子进化及其对宿主的适应性。值得注意的是，2020年和2022年马来西亚分离株的VP28序列之间的比较揭示了截然不同的模式：与已发表的VP28序列相比，2020年菌株具有更高的核苷酸一致性，而2022年菌株具有更高的肽一致性。这些差异表明VP28在全球暴发中的遗传变异和毒力可能受到宿主-病原体相互作用、环境因素和选择压力的影响。这项研究提供了对形成WSSV基因组的进化力量的见解。

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引用次数: 0

Association of CDH1 gene variant C > A (rs16260) with expression and treatment outcomes in cervical cancer patients receiving chemoradiotherapy CDH1基因变异C > A （rs16260）与宫颈癌放化疗患者的表达和治疗结果的关系

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.genrep.2025.102344

Shireen Masood , Atar Singh Kushwah , Kirti Srivastava , Monisha Banerjee

Background

The CDH1 gene promoter variant C > A (rs16260) is associated with downregulation of E-cadherin, which compromises epithelial integrity and has been linked to poor prognosis in various cancers. This study investigates the association of the CDH1 C > A variant with gene expression and its potential as a prognostic biomarker for cervical cancer in an Indian population.

Methods

This case-control study involved 107 cervical cancer patients and 96 age-matched healthy controls. Genotyping of the CDH1 C > A (rs16260) variant was performed using PCR-RFLP, and gene expression was analyzed through qPCR. Kaplan-Meier and Cox regression analyses were used to correlate genotypes and gene expression with treatment response and survival outcomes. Statistical analysis was conducted using QUANTO (v.1.2), GraphPad Prism (v. 10), SPSS (v. 25).

Results

The CA and CA + AA genotypes of the CDH1 variant were significantly associated with cervical cancer risk (P = 0.011 and P = 0.004, respectively). CDH1 gene expression was significantly downregulated in cervical cancer patients compared to controls (P = 0.023). While the CA genotype was protective against recurrence and treatment toxicity (P < 0.001 and P = 0.050, respectively), the CC genotype was linked to increased toxicity and recurrence. CA genotype shows a trend toward better overall survival (median 27 vs. 19 months; HR < 1), though not statistically significant (P = 0.079).

Conclusion

The CDH1 C > A (rs16260) variant may be a prognostic biomarker to predict toxicity and recurrence of cervical cancer, with implications for personalized treatment strategies. However, further studies in larger, more diverse cohorts are necessary to validate these findings.

CDH1基因启动子变异C >； A （rs16260）与e -钙粘蛋白下调有关，e -钙粘蛋白会损害上皮完整性，并与各种癌症的不良预后有关。本研究探讨了印度人群中cdh1c >； A变异与基因表达的关系及其作为宫颈癌预后生物标志物的潜力。方法对107例宫颈癌患者和96例年龄匹配的健康对照者进行病例对照研究。采用PCR-RFLP对CDH1 C >； A （rs16260）变异进行基因分型，并通过qPCR分析基因表达。Kaplan-Meier和Cox回归分析将基因型和基因表达与治疗反应和生存结果相关联。采用QUANTO （v.1.2）、GraphPad Prism （v. 10）、SPSS （v. 25）进行统计分析。结果CDH1变异的CA和CA + AA基因型与宫颈癌发病风险有显著相关性（P = 0.011和P = 0.004）。宫颈癌患者与对照组相比，CDH1基因表达明显下调（P = 0.023）。虽然CA基因型对复发和治疗毒性具有保护作用（P <； 0.001和P = 0.050分别），但CC基因型与毒性和复发增加有关。CA基因型患者的总生存期有提高的趋势（中位27个月vs. 19个月；HR < 1），但无统计学意义（P = 0.079）。结论cdh1c >； A （rs16260）变异可能是预测宫颈癌毒性和复发的预后生物标志物，对个性化治疗策略具有指导意义。然而，需要在更大、更多样化的人群中进行进一步的研究来验证这些发现。

{"title":"Association of CDH1 gene variant C > A (rs16260) with expression and treatment outcomes in cervical cancer patients receiving chemoradiotherapy","authors":"Shireen Masood , Atar Singh Kushwah , Kirti Srivastava , Monisha Banerjee","doi":"10.1016/j.genrep.2025.102344","DOIUrl":"10.1016/j.genrep.2025.102344","url":null,"abstract":"<div><h3>Background</h3><div>The <em>CDH1</em> gene promoter variant C > A (rs16260) is associated with downregulation of E-cadherin, which compromises epithelial integrity and has been linked to poor prognosis in various cancers. This study investigates the association of the <em>CDH1</em> C > A variant with gene expression and its potential as a prognostic biomarker for cervical cancer in an Indian population.</div></div><div><h3>Methods</h3><div>This case-control study involved 107 cervical cancer patients and 96 age-matched healthy controls. Genotyping of the <em>CDH1</em> C > A (rs16260) variant was performed using PCR-RFLP, and gene expression was analyzed through qPCR. Kaplan-Meier and Cox regression analyses were used to correlate genotypes and gene expression with treatment response and survival outcomes. Statistical analysis was conducted using QUANTO (v.1.2), GraphPad Prism (v. 10), SPSS (v. 25).</div></div><div><h3>Results</h3><div>The CA and CA + AA genotypes of the <em>CDH1</em> variant were significantly associated with cervical cancer risk (<em>P</em> = 0.011 and <em>P</em> = 0.004, respectively). <em>CDH1</em> gene expression was significantly downregulated in cervical cancer patients compared to controls (<em>P</em> = 0.023). While the CA genotype was protective against recurrence and treatment toxicity (<em>P</em> < 0.001 and <em>P</em> = 0.050, respectively), the CC genotype was linked to increased toxicity and recurrence. CA genotype shows a trend toward better overall survival (median 27 vs. 19 months; HR < 1), though not statistically significant (<em>P</em> = 0.079).</div></div><div><h3>Conclusion</h3><div>The <em>CDH1</em> C > A (rs16260) variant may be a prognostic biomarker to predict toxicity and recurrence of cervical cancer, with implications for personalized treatment strategies. However, further studies in larger, more diverse cohorts are necessary to validate these findings.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102344"},"PeriodicalIF":0.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109488","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}

引用次数: 0

Genetic and hormonal insights into PCOS: Role of FSHR rs6166 and LHCGR rs2293275 polymorphisms FSHR rs6166和LHCGR rs2293275多态性在多囊卵巢综合征中的作用

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-07-30 DOI: 10.1016/j.genrep.2025.102307

Dolly J. Patel , Kinnari N. Mistry , Jasmine Gujarathi , Piyush Chudasama

Background

PCOS (Polycystic ovary syndrome) is an intricate endocrine condition characterized by abnormal metabolic processes, hormonal inconsistencies, and higher estrogen production. This study assessed the biochemical, hormonal, and genetic differences between individuals with PCOS and healthy controls, focusing on the FSHR (Follicle-stimulating hormone receptor) rs6166 and LHCGR (luteinizing hormone-chorio-gonadotrophin receptor) rs2293275 polymorphisms.

Methods

A comparative cross-sectional study was conducted with patients diagnosed with PCOS and healthy controls. Fasting glucose, insulin, SHBG, LH, FSH, estradiol, progesterone, total testosterone, and DHEAS levels were measured in both groups. Genotyping of FSHR (rs6166) and LHCGR (rs2293275) was conducted using PCR-RFLP. Statistical analyses included odds ratios, genotype distributions, and hormone-genotype interaction analysis.

Results

Participants with PCOS exhibited significantly higher levels of fasting glucose, insulin, LH, testosterone, and DHEAS, as well as lower levels of SHBG and FSH. The AA genotype of FSHR rs6166 is more common in patients with PCOS and is associated with a higher LH: FSH ratio, indicating a gonadotropin imbalance. In contrast, the GG genotype of LHCGR rs2293275 was associated with increased LH, decreased FSH, and higher testosterone levels, suggesting its role in hyperandrogenism.

Conclusion

This study emphasizes the notable endocrine and genetic differences in PCOS, implicating FSHR rs6166 and LHCGR rs2293275 polymorphisms in the susceptibility and severity of the disease. The AA genotype of FSHR is primarily associated with gonadotropic dysfunction, whereas the GG genotype of LHCGR is associated with increased androgen excess. These findings highlight the importance of combining genetic screening with hormonal profiling for better diagnosis and personalized management of PCOS.

多囊卵巢综合征（pcos）是一种复杂的内分泌疾病，其特征是代谢过程异常、激素不一致和雌激素分泌过高。本研究评估了PCOS个体与健康对照之间的生化、激素和遗传差异，重点关注促卵泡激素受体（FSHR） rs6166和促黄体生成素-绒毛膜-促性腺激素受体（LHCGR） rs2293275多态性。方法对诊断为PCOS的患者与健康对照者进行对比横断面研究。测定两组患者的空腹血糖、胰岛素、SHBG、LH、FSH、雌二醇、孕酮、总睾酮和DHEAS水平。采用PCR-RFLP方法对FSHR （rs6166）和LHCGR （rs2293275）进行基因分型。统计分析包括优势比、基因型分布和激素-基因型相互作用分析。结果多囊卵巢综合征患者的空腹血糖、胰岛素、LH、睾酮和DHEAS水平明显升高，SHBG和FSH水平较低。FSHR rs6166的AA基因型在PCOS患者中更为常见，且与较高的LH: FSH比值相关，提示促性腺激素失衡。相比之下，LHCGR rs2293275的GG基因型与LH升高、FSH降低和睾酮水平升高相关，提示其在高雄激素症中起作用。结论本研究强调PCOS存在显著的内分泌和遗传差异，FSHR rs6166和LHCGR rs2293275多态性与PCOS的易感性和严重程度有关。FSHR的AA基因型主要与促性腺功能障碍有关，而LHCGR的GG基因型则与雄激素过量增加有关。这些发现强调了基因筛查与激素谱分析相结合对于多囊卵巢综合征更好的诊断和个性化治疗的重要性。

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引用次数: 0

Genetic susceptibility to severe COVID-19 in men: The impact of androgen receptor CAG repeat length 男性重症COVID-19的遗传易感性：雄激素受体CAG重复长度的影响

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-07-18 DOI: 10.1016/j.genrep.2025.102299

Arsalan Eskandarinezhad , Asra Moradkhani , Mobin Azami , Efat Shafiei , Sabah Hasani , Abbas Aghaei , Nariman Moradi , Shahnaz Ghafouri , Naseh Sigari , Asaad Azarnezhad

引用次数: 0

Comparative gonadal transcriptome analysis reveals sex-biased genes in Siniperca scherzeri 比较性腺转录组分析揭示了雪氏鳜的性别偏倚基因

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-09-12 DOI: 10.1016/j.genrep.2025.102340

Shengyue Lin , Dingxian Chen , Weiqian Liang , Weijian Chen , Weibin Li , Ziyan Deng , Guojun Cai , Sixun Li , Binhua Deng , Kaifeng Wang , Chong Han , Qiang Li

Siniperca scherzeri is a valuable freshwater fish in China. The economic value of female S. scherzeri far exceeds that of males. Nevertheless, the lack of sex-related research has significantly impeded the development of single-sex breeding programs for this species.

In this investigation, Illumina Novaseq technology was employed to perform a comparative analysis of the gonadal transcriptomes of S. scherzeri in the first time. Assembly yielded 33,690 unigenes, of which 31,395 were successfully annotated. A comparative analysis identified 15,146 differentially expressed genes between the ovary and testis. Specifically, 9514 genes were downregulated and 5632 genes were upregulated in the ovaries. Moreover, multiple genes participating in gonadal differentiation and development, steroid synthetic pathway, and gametogenesis were screened out. Among these genes, sox 1, sox3, cyp26a1, gdf9, bmp15, zp3, foxh1, and nr0b1 showed ovary-biased expression; Amh, dmrt1b, sox 4, and nanos 2 showed testis-bias expression. Our real-time PCR also confirmed the RNA-seq results of these genes. These results are of great significance for elucidating the molecular mechanisms of sex differentiation and development in S. scherzeri.

雪氏鳜是中国一种珍贵的淡水鱼。雌雪氏蜱的经济价值远远超过雄雪氏蜱。然而，性别相关研究的缺乏严重阻碍了该物种单性繁殖计划的发展。本研究首次采用Illumina Novaseq技术对舍氏弧菌的性腺转录组进行比较分析。组装得到33,690个unigenes，其中31,395个被成功注释。一项比较分析发现，卵巢和睾丸之间存在15,146个差异表达基因。具体来说，卵巢中9514个基因下调，5632个基因上调。此外，还筛选出了参与性腺分化发育、类固醇合成途径和配子体发生的多个基因。其中，sox1、sox3、cyp26a1、gdf9、bmp15、zp3、foxh1、nr0b1呈卵巢偏向性表达；Amh、dmrt1b、sox 4和nanos 2表现出睾丸偏倚表达。我们的real-time PCR也证实了这些基因的RNA-seq结果。这些结果对阐明沙蚕性别分化和发育的分子机制具有重要意义。

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引用次数: 0

Molecular characterization of current field isolates of zoonotic parapoxviruses and their growth characteristics 人畜共患副痘病毒分离株的分子特性及其生长特性

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-12-01 Epub Date: 2025-08-23 DOI: 10.1016/j.genrep.2025.102328

Gizem Aytoğu , Mevlüt Yaşar , Nilay Aybey , Zafer Mecitoğlu , Kadir Yeşilbağ

Parapoxviruses (PPVs), including Bovine papular stomatitis virus (BPSV), Pseudocowpox virus (PCPV), and ORF virus (ORFV), are zoonotic pathogens affecting wild and domesticated ruminants. Between 2023 and 2024, erosive papules and ulcers on the lips, nose, and tongue of calves, as well as proliferative oral lesions in lambs, were reported in various Turkish regions. In two geographically distant beef herds, nodular hand lesions in animal handlers indicated zoonotic transmission. Suspected samples were confirmed by PCR using B2L gene-specific primers. Three isolates representing BPSV, PCPV, and ORFV were sequenced and compared to global data. PCPV showed closest similarity to strains from Bangladesh and Finland, while BPSV was most similar to strains from China and Iran. Virus isolation was attempted on four cell lines: primary fetal lamb kidney (PLK), Madin-Darby bovine kidney (MDBK), sheep fetal thymus (SFT-R), and African green monkey kidney (VERO). PLK cells showed 100 % isolation success for all three viruses. In serial passages, ORFV replicated best in PLK cells, consistently yielding the highest viral titers. This study provides molecular and phylogenetic characterization of currently circulating zoonotic PPVs in Türkiye and compares their in vitro replication efficiency. PLK cells were identified as the most sensitive and productive system, particularly for ORFV, which is of interest due to its immunomodulatory potential.

副痘病毒（ppv），包括牛丘疹性口炎病毒（BPSV）、假牛痘病毒（PCPV）和ORF病毒（ORFV），是影响野生和家养反刍动物的人畜共患病原体。在2023年至2024年期间，土耳其各地区报告了小牛嘴唇、鼻子和舌头上的糜烂丘疹和溃疡，以及羔羊的增殖性口腔病变。在两个地理上相距遥远的肉牛群中，动物处理人员的手部结节性病变表明人畜共患病。用B2L基因特异性引物对疑似样本进行PCR鉴定。对代表BPSV、PCPV和ORFV的三个分离株进行测序并与全球数据进行比较。PCPV与来自孟加拉国和芬兰的毒株最相似，而BPSV与来自中国和伊朗的毒株最相似。在四种细胞系：原代胎羊肾（PLK）、马丁-达比牛肾（MDBK）、羊胎胸腺（SFT-R）和非洲绿猴肾（VERO）上尝试分离病毒。PLK细胞对这三种病毒的分离成功率均为100%。在连续传代中，ORFV在PLK细胞中复制最好，始终产生最高的病毒滴度。本研究提供了目前在 rkiye中流行的人畜共患ppv的分子和系统发育特征，并比较了它们的体外复制效率。PLK细胞被认为是最敏感和多产的系统，特别是ORFV，由于其免疫调节潜力而引起人们的兴趣。

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