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Deciphering functional genes and pathways associated with enzyme activity during fruiting development of Tremella fuciformis and Annulohypoxylon stygium 银耳和木耳果实发育过程中酶活性相关功能基因和途径的解读
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-12 DOI: 10.1016/j.genrep.2025.102382
Jia-Li Shi , Yong-Qiang Hu , Jian-Qiang Ye , Xu-Zhou Liu , Shi-Yan Wei , Li-Ying Li , Ming-Guo Jiang , Liang-Liang Qi
Tremella fuciformis relies on the nutrient supply from its host fungus Annulohypoxylon stygium during development, but the molecular basis of enzyme activity in their interaction remains unclear. Here, we measured the activities of cellulase, neutral xylanase, amylase, neutral protease, and chitinase during the fruiting process. Enzyme activities showed dynamic changes, with consistently higher levels in mixed mycelium than in A. stygium mycelium. To explore the underlying basis, transcriptome analyses were conducted at three stages, detecting 2533, 2276, and 1326 differentially expressed genes (DEGs) in BHy_14 vs AHy_14, BHy_21 vs AHy_21, and BHy_28 vs AHy_28, respectively (BHy represents the mixed mycelia of T. fuciformis and A. stygium, while AHy represents the mycelia of A. stygium alone; 14, 21, and 28 represent the 14th, 21st, and 28th days of cultivation, respectively). GO and KEGG enrichment indicated that DEGs were mainly enriched in carbohydrate and amino acid metabolism pathways. Notably, the largest number of upregulated genes occurred at 21 d, suggesting this as a key stage of metabolic regulation. Ten candidate DEGs from the BHy_21 vs AHy_21 comparison were validated by qRT-PCR, showing expression patterns consistent with the transcriptome data. Overall, this study reveals the pivotal roles of carbohydrate and amino acid metabolism in T. fuciformisA. stygium interaction, providing molecular insights into developmental regulation and cultivation improvement.
银耳在发育过程中依赖于宿主真菌的营养供给,但二者相互作用中酶活性的分子基础尚不清楚。在此,我们测定了纤维素酶、中性木聚糖酶、淀粉酶、中性蛋白酶和几丁质酶在结果子过程中的活性。酶活性呈动态变化,混合菌丝体的酶活性始终高于混合菌丝体。为了探究其潜在的基础,我们分三个阶段进行转录组分析,分别在BHy_14与AHy_14、BHy_21与AHy_21、BHy_28与AHy_28中检测到2533、2276和1326个差异表达基因(BHy代表T. fuciformis和a.s hegium的混合菌丝,AHy代表a.s hegium的单独菌丝;14,21和28分别代表培养的第14、21和28天)。GO和KEGG富集表明DEGs主要富集于碳水化合物和氨基酸代谢途径。值得注意的是,21 d时出现最多的上调基因,这表明这是代谢调节的关键阶段。通过qRT-PCR验证了BHy_21与AHy_21比较中的10个候选deg,显示出与转录组数据一致的表达模式。总的来说,本研究揭示了碳水化合物和氨基酸代谢在T. fuciformis-A中的关键作用。Stygium相互作用,为发育调控和培养改进提供分子见解。
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引用次数: 0
Therapeutic potential of cinnamaldehyde in melanoma: An in silico and in vitro analysis of stratifin and DNMT expression 肉桂醛在黑色素瘤中的治疗潜力:层析芬和DNMT表达的计算机和体外分析
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-11 DOI: 10.1016/j.genrep.2025.102380
Ali Afgar , Reza Vahidi , Mehrnaz Sadat Ravari , Maryam Samareh Salavatipour , Fatemeh Sharifi , Mahla Sattarzadeh Bardsiri , Mostafa Amopour Bahnamiry , Hoda Ebrahimi , Marzie Ghanbarian , Mohammad-Javad Sanaei
The improper expression of DNA methyltransferase (DNMTs) genes could affect various regions of tumor suppressor genes. MicroRNAs target the DNMTs and modulate gene expression of tumor suppressor genes like stratifin. Cinnamaldehyde is also a methylation modulator with anti-cancer properties. The study predicted the miRNA targeting DNMT3A, 3B, and 1 and evaluated the expression of DNMTs, stratifin, miR-548, miR-200c, miR-193a, and miR-148a-5p before and after treatment with cinnamaldehyde in A375 melanoma cell lines. MicroRNAs were predicted and selected by miRanda, miRDB, miRWalk, RNAhybrid, PICTAR4, PICTAR5, PITA, RNA22, and Targetsca. The analysis of this relationship included docking and 2D interaction plots, and the expression of stratifin, DNMTs, and miRNAs was determined by real-time PCR.
The expression of hsa-miR-548, miR-193a, and miR-148 was dramatically reduced, while the expression of hsa-miR-200c was elevated. Following treatment with Cinnamaldehyde, the results were reversed for DNMT3B and stratifin genes in melanoma compared with melanocytes. Additionally, molecular dynamics simulations showed increased RMSD and Rg values, reduced hydrogen bonding, and higher SASA following cinnamaldehyde binding to DNMT3B, supporting ligand-induced conformational shifts.
We hypothesized that abnormal microRNA expression may disrupt DNMT function by methylating stratifin, but this effect may be reversed with cinnamaldehyde treatment.
DNA甲基转移酶(DNA methyltransferase, dnmt)基因的异常表达可影响肿瘤抑制基因的多个区域。MicroRNAs以dnmt为靶点,调控肿瘤抑制基因如stratifin的基因表达。肉桂醛也是一种具有抗癌特性的甲基化调节剂。本研究预测了靶向DNMT3A、3B和1的miRNA,并评估了肉桂醛治疗A375黑色素瘤细胞系前后dnmt、stratifin、miR-548、miR-200c、miR-193a和miR-148a-5p的表达。通过miRanda、miRDB、miRWalk、RNAhybrid、PICTAR4、PICTAR5、PITA、RNA22和Targetsca预测和选择microrna。这种关系的分析包括对接和2D相互作用图,并通过实时PCR检测stratifin、dnmt和mirna的表达。hsa-miR-548、miR-193a和miR-148的表达显著降低,而hsa-miR-200c的表达升高。在肉桂醛治疗后,与黑色素细胞相比,黑色素瘤中DNMT3B和stratifin基因的结果是相反的。此外,分子动力学模拟显示,肉桂醛与DNMT3B结合后,RMSD和Rg值增加,氢键减少,SASA增加,支持配体诱导的构象转移。我们假设异常的microRNA表达可能通过甲基化stratifin破坏DNMT功能,但这种影响可能通过肉桂醛处理逆转。
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引用次数: 0
Estimating genetic basis of venous thromboembolism (VTE) risk in Indian population: A case control study 估计印度人群静脉血栓栓塞(VTE)风险的遗传基础:一项病例对照研究
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-07 DOI: 10.1016/j.genrep.2025.102379
Babita Kumari , Sunanda Arya , Rashi Khare , Iti Garg , Prince , Rajneesh Kumar Joshi , Rajiv Kumar , Swati Srivastava
Venous thromboembolism (VTE) is a potentially fatal, complex multifactorial disease involving acquired, clinical and genetic risk factors. VTE results in formation of abnormal blood clots affecting 1–3 individuals per thousand in general population. Etiology to VTE is largely attributed to presence of genetic risk factors such as increased activity of coagulation factors and decreased expression of natural anti-coagulants. In such a scenario, it becomes utmost important to have a genetic predictive tool based on which the individuals susceptible to VTE pre-disposition could be screened and prophylactic measures could be taken to mitigate morbidity and mortality. Present study screened sixteen single nucleotide polymorphism (SNP) markers in blood coagulation and anti-coagulation genes. A total of 89 VTE patients and 116 age-matched healthy controls were genotyped using TaqMan-based SNP real-time PCR assays targeting coagulation and anticoagulation pathway genes. Genotypic distribution of each SNP was compared between cases and controls using chi-square (χ2) and Student's t-tests. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess VTE risk. A p-value <0.05 was considered statistically significant. Genetic analysis revealed that variants in F7 (rs6046) and F13 (rs6003) were associated with increased risk of venous thromboembolism (VTE), whereas changes in F13 and F10 (rs321175) appeared protective. Among anticoagulant genes, a PLG rs4252125 variant showed strong risk association, while variations in COX2 rs5788 and COX1 rs3842788 showed protective associations. Other tested variants showed no significant association with VTE. This study identifies both novel and established SNPs associated with VTE risk in the Indian population, highlighting the importance of genetic screening for personalized risk prediction.
静脉血栓栓塞(VTE)是一种潜在致命的、复杂的多因素疾病,涉及获得性、临床和遗传危险因素。静脉血栓栓塞导致异常血凝块的形成,一般人群中每千人中有1-3人患病。静脉血栓栓塞的病因主要归因于遗传风险因素的存在,如凝血因子活性增加和天然抗凝血剂表达减少。在这种情况下,拥有一种遗传预测工具变得至关重要,基于这种工具,可以筛选易患静脉血栓栓塞的个体,并采取预防措施以降低发病率和死亡率。本研究筛选了16个凝血和抗凝基因的单核苷酸多态性(SNP)标记。采用基于taqman的针对凝血和抗凝血途径基因的SNP实时PCR方法,对89例静脉血栓栓塞患者和116例年龄匹配的健康对照进行基因分型。采用χ2和Student’st检验比较病例和对照组各SNP的基因型分布。计算95%置信区间(ci)的优势比(ORs)来评估静脉血栓栓塞风险。p值<;0.05被认为具有统计学意义。遗传分析显示,F7 (rs6046)和F13 (rs6003)的变异与静脉血栓栓塞(VTE)风险增加相关,而F13和F10 (rs321175)的变异则具有保护作用。在抗凝基因中,PLG rs4252125变异具有较强的风险相关性,而COX2 rss5788和COX1 rs3842788变异具有保护相关性。其他测试的变体显示与静脉血栓栓塞没有显著关联。本研究确定了印度人群中与静脉血栓栓塞风险相关的新的和已建立的snp,强调了遗传筛查对个性化风险预测的重要性。
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引用次数: 0
A comparative review of DNA assembly strategies: From traditional to modern DNA组装策略的比较综述:从传统到现代
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-05 DOI: 10.1016/j.genrep.2025.102376
Huynh Kim Khanh Ta , L. Minh Dang , Lan Thuy Ty Nguyen
Molecular Cloning is a cornerstone technology for amplifying, expressing, and manipulating specific DNA sequences. Traditional Restriction Enzyme Cloning (REC) methods are limited by sequence dependency and the introduction of undesirable “scar” sequences, which have driven the development of more advanced assembly strategies. In this review, we critically analyze major DNA Cloning techniques—from early methods to modern seamless assembly and in vivo systems. We delineate the fundamental differences between cloning vectors, which are primarily designed for DNA amplification and stable maintenance in host cells, and expression vectors, which incorporate regulatory elements that drive the expression of recombinant proteins or the transcription of guide RNAs (gRNAs) for cell therapy applications. We describe the mechanisms and enzymes involved in each approach and evaluate their key advantages and limitations. We emphasize the distinction between “scarred” methods (e.g., Restriction Enzyme Cloning, Gateway® Cloning) and “seamless” methods (e.g., Golden Gate Assembly, Exonuclease-based Seamless Cloning), highlighting the superior precision and multi-fragment assembly capability of seamless strategies for complex DNA Cloning projects in Synthetic Biology. Finally, we compare the trade-offs between in vitro systems, which are highly efficient but costly, and in vivo assembly approaches, which are simpler and more cost-effective but typically exhibit lower efficiency—making them suitable for self-sustained academic laboratories. We conclude that the optimal cloning strategy should be selected based on the specific requirements of the project, balancing junction type (scarred/seamless), sequence dependency, multi-fragment capability, flexibility, and cost to meet the needs of each experiment.
分子克隆是扩增、表达和操纵特定DNA序列的基础技术。传统的限制性内切酶克隆(REC)方法受到序列依赖性和引入不良“疤痕”序列的限制,这推动了更先进的组装策略的发展。在这篇综述中,我们批判性地分析了主要的DNA克隆技术-从早期的方法到现代的无缝组装和体内系统。我们描述了克隆载体和表达载体之间的根本区别,克隆载体主要用于宿主细胞中的DNA扩增和稳定维持,表达载体包含驱动重组蛋白表达或引导rna (gRNAs)转录的调控元件,用于细胞治疗应用。我们描述了每种方法中涉及的机制和酶,并评估了它们的主要优点和局限性。我们强调了“疤痕”方法(例如,限制性内切酶克隆,Gateway®克隆)和“无缝”方法(例如,金门组装,基于外切酶的无缝克隆)之间的区别,突出了无缝策略在合成生物学复杂DNA克隆项目中的优越精度和多片段组装能力。最后,我们比较了体外系统(高效但昂贵)和体内组装方法(更简单,更具成本效益,但通常表现出较低的效率)之间的权衡,使它们适合自我维持的学术实验室。我们认为,最优克隆策略应根据项目的具体要求,在连接类型(疤痕/无缝)、序列依赖性、多片段能力、灵活性和成本等方面进行权衡,以满足每个实验的需求。
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引用次数: 0
Carrier frequency of spinal muscular atrophy: a large-scale study in Iranian population 脊髓性肌萎缩症的携带者频率:伊朗人群的大规模研究
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-04 DOI: 10.1016/j.genrep.2025.102378
Shahram Savad , Mohammad-Hossein Modarressi , Mahnaz Seifi-Alan , Niusha Samadaian , Saloomeh Amidi , Mona Masoomy , Shima Norouzi , Sanaz Seifi-Alan , Alireza Ronagh , Shahab Nourian , Sarang Younesi , Mohammad Mahdi Taheri Amin , Maryam Eslami , Mostafa Iranpour , Asyeh Mohammadi , Bahar Parastooei , Mahdi Heydari , Amirreza Boroumand , Mahmoud Reza Ashrafi , Donya Jahedi , Soudeh Ghafouri-Fard
Copy number variation in the SMN1 gene is the main cause of Spinal Muscular Atrophy (SMA). We assessed the carrier frequency of SMA, which is the second most common genetic disease, in the Iranian population. This paper demonstrates the largest population including unrelated subjects and also provides an evaluation with variant analysis of SMN1 in cis. To acquire inclusive molecular data about the carrier frequency of SMA and the frequency of SMN1 polymorphisms g.27134T>G (c.*3+80T>G) among Iranian population, we analyzed data from 2157 individuals referred to the Pars-Genome and Genome-Nilou laboratories for SMA carrier detection between 2018 and 2024. A total of 2003 unrelated non-consanguineous healthy individuals were selected from 2157 individuals underwent MLPA using kit P460 or P021. We also assessed available whole exome sequencing (WES) data of another cohort of patients for the presence of the c.*3+80T>G variant in the SMN1. The results indicated that 3.5 % (n = 70) were carriers of the disease, possessing only one copy of the SMN1 gene. Totally, 89 % (n = 1783) of all participants exhibited two copies of SMN1. Among 526 cases underwent assessment by P460 kit and 2211 cases underwent WES, c.*3+80T>G variant was detected in 28 (1 %) cases. This data can be used in the genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran.
SMN1基因拷贝数变异是导致脊髓性肌萎缩症的主要原因。我们评估了SMA的携带者频率,这是伊朗人群中第二常见的遗传性疾病。本文论证了包括无亲缘关系受试者在内的最大种群,并对cis中SMN1的变异分析进行了评价。为了获得伊朗人群中SMA携带者频率和SMN1多态性G . 27134t>G (c.*3+80T>;G)频率的包容性分子数据,我们分析了Pars-Genome和Genome-Nilou实验室在2018年至2024年间提供的2157名个体的SMA携带者检测数据。使用试剂盒P460或P021,从2157例患者中选择2003例无血缘关系非近亲健康个体进行MLPA。我们还评估了另一组患者的全外显子组测序(WES)数据,以确定SMN1中存在c.*3+80T>;G变异。结果表明,3.5% (n = 70)是该病的携带者,仅具有一个拷贝的SMN1基因。总的来说,89% (n = 1783)的参与者表现出两个SMN1拷贝。在526例P460检测和2211例WES检测中,28例(1%)检测到c *3+80T>;G变异。这些数据可用于遗传咨询、携带者筛查和伊朗SMA的产前诊断。
{"title":"Carrier frequency of spinal muscular atrophy: a large-scale study in Iranian population","authors":"Shahram Savad ,&nbsp;Mohammad-Hossein Modarressi ,&nbsp;Mahnaz Seifi-Alan ,&nbsp;Niusha Samadaian ,&nbsp;Saloomeh Amidi ,&nbsp;Mona Masoomy ,&nbsp;Shima Norouzi ,&nbsp;Sanaz Seifi-Alan ,&nbsp;Alireza Ronagh ,&nbsp;Shahab Nourian ,&nbsp;Sarang Younesi ,&nbsp;Mohammad Mahdi Taheri Amin ,&nbsp;Maryam Eslami ,&nbsp;Mostafa Iranpour ,&nbsp;Asyeh Mohammadi ,&nbsp;Bahar Parastooei ,&nbsp;Mahdi Heydari ,&nbsp;Amirreza Boroumand ,&nbsp;Mahmoud Reza Ashrafi ,&nbsp;Donya Jahedi ,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1016/j.genrep.2025.102378","DOIUrl":"10.1016/j.genrep.2025.102378","url":null,"abstract":"<div><div>Copy number variation in the <em>SMN1</em> gene is the main cause of Spinal Muscular Atrophy (SMA). We assessed the carrier frequency of SMA, which is the second most common genetic disease, in the Iranian population. This paper demonstrates the largest population including unrelated subjects and also provides an evaluation with variant analysis of <em>SMN1</em> in <em>cis</em>. To acquire inclusive molecular data about the carrier frequency of SMA and the frequency of <em>SMN1</em> polymorphisms g.27134T&gt;G (c.*3+80T&gt;G) among Iranian population, we analyzed data from 2157 individuals referred to the Pars-Genome and Genome-Nilou laboratories for SMA carrier detection between 2018 and 2024. A total of 2003 unrelated non-consanguineous healthy individuals were selected from 2157 individuals underwent MLPA using kit P460 or P021. We also assessed available whole exome sequencing (WES) data of another cohort of patients for the presence of the c.*3+80T&gt;G variant in the <em>SMN1</em>. The results indicated that 3.5 % (<em>n</em> = 70) were carriers of the disease, possessing only one copy of the <em>SMN1</em> gene. Totally, 89 % (<em>n</em> = 1783) of all participants exhibited two copies of <em>SMN1</em>. Among 526 cases underwent assessment by P460 kit and 2211 cases underwent WES, c.*3+80T&gt;G variant was detected in 28 (1 %) cases. This data can be used in the genetic counseling, carrier screening, and prenatal diagnosis of SMA in Iran.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102378"},"PeriodicalIF":0.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462419","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
Effect of amino acid sequence similarity in viral protein 1 on herd immunity for predicting dominant genotypes in norovirus seasons in Japan 日本诺如病毒季节病毒蛋白1氨基酸序列相似性对群体免疫预测优势基因型的影响
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-02 DOI: 10.1016/j.genrep.2025.102374
Yoshiyuki Suzuki , Hirokazu Kimura , Kazuhiko Katayama
Norovirus norwalkense in humans (HuNoV) is a major cause of acute gastroenteritis, primarily consisting of genogroups GI and GII. Each genogroup is made of genotypes with distinct antigenicity, which is derived mainly from variations in P2 subdomain of viral protein 1 (VP1). Given that multiple genotypes circulate with varying prevalence, predicting dominant genotypes in a particular season could aid in vaccine development. Here, models for forecasting dominant genotypes were evaluated by analyzing observed genotype frequencies in Japan and amino acid sequences of P2 subdomain. Genotypes GI.1-GI.7 in GI, and GII.2-GII.4, GII.6, GII.7, GII.14, and GII.17 in GII were considered as potential candidates. In contrast to the null model, which assumes that genotype proportions are unchanged from the previous season, the fitness model, which takes into account genotype-specific proliferation efficiency and recombination, demonstrated better performance. The fitness model was improved when herd immunity was assumed to be triggered not only by identical amino acids but also by different amino acids with similar physicochemical properties in P2 subdomain across different strains. Moreover, it was suggested that herd immunity may persist for around a decade in GI and GII.
人类诺瓦克病毒(HuNoV)是急性胃肠炎的主要病因,主要由GI和GII基因群组成。每个基因组由具有不同抗原性的基因型组成,抗原性主要来源于病毒蛋白1 (VP1) P2亚结构域的变异。鉴于多种基因型以不同的流行率传播,预测特定季节的显性基因型可能有助于疫苗的开发。本文通过分析日本地区观察到的基因型频率和P2亚结构域的氨基酸序列,对优势基因型预测模型进行了评价。基因型GI.1-GI。GI为7,GI为2-GI。GII中的4、GII.6、GII.7、GII.14和GII.17被认为是潜在的候选文献。与假设基因型比例与前一季不变的零模型相比,考虑基因型特异性增殖效率和重组的适应度模型表现出更好的性能。假设群体免疫不仅由相同的氨基酸触发,而且由不同菌株P2亚结构域中具有相似理化性质的不同氨基酸触发,对适应度模型进行了改进。此外,有人认为群体免疫可能在GI和GII中持续10年左右。
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引用次数: 0
MTHFR C677T and HLA-DR3/4 genetic variants: Insights into their contribution to type 1 diabetes MTHFR C677T和HLA-DR3/4基因变异:对1型糖尿病的贡献
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-01 DOI: 10.1016/j.genrep.2025.102375
Shobana Manoharan , Gunavathy Nagarajan , Aarthy Amuthavel , Thirunavukkarasu Ramasamy , Chitra Ayyappan , Arthur Asirvatham , Jayalakshmi Mariakuttikan
Type 1 diabetes (T1D) is an autoimmune condition with a global prevalence of approximately 9 million cases. The HLA-DR3 and DR4 alleles have a closer association with T1D and the MTHFR gene polymorphism is an emerging potential risk factor in T1D. Hence, this study aimed to explore the potential genetic impact of the MTHFR C677T polymorphism, in combination with HLADR3and DR4 alleles, towards the development of T1D. In this pilot study, a total of 193 individuals (94 patients and 99 healthy individuals) were analyzed for MTHFR C677T polymorphism and HLA-DR3/4 alleles using RT-PCR and PCR-SSP, respectively. Allele and genotype frequencies were compared between the patient and healthy individuals. Increased frequencies of HLA-DR3 and DR4 alleles were observed in patients (OR = 3.4, pc = 0.0032), and the dominant model (OR = 0.36, pc = 0.00075) of the MTHFR gene was found to be associated with T1D. Combined analysis of MTHFR genotypes and HLA-DR3/4 alleles revealed higher frequencies of specific genotype-allele combinations among patients. Furthermore, meta-analysis suggested that the dominant genetic model of MTHFR C677T polymorphism could increase the risk of T1D. Our results indicate that MTHFR C677T polymorphism and HLA-DR3/4 alleles play important roles in genetic susceptibility towards T1D and provide preliminary evidence to support future large-scale studies.
1型糖尿病(T1D)是一种自身免疫性疾病,全球患病率约为900万例。HLA-DR3和DR4等位基因与T1D的相关性较强,MTHFR基因多态性是T1D的潜在危险因素。因此,本研究旨在探讨MTHFR C677T多态性与hladr3和DR4等位基因结合对T1D发展的潜在遗传影响。在本初步研究中,共193例(94例患者和99例健康个体)分别采用RT-PCR和PCR-SSP对MTHFR C677T多态性和HLA-DR3/4等位基因进行分析。比较患者与健康个体的等位基因和基因型频率。患者中HLA-DR3和DR4等位基因频率增加(OR = 3.4, pc = 0.0032), MTHFR基因的显性模式(OR = 0.36, pc = 0.00075)与T1D相关。MTHFR基因型和HLA-DR3/4等位基因的联合分析显示,患者中特定基因型-等位基因组合的频率较高。此外,荟萃分析表明MTHFR C677T多态性的显性遗传模式可增加T1D的风险。我们的研究结果表明MTHFR C677T多态性和HLA-DR3/4等位基因在T1D的遗传易感性中起重要作用,为未来的大规模研究提供了初步证据。
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引用次数: 0
Suppression of the long non-coding RNA, Malat1, enhances epithelial morphogenesis and differentiation in the fetal mouse submandibular gland 抑制长链非编码RNA Malat1可增强胎鼠颌下腺上皮的形态发生和分化
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-11-01 DOI: 10.1016/j.genrep.2025.102377
Toru Hayashi , Nonoka Nishimori , Kei Eto , Megumi Inomata , Masahiro Fukaya
During development, organogenesis, including gene expression control, regulated hierarchically. The genome contains regions that do not encode functional, continuous amino acid sequences, transcribing short and long non-coding RNAs. These non-coding RNAs are increasingly recognized for their involvement in diverse biological processes. Malat1, a long non-coding RNA (lncRNA), is extensively studied; however, its role in organogenesis is unclear. This study investigated Malat1 expression and its contribution to organogenesis using the fetal mouse submandibular gland as a model of epithelial organ development. Developmental changes in Malat1 expression and localization were assessed using gene expression quantification and in situ hybridization. Stage-dependent variation across tissue, cellular, and subcellular levels, predominantly cytoplasmic localization in epithelial cells at embryonic day 13, were observed. Suppressing Malat1 expression in cultured isolated epithelium increased the number and width of terminal buds, indicating enhanced morphogenesis. Gene expression analysis during Malat1 inhibition upregulated fibroblast growth factor signaling-related genes, differentiation marker genes, and downregulated progenitor marker expression. These findings suggest that Malat1 plays a regulatory and physiological role in SMG development, influencing epithelial differentiation and morphogenesis.
在发育过程中,包括基因表达控制在内的器官发生受层次调控。基因组包含不编码功能性连续氨基酸序列的区域,转录短和长非编码rna。这些非编码rna因其参与多种生物过程而日益得到认可。Malat1是一种长链非编码RNA (lncRNA),被广泛研究;然而,其在器官发生中的作用尚不清楚。本研究以胎儿小鼠下颌骨腺为上皮器官发育模型,研究了Malat1的表达及其在器官发生中的作用。利用基因表达量化和原位杂交技术评估Malat1表达和定位的发育变化。在胚胎第13天,观察到组织、细胞和亚细胞水平上的阶段依赖性变异,主要是上皮细胞的细胞质定位。在培养的离体上皮中,抑制Malat1的表达增加了顶芽的数量和宽度,表明形态发生增强。Malat1抑制期间的基因表达分析上调成纤维细胞生长因子信号相关基因、分化标记基因和下调祖细胞标记表达。这些发现表明,Malat1在SMG发育中起调节和生理作用,影响上皮分化和形态发生。
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引用次数: 0
Temporal expression patterns of SnRK1 and WRKY3 defense genes reveal cultivar-specific responses to tomato curly stunt virus infection SnRK1和WRKY3防御基因的时间表达模式揭示了品种对番茄卷曲矮病毒感染的特异性反应
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-10-30 DOI: 10.1016/j.genrep.2025.102373
Antzel Theron , Farhahna Allie
Tomato curly stunt virus (ToCSV) significantly impacts tomato production globally, yet the molecular mechanisms underlying cultivar-specific resistance responses remain poorly understood. We investigated the temporal expression of two key defense-related genes, Sucrose Non-Fermenting 1-Related Protein Kinase 1 (SnRK1) and WRKY transcription factor 3 (WRKY3), across four tomato cultivars with varying susceptibility to ToCSV: susceptible (Rooikhaki, Moneymaker), tolerant (NIL396), and resistant (ESTY). Using quantitative real-time PCR, we analyzed gene expression at 8, 15, and 35 days post-infection, representing early infection, symptom onset, and systemic viral movement stages. Viral quantification revealed distinct accumulation patterns, with susceptible cultivars showing 283–440 % increases in viral load between 15 and 35 dpi, while the tolerant cultivar maintained stable levels and the resistant cultivar remained undetectable. SnRK1 expression patterns differed between cultivars: susceptible lines showed initial downregulation (15 dpi) followed by upregulation (35 dpi), while the resistant cultivar exhibited consistent downregulation. WRKY3 displayed complex temporal patterns, with most cultivars showing early upregulation followed by late-stage downregulation, except the resistant cultivar, which maintained downregulation throughout. These results provide the first comparative temporal analysis of defense gene expression in the tomato-ToCSV pathosystem and suggest that resistance mechanisms involve distinct regulatory strategies rather than simple gene activation patterns.
番茄卷曲矮缩病毒(ToCSV)对全球番茄生产产生重大影响,但对品种特异性抗性反应的分子机制尚不清楚。我们研究了蔗糖非发酵1相关蛋白激酶1 (SnRK1)和WRKY转录因子3 (WRKY3)这两个关键防御相关基因在4个不同ToCSV易感性的番茄品种中的时间表达:易感(Rooikhaki, Moneymaker),耐受性(NIL396)和抗性(ESTY)。利用实时荧光定量PCR技术,我们分析了感染后8天、15天和35天的基因表达,分别代表了早期感染、症状发作和全身病毒运动阶段。病毒定量显示出不同的积累模式,在15 - 35 dpi之间,敏感品种的病毒载量增加了283 - 440%,而耐受性品种保持稳定水平,抗性品种仍未检测到。SnRK1的表达模式在不同品种间存在差异:敏感品系表现为初始下调(15 dpi),随后上调(35 dpi),而抗性品系表现为持续下调。WRKY3表现出复杂的时间模式,除抗性品种一直保持下调外,大多数品种均表现为早期上调后后期下调。这些结果首次提供了番茄- tocsv病理系统中防御基因表达的比较时间分析,并表明抗性机制涉及不同的调控策略,而不是简单的基因激活模式。
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引用次数: 0
Molecular insights of a novel Angiotensinogen homolog of Sebastes Schlegelii, revealing its transcriptional sensitivity to pathogenic infections 一种新的血管紧张素原Schlegelii同源物的分子见解,揭示其对致病性感染的转录敏感性
IF 0.9 Q4 GENETICS & HEREDITY Pub Date : 2025-10-30 DOI: 10.1016/j.genrep.2025.102371
Don Anushka Sandaruwan Elvitigala , Jehee Lee
Angiotensinogen (AGT) is a key component in renin-angiotensin system (RAS) in animals and primarily secreted as a precursor molecule. AGTs are known to play multiple roles in animals including maintaining homeostasis and mediating host immune responses as an acute phase protein. In this study complete coding sequence of AGT homolog with 1380 bps was identified from S. schlegelii and designated as SsAGT. The gene codes for a protein with 460 amino acids with a predicted molecular weight of 51.3 kDa. SsAGT resembled the common domain architecture of serpin family proteins and found to bear a signal peptide of 19 residues. Protein level sequence comparison revealed the homology of SsAGT with its known counterparts of teleosts and tetrapods and phylogenetic analysis confirmed its close evolutionary relationship with teleostan orthologues. Transcriptional profile of SsAGT in different tissues of the healthy fish obtained by using qPCR showed a constitutive expression in selected tissues with more pronounced expression level in liver tissues. However, its basal mRNA expression in liver tissues was found to be modulated by lipopolysaccharides, Poly I:C and live Streptococus iniae treatments, at different time points post treatment, suggesting its potential role under pathogenic stress. These findings highlight the immunophysiological significance of AGTs in teleosts and warrant further functional studies to elucidate their role in first-line host defense mechanisms.
血管紧张素原(AGT)是动物肾素-血管紧张素系统(RAS)的关键成分,主要作为前体分子分泌。已知agt在动物中发挥多种作用,包括维持体内平衡和作为急性期蛋白介导宿主免疫反应。本研究从施莱格氏链球菌中鉴定出全长1380个bps的AGT同源序列,并将其命名为SsAGT。该基因编码一种含有460个氨基酸的蛋白质,预计分子量为51.3 kDa。SsAGT类似于serpin家族蛋白的共同结构域结构,并被发现具有19个残基的信号肽。蛋白水平序列比较显示,SsAGT与已知的硬骨鱼和四足动物同源物具有同源性,系统发育分析证实了其与硬骨鱼同源物的密切进化关系。通过qPCR获得的健康鱼不同组织中SsAGT的转录谱显示,在选定的组织中有组成性表达,在肝组织中表达水平更为显著。然而,其在肝组织中的基础mRNA表达在处理后不同时间点受到脂多糖、Poly I:C和活链球菌的调节,提示其在致病应激下的潜在作用。这些发现强调了agt在硬骨鱼中的免疫生理意义,并为进一步的功能研究阐明其在一线宿主防御机制中的作用提供了依据。
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