IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-03-05 Epub Date: 2025-12-17 DOI: 10.1016/j.gene.2025.149964

D. Pereira , A.M. Almeida , J.A. Queiroz , F. Sousa , N. Alves , J.F.A. Valente , A. Sousa

Background

The infection by Human Papillomaviruses (HPV) has long been established as one of the main causes of cervical cancer, with HPV16/HPV18 high-risk types expressing E6/E7 oncoproteins that inhibit p53/pRB tumor suppressor proteins. Therefore, this work focuses on gene therapy, using the innovative minicircle DNA (mcDNA) vector to protect and express the pri-miR-375 in the cancer cell nucleus, ultimately originating the microRNA-375 (miR-375) in the cytoplasm. This miR-375, initially downregulated in cervical cancer cells, can silence HPV E6/E7 transcripts, thereby negatively regulating the expression of these oncoproteins.

Methods

The mcDNA-pri-miR-375 vector was successfully constructed, biosynthesized in the host cell, extracted, and purified, followed by several in vitro transfection studies in CaSKi cells (HPV16-infected cervical cancer model) to evaluate the mcDNA-pri-miR-375 effect.

Results

FITC-stained-mcDNA-pri-miR-375 was present in cancer cell nucleus, confirmed by confocal microscopy. RT-PCR analysis showed a more intense band of miR-375 transcripts, and RT-PCR/ RT-qPCR confirmed that E6/ E7 transcript levels were nearly 80 % diminished 24 h after CaSki cells transfection. Also, western-blot showed a decreased band intensity for E6/ E7 proteins on transfected cells. Proliferation and cell invasion studies demonstrated growth and migration arrest for CaSki cells throughout 72 h. Cell viability study of these cells also revealed a gradual decrease for the same period, while the NHDF cell viability was not affected, indicating specificity towards CaSki. The consequent effect of silencing the E6/ E7 transcripts was also observed through an increase in p53 protein levels (determined by western blot and ELISA) and caspase-3 activity, after 48 h of CaSki cell transfection.

Conclusions

These results suggest that mcDNA-pri-miR-375 vector has the potential to be further explored in gene therapy for the treatment of HPV-caused cervical cancer.

背景：人乳头瘤病毒（Human papillomavirus， HPV）感染早已被确定为宫颈癌的主要病因之一，HPV16/HPV18高危型表达抑制p53/pRB抑癌蛋白的E6/E7癌蛋白。因此，本工作的重点是基因治疗，利用创新的微环DNA （microiccircle DNA, mcDNA）载体在癌细胞细胞核中保护和表达pri-miR-375，最终在细胞质中产生microRNA-375 （miR-375）。这种最初在宫颈癌细胞中下调的miR-375可以沉默HPV E6/E7转录本，从而负向调节这些癌蛋白的表达。方法：构建mcDNA-pri-miR-375载体，在宿主细胞中进行生物合成、提取、纯化，并在CaSKi细胞（hpv16感染宫颈癌模型）中进行多次体外转染研究，评价mcDNA-pri-miR-375的作用。结果：经共聚焦显微镜证实，癌细胞细胞核中存在fitc染色的mcdna -pri- mir -375。RT-PCR分析显示miR-375转录物的条带更强，RT-PCR/ RT-qPCR证实，CaSki细胞转染后24 h， E6/ E7转录物水平降低了近80% %。western-blot也显示转染细胞上E6/ E7蛋白的条带强度降低。增殖和细胞侵袭研究表明，CaSki细胞在72 h内生长和迁移停滞。这些细胞的细胞活力研究也显示在同一时期逐渐下降，而NHDF细胞活力不受影响，表明对CaSki具有特异性。在CaSki细胞转染48 h后，通过p53蛋白水平（通过western blot和ELISA测定）和caspase-3活性的增加，也观察到E6/ E7转录物沉默的后续效果。结论：这些结果提示mcDNA-pri-miR-375载体在hpv致宫颈癌的基因治疗中具有进一步探索的潜力。

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引用次数: 0

Genetic and epigenetic determinants of injury risk and recovery in elite athletes: toward precision sports medicine 精英运动员损伤风险和恢复的遗传和表观遗传决定因素：走向精确运动医学。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-12 DOI: 10.1016/j.gene.2025.149957

Hao Ding , Qilu Deng , Zhenhua Guo

Musculoskeletal injuries and interindividual variability in recovery remain critical challenges for sustaining elite athletic performance. Despite advances in diagnostics, training, and rehabilitation, unexplained differences in injury risk and recovery efficiency persist. Growing evidence implicates genetic and epigenetic mechanisms in these disparities, influencing collagen integrity, inflammatory regulation, oxidative stress, and muscle regeneration. Key contributors include single-nucleotide polymorphisms (SNPs) in COL1A1, COL5A1, ACTN3, and IL6, as well as novel loci identified by genome-wide association studies (GWAS). Polygenic risk scores (PRS), which integrate the effects of multiple low-impact variants, enhance prediction compared to single-gene markers. Epigenetic regulators, including DNA methylation and exercise-responsive microRNAs (e.g., miR-206, miR-133a, miR-486), provide a dynamic interface linking genetic predisposition with environmental factors such as training load and nutrition. Integration of genomic data with wearable technologies and artificial intelligence enables real-time monitoring, adaptive recovery, and precision load management. Yet, clinical translation faces challenges including limited population diversity, interpretative complexity, and ethical concerns over data privacy and potential misuse. Advancing precision sports medicine will require multidisciplinary, systems-level strategies that unite molecular insights with practical implementation, ultimately enabling individualized injury prevention, optimized rehabilitation, and the preservation of long-term athlete health and performance.

肌肉骨骼损伤和恢复中的个体差异仍然是维持精英运动表现的关键挑战。尽管在诊断、训练和康复方面取得了进步，但无法解释的损伤风险和恢复效率差异仍然存在。越来越多的证据暗示这些差异的遗传和表观遗传机制，影响胶原完整性，炎症调节，氧化应激和肌肉再生。关键因素包括COL1A1、COL5A1、ACTN3和IL6的单核苷酸多态性（snp），以及全基因组关联研究（GWAS）发现的新位点。与单基因标记相比，多基因风险评分（PRS）整合了多个低影响变异的影响，提高了预测能力。表观遗传调控因子，包括DNA甲基化和运动反应性microrna（如miR-206， miR-133a, miR-486），提供了一个动态接口，将遗传易感性与环境因素（如训练负荷和营养）联系起来。基因组数据与可穿戴技术和人工智能的集成实现了实时监测、自适应恢复和精确负载管理。然而，临床翻译面临的挑战包括有限的人群多样性，解释的复杂性，以及对数据隐私和潜在滥用的伦理担忧。推进精准运动医学将需要多学科、系统级的策略，将分子见解与实际实施结合起来，最终实现个性化的损伤预防、优化的康复，并保持运动员的长期健康和表现。

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引用次数: 0

Inorganic nitrogen sources and light cooperatively stimulate gene regulation for non-photosynthetic phosphoenolpyruvate carboxylase in wheat leaves 无机氮源和光协同刺激小麦叶片非光合磷酸化烯醇丙酮酸羧化酶的基因调控。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-09 DOI: 10.1016/j.gene.2025.149950

Naoki Yamamoto , Jingru Jiang , Haoyu Deng , Ken-ichi Kurotani , Jiang Zou , Zaijun Yang

Phosphoenolpyruvate carboxylase (PEPC) is a bicarbonate fixation enzyme that is associated with nitrogen metabolism. We previously observed that NO₃^– affected the expression levels of PEPC genes differently in detached wheat leaves. Three types of PEPC isogenes, including the orthologous isogene group (Tappc1b) for C₄-photosynthetic PEPC, exhibited distinct transcriptionally up-regulated patterns from one another. However, it remains unclear which nitrogen compounds exactly trigger the gene expression responses and their light dependency. Here, we investigated the cause of isogene-specific expression responses of PEPCs to different forms of nitrogen supplementation. Detached leaves from wheat seedlings cultivated under a nitrogen-deficient condition were incubated with NO₃^–, NH₄⁺, and urea under both light and dark conditions. Notably, the genes analyzed exhibited markedly different expression patterns across the nitrogen forms under the light condition. Tappc1a, which did non-respond to NO₃^–, was up-regulated by NH₄⁺ exclusively under light. Tappc2 was also up-regulated by NO₃^– and NH₄⁺ only under light, and these up-regulations were suppressed under the dark condition. The candidate transcriptional regulator DOF1 for Tappc1b in wheat was also up-regulated by NO₃^– only under light condition, but earlier than Tappc1b, implicating a DOF1-mediated transcriptional response of Tappc1b to NO₃^–. Comparison of Tappc1b promoter sequences with that of NO₃^–-responsive maize C₄ PEPC revealed conserved light-responsive elements near the Dof1 binding site. These findings suggest that distinct transcriptional regulatory cascades would exist for non-photosynthetic PEPCs in response to different inorganic nitrogen forms.

磷酸烯醇丙酮酸羧化酶（PEPC）是一种与氮代谢有关的碳酸氢盐固定酶。NO3-对小麦离体叶片PEPC基因表达水平的影响存在差异。三种类型的PEPC同基因，包括c4 -光合PEPC的同源同基因组（Tappc1b），表现出不同的转录上调模式。然而，目前尚不清楚究竟是哪种氮化合物触发了基因表达反应及其对光的依赖性。在这里，我们研究了PEPCs对不同形式补氮的等基因特异性表达反应的原因。采用NO3-、NH4+和尿素对缺氮小麦幼苗离体叶片进行光照和暗培养。值得注意的是，在光照条件下，所分析的基因在不同氮形态下表现出明显不同的表达模式。对NO3-无反应的Tappc1a在光照条件下仅被NH4+上调。光照条件下，NO3-和NH4+也上调了Tappc2，而在黑暗条件下，这些上调被抑制。光照条件下，小麦中调控Tappc1b的候选转录调控因子DOF1也仅被NO3-上调，但上调时间早于Tappc1b，提示Tappc1b对NO3-的转录响应是由DOF1介导的。将Tappc1b启动子序列与NO3响应玉米C4PEPC的启动子序列进行比较，发现Dof1结合位点附近有保守的光响应元件。这些发现表明，非光合作用的PEPCs在对不同无机氮形式的响应中可能存在不同的转录调控级联。

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引用次数: 0

Identification of ascorbate peroxidase family genes reveals expression of TkAPX250a confers heat stress tolerance in Taraxacum kok-saghyz 抗坏血酸过氧化物酶家族基因的鉴定表明，TkAPX250a基因的表达使紫杉树具有耐热性。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-11-25 DOI: 10.1016/j.gene.2025.149918

Shiqi Long, Boxuan Yuan, Minmin He, Guoen Ao, Baoqiang Wang, Xuchu Wang

Ascorbate peroxidase (APX) enzymes are pivotal in scavenging reactive oxygen species (ROS) and maintaining redox homeostasis in plants, a function critical for survival under abiotic stress conditions. To investigate this key enzyme system in the rubber-producing dandelion Taraxacum kok-saghyz (Tk)—an emerging model for sustainable rubber production—we conducted a genome-wide analysis of its APX genes. We identified seven TkAPX genes, whose predicted subcellular localizations include the cytoplasm, plasma membrane, and chloroplasts. Promoter analysis revealed an abundance of stress-responsive motifs, supporting their potential role in stress adaptation. By integrating time-course qPCR of the TkAPX family under heat stress with transcriptome-wide expression profiling across tissues, we identified TkAPX250a as a pivotal candidate. This gene showed a remarkable ∼ 20-fold increase in transcript levels in subsequent transgenic lines compared to wild-type controls, confirming highly efficient transgene expression without silencing. Under thermal stress, these transgenic lines exhibited reduced ROS accumulation and membrane lipid peroxidation while maintaining higher chlorophyll content and biomass, demonstrating that TkAPX250a coordinately enhances thermotolerance and photosynthetic stability. Mechanistically, TkAPX250a overexpression not only enhanced APX activity and lowered H₂O₂ accumulation but also synergistically upregulated the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Time-resolved assays under heat stress further delineated a stratified antioxidant hierarchy within this coordinated response, with SOD and CAT acting as core responders. These findings establish TkAPX250a as a central genetic regulator in abiotic stress adaptation and provide a molecular basis for breeding stressresilient rubber crops, addressing a critical need in agriculture under changing climate conditions.

抗坏血酸过氧化物酶（APX）在清除活性氧（ROS）和维持植物氧化还原稳态中起着关键作用，是在非生物胁迫条件下生存的关键功能。为了研究生产橡胶的蒲公英Taraxacum kok-saghyz (Tk)（一种新兴的可持续橡胶生产模式）的关键酶系统，我们对其APX基因进行了全基因组分析。我们鉴定了7个TkAPX基因，其预测的亚细胞定位包括细胞质、质膜和叶绿体。启动子分析揭示了大量的应激反应基序，支持它们在应激适应中的潜在作用。通过整合热应激下TkAPX家族的时间过程qPCR和组织间转录组全表达谱，我们确定了TkAPX250a是一个关键的候选者。与野生型对照相比，该基因在随后的转基因系中转录水平显著增加 ~ 20倍，证实了高效的转基因表达而不沉默。在热胁迫下，这些转基因品系表现出ROS积累和膜脂过氧化的减少，同时保持较高的叶绿素含量和生物量，表明TkAPX250a协同增强了耐热性和光合稳定性。机制上，TkAPX250a过表达不仅能增强APX活性，降低H2O2积累，还能协同上调超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和过氧化物酶（POD）的活性。热应激下的时间分辨实验进一步描绘了这种协调反应中的分层抗氧化层次，SOD和CAT作为核心应答者。这些发现确立了TkAPX250a作为非生物胁迫适应的核心遗传调控因子，并为培育抗逆性橡胶作物提供了分子基础，解决了气候条件变化下农业的关键需求。

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引用次数: 0

Two transcription factors and one antisense RNA underlie the thermoregulated insect pathogenicity of Yersinia entomophaga MH96 两个转录因子和一个反义RNA是虫食耶尔森菌MH96热调控昆虫致病性的基础。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-11 DOI: 10.1016/j.gene.2025.149955

Amber R. Paulson , Maureen O’Callaghan , Xue-Xian Zhang , Naran Naren , Marion Schoof , Mark R.H. Hurst

Entomopathogenic bacteria express virulence genes in a temperature-dependent manner, but the underlying molecular mechanisms remain poorly understood. Here, we describe the roles of an unusual LytTR-containing transcription factor Yen6 in determining the virulence of Yersinia entomophaga (MH96). An initial transcriptome analysis in vivo revealed that yen6, located 1,372 bp upstream from genes encoding the Yen Toxin complex (Yen-Tc), exhibited significantly higher transcriptional activity at 37 °C compared to 25 °C (adjusted p-value < 0.001) during intrahemocoelic infection in the insect model Galleria‍ mellonella. Deletion of yen6 also significantly reduced MH96′s virulence in G.‍‍ mellonella by up to three-fold. Next, comparing the transcriptome of wild-type MH96 and its derived Δyen6 mutant revealed genes for ribose utilization were downregulated whereas genes for fructose utilization and the RNA-binding protein YhbY were upregulated in the yen6-deficient mutant. Subsequent electromobility shift assays showed that purified Yen6_His6 protein was capable of specifically binding to the promoter regions of the ribose and fructose utilization-related gene clusters, as well as yhbY. A 645-nucleotide-long 3′ untranslated region, designated yen7_AS, was identified extending from the yen6 coding region. Notably, yen7_AS completely overlaps the yen7 gene on the opposing strand and may therefore act as a cis anti-sense RNA regulating yen7 expression, which encodes a putative transcriptional regulator of the Yen-Tc. This study highlights the critical role of the yen6–yen7 locus in MH96 virulence during G.‍ mellonella infection, including the complex mechanisms controlling insecticidal exoprotein production.

昆虫致病细菌以温度依赖的方式表达毒力基因，但其潜在的分子机制仍然知之甚少。在这里，我们描述了一种不寻常的含有lyttr的转录因子Yen6在决定食虫耶尔森菌（MH96）毒力中的作用。初步的体内转录组分析显示，位于编码Yen毒素复合物（Yen- tc）基因上游1,372 bp处的yen6在37 °C时的转录活性明显高于25 °C（调整p值 ），His6蛋白能够特异性结合核糖和果糖利用相关基因簇的启动子区域，以及yhbY。从yen6编码区延伸出一个645个核苷酸长的3'非翻译区，命名为yen7_AS。值得注意的是，yen7_AS在相反的链上与yen7基因完全重叠，因此可能作为顺式反义RNA调节yen7的表达，从而编码推测的Yen-Tc的转录调节因子。该研究强调了yen6-yen7位点在G.‍mellonella感染期间MH96毒力中的关键作用，包括控制杀虫外蛋白产生的复杂机制。

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引用次数: 0

Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function 纯种马骨骼肌中年龄诱导的基因表达突出了增强肌肉结构和功能的基因。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-15 DOI: 10.1016/j.gene.2025.149951

Mian Feng , Thomas J. Hall , David E. MacHugh , Lisa M. Katz , Emmeline W. Hill

Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrichment analysis revealed that the DEGs were primarily associated with terms related to muscle assembly and system development, including Developmental process (GO:0032502), Anatomical structure development (GO:0048856), Actin cytoskeleton (GO:0015629), and Growth factor binding (GO:0019838). KEGG pathway analysis indicated that ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, and PI3K-Akt signalling pathway were the significant functional pathways. Protein-protein interaction network and hub gene analyses identified seven key regulatory genes: COL1A1, COL1A2, COL3A1, S100A4, NOTCH1, THY1 and MT-ND2. In addition, the MSTN, COL4A1, COL4A2, SPEN, S100A4, NOTCH1, NOTCH3, and THY1 genes were found to play key roles in the functional development of skeletal muscle. This study provides insight into the transcriptional landscape of skeletal muscle development in young Thoroughbred horses. The period between two and three years of age represents a crucial stage in skeletal muscle adaptation in the juvenile horse, with a particular emphasis on muscle structural and functional integrity.

早期骨骼肌发育对年轻赛马至关重要，但在这一时期对转录变化的研究有限。此外，年龄对马运动员运动训练转录反应的影响尚不清楚。研究人员对5匹未经训练的纯种马在2岁（UR2）和3岁（UR3）休息时进行了骨骼肌差异基因表达的转录组分析。共鉴定出136个差异表达基因（DEGs），其中95个表达增加，41个表达减少。氧化石墨烯富集分析显示，deg主要与肌肉组装和系统发育相关，包括发育过程（GO:0032502）、解剖结构发育（GO:0048856）、肌动蛋白细胞骨架（GO:0015629）和生长因子结合（GO:0019838）。KEGG通路分析表明，ecm受体相互作用、蛋白质消化吸收、局灶黏附和PI3K-Akt信号通路是重要的功能通路。蛋白-蛋白相互作用网络和枢纽基因分析鉴定出7个关键调控基因：COL1A1、COL1A2、COL3A1、S100A4、NOTCH1、THY1和MT-ND2。此外，还发现MSTN、COL4A1、COL4A2、SPEN、S100A4、NOTCH1、NOTCH3和THY1基因在骨骼肌功能发育中起关键作用。这项研究提供了对年轻纯种马骨骼肌发育的转录景观的见解。2 - 3岁是马幼马骨骼肌适应的关键阶段，特别强调肌肉结构和功能的完整性。

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引用次数: 0

Genome-wide association study of tolerance to acute hypoxia in the olive flounder (Paralichthys olivaceus) using individual blood cortisol levels as a physiological phenotype 橄榄比目鱼对急性缺氧耐受性的全基因组关联研究，使用个体血液皮质醇水平作为生理表型

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-11 DOI: 10.1016/j.gene.2025.149952

M.A.H. Dilshan , Gaeun Kim , W.K.M. Omeka , D.S. Liyanage , H.M.V. Udayantha , D.C.G. Rodrigo , G.A.N.P. Ganepola , H.A.C.R. Hanchapola , Y.K. Kodagoda , Po Gong , Jihun Lee , Sukkyoung Lee , Jeongeun Kim , Jehee Lee

Hypoxia, caused by reduced dissolved oxygen (DO) levels in water, is a critical challenge in aquaculture and often results in stress, anorexia, and mass mortality in fish. The olive flounder (Paralichthys olivaceus) is a key species in South Korea’s global aquaculture exports. However, aquaculture production of P. olivaceus experiences significant economic losses caused by hypoxia-induced fish mortality, highlighting the critical need for developing genetically improved hypoxia-tolerant strains. In this study, a genome-wide association study (GWAS) was performed to unveil single-nucleotide polymorphisms (SNPs) associated with acute hypoxia tolerance and elucidate underlying regulatory mechanisms. A total of 382 P. olivaceus fish were measured for blood serum cortisol level using enzyme-linked immunosorbent assay (ELISA) upon acute hypoxia stress. Blood plasma cortisol levels were used as a proxy phenotype of hypoxia tolerance, with the hypothesis that elevated concentrations indicate low tolerance, and minimized concentrations indicate high tolerance to acute hypoxia stress. Then, fish were genotyped using the Affymetrix® Axiom® myDesign™ genotype array, and 57,651 SNPs were retained after quality control filtering. A significant SNP was identified on chromosome 15 of the P. olivaceus genome, above the suggestive threshold (p < 1 × 10⁻⁴) for the stress cortisol level trait. A strongly associated SNP with accession number AX-419149718 was located in the zona pellucida-like domain-containing protein 1 (Zpld1) gene. Gene ontology (GO) analysis suggests that Zpld1 is involved in signaling pathways, including the integrin-mediated signaling pathway, thereby contributing to the mitigation of hypoxia stress effects. Collectively, this study provides insights into the genetic basis of acute hypoxia tolerance in P. olivaceus and may serve as a foundation for establishing genomic selection of olive flounders with acute hypoxia stress tolerance in aquaculture breeding programs.

由水中溶解氧（DO）水平降低引起的缺氧是水产养殖中的一个关键挑战，经常导致鱼类应激、厌食和大量死亡。橄榄比目鱼（palichthys olivaceus）是韩国全球水产养殖出口的关键品种。然而，由于缺氧导致鱼类死亡，olivaceus的水产养殖遭受了重大的经济损失，因此迫切需要开发基因改良的耐缺氧菌株。在这项研究中，进行了一项全基因组关联研究（GWAS），揭示了与急性缺氧耐受性相关的单核苷酸多态性（snp），并阐明了潜在的调控机制。采用酶联免疫吸附法（ELISA）测定了382条橄榄鱼急性缺氧应激时的血清皮质醇水平。血浆皮质醇水平被用作低氧耐受性的代用表型，假设浓度升高表明低耐受性，而浓度最小化表明对急性缺氧应激的高耐受性。然后，使用Affymetrix®Axiom®myDesign™基因型阵列对鱼进行基因分型，质量控制过滤后保留了57,651个snp。在p . olivaceus基因组的第15号染色体上发现了一个显著的SNP，高于应激皮质醇水平性状的提示阈值（p < 1 × 10−4）。在透明带样结构域蛋白1 （Zpld1）基因中发现了一个与加入号AX-419149718密切相关的SNP。基因本体论（GO）分析表明，Zpld1参与信号通路，包括整合素介导的信号通路，从而有助于减轻缺氧胁迫的影响。总的来说，本研究提供了橄榄比目鱼急性缺氧耐受性的遗传基础，并可为在水产养殖育种计划中建立具有急性缺氧胁迫耐受性的橄榄比目鱼基因组选择奠定基础。

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引用次数: 0

Differential genomic signatures of homozygosity and a haplotype sharing Extents across breeds associated with body size variation in Korean indigenous goats 韩国本土山羊体型变异与品种间纯合子性和单倍型共享程度的差异基因组特征。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-11 DOI: 10.1016/j.gene.2025.149956

Seongmin Kim , Hankyeol Jeong , Ga-Eun Kim , Kwan-Woo Kim , Woncheoul Park , Jaemin Kim , Bong-Hwan Choi

Korean indigenous goats are maintained as purebred lineages in geographically isolated populations such as Dangjin, Gyeongsang National University (GNU), Jangsu, and Tongyeong. However, their small population size and high rates of inbreeding have raised concerns regarding the preservation of genetic diversity. We generated SNP genotypes for 217 Korean indigenous goats using the GoatSNP50 BeadChip, and standardized body size measurements with complete metadata were available for 64 adult individuals. Principal component analysis (PCA) clearly separated the four lineages, with the GNU population showing particularly high values of inbreeding coefficient and proportion of runs of homozygosity, reflecting the impact of recent closed breeding. Genome-wide patterns of haplotype sharing revealed exploratory trends suggesting that introgression from global breeds tended to coincide with larger body size, whereas intensified inbreeding within the Korean population showed a general tendency toward reduced body size. Furthermore, cross-population extended haplotype homozygosity (XP-EHH) analysis revealed candidate genes, including ADGRL3, SP8, and ARL6IP5 that are likely involved in adaptation to seasonal environmental stress. Our findings highlight the global connectivity, functional relevance of body conformation traits, and selective signatures of Korean indigenous goats, providing a genomic foundation for preserving diversity and guiding future breeding.

在唐津、庆尚国立大学、长寿、统营等地理上孤立的地区，韩国本土山羊被维持为纯种。然而，它们的小种群规模和高近交率引起了人们对遗传多样性保护的关注。我们使用GoatSNP50 BeadChip对217只韩国本土山羊进行了SNP基因型分析，并对64只成年山羊进行了具有完整元数据的标准化体型测量。主成分分析（PCA）对4个世系进行了明显的分离，发现GNU群体的近交系系数和纯合子居次比例特别高，反映了近期封闭育种的影响。单倍型共享的全基因组模式揭示了探索性趋势，表明来自全球品种的基因渗入倾向于体型更大，而韩国种群内近亲繁殖的加剧则显示出体型变小的总体趋势。此外，跨群体扩展单倍型纯合分析（XP-EHH）揭示了候选基因，包括ADGRL3， SP8和ARL6IP5，可能参与适应季节性环境胁迫。我们的研究结果突出了韩国本土山羊的全球连通性、身体构象特征的功能相关性和选择性特征，为保护多样性和指导未来的育种提供了基因组基础。

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引用次数: 0

Gene therapy for Krabbe disease: evidence from mouse and canine models 克拉伯病的基因治疗：来自小鼠和犬模型的证据。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-20 Epub Date: 2025-12-09 DOI: 10.1016/j.gene.2025.149949

Yang Li , Xiang Dong , Jian Guo , Ya-feng Lv

Globoid cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-galactosylceramidase (GALC) gene, resulting in enzyme deficiency and the progressive accumulation of galactosylsphingosine and galactosylceramide in the white matter of the central nervous system and in peripheral nerves, which in turn triggers demyelination. Although no curative therapy is currently available, studies in animal models in recent years have shown that gene therapy can ameliorate pathological and biochemical abnormalities and holds considerable promise for clinical translation. This article reviews advances in gene therapy in animal models of GLD and discusses key directions and challenges for future treatments.

Globoid cell leukodystrophy （GLD）是一种常染色体隐性溶酶体贮积症，由β-半乳糖神经酰胺酶（GALC）基因突变引起，导致中枢神经系统白质和周围神经中半乳糖神经酰胺和半乳糖神经酰胺的酶缺乏和进行性积累，进而引发脱髓鞘。虽然目前还没有治愈性的治疗方法，但近年来在动物模型上的研究表明，基因治疗可以改善病理和生化异常，并且在临床转化方面具有相当大的前景。本文综述了GLD动物模型基因治疗的进展，并讨论了未来治疗的关键方向和挑战。

引用次数: 0

Bioinformatics applications in pharmacogenomics: towards personalized medicine 生物信息学在药物基因组学中的应用：走向个性化医疗

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-02-10 Epub Date: 2025-12-04 DOI: 10.1016/j.gene.2025.149935

Nabil Zaid , Lamyaa Benchikhi , Banacer Himmi , Hassan Ghazal

Pharmacogenomics investigates how genetic variation influences individual responses to drug therapy and aims to optimize treatment outcomes through personalized approaches. Bioinformatics plays a foundational role in this field, enabling the processing, annotation, and interpretation of complex genomic and multi-omics datasets. This review explores the current landscape of bioinformatics in pharmacogenomics, including key databases, variant analysis tools, and artificial intelligence-driven predictive models. It also discusses the integration of multi-omics data, real-world clinical applications, and the regulatory and ethical frameworks supporting clinical implementation. Finally, the role of pharmacogenomics in drug discovery and development is highlighted, illustrating how genetic insights contribute to target identification, trial design, and drug repurposing. Together, these components form the computational backbone of precision medicine and are essential for translating genomic knowledge into actionable, patient-centered care.

药物基因组学研究遗传变异如何影响个体对药物治疗的反应，旨在通过个性化方法优化治疗结果。生物信息学在这一领域起着基础作用，使复杂的基因组和多组学数据集的处理、注释和解释成为可能。本文综述了药物基因组学中生物信息学的现状，包括关键数据库、变异分析工具和人工智能驱动的预测模型。它还讨论了多组学数据的集成，现实世界的临床应用，以及支持临床实施的监管和伦理框架。最后，强调了药物基因组学在药物发现和开发中的作用，说明了遗传见解如何有助于目标识别，试验设计和药物再利用。这些组成部分共同构成了精准医疗的计算支柱，对于将基因组知识转化为可操作的、以患者为中心的护理至关重要。

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