搜索结果：Yi chuan = Hereditas

Genome-wide association study (GWAS) has identified a large number of genetic variations that are significantly associated with human diseases and animal and plant economic traits. However, the majority of these variants are located in non-coding regions of the genome, which makes it challenging to accurately pinpoint functional variants of biological significance from a vast number of candidate loci. In the post-GWAS era, high-throughput analytical approaches, such as high-throughput reporter gene analysis, CRISPR/Cas9-based gene editing technologies, and epigenetic analyses, have become powerful tools for systematically uncovering functional variants in the genome. These methods not only enable efficient identification of functional variants but also help elucidate the mechanisms through which they regulate gene expression, thereby clarifying the molecular basis underlying trait formation or disease pathogenesis. In this review, we systematically summarize current high-throughput strategies for identifying functional genomic variants, highlight their applications and recent advances in major agricultural animal species, and outline future research directions, with the aim of providing a reference for subsequent studies in related fields. 全基因组关联分析(genome-wide association study，GWAS)已鉴定出大量与人类疾病和动植物经济性状显著关联的遗传变异。然而，由于多数变异位于基因组的非编码区域，使得从众多变异位点中准确识别具有生物学功能的变异仍面临巨大挑战。进入后GWAS时代，以高通量报告基因分析、CRISPR/Cas9基因编辑技术及表观遗传学分析为代表的高通量解析方法，已成为系统揭示基因组中功能变异的有力工具。这些方法不仅能够有效识别功能性变异，还可以揭示其调控基因表达的机制，从而阐明影响性状或疾病形成的分子基础。本文系统综述了当前用于基因组功能性变异的高通量鉴定方法，总结了其在主要农业动物中的应用进展，并对其未来研究前景进行展望，以期为后续相关领域研究提供参考。.

The transition from solitary ancestral cockroaches to wood-feeding cockroaches exhibiting biparental care and termites displaying sibling altruism is closely linked to their ecological specialization in feeding on nutrient-poor dead wood. However, the underlying genomic evolutionary mechanisms remain unclear. To investigate this issue, the research team led by Sheng Li from South China Normal University conducted a multi-omics comparative analysis of genomes and transcriptomes across eight Blattodea species. They found that genomes progressively contracted during the evolution from cockroaches to termites. In wood-feeding cockroaches, the downregulation of genes associated with oxidative phosphorylation and peroxisomes constrained the growth and development rates of their offspring, which aligns with the observed slow larval growth. Termites, on the other hand, lost key genes involved in sperm motility, providing genomic support for the hypothesis that their reproductive division of labor is based on monogamy. Furthermore, termites achieved caste differentiation by co-opting nutrition-sensitive core developmental signaling pathways, such as juvenile hormone, insulin, epidermal growth factor receptor, and decapentaplegic (Dpp). This mechanism enables workers to exhibit high energy metabolism early in development to meet labor demands, while reproductive nymphs highly express energy metabolism-related genes later in development to ensure reproductive functions. This study systematically reveals the homeostatic maintenance mechanisms of termites as "superorganisms" and elucidates, at the molecular level, the evolutionary basis of social caste differentiation and energy allocation strategies. 从独居的祖先蟑螂演化出具备双亲抚育行为的木食性蟑螂及具有同胞利他行为的白蚁，其社会性的转变与其取食营养贫乏的枯木这一生态特化密切相关，然而其背后的基因组演化机制尚不清楚。为探究这一科学问题，华南师范大学李胜团队通过对8个蜚蠊目(Blattodea)物种进行基因组与转录组等多组学分析，发现从蟑螂到白蚁的演化过程中，基因组呈现逐步收缩的趋势。木食性蟑螂由于氧化磷酸化及过氧化物酶体相关基因的表达下调，制约了其后代的生长发育速率，这与其幼虫生长缓慢相一致。白蚁则丢失了与精子运动相关的关键基因，从基因组层面支持了其生殖分工建立在单配制基础上的假说。此外，白蚁通过协同利用保幼激素、胰岛素、表皮生长因子受体及Dpp等营养敏感的核心发育信号通路，实现了品级分化，即工蚁在发育早期呈现高能量代谢以适应劳动需求，而生殖型若蚁则在发育后期高表达能量代谢相关基因以保障繁殖功能。该研究系统揭示了白蚁作为“超个体”社群的稳态维持机制，并从分子层面阐明了社会性等级分化与能量分配策略的演化基础。.

Intracerebral Hemorrhage (ICH) is a stroke subtype with high mortality, and its core pathological mechanism involves the disruption of cerebrovascular homeostasis. Genetic factors play a crucial role in ICH pathogenesis, underscoring the importance of identifying core regulatory factors and delineating the associated pathological network. Here, through genome-wide association study (GWAS), we identified synaptopodin (SYNPO) as a genetic susceptibility gene for ICH. SYNPO is an evolutionarily conserved actin-binding protein previously shown to be highly expressed in cerebrovascular endothelial cells, where it regulates the actin cytoskeleton to maintain endothelial junction stability. However, its functional role in ICH remains unclear. To investigate this, we conducted a synpo mutant zebrafish line using CRISPR/Cas9. Following epinephrine challenge, synpo mutant larvae displayed significantly elevated cerebrovascular leakage compared with wild-type controls, and adult mutants showed a markedly higher incidence of ICH. Transcriptomic profiling revealed significant downregulation of the key adhesion gene cdh2 in mutant brains. Subsequent rescue experiments confirmed that cdh2 mRNA supplementation effectively ameliorated the cerebrovascular leakage. In summary, our study unveils a pathway in which synpo maintains cerebrovascular homeostasis by positively regulating cdh2, demonstrating that the synpo-cdh2 axis serves as a key regulatory pathway in ICH. These findings provide insights into the genetic mechanisms underlying ICH and highlight potential therapeutic targets. 颅内出血(intracerebral hemorrhage，ICH)是一种高致死率的卒中类型，其核心病理机制涉及脑血管稳态受损。遗传因素在ICH疾病发生中占据重要地位，因此挖掘关键调控因子、完善ICH的病理机制网络尤为重要。本研究通过全基因组关联分析，筛选到与ICH显著相关的遗传易感基因——突触足蛋白(synaptopodin)编码基因SYNPO。既往研究表明，SYNPO作为一种进化保守的肌动蛋白结合蛋白，在脑血管内皮细胞中高表达，通过调控肌动蛋白骨架维持内皮细胞连接稳态。然而，其在ICH中的具体作用尚不明确。为此，本研究进一步利用CRISPR/Cas9技术构建了synpo突变体斑马鱼。在肾上腺素刺激下，synpo突变体幼鱼脑血管渗漏率和成鱼ICH发生率都显著高于野生型。转录组分析发现，synpo突变体脑内细胞黏附通路关键基因cdh2显著下调，回补cdh2 mRNA可有效挽救突变体幼鱼的脑血管渗漏。本研究揭示了synpo通过正向调控cdh2维持脑血管稳态，明确“synpo-cdh2”轴是ICH的关键调控通路，为解析ICH的遗传机制及发现潜在干预靶点提供新视角。.

In recent years, multiple panels containing varying numbers of single nucleotide polymorphisms (SNPs) have been reported in forensic genetics for kinship inference. However, systematic exploration of the impact of SNP number on inference performance and the application of machine learning algorithms remains lacking. Therefore, we evaluated the impact of SNP number on kinship inference performance and the optimization effects of machine learning methods on the identity-by-state (IBS) algorithm. We constructed multiple SNP panels with SNP numbers ranging from 15,476 to 20,838, and evaluated the performance of the likelihood ratio (LR) method and the IBS algorithm for kinship inference under different SNP numbers based on simulated pedigrees. After selecting the optimal SNP panel, we validated it using real pedigrees and further combined the IBS algorithm with machine learning methods to enhance inference performance. Our results showed that for the LR method, the sensitivity in inferring sixth and seventh degree kinships exhibited a significant positive correlation with SNP number. For the IBS algorithm, although the sensitivity in inferring fourth to seventh degree kinships showed a significant positive correlation with SNP number, the actual improvement was limited (only 0.5%~2.2% increase). Based on these results, we determined the optimal panel containing 20,838 SNPs (21K panel). The 21K panel based on the LR method could accurately infer kinships within sixth degree (with a sensitivity of 93.65% for sixth degree kinship inference), and the 21K panel based on the IBS algorithm could accurately infer kinships within third degree (with a sensitivity of 86.79% for third degree kinship inference). After combining the IBS algorithm with machine learning, the sensitivity for fourth degree kinship inference improved from 69.10% to 87.66%, the sensitivities for fifth and sixth degree kinships improved from 38.03% and 21.41% to 48.75% and 37.80%, respectively. 近年来，法医遗传领域报道了多个包含不同数量单核苷酸多态性(single nucleotide polymorphism，SNP)组合(panel)用于亲缘关系推断，但SNP位点数量对推断效能的影响及机器学习算法的应用缺乏系统探索。为此，本研究评估了SNP位点数量对亲缘关系推断效能的影响及机器学习方法对状态一致性(identity-by-state，IBS)算法的优化效果。首先，构建位点数量在15,476~20,838范围内的多个SNP panel，基于模拟家系评估似然比法和IBS算法在不同位点数量下的亲缘关系推断效能。在筛选出最优SNP panel后，利用真实家系进行验证，并进一步将IBS算法与机器学习方法结合以提升推断效能。结果显示，似然比法在六级和七级亲缘关系推断中的灵敏度与位点数量呈显著正相关。IBS算法四至七级亲缘关系推断的灵敏度虽然与位点数量呈显著正相关，但实际提升幅度有限(仅提升0.5%~2.2%)。基于上述结果，本研究确定了包含20,838个SNP位点的最优panel(21K panel)。21K panel基于似然比法可准确推断六级以内亲缘关系(六级亲缘关系推断灵敏度为93.65%)；基于IBS算法可准确推断三级以内亲缘关系(三级亲缘关系推断灵敏度为86.79%)。IBS算法结合机器学习后，四级亲缘关系推断灵敏度从69.10%提升至87.66%，五级和六级亲缘关系推断灵敏度分别从38.03%和21.41%提升至48.75%和37.80%。.

China's soybean supply is heavily dependent on international markets, making it an urgent task to enhance domestic self-sufficiency to ensure food security. Data from the national soil census indicate that China possesses approximately 500 million mu of saline-alkali soil resources, of which about 200 million mu have potential for agricultural development. Against the backdrop of tight arable land resources, developing new soybean varieties tolerant to saline-alkali conditions represents a strategic initiative to effectively utilize saline-alkali land, expand cultivation areas, and address the challenge of soil salinization. Rapid alkalinization factors (RALFs) are a class of plant small peptides that act as ligands, initiating downstream signaling by binding to plasma membrane receptor complexes, thereby coordinating plant growth, development, and stress responses. However, the specific molecular mechanisms by which RALF peptides mediate responses to saline-alkali stress in important crops such as soybean remain unclear. Through expression profiling analysis of the soybean RALF family, combined with transcriptome data under alkaline salt treatment, this study identified two homologs of Arabidopsis thaliana AtRALF34, designated GmRALF34a and GmRALF34b, which are predominantly expressed in roots and whose expression is significantly suppressed following alkaline salt treatment. Using gene editing technology, we generated Gmralf34ab double mutants, which exhibited enhanced sensitivity to alkaline salt stress. In contrast, no significant differences were observed between the mutant and wild type plants under neutral salt stress. Field phenotypic characterization further demonstrated that the mutants showed significant reductions in agronomic traits, including plant height, node number, and yield per plant. In conclusion, this study preliminarily reveals that GmRALF34s play an important role in soybean response to alkaline salt stress and adaptation to saline-alkaline environments, provides valuable genetic materials for further elucidating their molecular mechanisms and establishing a theoretical and material foundation for breeding salt-alkali tolerant soybean varieties. 我国的大豆(Glycine max)供给严重依赖国际市场，提升国内自给能力已成为保障粮食安全的紧迫任务。全国土壤普查数据显示，我国拥有约5亿亩盐渍土资源，其中约2亿亩具备农业开发潜力。在耕地资源紧张的背景下，培育耐盐碱大豆新品种，是实现盐碱地资源有效利用、扩大种植面积并应对土壤盐渍化挑战的战略性举措。快速碱化因子(rapid alkalinization factor，RALF)是一类作为配体的植物小肽，通过结合质膜受体复合物启动下游信号，协调植物生长发育与逆境响应。然而RALF小肽在大豆等重要作物中介导盐碱胁迫应答的具体分子机制尚不明确。本研究通过对大豆RALF家族进行表达模式分析，并结合碱性盐处理下的转录组数据，发现拟南芥(Arabidopsis thaliana)的AtRALF34在大豆中的两个同源基因GmRALF34a和GmRALF34b在根中优势表达，且其表达在碱性盐处理后受到显著抑制。利用基因编辑技术获得Gmralf34ab双突变体，该突变体表现为对碱性盐胁迫敏感性增强，相比之下，在中性盐胁迫下，突变体与野生型无显著差异。大田表型鉴定进一步表明，突变体在株高、节数和单株产量等农艺性状上均显著降低。综上，本研究初步揭示了GmRALF34s在大豆响应碱性盐胁迫及盐碱地适应性中扮演着重要角色，为深入解析其分子机制提供了重要遗传材料，并为大豆耐盐碱育种奠定了理论与材料基础。.

Ecdysone signaling is necessary for maintaining intestinal homeostasis in adult Drosophila melanogaster by promoting stem cell proliferation and differentiation. However, the role of its downstream target broad (br) in this process remains largely unclear. Here, this study demonstrates that br is required for the maintenance of intestinal stem cells (ISCs) and intestinal injury repair. Clonal analysis shows that br regulates both the proliferation and differentiation of ISCs. Knockdown of br severely impairs the differentiation of stem cells into enterocytes (ECs), whereas overexpression of br promotes ECs differentiation. Further analysis reveals that br knockdown reduces Jak/STAT signaling activity in ISCs. Moreover, upregulating the activity of Jak/STAT or EGFR signaling significantly rescues the br knockdown phenotype. These results suggest that br may regulate the proliferation and differentiation of ISCs through Jak/STAT and EGFR signaling in adult Drosophila. This study highlights the critical role of br in adult Drosophila ISCs and provides a preliminary exploration of its underlying mechanism. 蜕皮激素信号通路(ecdysone signaling)通过促进干细胞增殖与分化，在成年黑腹果蝇(Drosophila melanogaster)肠道稳态维持中具有重要作用。然而，其下游靶基因broad(br)在该过程中的功能尚不明确。本研究证明，br基因对肠道干细胞(intestinal stem cells，ISCs)的维持及肠道损伤修复过程不可或缺。克隆分析结果显示，br同时调控ISCs的增殖与分化。敲低br表达会严重阻碍干细胞向肠上皮细胞(enterocytes，ECs)的分化，而过表达br则会促进其分化。进一步分析发现，敲低br表达会导致ISCs中Jak/STAT信号通路活性降低，而上调Jak/STAT或EGFR信号通路的活性都可以显著挽救br敲低导致的表型。这些结果表明，在成年果蝇中，br可能通过Jak/STAT和EGFR信号通路调控ISCs的增殖与分化。本研究揭示了br基因在果蝇成虫ISCs中的作用，并初步探讨了其机制。.

Cyclic peptides have emerged as a promising therapeutic modality for targeting classically deemed "undruggable" protein that defy conventional small-molecule intervention. Their rigid conformations improve binding affinity, selectivity and proteolytic stability, bridging the gap between low-molecular-weight drugs and large biologics. Early discovery of cyclic peptide relied on natural product isolation. However, display technologies now enable the generation and screening of libraries containing up to 1015 unique sequences. Among these, mRNA display technology offers a uniquely powerful in vitro platform that covalently links genotype (mRNA) to phenotype (encoded peptide), facilitating the ultrahigh-throughput interrogation of trillions of variants in a single selection cycle. Recent clinical translation of de novo mRNA display-derived cyclic peptides signals the approach's maturation. In this review, we systematically evaluate mRNA display technology by outlining its methodological framework and highlighting its unique advantages for engineering macrocyclic therapeutics. We critically examine its transformative potential as well as its inherent limitations in identifying bioactive cyclic peptides, with particular attention to library diversity and the precision of on-resin screening. Through this analysis, we aim to provide insightful perspectives and strategic recommendations to guide future efforts in exploiting mRNA display for the development of innovative cyclic peptide-based drugs. 环肽作为突破传统药物开发“难以成药”靶点的重要分子形式，凭借其独特的构象约束特性，成功弥补了小分子药物与生物制剂的治疗间隙。尽管早期环肽的发现依赖于天然产物的挖掘，但是展示技术的出现将库容量提升至1015，加速了全新环肽药物的研发。mRNA展示技术作为一种基因型(mRNA)与表型(蛋白质)融合的体外多肽/蛋白质筛选技术，可在一次实验中筛选数万亿蛋白质变体以实现所需功能。近年来，随着利用mRNA展示技术筛选出的多肽药物进入临床研发阶段，从头开始的环肽药物发现领域逐渐走向成熟。本文对mRNA展示技术的原理、特点以及其在环肽药物研发过程中的应用展开综述，以期为推动基于mRNA展示技术的原创性环肽药物发现提供新的思路和策略借鉴。.

The Vrtn gene, a recently identified regulator of embryonic development and stem cell pluripotency, is essential for embryonic survival, as its homozygous knockout (Vrtn-/-) leads to lethality in mice at approximately embryonic day 12.5 (E12.5). To elucidate the underlying lethal mechanism, an integrated approach combining morphological observation, multi-stage transcriptomic analysis, and functional validation experiments was employed to systematically investigate the developmental disorders caused by Vrtn deficiency. Morphological observation showed that Vrtn-/- embryos exhibited significant abnormalities at developmental stages E9.0, E9.5, E10.0, E10.5, and E11.0, including shortened body axis, defective neural tube closure, aberrant somite differentiation, and cardiovascular malformations, accompanied by overall developmental delay. At the molecular level, through RNA sequencing and qRT-PCR validation revealed that Vrtn deficiency not only suppressed the expression of genes critical for somitogenesis (Hoxa2, Hes5), neurodevelopment (Nefm, Nefl), and the hematopoietic system (Hbb-bh1, Klf1), but also aberrantly activated genes associated with apoptosis (Crabp2, Fam162a) and lipid metabolism (Apom, Apoe). TUNEL staining showed that the level of apoptosis was significantly increased in Vrtn-/- embryos. Meanwhile, immunofluorescence detection of Hif-1α indicated that the hypoxic stress response was aberrantly activated. Furthermore, the widespread dysregulation of genes involved in thyroid hormone transport (Ttr), DNA damage stress (Ddit4), and lipid metabolism (Apoa4, Apoa1) collectively exacerbated the developmental imbalance, ultimately leading to embryonic death. A cross-species analysis demonstrated that VRTN knockdown in human embryonic stem cells (hESCs) significantly suppressed the expression of core angiogenic genes (VEGFA, COL1A1 and HES1), a finding consistent with public database analyses indicating a strong association between VRTN and the hypoxic response. In conclusion, this study elucidates that Vrtn functions as a regulatory gene that maintains embryonic homeostasis by orchestrating multiple key developmental processes, including somitogenesis, neural differentiation, angiogenesis, and the hypoxic stress response. This discovery not only deepens the understanding of the role of Vrtn in embryonic development but also provides a new perspective for deciphering the pathogenesis of related hereditary diseases. Vrtn基因是新近发现的与胚胎发育和干细胞多能性相关的基因，其纯合敲除(Vrtn-/-)导致小鼠在胚胎期E12.5左右死亡。为阐明其致死机制，本研究整合形态学观察、多阶段转录组学分析及功能验证实验，揭示了由于Vrtn缺失引发的小鼠胚胎发育紊乱。形态学观察显示，Vrtn-/-胚胎在E9.0、E9.5、E10.0、E10.5和E11.0发育期均呈现显著异常，表现为体轴缩短、神经管闭合缺陷、体节分化异常及心血管发育畸形，并伴随胚胎整体发育迟缓。通过转录组测序并结合qRT-PCR验证发现，Vrtn缺失一方面下调了与体节形成(Hoxa2、Hes5)、神经发育(Nefm、Nefl)及造血系统(Hbb-bh1、Klf1)相关基因表达；另一方面异常激活了细胞凋亡通路(Crabp2、Fam162a)和脂质代谢(Apom、Apoe)相关基因。TUNEL染色显示，Vrtn-/-胚胎内细胞凋亡水平显著升高，同时Hif-1α免疫荧光检测表明缺氧应激反应被异常激活。甲状腺激素转运(Ttr)、DNA损伤应激(Ddit4)及脂质代谢(Apoa4、Apoa1)相关基因的广泛异常表达共同加剧了胚胎发育失衡，最终导致胚胎死亡。跨物种分析发现，在人类胚胎干细胞中敲降VRTN显著抑制血管生成核心基因(VEGFA、COL1A1和HES1)的表达，该结果与公共数据库中VRTN与缺氧响应的强关联性一致。综上所述，本研究阐明了Vrtn作为胚胎发育的调控基因，通过协调体节发生、神经分化、血管生成及缺氧应激响应等多个发育进程来维持胚胎稳态。这一发现不仅加深了对Vrtn基因在胚胎发育中作用机制的认识，也为解析相关遗传性疾病的发病机制提供了新视角。.

Examining a greater number of short tandem repeats (STRs) is essential for cases involving mutations, consanguinity, and complex kinship testing. However, previous population studies were mostly limited to fewer than 40 STRs. Therefore, this study investigated the genetic polymorphism, linkage disequilibrium, and mutation rates of 81 autosomal STR loci in the Han Chinese population of northern China. We confirmed the core repeat structure of STR loci, and focused on evaluating the forensic application value of the Category C and 21 additional STR loci not included in the standard "Forensic science-Data structures of selected loci from the DNA database" (GB/T 41009-2021). Blood samples from 400 unrelated healthy Northern Han Chinese individuals and parent-child blood samples from 157 families were detected using GSTAR TM25, GSTAR TM31FS, and GSTAR TM29HS kits. Genetic analysis was performed on genotyping data of 81 autosomal STR loci. The core sequence structures of newly added 15 STR loci were confirmed by sequencing the allelic ladder. After applying Bonferroni correction, all 81 autosomal STR loci conformed to Hardy-Weinberg equilibrium. The observed heterozygosity ranged from 0.4375 to 0.9075, discrimination power from 0.6332 to 0.9845 (lowest at LPL), polymorphism information content from 0.3938 to 0.9092, probability of exclusion for trios from 0.1384 to 0.8108, and for duos from 0.0955 to 0.7069. Significantly, linkage disequilibrium was observed between D5S2500 and D5S2800 loci. When excluding the D5S2800 locus, the cumulative discrimination power (CDP) of remaining 80 autosomal STR loci was 1-2.293×10-89, cumulative probability of exclusion (CPE) of trios was 1-5.074×10-31, and cumulative exclusion probability of duos was 1-1.400×10-19. A total of 13 mutations were observed across 508 meiotic events in 157 families at 10 STR loci. The mutation rates for D5S818, D11S2368 and D18S51 were 0.004, while those of D6S1043, D7S1517, D11S4463, D13S325, D14S1434, D20S482 and D20S85 were 0.002. In conclusion, the 81 genetic loci, including Category C and newly added STRs, exhibit good or moderate polymorphism and are suitable for individual identification, paternity testing, and kinship identification. Given the linkage disequilibrium between the D5S2500 and D5S2800, if simultaneous on the capillary electrophoresis platform, it is recommended to use only the test results from the D5S2500 locus for statistical analysis. This data generated provide allele frequency and mutation rate for a large number of STRs, along with the clarified core sequences, thus offering an important data foundation for DNA evidence evaluation. 在涉及突变、近亲和亲缘关系鉴定中，需要检验更多的短串联重复序列(short tandem repeat, STR)。然而既往群体研究几乎限于40个以内STR，为此本研究调查了81个常染色体STR基因座在中国北方汉族人群中的遗传多态性、连锁不平衡和突变率情况，确认了STR基因座的核心重复结构，并重点评价了《法庭科学 DNA数据库选用的基因座及其数据结构》(GB/T 41009-2021)中C类和该标准外新增21个STR基因座法医学应用价值。首先，采集400份中国北方汉族健康无关个体血样以及157个家系中父母与孩子血样，利用GSTAR TM25以及新研制的GSTAR TM31FS和GSTAR TM29HS试剂盒进行检测，对81个常染色体STR基因座分型数据进行遗传学分析。本研究对新增的15个STR基因座经测序明确核心序列结构。结果显示，81个常染色体STR基因座经Bonferroni校正之后均符合Hardy-Weinberg平衡，杂合度观测值在0.4375~0.9075之间，个体识别率在0.6332~0.9845之间(LPL基因座最低)，多态性信息含量在0.3938~0.9092之间，三联体非父排除率在0.1384~0.8108之间，二联体非父排除率在0.0955~0.7069之间，D5S2500与D5S2800基因座之间存在连锁不平衡，在不统计D5S2800基因座情形下，80个常染色体STR基因座的累积个体识别率为1-2.293×10-89，三联体累积非父排除率为1-5.074×10-31，二联体累积非父排除率为1-1.400×10-19。观察157个家系中508次减数分裂，在10个STR基因座上有13次突变，D5S818、D11S2368和D18S51基因座突变率为0.004，D6S1043、D7S1517、D11S4463、D13S325、D14S1434、D20S482和D20S85基因座突变率为0.002。结果表明，本研究使用的81个STR基因座多态性为良好或中等，适用于个体识别、亲子鉴定和亲缘关系鉴定。鉴于D5S2500与D5S2800基因座之间存在连锁不平衡，在毛细管电泳平台同时检验时建议仅用D5S2500基因座的检验结果进行统计学分析。本研究提供了大数量STR的等位基因频率数据、突变率，且明确了STR的核心序列，为DNA证据力评估提供重要的数据基础。.

Single nucleotide variants (SNVs) are among the primary pathogenic factors of human genetic diseases, accounting for a significant proportion of all mutation types. Conducting in-depth research on the pathogenic significance of these mutations in animal models is essential for understanding disease mechanisms and developing therapeutic strategies. The progress of such research largely depends on the continuous innovation and advancement of gene editing technologies. In recent years, base editing technology based on the CRISPR/Cas9 system has emerged, enabling precise conversion of individual nucleotides. Owing to its efficiency and convenience, base editing has been widely applied in gene therapy, the construction of animal models, and molecular breeding, bringing new breakthroughs and opportunities to life sciences and medical research. Zebrafish, with their advantages of small size, high fecundity, transparent embryos, and external development, have become an ideal model organism for studying disease mechanisms and drug screening. In this review, we summarize the development of CRISPR/Cas9-based base editing technologies, highlight the emergence of novel editing tools, and explore the application and progress of base editing in constructing precise zebrafish disease models. 单核苷酸变异是人类遗传疾病的主要致病因素之一，在所有致病突变类型中占据显著比例。在动物模型中深入研究这类突变的致病意义对于理解疾病机制和开发治疗方法至关重要。而此类研究的进展在很大程度上依赖于基因编辑技术的不断创新与发展。近年来，基于CRISPR/Cas9系统的碱基编辑技术应运而生，它能够精确实现单个碱基的特异性转换。凭借其高效性和便捷性，碱基编辑技术已被广泛应用于基因治疗、动物模型构建以及分子育种等多个领域，为生命科学研究和医学应用带来了新的突破和机遇。另一方面，斑马鱼(Danio rerio)凭借其体型小、产卵多、胚胎透明、体外发育等优势，在疾病机制和药物筛选研究中作为一种理想的模式生物发挥着重要作用。本文系统综述了基于CRISPR/Cas9的碱基编辑技术的发展历程，介绍了新型编辑工具的开发，并深入探讨了碱基编辑技术在构建斑马鱼精准模型中的应用与发展。.

Ancient DNA technology directly retrieves genetic information from preserved biological materials, thereby offering significant advantages for elucidating species origins and evolution. In recent years, ancient DNA studies have yielded significant advances in our understanding of human evolution and the origins and dispersal of animals. With the rapid development of ancient DNA extraction, library construction, and sequencing techniques, ancient DNA technology is increasingly contributing to plant research and is gradually developing into a standardized and systematic research area. These studies have not only deepened our understanding of the origins, dispersal routes, and evolutionary history of crop domestication, but have also provided novel perspectives for interpreting the interactive evolution among humans, plants, and the environment. In this review, we introduce the workflow of ancient plant DNA research and review the progress of ancient plant DNA technology in the fields of crop domestication, plant diseases, environmental reconstruction, and utilization of plant resources to provide a reference for the in-depth development of this field. 古DNA技术能够直接获取古代生物的遗传信息，在解析物种起源与演化方面具有独特优势。近年来，古DNA研究在人类演化及动物起源、扩散等领域取得了诸多突破性进展。随着古DNA提取、建库及测序技术的不断革新，该技术也被引入植物研究领域，并逐渐形成规范化、体系化的研究方法与技术流程。相关研究深化了作物驯化起源、传播路径及演化历史的认知，也为解析“人类−植物−环境”间的相互作用及协同演变机制提供了全新视角。本文介绍了植物古DNA研究的基本技术流程，综述了该技术在作物驯化、植物病理、环境重建及植物资源利用等方面的研究进展，以期为相关领域的深入研究提供参考。.

N4-acetylcytidine (ac4C) is an emerging RNA epigenetic modification that has attracted considerable attention in the field of epitranscriptomics in recent years. This modification is widely present in tRNA, rRNA, mRNA, and various non-coding RNAs. By precisely regulating RNA stability and translational efficiency, ac4C modulates the expression network of downstream genes, thereby playing a critical role in cellular function. In this review, we summarize recent advances in the distribution patterns, biological functions, and regulatory mechanisms of ac4C, highlight the associated writer enzymes, detection methodologies, and the involvement of ac4C in animal reproductive development. We aim to provide a solid theoretical foundation and valuable research insights for future investigations into the regulatory mechanisms of ac4C modification in animal and human reproduction. N4-乙酰胞苷(N4-acetylcytidine，ac4C)是一类新兴的RNA表观修饰，近年来在表观转录组学研究中被广泛关注。该修饰广泛存在于tRNA、rRNA、mRNA及非编码RNA中，通过精准调控RNA的稳定性与翻译效率，影响下游基因的表达网络，进而对细胞功能产生重要影响。本文综述了ac4C修饰的分布特征、生物学功能及复杂调控机制的最新研究进展，详细介绍了其编码器、检测方法以及在动物生殖发育中的作用，旨在为深入探讨ac4C修饰在动物繁殖与人类生殖等领域的调控机制提供坚实的理论基础与研究思路。.

Body size traits serve as crucial phenotypic indicators of body conformation and growth, showing a close correlation with production performance. To elucidate the genetic basis of these traits and identify potential molecular markers in Saanen dairy goats, we analyzed low-coverage whole-genome sequencing (lcWGS) data from 635 individuals. Following genotype imputation based on an in-house goat reference panel, we obtained 14 million single-nucleotide polymorphisms (SNPs) and 45 thousand structural variants (SVs). Genetic parameters were estimated using SNP data. Subsequently, single-trait (ST) and multi-trait genome-wide association studies (MT-GWAS) were conducted using both SNP and SV datasets. Results indicated that body height, body length, and rump height possess moderate heritability, with positive genetic and phenotypic correlations observed among these traits. ST-GWAS identified 56 significant SNPs and 3 significant SVs, mapping to 30 candidate genes, including TNFSF11, HDAC4, and MURC. Furthermore, MT-GWAS detected 2 significant SNPs and 2 significant SVs missed by ST-GWAS, identifying 4 additional candidate genes (S100A11, LOC108635595, GALNTL6, and FSIP2). Notably, overlapping association signals for body length and rump height were observed near NRXN3 on chromosome 10, with colocalization analysis supporting the existence of a shared causal variant in this region. KEGG enrichment analysis indicated that candidate genes were primarily enriched in fatty acid biosynthesis and related metabolic pathways. In conclusion, this study shows that integrating structural variants into MT-GWAS can reveal association signals beyond those captured by SNPs, providing a theoretical basis for marker-assisted selection and precision breeding for body conformation. 体尺性状作为衡量体型与生长水平的重要表型特征，与生产性能密切相关。为揭示萨能奶山羊体尺性状的遗传基础并发掘潜在分子标记，本研究基于635只萨能奶山羊的低深度全基因组测序数据，依托本课题组构建的山羊参考面板进行基因型填充后，共获得14M的单核苷酸多态位点(single nucleotide polymorphism，SNP)和45K的结构变异(structural variant，SV)。本研究利用SNP估计遗传参数，分别对SNP与SV开展单性状(single-trait，ST)和多性状全基因组关联分析(multi-trait genome-wide association study，MT-GWAS)。结果显示，体高、体长和十字部高3个性状均为中等遗传力，性状间的遗传与表型均为正相关。ST-GWAS共鉴定出56个显著SNP位点和3个显著SV位点，注释到TNFSF11、HDAC4、MURC等30个候选基因；MT-GWAS检测出ST-GWAS未发现的2个显著SNP位点和2个显著SV位点，注释后新增4个候选基因(S100A11、LOC108635595、GALNTL6和FSIP2)。值得注意的是，在第10号染色体的NRXN3附近发现了体长与十字部高的重叠关联信号，共定位分析支持该区域存在共享因果变异。KEGG富集分析显示候选基因主要富集于脂肪酸生物合成及相关代谢通路。本研究表明，整合SV的MT-GWAS可提供SNP之外的关联信号，为开展分子标记辅助选择与体型精准选育提供了理论基础。.

Accurate identification of transcription factor binding sites (TFBSs) at single-nucleotide resolution remains a central challenge in deciphering gene expression regulatory networks. To improve the performance of existing computational models for predicting TFBSs across different cell types, we presented a deep learning model integrating channel and spatial attention mechanisms. In this study, we trained and tested the model using a comprehensive dataset that included ChIP-seq data from 51 groups, involving 10 core transcription factors (e.g., CTCF, EGR1, FOXA1) across 13 human cell lines (e.g., A549, GM12878, H1-hESC), and DNase-seq data from 13 datasets. The results demonstrated that this model exhibited superior performance across 23 TF-cell type combinations, achieving a mean area under the receiver operating characteristic curve (AUROC) of 0.986, with 91% of samples yielding an AUROC above 0.970. Additionally, the mean area under the precision-recall curve (AUPRC) reached 0.169, over 1,000-fold higher than the random baseline 0.000156. When compared to state-of-the-art models in the field, such as FactorNet, Leopard, and DeepGRN, our model outperformed them in terms of AUROC on nine shared TF-cell type datasets. Visualization analyses further confirmed that our model enabled accurate identification of cell-type-specific TFBSs. This study provides an efficient computational framework for precise cross-cell-type TFBS prediction, thereby facilitating in-depth investigations into gene expression regulatory mechanisms and the molecular pathogenesis of related diseases. 精准识别单核苷酸分辨率下的转录因子结合位点(transcription factor binding sites, TFBSs)是解析基因表达调控网络的核心科学问题。为改进现有计算模型在跨细胞类型预测中的性能，本研究提出一种融合通道与空间注意力机制的深度学习模型。通过系统整合10个核心转录调控因子(包括CTCF、EGR1、FOXA1等)在13种典型人类细胞系(涵盖A549、GM12878、H1-hESC等)的51组染色质免疫沉淀测序(chromatin immunoprecipitation sequencing, ChIP-seq)数据和13组脱氧核糖核酸酶I高敏感位点测序(deoxyribonuclease I hypersensitive site sequencing, DNase-seq)数据对模型进行训练与测试，结果表明在23个测试的TF-细胞类型中表现出优异性能，平均受试者工作特征曲线下面积(area under receiver operating characteristic curve, AUROC)达到0.986，其中91%样本的AUROC超过0.970；平均精确率-召回率曲线下面积(area under precision recall curve, AUPRC)为0.169，较随机预测基线(0.000156)提升超1,000倍。相较于FactorNet、Leopard及DeepGRN等当前领域内具有代表性的模型，本模型在9个共有的TF-细胞类型数据集上，其AUROC均值展现出优势。可视化分析表明，模型能精准识别TF在不同细胞类型中的特异性结合位点。上述结果表明，本模型为跨细胞类型的TFBSs精准预测提供了高效计算工具，有望为基因表达调控机制的深入解析及相关疾病分子机理研究提供重要支撑。.

Sarcopenia is an age-related degenerative disease characterized by progressive loss of skeletal muscle mass and function, resulting severe clinical outcomes such as falls, disability, and increased all-cause mortality, thereby significantly reducing the quality of life in elderly population. With China's rapid demographic aging, sarcopenia is emerging as a critical public health challenge. In this review, we elaborate the pathogenesis of sarcopenia, identifying metabolic imbalance and cellular oxidative stress as major contributing factors to muscle degeneration. Also, this article indicates that life-style, physiological condition and genetic factors jointly influence the population susceptibility and progression of sarcopenia. On one hand, this article lists the non-genetic factors that accelerate the progression of sarcopenia; and on the other hand, it elaborates the role of multiple genes in maintaining muscle function, and the risk associations between genetic mutations and sarcopenia which has been revealed in studies from population cohort and animal models. Moreover, this article summarizes how epigenetic factors regulate muscle metabolism and aging, and comprehensively discusses the intervention effects and clinical limitations of treatment, nutritional support, and exercise therapy. We hope this review can provide a theoretical framework to advance both fundamental research and clinical strategies for sarcopenia prevention and management. 肌肉减少症(sarcopenia)简称“肌少症”，是以骨骼肌质量与功能进行性丧失为特征的年龄相关性退行性疾病，可引发跌倒、失能及全因死亡率递增等严重临床结局，显著降低老年群体生存质量。随着我国步入老龄化社会，肌少症将逐渐成为多数人群面临的健康威胁。本文系统归纳了导致肌少症的发病机制，指出代谢失衡和细胞氧化应激是肌肉功能退化的重要诱因，通过分析生活方式、生理特征和遗传因素的协同作用，阐释了人群易感性和疾病进展的病因学基础；重点总结了多个基因在维持肌肉功能中的作用，结合人群队列和动物模型研究阐明相关基因突变与肌少症的风险联系，同时揭示表观遗传因素对肌肉代谢和衰老的调控机制；最后，综合探讨了药物治疗、营养支持及运动疗法的干预效果与临床转化瓶颈。本文旨在为肌少症的基础研究和临床防控优化提供重要的理论支持。.

Given the inherent complexity, hierarchical organization, and dynamic nature of living systems, there is no single best strategy for investigation, and priorities shift with the evolution of the life sciences. In the 1990s, two classic stories, The Salvation of Doug and The Demise of Bill, used automobiles as analogies and satire to contrast two research strategies: dismantling components to uncover underlying mechanisms, or applying functional perturbations to identify critical elements. These heuristic parables stimulated broad discussion on the respective strengths and limitations of different research approaches and continue to be widely used in teaching today. The life sciences have since entered an era integrating high-throughput, high-resolution, and multidimensional approaches, where single-path strategies can no longer provide deep, systematic insights into complex biological processes. We view the intrinsic features of living systems, such as modular organization, regulatory networks, nonlinear responses, and adaptive compensation, as factors that make any single approach likely to capture only local, static aspects, thereby hindering the reconstruction of systems-level, dynamic properties. Against this backdrop, we present a modern continuation of the two parables, reimagined in a contemporary setting and featuring two protagonists with symbolic Chinese names, "Zhiwei" (meaning "decoding hidden mechanisms") and "Sixu" ("reasoning through order"), who personify biochemical and genetic mindsets. In our narrative, the two protagonists transition from working independently to collaborating, integrating high-throughput experimentation, systems-level analysis, and computational modeling to uncover structural and operational principles underlying complex systems. We believe this retelling reflects the growing emphasis on systems-level and dynamic perspectives in biology, highlighting the value of methodological integration and innovation. We hope it will serve as a valuable resource for teaching in genetics and related disciplines, while fostering reflection on the enduring relevance of genetic reasoning in contemporary research. 面对生命这一结构复杂、层级丰富、动态性强的系统，应当如何选择并采用更为有效的方法开展研究?这一问题的答案与重点在生命科学的不同发展阶段也不尽相同。20世纪90年代两则经典故事：《道格的救赎》(The Salvation of Doug)与《比尔的消亡》(The Demise of Bill)，曾以汽车为类比对象，用讽刺笔法生动呈现了遗传学家与生物化学家理解汽车运行机制所采用的不同研究策略：是通过拆解组分、解析互作来揭示潜在机制，还是借助功能扰动来识别系统的关键环节?哪种方法能更有效解析生命过程?作为启发式寓言，它们在当时引发了关于不同研究方法优劣与互补性的广泛讨论。时至今日，这两则故事仍是教学中的重要素材。当前，生命科学进入高通量、高精度、多维度融合的新阶段，传统的单一路径研究策略已难以支撑对复杂生命过程深入而系统地理解。生命活动具有模块化结构、调控网络、非线性响应以及适应性补偿等诸多特性，而单一策略往往仅能捕捉其局部、静态特征，难以还原整体的动态特征和调控规律，从而限制了对复杂生命过程的系统认知，也制约了理论深化与应用突破。基于此，本文尝试对上述两个经典故事进行了续写，将其延伸至更具时代特征的场景中，并赋予了主角具有象征意义的中文名字：“知微”(代表生化路径)和“思序”(象征遗传思路)。通过讲述他们在探索智能电动汽车系统的运行原理过程中，如何从各自为营的局面逐渐走向协作与共赢，运用高通量手段，开展系统性分析，并引入数字仿真建模，逐步揭示复杂系统行为背后的结构特性与运行逻辑。故事呼应当前生命科学对系统性与动态性研究的日益重视及其所面临的挑战，强调方法融合与创新的关键作用，鼓励读者思考遗传学方法在当代研究范式中的定位与价值，旨在为遗传学及相关学科的教学提供参考。.

Duck plague virus (DPV), a member of the alpha-herpesvirus, causes duck plague (DP), thereby posing a serious threat to the waterfowl industry. The DPV UL54-encoded protein shuttles between the nucleus and cytoplasm to modulate viral replication. However, the role of the UL54 protein in the evolutionary process remains unknown. This study is conducted from an evolutionary perspective to explore the nuclear-cytoplasmic shuttling characteristic of UL54 protein. First, we analyzed the co-evolution on DPV whole genome and its UL54 gene using molecular evolutionary methods. Next, we constructed phylogenetic trees based on UL54 nucleotide sequences and the corresponding amino-acid sequences from different alpha-herpesvirus stains. Based on these phylogenetic trees, we selected strains that are genetically close to DPV, and performed UL54 gene sequence alignment between DPV and those phylogenetically related strains. Then, we discovered there were specific mutation sites in UL54 gene of DPV. Finally, we constructed recombinant plasmids with genetic mutations to detect the influence of mutation sites on the nuclear-cytoplasmic shuttling property of the UL54-encoded proteins. The results showed that DPV exhibited dual modes comprising co-evolution with its natural hosts and cross-species transmission, meanwhile UL54 genes from different viral strains exhibited marked evolutionary divergence. Further investigation revealed there were three specific mutation sites (Lys269, Leu348 and Leu377) in UL54 amino acid sites, which were correlated with evolution of DPV. Mutation at these sites significantly impacted the nuclear-cytoplasmic shuttling property of the UL54-encoded protein. Our study provides a rationale for understanding the evolutionary mechanism of DPV and exploring new therapeutic strategy. 鸭瘟病毒(duck plague virus，DPV)是α-疱疹病毒的重要成员，可引发鸭瘟(duck plague，DP)，严重威胁水禽业。DPV UL54基因编码蛋白具有核质穿梭特性，影响病毒复制过程，但是其在进化过程中的作用尚不明确。本研究从进化角度出发，探究DPV UL54基因编码蛋白的核质穿梭特性。首先采用分子进化学方法对DPV全基因组及UL54基因进行共进化分析；接着，构建来自不同病毒源头的UL54基因的核苷酸和氨基酸系统进化树；然后，选取与DPV距离较近的病毒毒株和DPV进行UL54基因序列比对，发现DPV UL54基因具有特异性的突变位点；最后，构建UL54基因突变重组质粒，检测这些突变位点对其编码蛋白核质穿梭特性的影响。研究结果显示，在进化过程中DPV展现出与宿主共同进化以及跨越宿主传播的双重模式，同时源自不同病毒毒株的UL54基因呈现出显著的进化差异。进一步研究发现，UL54的氨基酸位点中具有与DPV进化关联的特定突变位点，即269位的赖氨酸(Lys)、348位的亮氨酸(Leu)和377位的亮氨酸(Leu)，这些位点的变异对UL54基因编码蛋白的核质穿梭特性具有显著影响。本研究结果为理解DPV的进化机制和开发新的治疗策略提供了重要理论依据。.

Caenorhabditis elegans (C. elegans), a classical model organism in the field of life sciences, possesses advantages including easy cultivation, a short life cycle, and a well-defined genetic background. It has been widely used in studies of developmental regulation, aging, genetics, and stress responses. To improve undergraduates' research literacy and experimental competence, we designed an experimental teaching system centered on C. elegans, which integrates both scientific and practical feasibility guided by the principles of "progressive learning" and inquiry-based teaching. Our system consists of four experimental modules: morphological observation, behavioral analysis, microscopic structure identification, and intestinal barrier assessment. Advanced techniques such as microscopic imaging and quantitative behavioral analysis are incorporated into the teaching process to cultivate students' experimental skills and scientific communication abilities. Teaching practice has demonstrated that our approach offers multiple advantages, including a short experimental cycle, low cost, high safety, and clear, intuitive results, which effectively stimulate students' interest in scientific research and foster the development of scientific thinking. This study provides valuable insights for teaching reform in undergraduate life science courses and for the broader application of genetic model organisms. 秀丽线虫(Caenorhabditis elegans)是生命科学领域的经典模式生物，具有易培养、生命周期短和遗传背景清晰等优势，已被广泛应用于发育调控、衰老、遗传及应激反应等研究中。本文基于递进式学习理念与探究式教学思路，以遗传学模式生物秀丽线虫为教学材料，针对衰老这一复杂的生理过程设计了包含形态观察、游泳行为分析、显微结构识别和肠屏障检测4个模块的实验教学体系。教学过程中融入显微成像、行为学定量分析等技术，培养学生的实验技能、逻辑推理与科学表达能力。教学实践结果表明，该实验教学方案具有周期短、成本低、安全性高和实验结果清晰直观等教学优势，能有效激发学生的科研兴趣，为生命科学本科教学改革与遗传学模式生物的教学应用提供参考。.

The medicinal preparation of Chilobrachys jingzhao possesses various therapeutic properties, including anti-inflammatory, detoxifying, analgesic, and anti-edema effects. However, research on its genetic background and toxin mechanisms is held back by the lack of chromosome karyotype and genome data. In this study, we analyzed the karyotype of C. jingzhao using chromosome preparation techniques, estimated the genome size using flow cytometry and K-mer analysis, and performed genome sequencing and assembly using second- and third-generation single molecule real-time sequencing technologies. The results showed that C. jingzhao has a diploid chromosome number of 2n=68, with a karyotype formula of 2n=46m+18sm+4st and a chromosomal complement of 2n=10L+18M2+38M1+2S. Using Solanum lycopersicum and Trichonephila clavata as references, flow cytometry estimates the genome size at 7,775.49 Mb and 7,680.26 Mb, respectively. The 19-mer analysis also estimated the genome size to be 7,626.00 Mb, consistent with the flow cytometry results. Further analysis indicated that the genome of C. jingzhao has a high level of heterozygosity (8.45%) and a high proportion of repetitive sequences (67.10%), classifying it as an ultra-high heterozygous and high-repeat genome. The initial genome assembly of C. jingzhao was 8,804.93 Mb in size, with a contig N50 of 55.55 Mb and a BUSCO completeness score of 95.9%, indicating high assembly quality. This study first reveals the karyotype and genome information of C. jingzhao, offering crucial data for future research on its whole genome, toxin mechanisms, genetics, origin, evolution, and taxonomy. 敬钊缨毛蛛(Chilobrachys jingzhao)制成的药物具有消肿、解毒、镇痛和抗炎等功效，但其染色体核型与基因组数据的匮乏，制约了其遗传背景解析及毒素分子机制的研究。为了明确敬钊缨毛蛛染色体核型特征和基因组基本信息，本研究采用染色体制片技术分析敬钊缨毛蛛的染色体核型，结合流式细胞术和K-mer分析估算基因组大小，并通过二代和三代单分子实时测序技术进行基因组测序和初步组装。结果表明，敬钊缨毛蛛的染色体数目为2n=68，核型公式为2n=46m+18sm+4st，染色体组式为2n=10L+18M2+38M1+2S。采用流式细胞仪，以番茄(Solanum lycopersicum)和棒络新妇(Trichonephila clavata)为内参，估测敬钊缨毛蛛基因组大小分别为7,775.49 Mb和7,680.26 Mb。19-mer分析结果显示，其基因组大小为7,626.00 Mb，与流式细胞术的测量结果相近。敬钊缨毛蛛基因组具有较高的杂合度(8.45%)和重复序列比例(67.10%)，属于超高杂合高重复基因组。初步组装的敬钊缨毛蛛基因组大小为8,804.93 Mb，contig N50达到55.55 Mb，BUSCO完整性评分为95.9%，组装质量较高。本研究首次揭示了敬钊缨毛蛛的染色体核型特征及其基因组信息，为未来深入研究其毒素分子机制、遗传学背景、起源、进化和分类学提供了重要的数据支持。.