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Integrating mRNA transcripts and genomic information into genomic prediction. 将 mRNA 转录本和基因组信息整合到基因组预测中。
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-096
Yu-Long Hu, Fang Yang, Yan-Tong Chen, Shuo-Kai Shen, Yu-Bo Yan, Yue-Bo Zhang, Xiao-Lin Wu, Jia-Ming Wang, Jun He, Ning Gao

Genomic prediction has emerged as a pivotal technology for the genetic evaluation of livestock, crops, and for predicting human disease risks. However, classical genomic prediction methods face challenges in incorporating biological prior information such as the genetic regulation mechanisms of traits. This study introduces a novel approach that integrates mRNA transcript information to predict complex trait phenotypes. To evaluate the accuracy of the new method, we utilized a Drosophila population that is widely employed in quantitative genetics researches globally. Results indicate that integrating mRNA transcript data can significantly enhance the genomic prediction accuracy for certain traits, though it does not improve phenotype prediction accuracy for all traits. Compared with GBLUP, the prediction accuracy for olfactory response to dCarvone in male Drosophila increased from 0.256 to 0.274. Similarly, the accuracy for cafe in male Drosophila rose from 0.355 to 0.401. The prediction accuracy for survival_paraquat in male Drosophila is improved from 0.101 to 0.138. In female Drosophila, the accuracy of olfactory response to 1hexanol increased from 0.147 to 0.210. In conclusion, integrating mRNA transcripts can substantially improve genomic prediction accuracy of certain traits by up to 43%, with range of 7% to 43%. Furthermore, for some traits, considering interaction effects along with mRNA transcript integration can lead to even higher prediction accuracy.

基因组预测已成为牲畜、农作物遗传评估和人类疾病风险预测的关键技术。然而,传统的基因组预测方法在整合生物先验信息(如性状的遗传调控机制)方面面临挑战。本研究介绍了一种整合 mRNA 转录本信息来预测复杂性状表型的新方法。为了评估新方法的准确性,我们利用了全球数量遗传学研究中广泛使用的果蝇种群。结果表明,整合 mRNA 转录本数据可显著提高某些性状的基因组预测准确性,但并不能提高所有性状的表型预测准确性。与 GBLUP 相比,雄果蝇对 dCarvone 的嗅觉反应的预测准确率从 0.256 提高到 0.274。同样,雄果蝇对咖啡的预测准确率也从 0.355 提高到了 0.401。雄果蝇的生存_百草枯预测准确率从 0.101 提高到 0.138。雌果蝇对 1hexanol 的嗅觉反应的预测准确率从 0.147 提高到 0.210。总之,整合 mRNA 转录本可以大幅提高某些性状的基因组预测准确率,最高可达 43%,范围在 7% 至 43% 之间。此外,对于某些性状,在整合 mRNA 转录本的同时考虑互作效应可以提高预测准确率。
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引用次数: 0
Classification accuracy of machine learning algorithms for Chinese local cattle breeds using genomic markers. 利用基因组标记对中国地方牛种进行机器学习算法分类的准确性。
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-059
Hui Liang, Xue Wang, Jing-Fang Si, Yi Zhang

Accurate breed classification is required for the conservation and utilization of farm animal genetic resources. Traditional classification methods mainly rely on phenotypic characterization. However, it is difficult to distinguish between the highly similar breeds due to the challenges in qualifying the phenotypic character. Machine learning algorithms show unique advantages in breed classification using genomic information. To evaluate the classification methods for Chinese cattle breeds, this study utilized genomic SNP data from 213 individuals across seven Chinese local breeds and compared the classification accuracies of three feature selection methods (FST value sorting and screening, mRMR, and Relief-F) and three machine learning algorithms (Random Forest, Support Vector Machine, and Naive Bayes). Results showed that: 1) using the FST method to screen more than 1500 SNPs, or using the mRMR algorithm to screen more than 1000 SNPs, the SVM classification algorithm can achieve more than 99.47% classification accuracy; 2) the most effective algorithm was SVM, followed by NB, while the best SNP selection method was FST and mRMR, followed by Relief-F; 3) species misclassification often occurs between breeds with high similarity. This study demonstrates that machine learning classification models combined with genomic data are effective methods for the classification of local cattle breeds, providing a technical basis for the rapid and accurate classification of cattle breeds in China.

农场动物遗传资源的保护和利用需要准确的品种分类。传统的分类方法主要依赖表型特征。然而,由于表型特征的鉴定存在困难,很难区分高度相似的品种。机器学习算法在利用基因组信息进行品种分类方面显示出独特的优势。为了评估中国牛的品种分类方法,本研究利用了来自中国 7 个地方品种 213 个个体的基因组 SNP 数据,比较了 3 种特征选择方法(FST 值排序和筛选、mRMR 和 Relief-F)和 3 种机器学习算法(随机森林、支持向量机和 Naive Bayes)的分类准确性。结果表明1)使用 FST 方法筛选超过 1500 个 SNPs,或使用 mRMR 算法筛选超过 1000 个 SNPs,SVM 分类算法的分类准确率可达 99.47% 以上;2)最有效的算法是 SVM,其次是 NB,而最佳 SNP 选择方法是 FST 和 mRMR,其次是 Relief-F;3)物种误分类经常发生在相似度高的品种之间。本研究表明,机器学习分类模型结合基因组数据是地方牛品种分类的有效方法,为我国牛品种的快速准确分类提供了技术基础。
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引用次数: 0
Teaching genetics with integrative thoughts of conservation biology. 用保护生物学的综合思想教授遗传学。
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-127
Jian-Qing Lin, Shao-Pan Ye, Shu-Qi Wang, Hong Du

Biodiversity losses along with the exponential growth of global human population and human-provoked over-exploitation of natural resources. Genetic factors played an important role in the conservation of endangered species. Conservation genetics is a cross-field disciplinary of genetics and conservation biology. The course of conservation genetics is not available in colleges and universities, and the course of genetics does not directly reflect the content of biological conservation. We have taught genetics with integrative thoughts of conservation biology. In the form of case studies, we have integrated recent advances of research and technology in the relevant fields into the genetics classroom. As a result, we improved the undergraduates' motivation and interest in active learning, provoked the mutual promotion of "basic knowledge of genetics, awareness of ecological protection, and cultivate interdisciplinary thinking", and set up the groundwork for cultivating interdisciplinary talents who not only master solid basic knowledge, but also have the concept of ecological civilization.

随着全球人口的急剧增长和人类对自然资源的过度开发,生物多样性也在不断丧失。遗传因素在保护濒危物种方面发挥着重要作用。保护遗传学是遗传学和保护生物学的交叉学科。高校没有开设保护遗传学课程,遗传学课程也没有直接体现生物保护的内容。我们在遗传学教学中融入了保护生物学的思想。我们以案例分析的形式,将相关领域的最新研究进展和技术融入遗传学课堂。由此,提高了本科生主动学习的积极性和兴趣,引发了 "遗传学基础知识、生态保护意识、跨学科思维培养 "的相互促进,为培养既掌握扎实基础知识,又具有生态文明理念的跨学科人才奠定了基础。
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引用次数: 0
Research progress on the effect of sperm chromatin integrity on function and its detection methods. 精子染色质完整性对功能的影响及其检测方法的研究进展。
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-106
Daiyuan Liu, Zhao-Hui Zhang, Xian-Jiang Kang

Sperm chromatin not only carries genetic information such as paternal DNA, but also carries structural proteins, epigenetic information, and higher-order chromatin structures (such as matrix attachment regions and telomeres), etc. These information play an important role in embryonic development. This article mainly reviews the effects of these different information carried by sperm chromatin on sperm function and embryonic development and the research progress of related detection methods, in order to provide a theoretical basis and scientific diagnosis and treatment strategies for the etiology screening of clinical infertility, embryo arrest and recurrent miscarriage, so as to improve the pregnancy outcomes of natural conception and assisted reproduction. Keywords: sperm chromatin; epigenetics; sperm DNA damage; sperm function; higher-order chromatin structures.

精子染色质不仅携带父系 DNA 等遗传信息,还携带结构蛋白、表观遗传信息和高阶染色质结构(如基质附着区和端粒)等。这些信息在胚胎发育过程中发挥着重要作用。本文主要综述了精子染色质所携带的这些不同信息对精子功能和胚胎发育的影响以及相关检测方法的研究进展,以期为临床不孕症、胚胎停育和复发性流产的病因筛查提供理论依据和科学的诊治策略,从而提高自然受孕和辅助生殖的妊娠结局。关键词:精子染色质;表观遗传学;精子DNA损伤;精子功能;高阶染色质结构。
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引用次数: 0
A case study of Duchenne muscular dystrophy caused by Alu element insertion in DMD gene and analysis of its gray-hair symptoms. 由 DMD 基因中的 Alu 元素插入引起的杜兴氏肌肉萎缩症病例研究及其灰发症状分析。
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-020
Hui Li, Ru-Yi Zhang, Chang-Ye Li, Xiao-Lin Zhang, Qing-Yin Zheng, Xiu-Zhen Liu

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

杜兴氏肌营养不良症(DMD)是一种严重的 X 连锁隐性遗传疾病,由 DMD 基因突变引起,导致肌营养蛋白缺乏。该基因的主要突变类型包括外显子缺失和重复、点突变和插入。这些突变会破坏肌营养不良蛋白的正常表达,最终导致该病。在这项研究中,我们报告了一例由 DMD 基因 59 号外显子(E59)插入突变引起的 DMD 病例。患儿表现出相关生化指标的明显异常、DMD 的早期症状和多根白发。他的母亲和姐姐是生化指标轻微异常的携带者。母亲有轻微的临床症状,而姐姐则没有临床症状。其他家庭成员的基因和身体状况正常。测序和序列比对显示,插入的片段是一个来自 AluYa5 亚家族的 Alu 元件。该插入片段产生了两个终止密码子和一个多聚腺苷酸(polyA)尾。为了了解该插入片段对 DMD 基因的影响及其与临床症状的关系,我们对外显子剪接增强子(ESE)进行了预测,结果表明该插入片段并不影响 E59 的剪接。因此,我们推测插入序列可能存在于 DMD 基因的 mRNA 序列中。两个终止密码子和 polyA 尾部可能会终止翻译,从而阻止产生功能性肌营养不良蛋白,这可能是导致 DMD 的机制。除了典型的 DMD 症状外,该患儿还表现出头发过早变白。本研究首次报告了一例因在 DMD 基因编码区插入 Alu 元素而导致的 DMD 病例。这一发现为研究 Alu 序列插入诱导的基因突变提供了线索,并拓展了人们对 DMD 基因突变的认识。
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引用次数: 0
The effect of centromere protein Fta2 phosphorylation during meiosis. 减数分裂过程中中心粒蛋白 Fta2 磷酸化的影响
Q3 Medicine Pub Date : 2024-07-01 DOI: 10.16288/j.yczz.24-038
Zi-Han Ni, Yu Min, Ling-Ling Ma, Yoshinori Watanabe

During meiosis, defects in cohesin localization within the centromere region can result in various diseases. Accurate cohesin localization depends on the Mis4-Ssl3 loading complex. Although it is known that cohesin completes the loading process with the help of the loading complex, the mechanisms underlying its localization in the centromere region remain unclear. Previous studies suggest cohesin localization in the centromere is mediated by phosphorylation of centromeric proteins. In this study, we focused on the Fta2 protein, a component of the Sim4 centromere protein complex. Using bioinformatics methods, potential phosphorylation sites were identified, and fta2-9A and fta2-9D mutants were constructed in Schizosaccharomyces pombe. The phenotypes of these mutants were characterized through testing thiabendazole (TBZ) sensitivity and fluorescent microscopy localization. Results indicated that Fta2 phosphorylation did not impact mitosis but affected chromosome segregation during meiosis. This study suggests that Fta2 phosphorylation is vital for meiosis and may be related to the specific localization of cohesin during this process.

在减数分裂过程中,中心粒区域内的凝聚素定位缺陷会导致各种疾病。凝聚素的准确定位取决于 Mis4-Ssl3 加载复合体。虽然已知凝聚素在装载复合体的帮助下完成装载过程,但其在中心粒区域定位的机制仍不清楚。以前的研究表明,凝聚素在中心粒的定位是由中心粒蛋白的磷酸化介导的。在这项研究中,我们重点研究了 Fta2 蛋白,它是 Sim4 中心粒蛋白复合物的一个组成部分。通过生物信息学方法,我们确定了潜在的磷酸化位点,并在小鼠中构建了 fta2-9A 和 fta2-9D 突变体。通过检测噻苯咪唑(TBZ)的敏感性和荧光显微镜定位,对这些突变体的表型进行了鉴定。结果表明,Fta2磷酸化不会影响有丝分裂,但会影响减数分裂过程中的染色体分离。这项研究表明,Fta2 磷酸化对减数分裂至关重要,可能与减数分裂过程中凝聚素的特异性定位有关。
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引用次数: 0
Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system. Il34能挽救甲硝唑诱导的斑马鱼中枢神经系统脊髓再生障碍。
Q3 Medicine Pub Date : 2024-06-20 DOI: 10.16288/j.yczz.24-083
Ji-Xiang Liu, Si-Ting Lai, Jing Bai, Jin Xu

Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.

甲硝唑(MTZ)是临床上常用的抗感染药物,在科学研究中也被用作细胞靶向消融系统的原药,具有重要的应用价值。然而,有研究表明,MTZ 在使用过程中会在一定程度上诱发神经毒性症状,目前在临床和研究中都缺乏有效的手段来规避其毒性,这限制了其应用。因此,探索MTZ诱发神经毒性症状的具体机制并阐明对策将提高MTZ的实用价值。在本研究中,我们利用斑马鱼脊髓损伤再生模型证实了MTZ神经毒性会导致中枢神经系统轴突再生受损。通过在斑马鱼中枢神经系统中过表达il34,我们消除了MTZ对轴突再生的抑制作用,并证明了抗MTZ神经毒性的促再生作用不是由白细胞介素34(Il34)过度趋化的巨噬细胞/小胶质细胞引起的。转录组测序分析和不同组间差异表达基因的GO富集分析表明,Il34可能通过增强细胞粘附和细胞定位的生物学过程来抵消MTZ的神经毒性并促进脊髓损伤的修复。总之,我们的研究发现了 MTZ 神经毒性的可能原因,为消除 MTZ 的毒性提供了新的视角。
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引用次数: 0
Retraction notice to "Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila" [Yi Chuan 46(6) (2024) 490-501]. Tip60-FOXO调控果蝇中JNK信号介导的细胞凋亡》的撤稿通知[《易传》46(6) (2024) 490-501]。
Q3 Medicine Pub Date : 2024-06-20 DOI: 10.16288/j.yczz.24-095
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引用次数: 0
Progress on the role of LIN28A/B in tumor development and progression. LIN28A/B 在肿瘤发生和发展中的作用研究取得进展。
Q3 Medicine Pub Date : 2024-06-20 DOI: 10.16288/j.yczz.24-056
Yi-Wen Zhang, Qin Huang, Yan-Yun Wu, Yue Sun, Yong-Long Wei

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.

LIN28A 及其同源物 LIN28B 是高度保守的 RNA 结合蛋白,在早期胚胎发育、体细胞重编程、新陈代谢和肿瘤发生中发挥重要作用。LIN28A/B 在乳腺癌等多种恶性肿瘤中高度表达。它们在肿瘤的发生、维持和转移过程中发挥重要作用,并与预后不良有关。以往的研究表明,LIN28A/B 的主要调控机制包括依赖 let-7s 的方式和独立于 let-7s 的方式,如直接靶向 mRNA。在这篇综述中,我们总结了 LIN28A/B 在肝癌、乳腺癌和结直肠癌等恶性肿瘤中的功能和分子调控机制,以期为进一步探索 LIN28A/B 的功能和机制及其在临床应用中可能发挥的作用提供参考。
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引用次数: 0
Tip60-FOXO regulates JNK signaling mediated apoptosis in Drosophila. Tip60-FOXO调节果蝇体内JNK信号介导的细胞凋亡。
Q3 Medicine Pub Date : 2024-06-20 DOI: 10.16288/j.yczz.24-105
Jian Yang, Guo-Juan Shi, Ang-Hui Peng, Qing-Bo Xu, Rui-Qi Wang, Lei Xue, Xin-Yang Yu, Yi-Hao Sun

The JNK signaling pathway plays crucial roles in various physiological processes, including cell proliferation, differentiation, migration, apoptosis, and stress response. Dysregulation of this pathway is closely linked to the onset and progression of numerous major diseases, such as developmental defects and tumors. Identifying and characterizing novel components of the JNK signaling pathway to enhance and refine its network hold significant scientific and clinical importance for the prevention and treatment of associated cancers. This study utilized the model organism Drosophila and employed multidisciplinary approaches encompassing genetics, developmental biology, biochemistry, and molecular biology to investigate the interplay between Tip60 and the JNK signaling pathway, and elucidated its regulatory mechanisms. Our findings suggest that loss of Tip60 acetyltransferase activity results in JNK signaling pathway activation and subsequent induction of JNK-dependent apoptosis. Genetic epistasis analysis reveals that Tip60 acts downstream of JNK, paralleling with the transcription factor FOXO. The biochemical results confirm that Tip60 can bind to FOXO and acetylate it. Introduction of human Tip60 into Drosophila effectively mitigates apoptosis induced by JNK signaling activation, underscoring conserved regulatory role of Tip60 in the JNK signaling pathway from Drosophila to humans. This study further enhances our understanding of the regulatory network of the JNK signaling pathway. By revealing the role and mechanism of Tip60 in JNK-dependent apoptosis, it unveils new insights and potential therapeutic avenues for preventing and treating associated cancers.

JNK 信号通路在细胞增殖、分化、迁移、凋亡和应激反应等各种生理过程中发挥着至关重要的作用。该通路的失调与发育缺陷和肿瘤等多种重大疾病的发生和发展密切相关。鉴定和描述 JNK 信号通路的新成分以增强和完善其网络,对于预防和治疗相关癌症具有重要的科学和临床意义。本研究以果蝇为模式生物,采用遗传学、发育生物学、生物化学和分子生物学等多学科方法,研究了Tip60与JNK信号通路之间的相互作用,并阐明了其调控机制。我们的研究结果表明,Tip60乙酰转移酶活性的丧失会导致JNK信号通路的激活,进而诱导依赖于JNK的细胞凋亡。遗传外显分析表明,Tip60与转录因子FOXO作用于JNK下游。生化结果证实,Tip60能与FOXO结合并使其乙酰化。将人类 Tip60 移植到果蝇体内可有效缓解 JNK 信号激活诱导的细胞凋亡,这表明从果蝇到人类,Tip60 在 JNK 信号通路中的调控作用是一致的。这项研究进一步加深了我们对JNK信号通路调控网络的理解。通过揭示 Tip60 在 JNK 依赖性凋亡中的作用和机制,它为预防和治疗相关癌症揭示了新的见解和潜在的治疗途径。
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