中国农业科学 ›› 2019, Vol. 52 ›› Issue (2): 350-358.doi: 10.3864/j.issn.0578-1752.2019.02.013

• 畜牧·兽医·资源昆虫 • 上一篇    下一篇

组学技术在奶牛乳房炎上应用的相关研究进展

李广栋1,吕东颖1,田秀芝2,姬鹏云1,郭江鹏3,路永强3,刘国世1()   

  1. 1 中国农业大学动物科学技术学院,北京 100193
    2 中国农业科学院北京畜牧兽医研究所,北京 100193
    3 北京市畜牧总站,北京 100101
  • 收稿日期:2017-12-05 接受日期:2017-12-22 出版日期:2019-01-16 发布日期:2019-01-21
  • 通讯作者: 刘国世
  • 作者简介:李广栋,E-mail: 15600911225@cau.edu.cn
  • 基金资助:
    转基因生物新品种培育重大专项(2014ZX0800802B);北京市奶牛创新团队(BAIC06-2017)

Research Progress of Omics Technologies in Cow Mastitis

LI GuangDong1,LÜ DongYing1,TIAN XiuZhi2,JI PengYun1,GUO JiangPeng3,LU YongQiang3,LIU GuoShi1()   

  1. 1 College of Animal Science and Technology,China Agriculture University,Beijing 100193
    2 Institute of Animal Sciences,Chinese Academy of Agricultural Sciences,Beijing 100193
    3 Beijing Animal Husbandry Station,Beijing 100101
  • Received:2017-12-05 Accepted:2017-12-22 Online:2019-01-16 Published:2019-01-21
  • Contact: GuoShi LIU

摘要:

奶牛乳房炎发病率较高、病因复杂,是影响世界奶牛业发展的主要常见疾病之一。由金黄色葡萄球菌、大肠杆菌、链球菌等病原体引起的临床和隐形乳房炎对动物性食品安全及畜牧业的正常发展构成巨大安全隐患,全球每年因奶牛乳房炎导致的经济损失多达数十亿美元。近年来随着测序技术的不断突破和测序成本的不断降低,生命科学的研究进入了多组学时代,其在畜牧业中的应用也越来越广泛。对奶牛乳房炎来说,传统的组织病理学筛查、体细胞计数、牛乳pH检测、牛乳电导率检测、酶活检验、红外热显影等诊断技术由于其自身的局限性难以充分全面地阐明其发病机理,已不能满足科研人员的需求。组学技术即Omics,主要包括基因组学技术、蛋白质组学技术和代谢组学技术等。通过基因组学研究不仅能从转录层面上揭示奶牛乳房炎复杂性状的表型变异及遗传基础,还能从转录后调控(miRNAs、LncRNAs等)和表观遗传学修饰(DNA甲基化、组蛋白修饰等)层面挖掘出相关的DNA和RNA变化及多分子间的相互作用规律,能够帮助我们更好地了解奶牛乳腺组织对病原体的免疫应答机制,筛选鉴定出乳房炎抗性的信号通路及关键候选基因,从而提高基因组预测或选择的准确性。利用蛋白质组学技术能够对不同环境不同状态的牛乳及乳腺组织的蛋白质种类、表达丰度、蛋白互作、翻译后修饰等进行比较分析,对差异表达的蛋白质经过COG功能注释、数据库比对、GO和Pathway富集分析,可以从蛋白水平揭示乳房炎发生及防御过程中的复杂调控机制,同时还能发现乳房炎诊断的标记分子,进而为乳房炎治疗药物的研发提供潜在的精准靶点。代谢组学是系统生物学的重要组成部分。通过代谢组学研究,能够同时对机体在内、外环境等复杂因素作用下及特定生理时期内所有低分子量代谢产物(如氨基酸、脂类、碳水化合物等)进行精准、高效的定性和定量分析,从而阐明相关的代谢途径;其作为基因表达的最下游,能使基因和蛋白质表达的微小变化在代谢物水平上得到放大,进而可以更充分地反映细胞功能。将代谢组学技术应用到奶牛乳房炎研究中,能够分析出差异代谢物、鉴定出相关的生物标志物,进而揭示奶牛乳腺的生理及病理变化过程。总之,将各组学技术及多组学整合关联分析应用到奶牛乳房炎研究中可以更深入地揭示其病原防御机制,进而为乳房炎的预测、诊断和治疗提供有价值的参考和借鉴。本文就最近几年组学技术在奶牛乳房炎领域的研究进展进行综述,以期为我国奶牛健康及奶业安全发展提供指导。

关键词: 组学技术, 奶牛, 乳房炎

Abstract:

Dairy mastitis, a common and complex disease with a high incidence, takes its toll on the development of world dairy industry, brings economic losses of billions of dollars per year. Clinical and subclinical mastitis, caused by pathogens such as Staphylococcus aureus, Escherichia coli and Streptococcus agalactiae, posed a huge security risk to milk industry. In recent years, with the continuous breakthrough of sequencing technology and decline of sequencing cost, the research of life science has entered into the Omics era. The traditional methods such as histopathological screening, somatic cell counting, milk PH value detection, detection of milk conductivity, enzyme activity test, infrared thermal imaging can be employed for clinical diagnosis of dairy cow mastitis, but these methods are not powerful enough to elucidate the pathogenesis in a cellular or molecular view. Omics technologies are mainly composed of genomics, proteomics and metabolomics. Genomics can not only reveal the phenotypic variation and genetic basis of the complex trait of dairy mastitis at the transcriptional level, but also reveal the molecular patterns of the mastitis from the aspects of transcriptional regulation (miRNAs, LncRNAs, etc.) and epigenetic modification (DNA methylation, histone modification, etc.). Genomic analysis of mastitis can also dig out the related changes of DNA, RNA and the rules of multi-molecule interaction, which accounts for a better understanding of the immune mechanism of the host against the pathogen, so as to screen and identify the signal pathways and key candidate genes of mastitis resistance, thus improving the accuracy of genome prediction or selection. Proteomics can not only compare milk protein type and abundance but also analyze protein interaction and post-translational modification in breast tissues under different states and environments. The differentially expressed proteins are annotated by COG (Cluster of Orthologous Groups of protein) function followed by database comparison, GO and Pathway enrichment analysis, which help bring to light the complex regulatory mechanism of mastitis occurrence and defense process at protein level. Proteomic analysis can also be used to find molecular marker of mastitis diagnosis, which will provide a potential precise target for the development of therapeutic drugs. Metabolomics, an important part of the system biology, can detect metabolites of low molecular weight (such as amino acids, lipids, carbohydrates, etc.) of the specific tissues or organs in specific environment or specific physiological states. Efficient qualitative and quantitative analysis will elucidate the relevant metabolic pathways. As the ultimate downstream of gene expression, metabolomics technology enables small changes in gene expression and protein synthesis to be amplified at metabolite levels to fully reflect cellular functions, whose application in dairy mastitis will be able to identify related biomarkers and reveal the physiological and pathological changes of dairy breasts. In conclusion, applying Omics or multi-Omics association analysis techniques to mastitis can further reveal the pathogenic defense mechanism, which will provide valuable reference for disease prediction, diagnosis and treatment. This paper reviews the latest research progress about application of Omics in the field of cow mastitis, aiming to provide solid theoretical bases and practical references for cow health and safety of dairy industry in China.

Key words: Omics, cow, mastitis