Multi-omics-approach in dairy cattle to analyse the impact of intra-uterine heat stress during late pregnancy on production and health traits with special consideration of metabolomics and epigenetics

奶牛多组学方法分析妊娠后期子宫内热应激对生产和健康特征的影响，特别考虑代谢组学和表观遗传学

• 批准号: 422003751
• 负责人: Dr. Stefan Krebs
• 金额: --
• 依托单位: Genzentrum - Laboratorium für molekulare Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/422003751?language=en
• 关键词: Multi; omics; approach; dairy; cattle

The project aims on the implementation of a multi-generation-animal-model. This model on a transgenerational level allows studying the impact of uterine heat stress during late pregnancy on productivity, health and metabolic parameters (metabolites) in dams and their offspring. In this regard, phenotypes will be related to genomic variants, gene expressions and DNA-methylation profiles, in order to analyse the different "omics Levels" including phenomics, metabolomics, (epi-)genomics and transcriptomics. Of specific relevance is the identification of epigenetic imprinting effects, which will be inferred using a holistic approach. Initially, genetic-statistical modelling bases on more than 20,000 genotyped dairy cows (including multiple generations) from so-called contract-herds, with phenotypes for production and health traits. Estimation of possible imprinting effects and the localisation of respective chromosome segments bases on the generation of a specific genomic relationship matrix, and of a (co)variance matrix for imprinting effects via SNP marker data. The modelling simultaneously allows an estimation of additive-genetic and dominance effects. The quantitative-genetic and genomic statistical analyses are carried out by the group of Prof. König from UGI (expertise in quantitative-genetic and genomic modelling). The identified genomic regions associated with imprinting effects are the basis for analyses on epigenetic processes at the sequence level, i.e., DNA-methylation and gene expression analyses via targeted methylome- and transcriptome-sequencing approaches. The analysis of dynamics in DNA-methylation and gene expression patterns will be studied in a multi-generation-animal-model. In this regard, we extend the phenome database with innovative dairy cow phenotypes from the research station “Hofgut Neumühle” (expertise in phenotyping metabolomics data). Blood samples will be collected in the three generations G0 (dam), G1 (daughter) and G2 (granddaughter), in order to depict the multi-organ transcriptome and epigenome. For epigenetically influenced genomic regions, the specific molecular genetic analyses of the existing DNA methylation patterns and transcriptome profiles are carried out via targeted-sequencing approaches, i.e. bisulphite- or cDNA-sequencing using next-generation sequencing technology. The sequence analyses are mainly carried out by the group of Dr. Krebs from TUM (expertise in next-generation-sequencing, transcriptome analysis).

该项目旨在实施多代动物模型，该模型可以在跨代水平上研究妊娠后期子宫热应激对母鼠及其后代的生产力、健康和代谢参数（代谢物）的影响。在这方面，表型将与基因组变异、基因表达和DNA甲基化谱相关，以便分析不同的“组学水平”，包括表型组学、代谢组学、（表观）基因组学和转录组学特别重要的是表观遗传印记效应的识别，该效应最初将基于来自所谓合同牛群的 20,000 多头基因型奶牛（包括多代）进行推断。生产和健康性状的表型基于特定基因组关系矩阵和（共）方差矩阵的生成来估计可能的印记效应和各个染色体片段的定位。该模型同时允许估计加性遗传和显性效应。定量遗传和基因组统计分析由 UGI 的 König 教授团队（定量遗传和基因组建模方面的专家）进行。 ）。已确定的与印记效应相关的基因组区域是序列水平上表观遗传过程分析的基础，即通过靶向甲基化组和转录组测序方法进行 DNA 甲基化和基因表达分析。 DNA 甲基化和基因表达模式的动态将在多代动物模型中进行研究。在这方面，我们利用“Hofgut Neumühle”研究站（表型代谢组学数据的专业知识）的创新奶牛表型来扩展表型数据库。将采集G0（母亲）、G1（女儿）和G2（孙女）三代的血液样本，以描绘多器官转录组和表观基因组。受表观遗传影响的基因组区域，通过靶向测序方法对现有DNA甲基化模式和转录组图谱进行特定的分子遗传学分析，即使用下一代测序技术进行亚硫酸氢盐测序或cDNA测序。来自 TUM 的 Krebs 博士团队（下一代测序、转录组分析方面的专业知识）。