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

• Applicants: Dr. Stefan Krebs; Professor Dr. Sven König
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422003751

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).

• DFG Programme: Research Grants