The BovReg Conceptual Approach

The BovReg consortium aims to provide a comprehensive map of functionally active genomic features in cattle and how their (epi)genetic variation in beef and dairy breeds translates into phenotypes. This constitutes key knowledge for biology-driven genomic prediction needed by scientific and industry livestock communities in order to address the challenges facing agriculture in the 21st century.

For this, functional genome data sets based on FAANG core assays are generated from a large set of bovine tissues and newly established cell lines. The sets cover different ontological stages and phenotypes and are analysed with novel bioinformatic pipelines.

Detailed knowledge on the following three key phenotypic traits will thus be established:

1. biological efficiency (nutrient conversion, greenhouse gas emission),

2. health (mastitis susceptibility) and

3. robustness (fertility) in dairy and beef cattle.

BovReg intends to fill a gap in understanding the genetic architecture of complex traits providing comprehensive cattle genome annotation. The generated tools, resource and know-how will provide the missing components to establish a more precise and detailed understanding of the genetic and epigenetic make-up of individual cows and on how this translates into cattle phenotypes.

The cell lines established in WP1 serve as the gold standard within the project and as a legacy product for future projects to identify functionally active structural elements in the bovine genome and to functionally validate candidate regulatory variants.

In WP2, project partners establish a comprehensive map of these elements based on the new cell lines and a catalogue of 24 tissues collected from animals with comprehensive phenotypic metadata. Animals selected for providing samples for the annotation map represent a spectrum of the bovine breeds including both genders, which are kept in divergent environments.

Development and standardization of the pipelines for the respective data analyses and deposition into public domain archives are provided under WP3 and WP10. The project partner and FAANG Data Coordination Center EMBL-EBI guarantees the long-term availability of data and targeted dissemination and communication activities.

Complementary to the annotation efforts in WP2, work in WP4 provides a resource for prioritising variants and identifying potential mechanisms underlying genetic associations. Data of whole-genome association studies for BovReg target traits are integrated with data on expression and metabolomic QTL and the effects of mobile genomic elements.

WP5 adds epigenomic data to the annotation map and models epigenetic inter- and transgenerational effects of heat and metabolic stress in specific fertility-related tissues. Respective candidate regulatory variants are used for functional confirmation in WP6. Information on regulatory variants and functionally active genomic regions feed into models

for the development of novel biology-driven genomic prediction tools in WP7, which also consider application in small cattle breeds of limited population size.

WP8 and WP9 include strong dissemination and communication components. They cover forging and maintaining strong links to the other cluster projects funded under the EU Horizon 2020 SFS-30-2018-2019-2020: Agri-Aqua Labs call and to the global FAANG community ( WP 8 and 9 engage with the public on the ethical and societal perceptions of new breeding technologies. The research will finally lead to a framework with recommendation for stakeholders.

With its predictive biology approach BovReg aims to enable the perfect matching of an individual animal’s phenotypic capacities with its demands, given its (epi)genomic configuration. This achievement will allow producers and breeding organizations to provide individualized breeding and management strategies and achieve high standards in animal health and welfare and in resource efficiency.