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Towards improvement of ruminant breeding through genomic and epigenomic approaches

Periodic Reporting for period 1 - RUMIGEN (Towards improvement of ruminant breeding through genomic and epigenomic approaches)

Berichtszeitraum: 2021-06-01 bis 2022-11-30

RUMIGEN aims at developing and comparing sustainable and socially acceptable breeding programs and management practices that would result in future generations of animals that are efficient and resilient while maintaining genetic diversity. RUMIGEN seeks to ensure that proposed breeding scenarios are acceptable to stakeholders and citizens. Currently, end-users general aim is to improve future generations of livestock using genomic selection, which results in an increase of short-term genetic improvement. However, the lower long-term genetic improvement had as consequence an increased loss of genetic diversity, a low exploitation of de novo mutations and a poor consideration of the environment impact on the expression of the genetic potential of an animal.

RUMIGEN seeks to address the question of trade-offs, through the adaptation of dairy cattle to heat stress. Statistical analyses are performed using large-scale data from commercial farms, including performances, pedigrees and genotypes, combined with meteorological records. Knowing the genomic regions that contribute to trade-offs may help to develop breeding strategies that yield optimized genetic improvement in efficiency and resilience. The project will explore whether epigenetics may provide opportunities for more efficient selection and precision farming, by assessing the transmission of epigenetic marks to the next generation and investigating how they reflect the adaptation to the environment. The development of cost-effective epigenetic tools are instrumental to address these questions with sufficient statistical power and understand how complex traits are regulated, and what genetic and environmental stressor may modulate the epigenome. Such a knowledge will contribute to design more efficient and sustainable practice and increase animal welfare.

RUMIGEN also aims to use new genomic tools for distinguishing genetic diversity, genetic drift, genetic load and genomic polymorphisms such as structural variants. They will allow to describe and optimize the impact of genomic selection schemes, localize genetic load and inbreeding depression, describe breed specific genomic polymorphisms and provide genomes sequence graphs of reference.

Beside, Genome Editing is also a new genomic tool that RUMIGEN aims to test theoretically and practically to improve genetic selection and to maintain or restore genetic diversity, especially in small local breeds.

Thus, overall, RUMIGEN breeding programs will be based on the RUMIGEN’s acquired knowledge on the understanding and studying of stakeholder and citizen views on new technologies (called “Room of Acceptance”), but also on acquired new genomic, epigenomic, and genome editing information.

Participation and dialogue with stakeholders and existing networks are critical points of this strategy, strengthening the interaction and exchange between project researchers and the stakeholders. It should ensure the sustainability and uptake of project outcomes by the scientific community and the market, increasing the likelihood that the breeding approaches developed in RUMIGEN will be implemented in practice and provide value to the whole value-chain, including EU citizens.
Concerning the social aspect of RUMIGEN, a series of multi-actor engagement workshops have been organized to identify and quantify the relevant dimensions that should be included in the Room of Acceptance. From this, a draft version of the “Room of Acceptance ex-ante”, identifying the most likely dimensions to be relevant to the social acceptability of new breeding approaches, has been written and will be used to create the breeding scenarios that will later form the basis of the citizen engagement process.

From a genetics point of view, RUMIGEN already got many results on the impact of heat stress on different traits and thus on a large panel of populations (Holstein cows in 3 different European countries, Dutch MRY and French Montbéliarde). Heat stress negatively affects milk production and the decline was steeper for the high productive cows. Moreover, heat stress increases the number of SCS (Somatic Cell Scores) in the milk, indicating that it amplifies the susceptibility to mastitis. For genetic diversity assessment, RUMIGEN investigated the changes in rates of inbreeding by the introduction of genomic selection in six small breeding populations in France, The Netherlands and Norway. Although there were changes in inbreeding rates, the expected large increases due to the introduction of genomic selection have been mitigated by the selection of more bulls in the genomic selection period. RUMIGEN also made significant progresses on the genome editing part with on one hand a meta-analysis of the current applications of GE in Ruminants and on a second hand, the birth of genome edited founder animals in both practical examples proposed, Prion-resistant goats and heat stress resistant sheep. Concerning epigenetics, RUMIGEN work is progressing as expected with the setting up of all experimental designs and the sequencing and selection of relevant epigenetic marks for the design of epigenotyping tools, the collection of biological samples and their storage in new created biobanks. Negotiations with private partners for the development and construction of the epigenotyping tools (epiChIP) should lead to an agreement very quickly.

Finally during this period, efforts have been made to collect all the required ethical approvals and to set-up all planned communication packages to define the project identity. RUMIGEN developed close interactions with six other H2020 European projects to share dissemination efforts and tools.
RUMIGEN is the first project to use the “Room of Acceptance” method to understand social acceptability of new technologies, and the method has been developed within the project. This RUMIGEN approach should provide new insight into the breeding approaches we should be pursuing in the livestock sector, thereby creating value for EU consumers and producers of livestock.

Moreover, one ambition of RUMIGEN is to provide a comprehensive overview of the genetic determinism of heat tolerance and of its complex relationship with the abilities currently selected in dairy cattle. This work covers a range of situations (traits, European breeds and regions) never reached in previous research studies, to guarantee the quality and the robustness of our findings. We will show if heat tolerance is the same trait across countries with different climate, if we can predict adaptation from genomic information and identify the genome regionses involved in heat tolerance. This work will provide essential information to assess possibilities of improving livestock regarding adaptation to global warming, while limiting the impact on production traits and preserving genetic diversity. The analysis of the experimental design created in the first period will provide original results on the transmission of epigenetic marks to the progeny and their effects on progeny’s performances. With these results, we aim to improve genomic prediction models by adding epigenetic information.
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