Michèle Tixier-Boichard

Genotype-to-phenotype (G2P) research in farmed animals has entered a phase in which deep genome annotation, multi-omics and AI-enabled prediction can nominate variants, regulatory mechanisms and cellular pathways at scale, but causal validation remains a major bottleneck. In vitro cellular systems, from tractable primary cells to organoids and other advanced models, provide experimentally controlled contexts in which massively parallel reporter assays and CRISPR-based perturbations can test variant effects and define cellular phenotypes. Here, we examine how in vitro approaches can be deployed across host–pathogen interactions, genotype-by-environment responses, nutrition, adaptation and One Health research, and outline priorities for integrating in vivo, in vitro and in silico data into mechanistic G2P workflows.

The well-being of farmed and companion animals is increasingly recognised as integral to sustainable agroecosystems, companionship, and the One Health approach, which emphasises the interconnected health of people, animals, and the environment. The ELIXIR Domestic Animals Genome and Phenome (DAGP) Community supports genome-to-phenome analyses for farmed and companion animal species. Its aim is to coordinate, discuss, and explore the potential of data technology solutions to address key issues in animal welfare, behaviour, health, infectious diseases, metabolism, nutritional efficiency, and the preservation of genetic diversity and the environment. Through consolidating efforts to develop data standards, coordination, workflows, and visualisation, it will enhance the science underpinning rapidly growing fields in domestic animal genomics, including genome-enabled breeding, population genomics, pangenome analysis, functional genomics, genome editing, paleogenomics, phenotyping, and bio-banking. These standards will adhere to the FAIR data principles and leverage established ontologies to promote best practices in data coordination and archiving. This white paper, prepared by the ELIXIR DAGP Focus Group, summarises the current data infrastructure, resources, and tools available for domestic animal genomics and phenomics, and presents community-led plans and priorities to be implemented to meet the requirements of ELIXIR services and the animal science community. We describe how ELIXIR services can be applied in the domestic animal genomics and phenomics fields, and how we can connect projects and infrastructures that are active in the animal sciences domain. We also discuss three key priority areas: i) expanding the FAANG Data Portal for phenotype data with ELIXIR Data Platforms; ii) supporting submissions of new data types across ELIXIR Core Data Resources , including proprietary data from industry partners; and iii) strengthening connections to existing ELIXIR Communities and international consortia. This article provides a set of priorities for a Domestic Animals Genome and Phenome Community in ELIXIR and outlines the next steps to engage across stakeholders and to consolidate data for domestic animal science in Europe.

Chickens - Understanding their visible genetic diversity - (EAN13 : 9782759240395)

Livestock biodiversity is declining globally at rates unprecedented in human history. Of all avian species, chickens are among the most affected ones because many local breeds have a small effective population size that makes them more susceptible to demographic and genetic stochasticity. The maintenance of genetic diversity and control over genetic drift and inbreeding by conservation programs are fundamental to ensure the long-term survival and adaptive potential of a breed. However, while the benefits of a conservation program are well understood, they are often overlooked. We here used temporal whole-genome sequencing data to assess the effects of a conservation program on the genetic diversity (Δπ), deleterious variation (ΔL), and inbreeding (ΔF) of two local French chicken breeds, the Barbezieux and Gasconne. We showed that when the conservation program is consistent over time and does not undergo any major organisational changes (i.e., Barbezieux), the loss of genetic diversity is limited. This was true for both pedigree and genomic inbreeding but also for the genetic load estimated from functionally important genome-wide variants. However, when a conservation program is interrupted or re-initiated from scratch (i.e., Gasconne), the loss of genetic diversity can hardly be limited as a result of the bottleneck effect associated with the re-sampling. Our results reinforce the imperative to establish and sustain existing conservation programs that aim to keep populations with a relatively small effective population size from the brink of extinction. Moreover, we conclude by encouraging the use of molecular data to more effectively monitor inbreeding at the genome level while improving fitness by tracking protein-coding and non-coding deleterious variants.

A bstract: Background: Genetic diversity is essential for the sustainability and adaptability of populations, and is thus a central pillar of the agro-ecological transition. However, within a population it is inevitable that some amount of genetic variability is lost, and efforts must be made to limit this as much as possible. A valuable tool in this endeavor could be the use of cryopreserved genetic resources in cryobanks, which could assist in the management of various animal populations in the contexts of both selection and conservation. Results: We performed simulations that revealed that the most appropriate use of ex situ genetic resources differs radically depending on characteristics of the target population and its management objectives. With populations under conservation, the aim is the management of genetic diversity, which was optimized by the regular use of cryopreserved genetic resources at each generation. For populations under selection, instead, the concern is the addition of additive genetic variability, which benefited from the use of cryopreserved collections over only a few generations based primarily on the genetic values of donors. In both cases, the use of cryopreserved individuals in animal populations requires a large amount of material: for breeds under selection because the number of offspring is high, and for breeds under conservation because the frozen semen is used repeatedly over a long period. Conclusions: The use of cryopreserved material appears to be an effective means of managing the genetic variability of an animal population, either by slowing down the erosion of variability or by helping to redirect a selection objective. However, care must be taken with populations under selection to limit the disadvantages associated with the reintroduction of old genetic material, in particular the gap in breeding values for traits of interest. Finally, our study highlights the need for a sufficiently large stock of cryopreserved material in collections (e.g., number of doses, straws) to ensure the most efficient use.

Livestock biodiversity is declining globally at rates unprecedented in human history. Of all avian species, chickens are among the most affected ones because many local breeds have a small effective population size that makes them more susceptible to demographic and genetic stochasticity. The maintenance of genetic diversity and control over genetic drift and inbreeding by conservation programs are fundamental to ensure the long-term survival and adaptive potential of a breed. However, while the benefits of a conservation program are well understood, they are often overlooked. We here used temporal whole-genome sequencing data to assess the effects of a conservation program on the genetic diversity (Δ π ), deleterious variation (ΔL), and inbreeding (ΔF) of two local French chicken breeds, the Barbezieux and Gasconne. We showed that when the conservation program is consistent over time and does not undergo any major organisational changes (i.e., Barbezieux), the loss of genetic diversity is limited. This was true for both pedigree and genomic inbreeding but also for the genetic load estimated from functionally important genome-wide variants. However, when a conservation program is interrupted or re-initiated from scratch (i.e., Gasconne), the loss of genetic diversity can hardly be limited as a result of the bottleneck effect associated with the re-sampling. Our results reinforce the imperative to establish and sustain existing conservation programs that aim to keep populations with a relatively small effective population size from the brink of extinction. Moreover, we conclude by encouraging the use of molecular data to more effectively monitor inbreeding at the genome level while improving fitness by tracking protein-coding and non-coding deleterious variants.

Background: Genetic diversity is a necessary condition for populations to evolve under natural adaptation, artificial selection, or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources are a promising option to reintroduce lost variants and to limit inbreeding. However, while the use of ancient genetic resources is more common in plant breeding, it is less documented in animals due to a longer generation interval, making it difficult to fill the gap in performance due to continuous selection. This study investigates one of the only concrete cases available in animals, for which cryopreserved semen from a bull born in 1977 in a lost lineage was introduced into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later. Results: We found that this re-introduced bull was genetically distinct with respect to the current population and thus allowed part of the genetic diversity lost over time to be restored. The expected negative gap in milk production due to continuous selection was absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this bull more than two decades later did not increase the level of inbreeding, and even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of a bull from a lost lineage in the breeding scheme allowed for improved performance for reproductive abilities, a trait that was less subject to selection in the past. Conclusions: The use of cryopreserved material is an efficient way to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid to mating of animals to limit the disadvantages associated with incorporating original genetic material, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations, in particular local or small populations. These results could also be transferred to the conservation of wild threatened populations.

Background Genetic diversity is a necessary condition for populations to evolve under adaptation, selection or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources appear as a promising option to reintroduce lost variants and to limit inbreeding. However, while more common in plant breeding, the use of cryopreserved resources is less documented in animals due to a longer generation interval making it difficult to fill the performance gap due to continuous selection. Thus, this study investigates one of the only concrete cases presenting the results of the use of cryopreserved semen of a bull born in 1977 and belonging to a disappeared lineage, into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later. Results We found that this re-used bull was very original relative to the current population and thus allowed to restore genetic diversity lost over time. The expected negative gap in milk production due to continuous selection has been absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this old bull did not increase the level of inbreeding, it even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of an old bull in the breeding scheme allowed for increased performance for reproductive abilities, a trait that was less subject to selection in the past. Conclusions The use of cryopreserved material was efficient to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid toward mating in order to limit the disadvantages associated with the provision of genetic originality, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, a careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations and of local or small ones in particular. These results could also be transferred to the conservation of wild populations.