Genome editing approaches to augment livestock breeding programs

Abstract

The prospect of genome editing offers a number of promising opportunities for livestock breeders. Firstly, these tools can be used in functional genomics to elucidate gene function, and identify causal variants underlying monogenic traits. Secondly, they can be used to precisely introduce useful genetic variation into structured livestock breeding programs. Such variation may include repair of genetic defects, the inactivation of undesired genes, and the moving of useful alleles and haplotypes between breeds in the absence of linkage drag. Editing could also be used to accelerate the rate of genetic progress by enabling the replacement of the germ cell lineage of commercial breeding animals with cells derived from genetically elite lines. In the future, editing may also provide a useful complement to evolving approaches to decrease the length of the generation interval through in vitro generation of gametes. For editing to be adopted, it will need to seamlessly integrate with livestock breeding schemes. This will likely involve introducing edits into multiple elite animals to avoid genetic bottlenecks. It will also require editing of different breeds and lines to maintain genetic diversity, and enable structured crossbreeding. This requirement is at odds with the process-based trigger and event-based regulatory approach that has been proposed for the products of genome editing by several countries. In the absence of regulatory harmony, researchers in some countries will have the ability to use genome editing in food animals, while others will not, resulting in disparate access to these tools, and ultimately the potential for global trade disruptions.

Evaluation of Mosaicism and Off Target Mutations in CRISPR-Mediated Genome Edited Bovine Embryos

“…Further, we considered an embryo containing more than one population of genetically distinct cells to be mosaic irrespective of whether the edit resulted in a missense or nonsense mutation. It is important to determine if founder animals are mosaic because mosaicism complicates the interpretation of the effect of a given genome alteration 5 , and subsequent breeding of mosaic founder animals to achieve non-mosaic animals can take years 13 . Additionally, mosaics do not fit easily into the proposed regulatory framework for genome edited food animals 14 .…”

The coding loci of evolution and domestication: current knowledge and implications for bio-inspired genome editing

“…For example, dairy cattle typically grow horns and are subject to the expensive and distressing practice of disbudding or dehorning. Meanwhile, the cisregulatory alleles responsible for hornlessness in meat cattle breeds are known (Medugorac et al, 2012), and have been transferred to dairy cattle backgrounds by genome editing (Carlson et al, 2016;Young et al, 2019;Bishop and Van Eenennaam, 2020). The genome editing route is proposed as a faster, transgene-free path for improvement, compared with backcross introgressions of the existing allele into dairy cattle breeds (Mueller et al, 2019).…”

Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria

“…Therefore, it provides a novel framework for integrative genomics studies of complex infectious disease resistance traits in livestock, particularly those involving other intracellular bacterial pathogens such as Brucella abortus, Mycobacterium avium subsp. initiative (Giuffra et al 2019) and for identification and prioritization of targets for genome editing to enhance resistance to infection in domestic livestock species (Bishop & Van Eenennaam 2020).…”