Genome editing for quantitative traits in livestock

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This project will develop new laboratory techniques and new breeding methods to enhance livestock breeding programmes by genome editing. Genome editing is used to increase the numbers of animals in the breeding herd that carry beneficial genome variants. This makes it possible to conserve valuable genome variants that would otherwise be lost because they tend to be inherited together with harmful variants that must be bred out.Although the traits that animal breeders seek to improve are each controlled by thousands of genome variants, we have shown that it is theoretically possible to produce a 33% improvement in genetic gain in a livestock breeding programme by editing as few as 5 variants.The aim of this project is to make this theoretical possibility a practical reality by developing the techniques to do multiple edits on the same individual and the breeding methods to decide on the best edits, the best animals to edit and how best to manage the breeding programme.The project consists of two strands of work, one will develop the genome editing methods, the other will develop the breeding methods.The editing methods will be developed in three stages. 1. We will develop the tools to make multiple edits that do not change the function of the genome in any way. It will be much easier to test the safety and efficacy of the tools if the edits do not alter genetic function.2. When we can make multiple edits we will configure the tools to produce edits that should improve breeding and test them on cells in culture.3. When the tools work on cells in culture, we will use them to edit single-cell embryos and produce live, edited pigs.We need the breeding methods to design the most useful set of edits and to deploy them most effectively in a breeding programme. The methods will be developed in the form of computer programmes that support the following three operations.1. Analysis of a huge dataset, containing the genome sequences of 325000 pigs together with information about their pedigrees and their breeding traits, in order to decide on the most effective edits and the most useful individuals to edit.2. A strategy for selecting which pigs to breed from that will prevent the loss of valuable genes by inbreeding.3. A strategy for managing the breeding programme so that it generates the data needed to test the effectiveness of current edits and identify the best potential future edits.Our industrial partner, PIC, has a breeding programme that generates the genetics in over 100 million slaughter pigs every year. This project will help make those pigs healthier and make them produce better meat with lower inputs and lower environmental impact. The breeding methods and software will be made available to other companies breeding pigs and other livestock species. The results will also be useful for understanding the genetic basis of quantitative traits, like height and health, in humans.