Genome-edited livestock to secure sustainability

Sustainable improvement of production in most tropical dairy systems is a significant challenge, because the cattle breeds with the most genetic potential for milk output relative to native tropical breeds have not been selected for these types of environments. Multiplex genome editing provides a potential solution to introduce beneficial sequence variants (SVs) into elite animals for tropical adaptation in a single generation. Bovine sequence variants for heat tolerance, stature, milk yield, and disease-tolerance traits were identified and genotyped across indigenous African, dairy Zebu, and dairy Taurine breeds to validate those targets best suited for introgression by genome editing. In vitro fertilized embryos from a series of matings were used to produce embryonic stem cells (ESCs) and were subsequently multiplexed edited prior to cloning by somatic cell nuclear transfer. A set of best target SVs for genome editing was established for the Holstein and Gir breeds. ESCs were produced and cloned following treatment and validation screening for multiplex alterations of up to four target genes. Currently, 12 animals have been born, and all the mature males have produced viable semen that will be submitted for regulatory review in a series of countries in Sub-Saharan Africa and South America. Multiplex genome editing based on homology-directed repair combined with cloning of bovine ESCs provides an opportunity to initiate genetic improvement of polygenic traits in cattle. Combining genomics and genome editing provides new opportunities to breed more resilient dairy animals for the tropics that should improve animal and farmer livelihoods.