Precision Editing of Large Animal Genomes

Abstract

Transgenic animals are an important source of protein and nutrition for most humans and will play key roles in satisfying the increasing demand for food in an ever-increasing world population. The past decade has experienced a revolution in the development of methods that permit the introduction of specific alterations to complex genomes. This precision will enhance genome-based improvement of farm animals for food production. Precision genetics also will enhance the development of therapeutic biomaterials and models of human disease as resources for the development of advanced patient therapies.

Efficient nonmeiotic allele introgression in livestock using custom endonucleases

“…The high efficiency and precision reported here are astonishing compared with what was feasible only a few years ago (2).…”

“…Regardless of the mechanism, this approach offers a straightforward strategy for recovering cells with precise introgression of SNP alleles. As to the second concern, the frequency of modification at unintended sites is exceedingly low and in the context of livestock breeding will be lost by independent segregation in subsequent generations (2).…”

“…Our results suggest that gene editing can be incorporated into selection programs to accelerate genetic improvement when selective breeding is either inefficient or impossible. Nonmeiotic introgression provides a genetic method for precisely crossbreeding for large effect alleles without compromising the genetic merit of indigenous or purpose-bred populations by whole-genome admixtures (2). By allowing such single-generation introgression of select alleles, it will accelerate genetic improvement based on local ecologies and needs that may derive from climate change and emerging diseases.…”

“…M eeting global challenges presented by climate change and burgeoning populations requires development and application of biotechnologies that enhance productivity while reducing environmental footprints and improving animal welfare (1,2). Since the creation of the first transgenic pig (3), more than 180 trials have been recorded to genetically engineer livestock in various ways (2).…”

“…Since the creation of the first transgenic pig (3), more than 180 trials have been recorded to genetically engineer livestock in various ways (2). Until recently, most were accomplished by random insertions of expression cassettes, which suffered from low efficiency and unpredictable expression, or homologous recombination (efficiency <1 in 10 4 ) with linked selection markers.…”