What is Gene Editing?
A new set of technologies that collectively are being used to edit genes are deriving a lot of media attention. As the name "gene editing" suggests, these technologies enable researchers to add, delete, or replace letters in the genetic code. In the same way that spell check identifies and corrects single letter errors in a word, or grammar errors in a sentence, gene editing can be used to identify and change the letters that make up the genetic code (i.e. DNA) within a species.
Gene editing has many potential applications. For example, it can be used to correct diseases and disorders that have a genetic basis. It could also be used to change one less desirable allele of a gene to a more desirable allele without the need to introgress (repeatedly backcross) or bring in that allele through outcrossing with an animal that carries the desirable allele.
Gene editing is different from traditional genetic engineering. Continuing with the analogy of a word processor, genetic engineering enables a gene sequence of "foreign DNA" to be "cut and pasted" from one species to another, whereas gene editing can add, delete, or replace a series of letters in the genetic code. There are many potential uses of this technology ranging from human medicine to plant and animal breeding.
The basic idea behind gene editing is that molecular scissors called nucleases are used to cut DNA at a specific location in the genome based on recognition of the specific, unique target DNA sequence. The cut site is then repaired using the DNA repair mechanisms of the cell. These repairs can be directed to introduce, delete, or replace a series of letters in the genetic code. This essentially enables the introduction of known, desired alleles based on what is understood about naturally-occurring genetic variation in the target species.
Where might gene editing be used in animal breeding?
The currently available set of gene editing technologies (zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regulatory interspersed short palindromic repeats (CRISPRs) associated system have been used for a relatively small number of livestock applications to date.
Gene editing has been used to produce genetically hornless Holstein dairy cattle by introducing the naturally-occurring Angus "polled" allele into the gene that is responsible for horns, and to generate pigs with a single base deletion in a gene that may confer resilience to African Swine Fever Virus. It has also been used to introduce changes in the myostatin gene in sheep and cattle. As the Latin origin of the word myostatin (muscle/stop) suggests, turning off this gene results in muscle growth. Naturally-occurring mutations in this gene have historically been selected by conventional animal breeders and are the genetic basis for the "double muscled" phenotype that is seen in cattle breeds like the Belgian Blue, and the "bully" phenotype in whippet dogs.
In this way, gene editing really mimics the natural processes that form the basis of selective breeding programs, and for that matter, evolution itself. Breeders work with the genetic variation that exists within a species, and that genetic variation ultimately arises from naturally-occurring mutations. Although the word "mutation" sounds negative, it simply refers to variations in DNA sequences. These variations, or mutations, are responsible for virtually all genetic differences that exist between individuals, such as having blue eyes instead of brown.
Although different mammals have many of the same genes, many people do not appreciate that the genetic code that makes up those genes differs among animals of different breeds, and even among animals within the same breed. In fact, with the exception of identical twins, there are literally thousands of DNA sequence variations between two individuals of any species.
For example, an enormous number of genetic variants have accumulated within cattle since the advent of domestication and selective breeding due to the naturally-occurring processes that lead to a small number of mutations each generation. In one recent analysis of whole-genome sequence data from 234 taurine cattle representing 3 breeds, more than 28 million variants were observed, including insertions, deletions and single nucleotide variants. A small fraction of these mutations are those that have been selected by breeders; most of them are silent and have no impact on traits of importance to breeding programs. Occasionally, such mutations result in a genetic condition such as red or black coat color or an undesirable disease condition such as dwarfism.
How might gene editing intersect with conventional breeding?
Data coming out of some of the large-scale genomics and sequencing projects are revealing situations in which the sequence of one naturally-occurring allele results in a superior phenotype to that observed when animals inherit an alternative allele of that gene. It is envisioned that it might be possible to edit an animal's genome to the superior allele, and to do that at several genomic locations, or for several different genes. The advantage of gene editing over conventional selection to move these naturally-occurring alleles from one animal to another is that favorable alleles rarely all occur in one single individual and editing offers the opportunity to increase the frequency of desirable alleles in an individual or a breed more rapidly than could occur through conventional breeding.
One could potentially envision editing several alleles for different traits - disease resistance, polled and to correct a known genetic defect - all while using conventional selection methods to keep making genetic progress towards the selection objective. One study found that combining gene editing with genomic selection could improve the response to selection four fold after 20 generations.
Gene editing offers an approach to translate the thousands of SNP markers discovered through livestock sequencing projects, the information obtained from numerous genome wide association studies, and the discovery of causative SNPs (QTNs) into useful genetic variation for use in animal breeding programs.
Will gene editing be regulated?
At the current time it is unclear whether gene editing will be formally regulated. Animal breeding per se is not regulated by the federal government, although it is illegal to sell an unsafe food product regardless of the breeding method that was used to produce it. Gene editing does not necessarily introduce any foreign genetic DNA or "transgenic sequences" into the genome, and many of the changes produced would not be distinguishable from naturally-occurring mutations. As such, it does not fit the classical definition of genetic engineering. It is not evident what unique risks might be associated with an animal that is carrying a naturally-occurring allele or a gene deletion produced through gene editing.
Governments and regulators globally are currently contemplating whether gene edited animals should be regulated, and if so how and by whom. This question is of course important from the point of view of both technology development and innovation, and international trade.
