Cows made hornless through gene-editing, with no off-target effects

A letter in Nature Biotechnology reports the rearing of two young dairy cows whose genomes were edited to make them hornless. A genetic variant found in hornless cattle was inserted in the calves’ genomes, and after sequencing the researchers found no off-target effects. The researchers say the gene-edited calves could improve the welfare of dairy cattle, who typically have their horns removed manually.

 

Dr. William Muir, Professor Genetics, Department of Animal Sciences, Purdue University (webpage):

Expertise: Genetic methods to improve adaptability, stress resistance, and animal well-being.

“This is very exciting for several reasons. First, it is possible to insert an important natural genetic difference causing hornless cattle in a very elite animal of high genetic worth in a short period of time. The same results can be accomplished by classical breeding, and with the same gene, but would take five to six generations of crossing and backcrossing and almost 20 years to accomplish. 

“Second, this tackles a major animal welfare issue. De-horning animals is a bloody and painful process that no one likes to do, and horns are a danger to those working with the animals.  Thus, removing horns through genetics is a win-win both for the animal and for the farmer. Gene-editing technology also opens the field for other improvements in animal wellbeing, such as tail docking in pigs.

 “Finally, lack of off-target effects means that there are no unintended consequences, so we don’t have to worry about what else has changed!  This is not a transgenic animal, but simply the insertion of a gene that naturally exists in cattle.  With transgenic animals, genes can be inserted from other species and the technique is much less precise than gene-editing since the insertion site of the transgene is random and not known, thus unintended consequences can occur if the gene inserts itself into the wrong area(s). This is why it takes so long for the regulatory process to work, as they have to examine all possible intended and unintended consequences of gene modification. On the other hand, the lack of off-target effects in the gene-edited cows means regulatory approval should be swift.”

 

Dr. Willard Eyestone, Research Associate Professor, Reproductive Biology / Biotechnology, Virginia Tech (webpage): 

Expertise: Developmental biology and genetic modification of animals.

“Although these cattle have been in the works for some time, this is the first peer-reviewed paper to document that editing the genetic sequence responsible for horns does in fact yield ‘hornless’ or polled animals.  Not only does this demonstrate the technical feasibility of this approach to generating polled cattle, it also confirms the genetic sequence responsible for polling.  It is also very encouraging that a genome-wide screen revealed no off-target mutations in this case, which is a persistent concern when using gene-editing technologies.  

“Compared to other examples of gene-editing in domestic animals to date, such as the micropigs, double-muscled beagles, and others which were developed as biomedical models for disease research, these polled cattle represent the first gene-edited agricultural animals used in food production.  While polling cattle in this way has obvious benefits to animal welfare and farm worker safety, as food animals they also present a clear challenge to regulatory authorities.  Gene-editing, at least as described here, does not introduce any gene sequences into lines of horned cattle that are not already present (and thus consumed) in naturally polled cattle.  Moreover gene-editing is “footprint free” and leaves no trace of residual gene sequence in the animal that would indicate it was the product of gene-editing.  The resulting gene sequence of the edited, polled animals is identical to that of naturally-occurring polled cattle.  

“Numerous other beneficial traits (e.g. resistance to various diseases) can be introduced by gene-editing in food animals. Regulatory agencies must decide if this sort of change is subject to regulation according to the process by which it was achieved, or by the resulting gene sequence. Gene-editing thus has the potential to facilitate the rapid introduction of highly beneficial traits into food animals without the biosafety, health and welfare concerns of traditional methods of modifying the genome.”

 

Dr. Max Rothschild, Distinguished Professor in Agriculture and Life Sciences, Iowa State University (webpage):

Expertise: Animal breeding and genetics, large animals, companion species.

This research example is particularly important because it clearly demonstrates the viability of using gene editing to reduce a costly health/welfare issue in cattle.    Furthermore, given there were no off-target effects this means the approach is well directed and there are no errors with negative effects. 

“This shows that there are serious issues in animal agriculture that can be reduced by gene-editing and that this approach is now well beyond the show and tell stage of micropigs and heavily muscled dogs.”

 

Dr. James Reecy, Professor of Animal Science, Iowa State University (webpage):

Expertise: Beef cattle genetics/genomics; bioinformatics.

“The most humane way to dehorn a calf is to use genetics.  In the absence of the this ‘polled’ locus in some cattle breeds, gene-editing is a great way to dehorn cattle.  Utilization of gene-editing in this case demonstrated that the identified mutation was causal and at the same time improved animal welfare in dairy cattle.  A real win win situation.  This case also opens an interesting discussion, if gene editing is used to introduce a naturally occurring mutation in a breed that did not harbor it, should it be considered natural?  I believe that it should be.”

 

Declared interests (see GENeS register of interests policy):

 

None declared.

 

Reference:

Production of hornless dairy cattle from genome-edited cell lines‘ by Carlson et al, published in Nature Biotechnology on Friday, May 6, 2016.

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