Cows have a protein in their white blood cells helps to make nitric oxide (a molecule very toxic to bacteria, including tuberculosis). It has been shown in other instances that if you have more of the protein (NRAMP1), then you tend to be more resistant to tuberculosis, and less of the protein, then you are less resistant to a tuberculosis infection. The protein itself is a transmembrane iron transporter. It just shuffles iron from one side of the membrane to another.
Cows already have the dna that encodes for NRAMP1, but in order to demonstrate their prowess with CRISPR technology, this group found a dormant location in the cow's genome in order to insert DNA that encodes a second copy of the same protein. The expectation being that by having a duplicate copy of the DNA that encodes for the NRAMP1 protein, more of the protein would be produced, and the cows would be less susceptible to tuberculosis. This seems to have been the case.
So here, adding DNA encoding a protein that already existed in the cow's genome allowed more of the protein (NRAMP1 - an iron transport machine) to be produced, thus conferring some tuberculosis resistance by means of allowing the cows white blood cells to produce nitric oxide more efficiently.
"Ishee was preparing for a project that sought to cure hyperuricemia in Dalmatians—a common liver malfunction that frequently results in kidney stones, bladder stones or gout.
"It should be straight forward," he told Gizmodo. Ishee plans to use the gene-editing technique CRISPR to correct the single errant nucleotide that causes the condition, reversing the mutation to turn a T in the genetic code back into the correct G. Then he'll use a technique called sperm-mediated gene transfer, which will allow him to transfer his engineered Dalmation DNA to a female Dalmation, resulting, he hopes, in a fertilized egg that'll produce hyperuricemia-free pups.
"The animals just get molecular surgery to fix a broken gene that causes their bladders to explode," he said. "Then those animals can become the founders on a healthy generation of Dalmatians and breed the disease away in a few years.""
If it's such a simple genetic flaw, why isn't marker assisted selection breeding used to eradicate the problem? Such a thing could even easily be mandated by law.
Tangent: This is nice popsci reporting. Reasonable, not very hyped, contextualized laymen explanation of a technical paper, with a link at the bottom direct to the source.
One interesting thing about what they did was they assayed potential insertion sites with ChIP-seq to see how much off-target effects there are. They used a catalytically inactive cas9 for IP to see the quantity and strength of off-targets.
Cows already have the dna that encodes for NRAMP1, but in order to demonstrate their prowess with CRISPR technology, this group found a dormant location in the cow's genome in order to insert DNA that encodes a second copy of the same protein. The expectation being that by having a duplicate copy of the DNA that encodes for the NRAMP1 protein, more of the protein would be produced, and the cows would be less susceptible to tuberculosis. This seems to have been the case.
So here, adding DNA encoding a protein that already existed in the cow's genome allowed more of the protein (NRAMP1 - an iron transport machine) to be produced, thus conferring some tuberculosis resistance by means of allowing the cows white blood cells to produce nitric oxide more efficiently.