You bring a desired gene into a breed in the same way that you introduce a desired trait into a line within a breed. You outcross to a dog with the gene you want. You then breed back to type using only those offspring that inherited the gene you are introducing. The gene for normal uric acid metabolism (U) no longer existed in Dalmatians, who all had two copies of the mutant gene (u). It could only be reintroduced by using a dog of a different breed.
The Start of the Backcross Project
In 1973 Dr Robert Schaible mated a Champion Pointer to an AKC registered Dalmatian bitch in order to get a copy of the gene for normal uric acid. This was the one and only time a Pointer was used in the Project. The pups were all Uu as would be expected. They were also far from typical Dalmatians. He chose a single pup from this litter and bred again to an AKC-registered Dalmatian (Uu x uu). The resulting pups from such a breeding are, on average, half Uu and half uu. Those that are Uu carry the recessive gene, but produce normal levels of uric acid.
Development
The Backcross Project continued to select pups that combined the NUA gene with the best adherence to Dalmatian type and bred them to champion or show-winning AKC-registered Dals (all HUA). The pups were all on average 50% HUA (uu) and 50% NUA (Uu). This practice not only increased Dalmatian type in the offspring, but ensured that the NUA gene was distributed as widely as possible among the existing Dalmatian bloodlines, thus avoiding the risks of inbreeding and genetic bottlenecks.
Currently some Uu Dals are being crossed with other Uu Dals, resulting in litters that are ¼ UU, ¼ uu, and ½ Uu. All the pups bred from the UU Dals will enjoy normal uric acid levels, For the most part, however, the NUA Dals continue to be mated to HUA ones. Genetic diversity within the breed remains an important goal of this Project.
Backcross Dalmatians Today
After 14 generations, the Dalmatians of the Backcross Project are typical of the breed in conformation and temperament. Their spotting, once a source of concern, is now well within the size dictated by the Standard. With each generation, fewer genes from the Pointer are carried forward. Only tests for uric acid levels and (since 2008) genetic tests ensure that the healthy NUA gene has been passed on. The only difference between NUA and HUA Dalmatians is that NUAs have had a working copy of gene SLC2A9 restored to them along with the ability to form allantoin instead of urate stones and crystals.