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A mastiff dog poses lying down on its stomach,with reading glasses on its face, and a book at its side.

It was after a home invasion almost a decade ago that David Ishee first got interested in breeding dogs. A burglar with a gun had broken into his home in Jackson, Mississippi, where Ishee was asleep along with his wife, 3-year-old-daughter and newborn son. Ishee pulled out his own shotgun and scared the would-be thief off. But he was unsettled wondering what might have happened had he not been around.

Ishee wanted a guard dog, and giant, docile mastiffs are good ones to have around little kids. Like so many carefully bred dogs, though, mastiffs are riddled with genetic disorders. So Ishee decided to start breeding them himself, with plans to increase their genetic diversity and hopefully make them healthier, happier and more fit. Over just a few generations, he saw results. Gone was the sagging skin and oversized head that makes so many mastiffs look goofy. He told me his dogs could jump higher and run faster than most other Mastiffs can.

But because the majority of the genetic disorders dogs suffer from are recessive, Ishee...