081998 · The lethal white
In 1998 somebody found the letter, and the worst thing about this breed became avoidable.
One copy of the frame gene gives you a frame overo horse and costs it nothing. Carriers are ordinary healthy animals with no condition attached to carrying it. Two copies is a different thing entirely.
A foal born with two copies goes the full eleven months and arrives looking perfect, almost entirely white, with blue eyes. Inside, its colon has never developed the nerves it needs to work. Colic starts within hours, there is no treatment, and the cruelty of it is that the foal looks completely well.
It was traced in 1998 to a single letter changed in a gene called EDNRB, the same gene behind Hirschsprung's disease in people. Every frame overo horse tested carried one copy. That was the whole answer, because a gene you can name is a gene you can test for.
It only ever happens when two carriers are bred together, and it has been avoidable for a quarter of a century, because the test takes a few hairs from a mane. There is no reason to take the risk either: breeding two frames gives exactly the same odds of a live frame foal as breeding one frame to a non carrier.
The catch is that you cannot do this by eye. Frame hides. Testing finds carriers among horses filed as breeding stock solids and among horses filed as tobiano, which is how the accidents happen. Read that next to the 1940 rule and it is the same fact from the other end: white on a horse never did tell you what it was carrying.