Dear 100 Hour Board,
Are all dog breeds genetically compatible? What if a mad veterinarian inseminated a female chihuahua with saint bernard sperm?
Mico actually answered this in Board Question #61426. Basically, all dog breeds are genetically compatible, but if the female dog was significantly smaller than the male (as in your example) it is likely the mother would not survive the pregnancy, and the puppies probably wouldn't either.