@shikamaru317 - I wouldn't take MatPat as a deep, meaningful analysis on anything. His purpose has aways been to entertain his audience with ludicrous ideas peppered with some didactic science, conspiracy theory style. See Mario is an evil communist, for instance.
Usually I would agree, and alot of his theories I have found to be downright asinine, but in this case his theory turned out to be 100% right in the end, and his science was sound.
I think someone did the maths of the inbreeding coefficients for all the generations of Targaryens, and they're actually sky high, even for Jon. In fact to the point the family is close to a homozygous group of individuals differing only by their sexual chromosomes.
(Fun trivia: such groups of individuals do exist in real life - lab rats, for instance. With proper eugenics, paradoxically, it's outbreeding that would increase the risk of harmful recessive genes contaminating the pool. Assuming random mutation doesn't work faster between generations, that is.)
And considering the whole Lannister-Baratheon plot involved a piece of Mendelian genetics inacessible to the brighest medieval thinkers and the whole "family look" being fixed for centuries, it seems we should give GRRM's biology a pass here.