It has been confirmed by the programmers and writers of the game that while Altaïr (of the first game in the franchise) and Ezio are both ancestors of Desmond Miles, they are both from different bloodlines and not related to each other.
Fans often confuse this game as being Assassins Creed III because it was the third major release in the franchise. Assassins Creed: Brotherhood and Assassins Creed: Revelations are continuations of Ezio Auditore's story while Assassins Creed III featured a new ancestor.
Desmond tells Rebecca that there are still some problems with the translation. Rebecca tells Desmond to be careful if he encounters any French or Germans. But when you meet the French captain he speaks better English than the Italians.
Juno: In the beginning, we set our truths to parchment. To stone. To the memory of men. These proved impermanent things. Cleansed by fire. Cleansed by famine. Cleansed by flood. All the world is innocent once more. Innocent and ignorant.