Yeah, the secret I was keeping is out. Your sibling companion is guaranteed to leave at the end of Act 1. They remain gone until the end of Act 3, though that is not guaranteed, depending on what happens during the expedition.

No matter where you are in the story, starting the 'Legacy' DLC involves your sibling. In the 'Mark of the Assassin' DLC, you can also choose your sibling as well, no matter where in the story.

As for Isabela: getting her approval is generally more difficult because she has no strong opinion on the Mage/Templar debate, though she probably leans towards mages, as she believes in freedom. She's also a mite tricky because she's pretty much the only companion who sometimes disapproves if you go out of your way to help people. She's probably the most difficult member to befriend.