Welcome, Batjon! Yes, you absolutely can make those changes for your chronicle. In the book, this is explicitly laid out on page 6. You don't have to start with the first generation of the family to be cursed. Part of the normal family and character generation process is deciding how long ago the curse began, so it is fairly typical to be at least several generations removed from the first Rookwood to bear the curse. The book is set up to allow the Chronicler and players to decide the family history and the starting time and place together, but it also says the Chronicler may decide one or more things in advance in order to do research and prepare reference materials. If you want to make all the decisions yourself before starting, you can do that. Although, I would recommend leaving a few things to be determined by the players, because it can help get them more invested in the campaign. (Some players prefer to focus entirely on playing their character and they don't want to know about or control anything that their character doesn't. The only input they want to have over the setting is whether or not to play in it. They might prefer it if you decided everything in advance and just threw them into the setting to explore everything without any "spoilers" from seeing behind the scenes. You know your players better than I do, so you'll have to do what's best for your particular group's style.)
The default setting assumes that the Rookwood family are somehow cursed with dark Gothic powers that slowly consume them, but you can alter that a lot and still benefit from the game's dramatic systems. There will be an expansion called "Rookwood Roots" that demonstrates how much you can change the game to fit other settings and other families or close-knit groups that aren't necessarily blood relatives (see Update #15 on the Rookwood Kickstarter page). If "The Curse of the House of Rookwood" can be used for Philippine revolutionaries, a team of mutant superheroes, or a starship crew, then it can easily handle a family with a vampire great-uncle which is already fairly close to the default game setting.
If you want to make vampirism the family curse, you can customize it however you like. That's a very versatile curse! You could decide that the vampirism comes with a specific set of powers and weaknesses or you could go the Anne Rice/White Wolf route and say "there are a few things they all have in common, but the gift is different for everyone" so each vampire can have their own unique talents. The same for lycanthropy. Will it be the classic Lon Chaney/"Teen Wolf"/Chewbacca-style wolfman or the "American Werewolf in London/Paris" type or even the traditional type that just looks like a regular wolf? Is silver a weakness or is that just an invention of the movies? If your players want to figure these things out in play, then I would suggest making some minor changes to the standard vampire and werewolf just to give them some surprises. It's almost a cliche at this point for vampire movies to include a scene where someone explains vampires with the introductory phrase "Forget what you've seen in the movies", but that can be fun in an RPG because the players can discover the new facts themselves in play instead of having them explained to them as a passive audience. One of my favorite scenes in "From Dusk 'til Dawn" is when they decide that they are dealing with vampires and try to figure out what to do. "Forget about what you've seen in some movie. What do we know about these vampires?"
Keep us informed and let us know how it goes. If you have any questions or cool ideas to share, post them here and the community can help out. (I just recommended Rookwood in a Dark Shadows thread on rpg.net, so if that's where you found out about Rookwood, it would be good to post about it over there too. That forum is obviously much larger and more active than our little corner of the internet here.)