Thread: Verbal negation in a sentence - both accusative and genitive?

I was always told that if I have an animate noun after a verb like знать I use genitive
For instance,

Я знаю этого человека.

However, I found that having negation in the sentence can turn it to accusative

Ты не знаешь его жену?

But can I still say

Ты не знаешь его жены?

If I can use both...then my questions are:
Is there a big difference? What would you say?