You know two guys who are brothers but don't look or act the same at all. You're talking about them with a friend who just met them. You say:
You'd never guess they were related.
The meaning of "You'd never know ___" is "You would never guess ___ if someone didn't tell you." In other words, this means that something isn't easy to guess on your own. For example:
Look at this gorgeous pair of shoes! You'd never guess that they were only $30.
You'd never guess that she's 60 years old. She looks like she's in her 40s at most.
"You'd never guess" is followed by a clause, which is kind of like a sentence inside of another sentence. That clause is usually written in the past tense ("they were related" instead of "they are"). In written English or more formal speaking, you'd say it this way:
You would never guess that they were related to each other.
You can also use other words like "know" and "think":
You'd never know that this neighborhood was once one of the roughest parts of town.
You'd never think that such a tiny amount of water could cause so much damage.
People who belong to the same family by birth "are related to" each other:
I grew up calling him "grandpa", but we're not technically related to each other.
You can say that people are "related to" each other, or you can just say that they are "related". But you can't just say that one person is related:
A: Johanna is related.
B: Huh? What do you mean? Related to who?
A: I mean, she's related to me.
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