While George is Lennie's best friend, he still mistreats him a lot. George often speaks to Lennie about how much easier (and better) his life would be if he didn't have to take care of him. He also admits to playing hurtful pranks on Lennie in the past, which would often cause Lennie to be injured (or for him to do something ridiculous). George also belittles Lennie by expressing his relief that they're not related. George doesn't understand Lennie's disability fully, which is why he falls into the pattern of mocking and belittling Lennie. This also shows that other characters define Lennie as a product of his disability. This promotes a culture of misunderstanding. Some view Lennie as a child-like, harmless man, while others view him as a dangerous and unintelligent man. These two views (and the ways in which those on the farm don't seek to fully understand him) leads to his isolation and eventual murder of Curley's wife.
[P1] Lennie is often mistreated by others (specifically George) for his disability. [P2] Due to the way in which George and others treat him, Lennie is not able to be fully understood by others. [P3] Since Lennie is not understood by those around him, he stays isolated from others. [P4] Lennie's isolation causes him to be in an environment where he was able to kill the puppy without anyone noticing (which then leads to him accidentally killing Curley's wife).