I'm trying to piece it together, too, but here we go:
In addition to what's been said here already -
Aunt Martha talking about how the body is a prison, and we don't chose how we're born (sick, ugly, man, woman). Her daughter was born a girl, but may have had "gender identity disorder" as we know it today - that is, George felt he was a man trapped in a woman's body.
But, the "you wouldn't let me live a normal childhood" line, combined with "YOU can be my son" from Aunt Martha at the end, leads me to believe that male-ness may have been forced upon George by his/her mother.
But then, the way he injected the water-filled blow-up-doll with his blood. It was VERY reminiscent of male ejaculation. The syringe seemed like a surrogate penis, as well a way for George to get his DNA inside the doll. So then perhaps he is male on the inside and uses this as his release. Maybe his mother made him be a girl in his youth (as his physical gender prescribed) and this is how she ruined his childhood. After all, she is somewhat religious and doesn't seem too open minded about things like gender identity.
Also, if George is indeed Martha's blood relative, it still wouldn't be incest for him to pursue Cheryl. Cheryl came to the hotel looking for her uncle, and found his wife. Her uncle is dead. She's only related to Martha by marriage, and since Martha (presumably) conceived George without her uncle ("there are other ways") then they are not related by blood.
I believe it was Martha who killed Alice. When she was coming after Cheryl with the machete, Cheryl said, "don't hurt me!" Martha said, "it won't hurt. It'll be quick, just like with Alice."
Additional thoughts totally appreciated.
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