Pete Carrol's USC lost to Stanford (when Walt Harris was coaching there) and was a 30+ OT favorite.
Michigan list to Appy State and that was +35 I believe.
It can happen especially if game 1 is vs a supposed 1-aa tomato can if the favored home team isn't focused. Heck GA southern when they were 1-aa beat Florida in the swamp on SEC cream puff Saturday in November.
Leach shouldn't be losing that game though. His situation and that kind of game can get him canned.