After cloning OS 10.8 mountain lion onto a 4 TB external hard drive with USB 3.0 support and a Sata III enclosure, it turns out that the computer cannot see the drive at boot holding the option key.
After testing, it's not the 3.0 USB enclosure the issue, an OSX clone on a 2TB Sata II drive boots fine.
So the issue is either the 4TB drive or the Sata III. I would suspect it is the 4TB disk capacity that is not supported for boot.
Since Sata III is backward compatible, it shouldn't be the issue.