We also have shown that almost all of the known mouse exons have corresponding orthologs within the human OPRM1 gene locus and thus the genetic structure of human OPRM1 is much more complex than is currently appreciated. According to recent studies, at least 50% or more of human genome is expressed in alternatively spliced isoforms (63). There is a number of both computational and molecular biological difficulties that make computational predictions and cloning of the genetic variants of OPRM1 highly challenging. The novel approaches used in this study overcame these difficulties. The discovery of a much more complicated receptor structure makes possible new interpretations of existing results and permits the generation of novel testable hypotheses in diverse disciplines that have interest in studying the OPRM1 function.