Mouse geneticists have classically used one of two approaches to analyze a murine genetic model. The first approach is to conduct linkage (quantitative trait loci, QTL) studies on mice derived from the interbreeding two or more strains of mice. The identification of the Gnao1 as a regulator of opioid physical dependence provides an important successful example for pain research [16]. The recombinant inbred strains produced by the Collaborative Cross have enhanced the power of this approach [17, 18], and sophisticated data analysis tools are now available [19]. As an alternative approach, HBCGM can be used to conduct a genetic association study, which correlates phenotypic responses with the patterns of genetic variation present in a panel of 10 or more inbred strains [20]. The pattern of genetic variation is represented by haplotypes, which were constructed from analysis of sequence data obtained from a large number of inbred strains. This approach has identified several genes involved in opioid maladaptive responses [12–14]. However, the lack of genome-wide sequence information for an adequate numbers of inbred mouse strains has previously limited the power of
