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Chunk #15 — Discussion

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The Netrin-1 receptor DCC is a regulator of maladaptive responses to chronic morphine administration.
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Our experiments were designed to help us better understand the maladaptations to chronic opioid administration that limit the clinical utility of our most powerful class of analgesics. A significant number of molecules have been mechanistically linked to opioid maladaptations including cell surface receptors, ion channels, drug transporters and other proteins. However, very few studies have leveraged genetic techniques to discover the genes involved in hypothesis-free fashion. One technique, HBCGM, has shown great promise in this respect, but has to this time been limited by the lack of whole genome sequence information and the availability of the informatics required to use this information. The present results demonstrate that robust mapping studies can be completed using newly developed tools and relatively easily obtainable whole genome sequence information thus largely overcoming the previous limitations. Our principal findings were, 1) that multiple candidate genes could be identified by the whole genome mapping of 23 strains of common inbred mice, 2) that techniques such as combining the mapping results of related phenotypes and re-sampling of strain information can be used to help rank the candidate