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Integrative Analysis Of Drug Addiction

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Substance abuse disorders are prevalent and present a tremendous societal cost. An important strategy to categorize and understand the underlying biology of addiction is functional genomics. Aggregated evidence from numerous heterogeneous functional genomics studies can be employed to nominate genes and variants underlying disorders of addiction. Through our web based software system and database of heterogeneous functional genomics studies of addiction, GeneWeaver.org, we provide the facility to identify plausible molecular mechanisms for addiction related behavior through integrative analysis of genomic data sets that span multiple experimental platforms and species. Here, we apply this approach to identify a gene involved in the acute cocaine locomotor response. …show more content…
Combinatorial analysis using GeneWeaver identified Rab3b, based on its co-occurrence with previously published QTL mapping studies of cocaine related behaviors; methamphetamine related climbing and Cartpt (Cocaine- and amphetamine-regulated transcript prepropeptide) abundance; convergent evidence related to other abused substances; density of polymorphisms; and its expression pattern in reward pathways. Experimental evaluation of the Rab3 complex in cocaine response using B6;129-Rab3btm1Sud Rab3ctm1sud Rab3dtm1sud triple null mice (Rab3bcd-/-) supports a role in acute cocaine response. These results demonstrate the value of functional genomic data integration toward the identification of molecular mechanisms of addiction and other

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