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Director: Judy Cameron
Co-Directors: John Crabbe, Chris Cunningham, Theodore Hobbs, Douglas Williamson

To build on the long history of the PARC of seeking to identify the genetic underpinnings of alcohol-associated traits in rodent species, we propose a novel and potentially very powerful approach in nonhuman primates in this component.

This project will seek to identify genes associated with individual differences in behavioral and physiological measures that have been identified as indicators of risk of alcoholism in humans or of an increased propensity to consume alcohol in animal species.

Specifically, we propose to capitalize on an ongoing linkage study in young rhesus monkeys designed to identify the genes underlying anxious and depressive behaviors (behaviors which themselves have been linked to increased consumption of alcohol), by screening the same monkeys for additional behavioral and physiological responses.

This ongoing linkage study utilizes a very large group of the rhesus monkeys at the Oregon National Primate Research Center (ONPRC), and involves phenotyping and genotyping approximately 800 infants and 400 parents over a five-year period (supported by an already funded NIMH grant, MH62568, J. Cameron, PI). The power in the study comes from the fact that the whole population is highly related, and can be mapped into a single pedigree, so that each infant is expected to have an average of 23 half-siblings, several full siblings, and a number of cousins, and there is the ability to study parents, grandparents, and many greatgrandparents.

Our ability to use this population of already-genotyped monkeys represents a truly unique opportunity in that (a) worldwide, no other colony of monkeys has been similarly genotyped, (b) no other colony of monkeys has been as extensively phenotyped for anxious behaviors, (c) this is a highly interrelated group of monkeys which greatly increases the power for linkage analyses, and (d) ONPRC plans to maintain these already established groups of breeding monkeys for the next five years.

The specific aims of this project are to (1) phenotype this large cohort of monkeys and their parents for alcohol-induced behavioral and physiological changes and CSF serotonin and 5HIAA levels, (2) do a genome scan to identify QTLs underlying these phenotypes, (3) begin to examine candidate genes linked to alcohol-associated traits starting with the serotonin transporter polymorphism (HTTLPR), and (4) to ascertain whether temperamental characteristics related to anxious behavior predict an animal's responsiveness to ethanol.

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by Mark Rutledge-Gorman
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