Project Summary/Abstract (Core B: HS Breeding Core) The heterogeneous stock (HS) Breeding Core (PI: Dr. Leah Solberg Woods) will maintain an HS rat colony at the Wake Forest University School of Medicine (WFUSM), and a satellite colony at the University of California San Diego (UCSD). These colonies will produce and distribute HS rats at a subsidized price to encourage their widespread use. HS rats were created in 1984 by interbreeding eight inbred rat strains. Since their creation, HS rats have been maintained as an outbred population for almost 100 generations. Recombinations have accumulated over those generations, which break the founder chromosomes into small haplotypes, which is essential for fine-mapping of genetic loci. Dr. Solberg Woods has maintained the HS rat colony since 2006; the colonies at WFUSM and UCSD are the only HS rat colonies in the world. Over the last decade, the HS rat Breeding Core supported by our P50 center became a heavily used national resource. That core sent out more than 16,000 rats to more than 25 universities in the US and to Italy, Germany and Spain. This core will support numerous funded and submitted grants. In addition to providing HS rats, this core also supports a new and innovative paradigm called RATTACA (RAT Trait Ascertainment using Common Alleles) that uses data collected over the last decade to predict the phenotypes of newborn HS rats based on their genotype. As we describe, RATTACA can be used to predict any of the phenotypes that have been the subject of prior genome wide association studies (GWAS) in HS rats. This allows this core to provide rats that are likely to display extreme phenotypes, somewhat analogous to what has previously been available using genetically selected lines. RATTACA will allow us to expand the center’s impact by supporting scientists who are not geneticists. RATTACA prediction works best when a few rats can be genetically selected from a larger population, making it a perfect complement to an HS Breeding Core that produces large numbers of HS rats. RATTACA rats can be used for unique study designs. For example, we can identify rats that would show strong susceptibility or resilience to cocaine addiction-like behaviors. Normally, such rats would be identified based on their observed phenotype. However, differences between such groups might then be due to the different levels of cocaine exposure in the high and low groups, or to the genetic predisposition that led them to self-administer different amounts of cocaine. Using RATTACA, cocaine naive groups that are genetically susceptible or resilient to cocaine addiction-like behavior can be compared; observed differences must be due to this genetic predisposition. Thus, RATTACA is an innovative experimental paradigm that will be offered as subsidized service by this core, thus broadening the impact of our center.