The sequencing of the human genome, along with the development of high-throughtput technologies in genomics, provides an unparalleled opportunity to advance our understanding of the roles of genetic factors in human health, disease, and drug response. Genetic dissection of complex disease and variations of drug response has become one of the most important genetic research topics in recent years. Although genome-wide association studies are thought to hold the promise to identify susceptibility genes responsible to complex diseases, methodologies to take full advantage of the genotyping data are still lacking. Standard approaches typically only consider a limited number of hypotheses, most of which are on the effect of a single locus or a relative few loci, therefore do not accommodate the full range of genetic mechanisms that may contribute to the disease phenotype and variations of drug response. First Genetic Trust Inc. (FGT) has developed an innovative pattern discovery-based method to identify multi-locus genetic associations (enGENIOUS). Upon successful demonstration of the utilities and power of enGENIOUS in a SBIR phase I grant awarded by NCI in 2003, FGT intends to use this SBIR phase II proposal to further develop its proprietary genetic analysis methodology as well as to develop a software platform to commercialize the novel methodology along with others as a general tool box. In phase II of the project, FGT will extend enGENIOUS on a genome-wide scale, and will demonstrate the utility of combining enGENIOUS and selected conventional methodologies in whole genome association analysis by using whole-genome datasets from a FGT collaborator. Additionally, FGT will develop a comprehensive software package including an object data model for the representation of concepts (like data, analyses, results, etc.) in genetic analysis, an extensible Java software development toolkit for genetics (enGENUITYsdk) that implement the object model, an object-relational database for storing phenotypic and genotypic data, and a genetic analysis workbench (enGENUITY Workbench) that is either tightly integrated with FGT's enTRUST Genetic Banking System or as a stand-alone application. The proposed software package will significantly enhance the competitive advantage of FGT, result in the generation of an important new source of revenue, and significantly contribute to the discovery of susceptibility genes in complex diseases and variation of drug response.