Special Scientific Procedures Core: Genomics

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In the last two years, there has been an explosion of novel technologies for the acquisition and interpretation of genomewide human molecular genetic data, including development of whole genome association (WGA) microarrays and statistical methods, as well as the publication of the HapMap to provide a context for accelerating the analysis and synthesis of such genomics data. Having published the first WGA study of schizophrenia (Lencz et al. 2007), we are cognizant of the technical and statistical complexities involved in applying these novel technologies. Therefore, the Special Scientific Procedures Core: Genomics plays a critical supportive role in the proposed CIDAR. The Genomics Core has three primary aims, necessary to the completion of CIDAR goals: (1) to provide basic laboratory services to CIDAR investigators such as blood draws, DMA extraction, creation of immortalized cell lines, and sample storage; (2) to provide methodological expertise in state-of-the-art genotyping and sequencing platforms, including high-precision QA/QC procedures; and (3) to provide advanced statistical support, including development of new techniques, relevant to this large scale, genomewide data collection. Laboratory services are well-equipped to store, track, and genotype large numbers (thousands) of patient samples rapidly and accurately using high-throughput technologies and robotics. Genotyping platforms include scanners for both Affymetrix microarray chip sets and Illumina Bead Arrays, and can support high density whole genome association studies and comprehensive SNP tagging strategies. In the last 18 months, more than 1 billion genotypes have been generated in our facility, and maintenance of high standards for genotyping QA/QC is a central focus of the Core, resulting in several top-tier publications. Statistical services provide expertise and published track records in critical issues for large genetic datasets, including: data reduction and complexity reduction methods, haplotype estimation and haplotype tagging strategies, gene-gene and genotype-phenotype interactions, and Bayesian and other multivariate modelling techniques. Development of novel methods (such as whole genome homozygosity analysis and analysis of copy number variation) is a priority of the Core. The Genomics Core will work together with both the Operations and Clinical Assessment Core, and the Research Methods Core: Cognitive Neuroscience, to apply genomics to prediction of both clinical treatment response phenotypes and neuroscientific endophenotypes.