We propose to purchase a Solexa Genome Analyzer System from Illumina. High throughput sequence data will positively impact campus research. Twenty-one investigators will be enabled to perform projects in the areas of: 1) genome resequencing to identify bacterial virulence determinants and to correlate human gene variants with disease susceptibility;2) interaction of proteins with chromosomal DNA throughout the genome in order to understand transcriptional and epigenetic regulation;and 3) genomewide gene expression to enable understanding of the comprehensive picture of transcription from coding sequences to noncoding RNAs. High throughput DNA sequence technologies have two very significant advantages over current technologies. First, data are collected so efficiently that fundamental changes in experimental design are enabled, for example by allowing rapid resequencing of bacterial genomes for variations association with virulence or resequencing segment of the human genome for SNP association studies. Second, most applications of sequencing are less dependent on what is already known than microarrays, the other major genome wide analysis tool which is completely dependent upon knowledge of target genome sequence or in the case of some gene expression arrays, also dependent on knowledge about what is transcribed and even what is spliced. The sequencer will be added to the current DNA and Protein MicroArray Facility to form a UCI Genomics Core Facility. Funds have been committed by the campus to complete purchase of the Solexa instrument and extended warranties and purchase the necessary accessory equipment, and to hire a full time technician and part time systems administrator to staff this expansion. Acquisition of the sequencer will have a high positive impact on research and training at this rapidly growing UC campus. PUBLIC HEALTH RELEVANCE: A consortium of investigators from across campus proposes to acquire a Solexa high throughput sequencer from Illumina for the UCI Genomics Core Facility. High throughput sequencing dramatically increases the amount of sequence which can be collected in one experimental operation. Addition of this instrument to the Core Facility will enable exciting biomedical research. Projects include sequencing entire bacterial genomes to discover virulence determinants, analysis of human genomes to identify sequence variants associated with disease, identification of sites across the human genome where cancer-related regulatory proteins bind to control gene expression, and quantification of changes in gene expression in a sheep model for lung cancer.