This proposal requests funds to upgrade an Illumina Genome Analyzer IIx (GAIIx) to an Illumina HiSeq 2500 (HiSeq 2500). The HiSeq 2500 is a state-of-the-art high-throughput DNA sequencer that has the ability to generate many hundreds of millions of reads per sequencing run. The proposed instrument will be housed and maintained by the Stanford Functional Genomics Facility (SFGF), a service center in the School of Medicine at Stanford University. The facility offers expertise, support, resources, and services for genomics and proteomics based research utilizing microarray technologies and high-throughput sequencing to NIH researchers at Stanford University and other local research institutions. As many investigators have turned to high-throughput sequencing (HTS) for functional genomic studies and will continue to do so in the future, it is critical that the servic center maintain current state-of-the- art instrumentation so that the pioneering research pursued by Stanford researchers can continue. The HTS capabilities of the propose Illumina HiSeq 2500 are required to meet the demands for HTS and give NIH-funded researchers at Stanford University and elsewhere the ability to further understand how our genetic code affects human health and disease.