We propose the acquisition of a new Illumina HiSeq 2500 1Tb high-throughput DNA sequencing instrument. The instrument will reside in a service center core and serve at a minimum 25 laboratories and hundreds of Stanford biomedical researchers. The sequencer will greatly increase throughput and shorten turnaround time while dramatically reducing costs. Moreover, the instruments that are currently present in the DNA sequencing core are at the end of their lifetimes (well over four years by the earliest start date of this grant) and lack the hardware specifications that are needed to meet the vendor's requirements for upgrade eligibility. There is sufficient demand that the HiSeq 2500 1Tb instrument will run at maximum capacity. The Major and Minor Users highlighted in this proposal range from junior faculty who are just starting their own laboratories to established full professors with over 30 years of research experience. Nearly all of the Users have NIH funding, and their genomics studies depend on affordable and customizable ultra high-throughput, next generation sequencing technologies. DNA sequence data collected with the proposed instrument will positively impact a broad cross section of human diseases and disabilities, notably: cardiovascular disease, hypertension, type 2 diabetes mellitus, inflammatory bowel diseases, developmental defects, cancer, sleep disorders, schizophrenia, autism, and aging. Several of the investigations examine environmental stressors as well. The research performed in these studies will help pave the way for better interpretations of human genome polymorphisms as well as the translation of new assays and technologies to the clinic. Stanford researchers who perform DNA sequencing assays made possible by this instrument publish very high profile studies, and so we expect this instrument to have a major impact in biomedical research.