The goals of this program project are to establish a coordinated team which will make a significant contribution to the sequencing and analysis of the human genome. Our goal is to produce highly accurate sequence in a cost effective manner. The goal of the immediate 3 year period for which funding is requested is to sequence a major portion of chromosome 18. We are requesting this 3 years of funding as part of a more extended effort to scale up to 50-100 megabases per year in a 4-5 year period and use this capacity in other areas of the genome that require sequencing. A unique aspect of this program is the intensive external verification we are proposing to build into the sequencing process. This holds the promise of not only assuring the high quality of the resulting sequence, but of greatly facilitating the assembly process; which is the rate limiting step in large-scale DNA sequencing.