ABI 48-capillary 3730 DNA Sequencer is the major sequencing instrument of the DNA Sequencing Facility at the University of Pennsylvania. This NCRR Shared Instrument Grant application requests funding for an upgrade of the 48-capillary Sequencer to 96-capillary 3730XL format to meet the increased demand for high throughput DNA sequencing at a reduced cost and faster turn-around time. The 3730 sequencer is currently used to provide institutional investigators reliable, long read, automated DNA sequencing, and microsatellite-based genotyping. These services are essential to investigators for various purposes including, but not limited to, searching for alterations in candidate genes that may be associated with the pathogenesis of disease including cancer and diabetes or studying the evolutionary significance of sequence variations found among various DNA repeat elements observed in the genome. The integrated service for DNA sequencing, genotyping, template preparation, and other molecular biological procedures enables this core to provide full support for molecular genetic investigations, from consultation in experimental design to bioinformatic support for analysis and interpretation of the acquired data. [unreadable] [unreadable] The DNA Sequencing Facility is a major research service at Penn as demonstrated by a steady increase (~25%) in the number of sequencing samples processed during last three years. The projected number in 2005 is 104,000. Recently, following the recommendation of the core advisory committee, the facility has introduced high throughput sequencing at a very affordable cost to meet the large scale sequencing requirements of the investigators mentioned in this application. As a result, the number of sequencing samples is now projected to increase by an additional 25% every year. The turnaround time is likely to be compromised with the existing capacity since, at present, the 48-capillary sequencer is being operated almost at full capacity. To keep pace with the latest growth in usage from the high volume users and maintain the current turnaround time of 24 hrs, we propose to upgrade to 96-capillary sequencer. The cost of this upgrade is about half the price of a new 48-capillary sequencer. This will double the capabilities for sequencing and genotyping and will lead to higher throughput, faster turnaround time, and a further lowering of cost that will be beneficial to the high volume users as well as to all NIH funded and other users at Penn. [unreadable] [unreadable] [unreadable]