The University of Washington Genome Center (UWGC) proposes continued participation in the National Human Genome Research Institute (NHGRI) Research Network for Large-Scale Sequencing. The UWGC has participated in the network since its inception in 1998 and is on track to contribute approximately 140 Mbp of finished human sequence to the Human Genome Project (HGP). To achieve this goal, the UWGC has implemented a highly automated process for the finishing stages of large-scale sequencing. The UWGC has also put in place sufficient capacity to produce raw sequencing data to support its finishing efforts, as well as raw-data collection for other sequencing projects on a scale of tens of megabase pairs. For large projects, including much of the UWGC's contributions to the HGP, the UWGC has pioneered large-scale outsourcing of raw-data production, a model that is likely to be increasingly relevant to large-scale sequencing as raw sequencing data become a commodity that can be routinely produced. The UWGC proposes, as its next production objective, to resolve gaps and suspected large-scale misassemblies associated with genomic duplications, in the April, 2003, release of the human-reference sequence. A unique feature of the proposal is the use of new technology developed at the UWGC for comparing high-resolution, clone-based physical maps of targeted regions in multiple humans. Hence, the proposed work will improve the quality of the human-reference sequence in targeted regions, confirm that the sequence of these regions reflects the common sequence organization found in the human population, and provide information about the extent of structural polymorphism in the region. When appropriate multiple alternative sequences of structurally polymorphic regions will be determined. Other capabilities of the UWGC such as its automated finishing capacity will be made available to the NHGRI network on an as-needed basis. ? ? ?
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