The Baylor College of Medicine Human Genome Sequencing Center will produce draft sequences of the rhesus macaque and bovine genomes and extract maximal biological information from these data. At the same time the technology for deciphering large genomes will be improved. To do this, shotgun sequencing capabilities will be expanded (to 3.5 million reads/month) while reducing costs (to $0.50/read). A combined approach using both BAC and Whole Genome Shotgun reads will be employed, with the BAC sequencing employing the Clone Array Pooled Shotgun Sequencing strategy that has been developed at the BCM-HGSC. Assembly of the genomes will use the ATLAS genome assembly software, developed for the rat genome project at the BCM-HGSC, which will be enhanced during this project. The draft sequence products will also include 10-15% finished sequence. To achieve this, finishing capacity will be increased through the combination of incremental improvements in existing methods, application of the Genome Wide strategy used in the Drosophila melanogaster project, and a novel procedure using massive numbers of short inexpensive reads. Numerous other developments will occur throughout the BCM-HGSC operation during this project including establishment of a second more cost efficient facility for production sequencing, introduction of 192 plate formats and microfluidics in production sequencing, expansion of annotation capabilities, establishment of a software engineering team, and development of a high performance computing architecture. Augmenting the draft sequence products will be cDNA sequencing to assist in gene modeling.