The central goal of the Berkeley PGA is to accelerate heart, lung and blood (HL&B) researchers use of comparative genomics for deciphering biomedically relevant features in the human genome. Towards this end, in the prior funding cycle our major production activities involved: 1) the development of an extremely popular suite of comparative genomic tools (VISTA) and associated databases targeted at HL&B investigators, and 2) the generation of DNA sequence data from multiple species for genomic intervals requested by a large number of biomedical investigators. We advertised these resources through our education programs and provided key examples of the power of these datasets and tools through several internal PGA demonstration projects. The latter lead to several high-profile publications (Pennacchio et al., Science 294:169-73; Boffelli et al., Science 299:1391-4; Nobrega et al., Science 302:413; Nobrega et al., Nature 431:988-93; Noonan et al., Science 309:597-9) demonstrating the utilities of the resources generated by this PGA. In the next 4 years, we will continue popularizing comparative genomics for biomedical investigators through: 1) sequencing for HL&B investigators regions in the genomes of organisms not being sequenced by the public sequencing efforts, 2) the development of new user-friendly comparative genomic tools focused on aiding biomedical investigators, 3) "high throughput" in vivo assessment of putative gene regulatory elements identified by cross-species sequence comparisons in genetically engineered mice, 4) clinical resequencing projects to examine a large set of candidate genes suspected to cause sporadic HL&B disorders, and 5) a multi-faceted education program. Specific Aims      Components      Research Group Organization Quality Control