Component 1. Mapping and Sequencing - This component provides targeted sequencing data in the forms of BACs or targeted genes to assist biomedical investigators in addressing sequence-based biological hypotheses. We are working with the HL&B research community to sequence relevant genomic regions from appropriate organisms that are not being sequenced by public efforts.

Component 2. Comparative Genomic Informatics - The major goal of the informatics component will be to develop the next generation of comparative genomics tools and databases to meet the opportunities present in increasingly evolutionarily complex sequence datasets. The target users of these informatic resources will continue to be biomedical researchers, and thus focus will be placed on generating tools and databases that will be easy to use with readily interpretable results.

Component 3. In Vivo Regulatory Element Analysis - A large number of genetically engineered mice were created to assess the function of sequences identified through the Berkeley PGA sequencing and informatic resources. The biological insights derived from these studies served to advertise the utility of the resources generated by the Berkeley PGA. This component contributes to biological demonstrations of this PGA's resources as well as building a catalog of functional human enhancers.

Component 4: Clinical Re-Sequencing - The genetic basis of sporadic congenital disorders has increasingly been shown to be due to mutations in "candidate" genes. The reference human genome and our recent alignment with the Joint Genome Institute, the Berkeley PGA is poised to further explore this new area in human/clinical genetics. Accordingly, we will devote a small portion of the Berkeley PGA sequencing capacity to re-sequence appropriate sets of candidate genes in individuals with idiopathic HL&B congenital disorders.

Component 5. Education and Outreach Programs - We have been introducing HL&B researchers to genome bioinformatics and the resources developed by this PGA, through a combination of publications, our web site, presentations at scientific meetings, several 3-day long courses organized in Berkeley. We will continue to use all of these venues to increase awareness and accessibility of genomic information to HL&B investigators.