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Functional Genomics of Cardiovascular Disease

Stephen G. Young¹, William Skarnes², Patricia C. Babbitt³, Conrad C. Huang4, and Thomas E. Ferrin4

¹ J. David Gladstone Institute for Cardiovascular Research
San Francisco

² University of California at Berkeley

³ Department of Biopharmaceutical Sciences
University of California, San Francisco

4 Computer Graphics Laboratory
University of California, San Francisco


This project is part of a major initiative known as the Programs for Genomic Applications (PGA) whose vision is to advance functional genomic research pertaining to cardiopulmonary and related diseases. Aims include the generation of broad and multidisciplinary approaches to understanding genetics-based characteristics of normal and abnormal cardiopulmonary function. The overall goals of the PGAs specify the development of information, tools, and resources to link genes to biological function on a genomic scale and to share all of the results freely and quickly with the larger research community. The Bay Area Functional Genomics Consortium (BayGenomics) comprises scientists from the J. David Gladstone Institute for Cardiovascular Research (Steven G. Young, overall PI), the University of California at Berkeley, and the University of California at San Francisco.

BayGenomics is using gene-trap vectors to inactivate genes in mouse embryonic stem (ES) cells for the purpose of generating knockout mice. This allows us to study a variety of phenotypes relevant to cardiovascular and pulmonary disease. To date, we have trapped hundreds of mouse genes, many corresponding to novel genes or ESTs. Some of these insertional mutants have already been transmitted through the germline. The characterization of these mice has uncovered completely novel gene products with important roles in cardiopulmonary development and disease.

Central to the success of these aims is a computational component (P.C. Babbitt, PI) charged with developing and applying bioinformatics protocols for handling, storage, annotation and presentation of all of the gene trap sequence data and in situ hybridization images. This aspect of the project entails development and maintenance of an extensive web site to provide public data access and search capabilities to our sequence tags database. The RBVI acts as the bioinformatics core to enable these objectives as well as provide the required database, ancillary software, and hardware infrastructure.

Another key component in these effort is hands-on training for scientists and researchers through the offering of regularly scheduled bioinformatics workshops. The workshops provides an environment in which participants explore web-based tools for the characterization of protein sequence and structure using database, motif, and profile searching, as well as transmembrane prediction, multiple alignment, and structure visualization tools.


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