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David C. Schwartz

Professor of Chemistry and Genetics

Lab Home Page:

Schwartz Lab

Address:

5434 Genetics/Biotech

Telephone:

265-0546

Email:

dcschwartz@wisc.edu

Research Fields:

Genomics

Research Interests

Single molecule approaches to whole genome analysis

Research Description

The human genome is formidably complex, consisting of over 3 billion basepairs. Efforts to sequence and to ultimately understand the function of all 100,000 genes has been a major focus of the Human Genome Initiative. Only recently has the genomics community come to grips with the need to analyze in detail, large numbers of individuals in terms of detailed sequence information and careful annotation. Unfortunately, the physical and computational means to accomplish these goals are rather nascent. Our laboratory is developing genome analysis approaches based on using individual DNA molecules as the main substrate for our analysis. Remarkably, single DNA molecules can be readily imaged using fluorescence microscopy. Developments in our laboratory have enabled the biochemical analysis of individual DNA molecules that we fix in large numbers to positively charged surfaces. An automated system combining image analysis and map construction algorithms (Optical Mapping), enables construction of high-resolution restriction maps from a variety of DNA sources. Using large DNA molecules directly extracted from genomes, Optical mapping generated whole genome maps of several microorganisms, including Deinocccus radiodurans, Plasmodium falciparum, and several strains of E. coli. Recent accomplishments have included the mapping of over 60% of the human genome. Such maps are useful scaffolds for sequence assembly, and point the way to large-scale genome analysis of large populations.

Representative Publications

• Ramanathan, A., Huff, E.J., Lamers, C.C., Potamousis, K.D., Forrest, D.K., and Schwartz, D.C. 2004. An integrative approach for the Optical Sequencing of single DNA molecules. Anal. Biochem. 330:227-241.
• Zhou, S., Kile, A., Bechner, M., Place, M., Kvikstad, E., Deng, W., Wei, J., Severin, J., Runnheim, R., Churas, C., Forrest, D., Dimalanta, E., Lamers, C., Burland, V., Blattner, F., and Schwartz, D. 2004. Single-molecule approach to bacterial genomic comparisons via Optical Mapping. J. Bacteriol. 186:7773-7782.
• Ambrust, E.V., Berges, J.A., Bowler, C., Green, B.R., Martinez, D., Putnam, N.H., Zhou, S., Allen, A.E., Apt, K.E., Bechner, M., Brzezinski, M.A., Chaal, B.K., Chiovitti, A., Davis, A.K., Demarest, M.S., Detter, J.C., Glavina, T., Goodstein, D., Hadi, M.Z., Hellsten, U., Hildebrand, M., Jenkins, B.D., Jurka, J., Kapitonov, V.V., Kröger, N., Lau, W.W.Y., Lane, T.W., Larimer, F.W., Lippmeier, J.C., Lucas, S., Medina, M., Montsant, A., Obornik, M., Parker, M.S., Palenik, B., Pazour, G.J., Richardson, P.M., Rynearson, T.A., Saito, M.A., Schwartz, D.C., Thamatrakoln, K., Valentin, K., Vardi, A., Wilkerson, F.P., and Rokhsar, D.S. The genome of the diatom Thalassiosira pseudonana: Ecology, evolution, and metabolism. Science 306:79-86, 2004.
• Schwartz, D.C. 2004. The new biology. The Markey Scholars Conference Proceedings (Ed., G.R. Reinhart) National Academies Press, pp. 73-79.
• Dimalanta, E.T., Lim, A., Runnheim, R., Lamers, C., Churas, C., Forrest, D.K., dePablo, J.J., Graham, M.D., Coppersmith, S.N., and Schwartz, D.C. 2004. A microfluidic system for large DNA molecule arrays. Anal. Chem. 76:5293-5301.