George M. Church, Richard Baldarelli, James Chou, Poguang Wang, Helena Graner, Linxiao Xu, Pete Estep, Dereth Phillips, Saeed Tavazoie, and Keith Robison
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, Church@Rascal.Med.Harvard.Edu
DNA sequencing for genome projects, diagnostics (microbial, agricultural, human, immunogenetics and oncogenetics) and industrial QC will push well beyond the 3 Gbp and 0.1% error rates originally targeted for one human genome. To increase accuracy and efficiency of data acquisition, two new technologies are in development: 1) An automated multiplex sequencer is being built to use 400 mass-spectral tags for primers per electrophoretic lane (in collaboration with Bruker Instruments, Genome Therapeutics, and Dr. Roger Giese's laboratory at Northeastern University). 2) Conductance measurements of DNA moving through single ion channels, such as lambda phage clone DNA injected into LamB receptor pores. To increase the accuracy of microbial genome sequence checking and database annotation we are developing methods for 3) computational genome comparisons in putative non-coding regions, 4) multiplex homologous recombination knockout analyses, 5) whole genome in vivo footprinting, and 6) locating point mutations using mismatch recognition proteins.
*Supported by a grant from the U.S. Department of Energy DE-FG02-87ER60565