An approach to acquiring DNA sequence data is proposed that involves the imaging of single DNA molecules. Specific or random priming sites throughout the molecules will be tested for their ability to have a fluorescent nucleotide added by a polymerase. An imaging system will detect the single fluorochromes and document the next base in the sequence series for each site. Potential acquisition of 20 Kb of DNA sequence data contained within 10-40 digital images is described. The proposed potential rate of sequence acquisition is 180 Kb per hr. A similar approach to detecting single base polymorphisms is proposed that does not require directly detecting a single molecule, but instead tests whether multiple labeled nucleotides are added to a site that may or may not terminate with a dideoxynucleotide. A plan to map and subclone BACs as a paradigm for eventual DNA sequencing is proposed. A plan to improve charge density on glass surfaces as a way to optimize DNA fixation for optical mapping is also proposed.
Krerowicz, Samuel J W; Hernandez-Ortiz, Juan P; Schwartz, David C (2018) Microscale Objects via Restructuring of Large, Double-Stranded DNA Molecules. ACS Appl Mater Interfaces : |
Kounovsky-Shafer, Kristy L; Hernandez-Ortiz, Juan P; Potamousis, Konstantinos et al. (2017) Electrostatic confinement and manipulation of DNA molecules for genome analysis. Proc Natl Acad Sci U S A 114:13400-13405 |
Lequieu, Joshua; Schwartz, David C; de Pablo, Juan J (2017) In silico evidence for sequence-dependent nucleosome sliding. Proc Natl Acad Sci U S A 114:E9197-E9205 |
Lequieu, Joshua; Córdoba, Andrés; Schwartz, David C et al. (2016) Tension-Dependent Free Energies of Nucleosome Unwrapping. ACS Cent Sci 2:660-666 |
Li, Yang; Zhou, Shiguo; Schwartz, David C et al. (2016) Allele-Specific Quantification of Structural Variations in Cancer Genomes. Cell Syst 3:21-34 |
Mendelowitz, Lee M; Schwartz, David C; Pop, Mihai (2016) Maligner: a fast ordered restriction map aligner. Bioinformatics 32:1016-22 |
Park, Dong-Wook; Kim, Hyungsoo; Bong, Jihye et al. (2016) Flexible bottom-gate graphene transistors on Parylene C substrate and the effect of current annealing. Appl Phys Lett 109:152105 |
Lee, Seonghyun; Oh, Yeeun; Lee, Jungyoon et al. (2016) DNA binding fluorescent proteins for the direct visualization of large DNA molecules. Nucleic Acids Res 44:e6 |
Zhou, Shiguo; Goldstein, Steve; Place, Michael et al. (2015) A clone-free, single molecule map of the domestic cow (Bos taurus) genome. BMC Genomics 16:644 |
Hernández-Ortiz, Juan P; de Pablo, Juan J (2015) Self-consistent description of electrokinetic phenomena in particle-based simulations. J Chem Phys 143:014108 |
Showing the most recent 10 out of 60 publications