Direct haplotyping of kilobase-size DNA using carbon nanotube probes

Adam T. Woolley, Chantal Guillemette, Chin Li Cheung, David E. Housman, Charles M. Lieber

Research output: Contribution to journalArticle

155 Scopus citations

Abstract

We have implemented a method for multiplexed detection of polymorphic sites and direct determination of haplotypes in 10-kilobase-size DNA fragments using single-walled carbon nanotube (SWNT) atomic force microscopy (AFM) probes. Labeled oligonucleotides are hybridized specifically to complementary target sequences in template DNA, and the positions of the tagged sequences are detected by direct SWNT tip imaging. We demonstrated this concept by detecting streptavidin and IRD800 labels at two different sequences in M13mp18. Our approach also permits haplotype determination from simple visual inspection of AFM images of individual DNA molecules, which we have done on UGT1A7, a gene under study as a cancer risk factor. The haplotypes of individuals heterozygous at two critical loci, which together influence cancer risk, can be easily and directly distinguished from AFM images. The application of this technique to haplotyping in population-based genetic disease studies and other genomic screening problems is discussed.

Original languageEnglish (US)
Pages (from-to)760-763
Number of pages4
JournalNature Biotechnology
Volume18
Issue number7
DOIs
StatePublished - Jul 2000

Keywords

  • Atomic force microscopy
  • Carbon nanotube
  • DNA sequencing
  • Haplotype
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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    Woolley, A. T., Guillemette, C., Cheung, C. L., Housman, D. E., & Lieber, C. M. (2000). Direct haplotyping of kilobase-size DNA using carbon nanotube probes. Nature Biotechnology, 18(7), 760-763. https://doi.org/10.1038/77760