Direct haplotyping of kilobase-size DNA using carbon nanotube probes

被引：139
作者：
Woolley, AT
Guillemette, C
Cheung, CL
Housman, DE
Lieber, CM [1 ]
机构：
[1] MIT, Ctr Canc Res, Cambridge, MA 02139 USA
[2] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA
来源：
NATURE BIOTECHNOLOGY | 2000年 / 18卷 / 07期
基金：
英国医学研究理事会;
关键词：
atomic force microscopy; haplotype; carbon nanotube; single-nucleotide polymorphism; DNA sequencing;
D O I：
10.1038/77760
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
引用
收藏
页码：760 / 763
页数：4
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