Direct determination of haplotypes from single DNA molecules.
Determining the long-range haplotypes in a diploid individual is a major technical challenge. Here we report a method of molecular haplotyping by directly imaging multiple polymorphic sites on individual human DNA molecules simultaneously. We demonstrate the utility of this technology by accurately determining the haplotypes consisting of up to 16 single-nucleotide polymorphisms in genomic regions up to 50 kilobases.
Xiao
Ming
M
Cardiovascular Research Institute, University of California-San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA. mingx@bionanomatrix.com
Wan
Eunice
E
Chu
Catherine
C
Hsueh
Wen-Chi
WC
Cao
Yang
Y
Kwok
Pui-Yan
PY
D002232:Carbocyanines / Q000737:chemistry; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry; D005090:Exodeoxyribonucleases / Q000737:chemistry; D005821:Genetic Techniques; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D013194:Staining and Labeling / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000235:genetics
D002232:Carbocyanines; D017931:DNA Primers; D004277:DNA, Single-Stranded; C089187:cyanine dye 3; C085321:cyanine dye 5; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator