Long-range polony haplotyping of individual human chromosome molecules
- 19 February 2006
- journal article
- Published by Springer Nature in Nature Genetics
- Vol. 38 (3) , 382-387
- https://doi.org/10.1038/ng1741
Abstract
We report a method for multilocus long-range haplotyping on human chromosome molecules in vitro based on the DNA polymerase colony (polony) technology. By immobilizing thousands of intact chromosome molecules within a polyacrylamide gel on a microscope slide and performing multiple amplifications from single molecules, we determined long-range haplotypes spanning a 153-Mb region of human chromosome 7 and found evidence of rare mitotic recombination events in human lymphocytes. Furthermore, the parallel nature of DNA polony technology allows efficient haplotyping on pooled DNAs from a population on one slide, with a throughput three orders of magnitudes higher than current molecular haplotyping methods. Linkage disequilibrium statistics established by our pooled DNA haplotyping method are more accurate than statistically inferred haplotypes. This haplotyping method is well suited for candidate gene-based association studies as well as for investigating the pattern of recombination in mammalian cells.Keywords
This publication has 28 references indexed in Scilit:
- The Thermodynamics of DNA Structural MotifsAnnual Review of Biophysics, 2004
- Single Molecule Profiling of Alternative Pre-mRNA SplicingScience, 2003
- Direct molecular haplotyping of long-range genomic DNA with M1-PCRProceedings of the National Academy of Sciences, 2003
- Digital genotyping and haplotyping with polymerase coloniesProceedings of the National Academy of Sciences, 2003
- Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21Science, 2001
- Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studiesNature Genetics, 2001
- A New Statistical Method for Haplotype Reconstruction from Population DataAmerican Journal of Human Genetics, 2001
- Direct haplotyping of kilobase-size DNA using carbon nanotube probesNature Biotechnology, 2000
- In situ localized amplification and contact replication of many individual DNA moleculesNucleic Acids Research, 1999
- Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCRNucleic Acids Research, 1996