The Molecular Inversion Probe method will be used in a collaboration between ParAllele Biosciences and the BCM- Human Genome Sequencing Center to generate a haplotype map of one third of the human genome. This method is based upon Ulf Landegren's 'Padlock Probe' technology and can be multiplexed to simultaneously assay > 1,000 SNPs in a single test. A single PCR is used to amplify the entire set of probes and the final read out is from a universal DNA tag chip with up to 16,000 detection features. The method has a very high sensitivity, accuracy and reproducibility and should be the preferred technology for all subsequent large-scale genotyping. This project will assay a total of 333,000 markers with the expectation that > 163,000 (49%) will contribute to the final map. The efficiency of SNP assay design and placement will be enhanced by an iterative hierarchical selection method that establishes large haplotypes in early rounds, to ensure subsequent probes are directed to where they are to be most informative.
| Hardenbol, Paul; Yu, Fuli; Belmont, John et al. (2005) Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay. Genome Res 15:269-75 |
| Belmont, John W; Gibbs, Richard A (2004) Genome-wide linkage disequilibrium and haplotype maps. Am J Pharmacogenomics 4:253-62 |
