Mitra Lecture - 1 Next Generation Sequencing Technologies...

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Unformatted text preview: 1 Next Generation Sequencing Technologies Rob Mitra 11/15/10 Forward Genetics Genotype Phenotype Hypothesis Test Hypothesis By Genetic Manipulation Forward Genetics Genotype Two groups: 1. Develop Colorectal cancer Mutation in APC Gene Phenotype Hypothesis Test Hypothesis By Genetic Manipulation At Young Age 2. Do not APC is a Tumor Supressor Gene Delete APC in Mouse Control: Isogenic APC+ The Cycle of Forward Genetics Genotype Observation ?Sequencing? Thinking In 2005 $9 million/genome Not feasible Phenotype Hypothesis Test Hypothesis By Genetic Manipulation Gene Deletion/Replacement Recombinant Technology End Runs Linkage Studies (Humans, Model Organisms) Association Studies (GWAS) BUT, these end runs have a cost! 1. Requires a large family (many crosses in model organisms); very difficult to analyze multi-factorial traits 2. Common variants But, these end runs will not be needed in 5-10 years. Why? The Problem with Forward Genetics Genotype Observation Sequencing Thinking Currently $40,000* /genome Cost is rapidly dropping Phenotype Hypothesis Test Hypothesis By Genetic Manipulation Gene Deletion/Replacement Recombinant Technology 2 Bp/US dollar: increases exponentially with time Adapted from Shendure et al 2004 Two questions: How was this dramatic acceleration achieved? What will it mean? How was this achieved? Integration (Think about sequencing pipeline) Parallelization Miniaturization Same concepts the revolutionarized integrated circuits Plus one additional insight Read Length is Not As Important For Resequencing 0% 10% 20% 30% 40% 50% 8 10 12 14 16 18 20 Length of K-mer Reads (bp)...
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Mitra Lecture - 1 Next Generation Sequencing Technologies...

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