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$399 Personal Genome Service

$985 deCODEme. (November 2007). $399 Personal Genome Service. (November 2007). $2,500 Health Compass service. (April 2008). Genetic Information Nondiscrimination Act. (May 2008). $350,000 Whole-genome sequencing. (November 2007). Applications. Whole-genome sequencing

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$399 Personal Genome Service

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  1. $985 deCODEme (November 2007) $399 Personal Genome Service (November 2007) $2,500 Health Compass service (April 2008) Genetic Information Nondiscrimination Act (May 2008) $350,000 Whole-genome sequencing (November 2007)

  2. Applications Whole-genome sequencing Comparative genomics Genome resequencing Structural variation analysis Polymorphism discovery Metagenomics Environmental sequencing Gene expression profiling Genotyping Population genetics Migration studies Ancestry inference Relationship inference Genetic screening Drug targeting Forensics

  3. New sequencing applications Sequencing applications Increase in sequencing data output Demand for more sequencing Sequencing technology improvement

  4. Sequencing technology Sanger sequencing $10.00 $1.00 Cost per finished bp: $0.10 $0.01 1975 1980 1990 2000 2008 Fred Sanger Read length: 15 – 200 bp 500 – 1,000 bp Throughput: “grad-student years” 2 ∙ 106 bp/day

  5. Sequencing technology Sanger sequencing 3 ∙ 109 bp 1x coverage 10x coverage × 3 ∙ 109 bp = 40 years 2 ∙ 106 bp/day = $30 million 10x coverage × 3 ∙ 109 bp × $0.001/bp

  6. Pyrosequencing on a chip • Mostafa Ronaghi, Stanford Genome Technologies Center • 454 Life Sciences

  7. Sequencing technology Next-generation sequencing “short reads” Read length: 250 bp Throughput: 300 Mb/day Cost: ~ 10,000 bp/$ De novo: yes Genome Sequencer / FLX

  8. Single Molecule Array for Genotyping—Solexa

  9. Polony Sequencing

  10. Sequencing technology Next-generation sequencing Genome Analyzer SOLiD Analyzer “microreads” Read length: ~ 35 bp Throughput: 300 – 500 Mb/day Cost: ~ 100,000 bp/$ De novo: yes

  11. Molecular Inversion Probes

  12. Illumina Genotype Arrays

  13. Sequencing technology Next-generation sequencing “SNP chips” Infinium Assay GeneChip Array genotypes Read length: 1bp Throughput: 1 – 2 Mb/day Cost: 5,000 bp/$ De novo: no

  14. Nanopore Sequencing http://www.mcb.harvard.edu/branton/index.htm

  15. Sequencing technology Next-generation sequencing

  16. Sequencing technology

  17. Multiple Sequence Alignment

  18. Evolution at the DNA level Deletion Mutation …ACGGTGCAGTTACCA… SEQUENCE EDITS …AC----CAGTCCACCA… REARRANGEMENTS Inversion Translocation Duplication

  19. Evolutionary Rates next generation OK OK OK X X Still OK?

  20. Orthology, Paralogy, Inparalogs, Outparalogs

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