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Tools in Human Genomics

Tools in Human Genomics. Brett Bowman March 3 rd , 2013. Summary. Brief Bio Review of Genotyping Technologies SNP-chips (23andMe) Exome Sequencing (In Clinical Use) Whole Genome Sequencing Review of SNP Analysis tools SNP Databases Report Tools OMIM. My (Sort of) Karyotype.

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Tools in Human Genomics

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  1. Tools in Human Genomics Brett Bowman March 3rd, 2013

  2. Summary • Brief Bio • Review of Genotyping Technologies • SNP-chips (23andMe) • Exome Sequencing (In Clinical Use) • Whole Genome Sequencing • Review of SNP Analysis tools • SNP Databases • Report Tools • OMIM

  3. My (Sort of) Karyotype

  4. Genotyping TECHNOLOGIES

  5. 23andMe – How They Do It

  6. 23andMe – How it Works • Attach un-labeled sequence probes to array surface • Extract and Amplify sample DNA • Fragment • Wash over and bind to array probes • Extend probe 1 bpwith polymerase and labeled dNTPs • Photograph!

  7. 23andMe – Processed Output • rsid == refSNP id == dbSNP id • Two letter genotype representing both alleles • NOT phased data • No quality information

  8. SNP-Chips Limitations • Requires a priori knowledge of SNPs of interest • Requires individual probes be designed and manufactured for each SNP • SNP-Chips limited by size in the number of probes they can contain • Cannot determine phase • Cannot determine copy number • Small Error Rate * Large Number = High Error Count

  9. Exome Sequencing – How it Works • Prepare labeled sequence probes • Extract, Sheer, and clean-up DNA • Mix probes with DNA • Wash away un-bound DNA • Digest probes • Sequence!

  10. Exome Sequencing – Raw Output

  11. PHRED Quality Scores Encoded Score (E) = chr(Q + 33) Numerical Score (Q) = ord(E) - 33

  12. Exome Sequencing – Processed Output

  13. Exome Sequencing Limitations • Requires a priori knowledge of Genes of interest • Requires individual probes be designed and manufactured for each exon/gene • Hard to infer copy number • Very limited ability to phase data • Hard to make sense of novel data • Contains very little regulatory data • Complicated, unstandardized, computationally intensive analysis processes

  14. SNP-Chip vsExome SNP-Chip • Cheaper (~$100) • Lower Accuracy • Requires precise knowledge a priori • At best gets 10-20% of known variants • No phasing data • No structural data • Simple analysis tools Exome • Expensive (~$1000) • Higher Accuracy • Requires general knowledge a priori • At best gets 80-90% of known variants • Some phasing data • Some structural data • Complex analysis tools

  15. Full Genome Sequencing How many human genomes have been completely sequenced end-to-end?

  16. Full Genome Sequencing How many human genomes have been completely sequenced end-to-end? 0

  17. Full Genome Sequencing - Challenges • Sequence Repeats • Secondary Structure • Particularly • Telemeric Region • Centromeric Region • Methylation • Regulation • Interpretation

  18. Analysis Tools

  19. SNPedia

  20. SNPedia

  21. SNPedia - Promethease

  22. openSNP

  23. OMIM

  24. 23andMe API

  25. Genomes Unzipped

  26. Questions?

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