Your SlideShare is downloading. ×
0
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Fundamentals of Analysis of Exomes
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Fundamentals of Analysis of Exomes

1,066

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
1,066
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
71
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Fundamentals of Analysis of Exomes Diego Forero, MD, PhD Assistant Professor Director, Laboratory of NeuroPsychiatric Genetics Director, Medical Research Office School of Medicine Antonio Nariño University Bogotá, Colombia Editor, hum-molgen.org diego.forero@uan.edu.co
  • 2. CAUSAL GENES FOR MENDELIAN DISORDERS Mendelian Autosomal Sex-linked Total DisordersCausal Gene 3.175 266 3.441 KnownCausal Gene 1.633 140 1.773 Unknown Online Mendelian Inheritance in Man
  • 3. Exomes: Publication Trends 600 Total: 925 (Oct 2012) 500 400Papers 300 200 100 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 Year 2013: ~ 800 papers 2014: ~ 1200 papers Forero DA, 2012
  • 4. GENOMICS: PLATFORMS
  • 5. Majewski, J Med Genet 2011
  • 6. Majewski, J Med Genet 2011
  • 7. From Data Generation to Data Analysis
  • 8. A timeline illustrating technological breakthroughs and hallmark publications for Mendelian disease gene identification Gilissen, Genom Biol 2011
  • 9. A timeline illustrating technological breakthroughs and hallmark publications for Mendelian disease gene identification Gilissen, Genom Biol 2011
  • 10. First Published Exome"We focus here on the variants in a person’s ‘exome,’ which is the set of exons in a genome..." Ng, PLoS Genet 2008
  • 11. A representation of the relationship between the size of the mutational target and the frequency of disease for disorders caused by de novo mutations Gilissen, Genom Biol 2011
  • 12. Majewski, J Med Genet 2011
  • 13. Strategies for finding disease-causing rare variants using exome sequencing Bamshad, Nat Rev Genet 2011
  • 14. Typical heuristic filtering applied to exome sequencing projects aimed at novel gene discovery for Mendelian disorders Stitziel, Genom Biol 2011
  • 15. Mean number of coding variants in two populations Bamshad, Nat Rev Genet 2011
  • 16. First identification of the causal gene for a monogenic disorder by exome sequencing Freeman–Sheldon syndrome (MYH3) Ng, Nature 2009
  • 17. Exome Analysis for One Patient Perrault syndrome (HSD17B4) Pierce, Am J Hum Genet 2010
  • 18. Useful In Silico Tools VarSifterhttp://research.nhgri.nih.gov/software/VarSifter/index.shtml Exome Variant Server (6503 exomes) http://evs.gs.washington.edu/EVS/ wANNOVAR http://wannovar.usc.edu/
  • 19. Useful In Silico Tools Atlas2 Suitehttp://sourceforge.net/p/atlas2/wiki/Atlas2%20Suite/ IBD2http://compbio.charite.de/contao/index.php/ibd2.html EVAhttp://plateforme-genomique-irib.univ-rouen.fr/EVA/index.php TREAThttp://ndc.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm KGGSeqhttp://statgenpro.psychiatry.hku.hk/limx/kggseq/
  • 20. Exomes-Service Providers Axeq (USA)50x; Illumina TrueSeq/HiSeq200. $2,300 USD per sample Macrogen (Korea)50x; Illumina TrueSeq/HiSeq200. $2,499 USD per sample BaseClear (Netherlands) 30x; Nimblegen/Illumina. € 2,499 per sample PerkinElmer (USA) 30x; Agilent/Illumina. $3,500 USD per sample BGI Americas (USA) 30x; $3,500 USD per sample EdgeBio (USA) 50x; SOLiD 4. $5,500 USD per sample DNAVision (Belgium) 30x; Agilent/Illumina. 5,990 € per sample Knome (USA) 30x; Illumina. $8,750 USD per sample Source BioScience (UK) 50x; Agilent/Illumina. 5,850GBP per sample
  • 21. Example of Data Provided http://www.ncbi.nlm.nih.gov/omim Need for in-house exome data. Possible Noise from dbSNP and OMIMData from Human Gene Mutation Database?
  • 22. Candidate genes prioritization Endeavourhttp://homes.esat.kuleuven.be/~bioiuser/endeavour/tool/endeavourweb.php ToppGene http://toppgene.cchmc.org/prioritization.jsp
  • 23. Tools for mutation pathogenicity prediction Thusberg J, Olatubosun A, Vihinen M.Performance of mutation pathogenicity prediction methods on missense variants. Hum Mutat. 2011 Apr;32(4):358-68.
  • 24. Tools for mutation pathogenicity prediction MutPred http://mutpred.mutdb.org/ SNPs&GOhttp://snps-and-go.biocomp.unibo.it/snps-and-go/ PolyPhen-2 http://genetics.bwh.harvard.edu/pph2/ SIFT http://sift.bii.a-star.edu.sg/
  • 25. www.daforerog.co.cc“This is an excellent resource for anyone who is generally interested inhow these technologies work”.Stephen Turner, PhDCenter for Human Genetics Research, Vanderbilt University.
  • 26. www.daforerog.co.cc

×