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BMI217 Evolution & Medicine Shai Shen-Orr shenorr@stanford.edu
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Shai Shen-Orr shenorr@stanford.edu. Nothing in Biology Makes Sense Except in the Light of Evolution Theodosius Dobzhansky 1973.

Dec 23, 2015

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  • Slide 1
  • Shai Shen-Orr shenorr@stanford.edu
  • Slide 2
  • Nothing in Biology Makes Sense Except in the Light of Evolution Theodosius Dobzhansky 1973
  • Slide 3
  • Jeffrey Decoster, Stanford Medical Magazine, Summer 06 http://stanmed.stanford.edu/2006summer/ev olutionary-medicine.html
  • Slide 4
  • Negative (purifying) selection selective removal of rare alleles that are deleterious Positive selection selection due to added fitness to a particular allele Balancing selection Selection due to heterozygote or frequency dependent advantage
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  • http://www.genomesonline.org/gold.cgi
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  • Fitch et al. PNAS 1997
  • Slide 10
  • Bush et al. Science 1999
  • Slide 11
  • Sawyer et al. PNAS 2005
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  • Kaiser et al. Science 2007
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  • Arabidopsis thaliana 114.5 Mb genome (Sequenced 2000 ) Chlamydomonas reinhardtii 95 Mb genome (Sequenced 2004)
  • Slide 18
  • Li et al. Cell 2004
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  • Ala et al. PLoS Comp Bio 2008
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  • Slide 22
  • How similar is the Disease Gene Expression Profile of a human disease and its mouse model ?
  • Slide 23
  • Diseased Subjects Control subjects Subtract Disease gene expression signature Rank Normalize
  • Slide 24
  • MDX mouseWildtype ControlDMD patientsControl Disease gene expression signature Human Mouse Limit to Human Mouse 1:1 orthologs
  • Slide 25
  • Human Disease gene expression signature Mouse Disease gene expression signature Spearmans = 0.28
  • Slide 26
  • Human Disease gene expression signature Mouse Disease gene expression signature Spearmans = 0.28 Spearmans Rank Correlation
  • Slide 27
  • Cross-species Mouse X Mouse Human X Human
  • Slide 28
  • Spearmans Rank Correlation Cross-species Mouse X Mouse Human X Human
  • Slide 29
  • Spearmans Rank Correlation Cross-species Mouse X Mouse Human X Human
  • Slide 30
  • Spearmans Rank Correlation Cross-species Mouse X Mouse Human X Human