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Functional profiling of the S. cerevisiae genome

Functional profiling of the S. cerevisiae genome. G Giaever, et al. What is the question? What are they looking at? Why is this genomics instead of genetics?. Why is this better than classical genetics?. Mutant phenotype reflects a deletion, i.e. complete loss of function

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Functional profiling of the S. cerevisiae genome

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  1. Functional profiling of the S. cerevisiae genome G Giaever, et al

  2. What is the question? • What are they looking at? • Why is this genomics instead of genetics?

  3. Why is this better than classical genetics? • Mutant phenotype reflects a deletion, i.e. complete loss of function • This is “reverse genetics” – so you know the gene that is affected ahead of time • In contrast to random mutagenesis, mutant “saturation” of the genome is assured.

  4. First results • Deleted 5916 genes (96.5% of those attempted) • 1105 (18.7%) were essential • 17% of non-essential ORFs encoded new proteins • 82% of essential genes had human homologs

  5. Where’s the data? • http://genomics.lbl.gov/YeastFitnessData • 15% show slow growth in YPD at 30oC. • There is a continuous range of growth defects 12% to 90% of wt

  6. What is the relationship between expression under a particular condition and fitness of a deletion mutant under that condition?

  7. They found 673 genes (15%) involved in morphology. These were grouped into 7 classes. Clumped and elongated – enriched for cell growth, division, and DNA synthesis. Round – enriched for protein synthesis genes and defective for bud site selection.

  8. What else can we think of doing? • Let’s find a question.

  9. What did Guri do that year?

  10. Mitochondrial mutants are often important in human disease – how would you use the deletion set to find these?

  11. This paper was important and useful

  12. Citations are often an indication of the usefulness or importance of a discovery- but not always

  13. Andreas Wagner – using these datasets to understand living systems

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