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Marker is linked to polymorphism in expression regulation cascade

Office hours 3-4pm Wednesday, Dec. 10 304A Stanley Hall Review session 5pm Thursday, Dec. 11 GPB100 Final exam 12:30pm Saturday, Dec. 13 277 Cory Hall (NE campus). Marker is linked to polymorphism in expression regulation cascade. G. kinase. TF. TF. TF. ORF. G. G.

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Marker is linked to polymorphism in expression regulation cascade

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  1. Office hours3-4pm Wednesday, Dec. 10304A Stanley HallReview session5pm Thursday, Dec. 11GPB100Final exam12:30pm Saturday, Dec. 13277 Cory Hall (NE campus)

  2. Marker is linked to polymorphism in expression regulation cascade G kinase TF TF TF ORF G G

  3. Locally acting regulatory variant G kinase TF TF TF ORF

  4. Locally acting polymorphisms ~25% of varying mRNAs are caused by locally acting polymorphism Polymorphism responsible for mRNA difference is at the locus of the gene itself

  5. Nonlocal polymorphisms

  6. Association in multiple populations

  7. Association of human transcripts linkage (families) assoc (unrelated)

  8. A new brand of genetic variation

  9. Translation Fig. 8.25

  10. Translation Fig. 8.25

  11. PSI+ yeast read through STOPs

  12. PSI+ yeast read through STOPs

  13. PSI+ yeast read through STOPs 40-150 bp

  14. Weird genetics of read-through Haploid PSI+ Haploid psi- Diploid PSI+

  15. Weird genetics of read-through Haploid PSI+ Haploid psi- Diploid PSI+ sporulate … Haploid PSI+ Haploid PSI+ Haploid PSI+ Haploid PSI+

  16. Cytoplasmic aggregates of Sup35

  17. Cytoplasmic aggregates of Sup35 How would this explain the results?

  18. Hard to make aggregate, easy to join

  19. Protein inheritance

  20. Protein inheritance Original from PSI+ nucleates in all progeny

  21. PSI+ begets more PSI+ Not due to dominant genetics in the usual way.

  22. Nucleating prions in mad cow disease

  23. Is PSI+ the yeast analog of mad cow or Alzheimer’s?

  24. If bad, would be lost

  25. If bad, would be lost (Pichia methanolica vs. S. cerevisiae)

  26. PSI+ phenotypes

  27. PSI+ phenotypes Genetically distinct S. cerevisiae strains

  28. PSI+ phenotypes Genetically distinct S. cerevisiae strains

  29. PSI+ phenotypes Genetically distinct S. cerevisiae strains 50°C

  30. PSI+ phenotypes Genetically distinct S. cerevisiae strains 50°C

  31. PSI+ phenotypes Why would aggregates result in so many novel abilities and traits??

  32. PSI+ phenotypes Why would aggregates result in so many novel abilities and traits?? Apparently does not happen in Alzheimer’s…

  33. The clincher

  34. The clincher (partial LOF)

  35. The clincher (partial LOF) What do you conclude? Sup35 does not cause resistance to paraquat. Prions do not cause resistance to paraquat. Aggregation is not necessary to cause resistance to paraquat. Aggregation is not sufficient to cause resistance to paraquat.

  36. The clincher (partial LOF) Aggregates per se don’t cause resistance.

  37. The clincher (partial LOF) Aggregates per se don’t cause resistance. Losing function of sup35 does.

  38. Aggregation = more read-through

  39. Aggregation = more read-through New extra-long forms of proteins cause new traits.

  40. PSI+ allows epigenetic change in protein sequence.

  41. Genetic effects? Phenotypes varied between genetically diverse PSI+ strains. Genetically distinct S. cerevisiae strains

  42. Genetic effects? Phenotypes varied between genetically diverse PSI+ strains. How can the cause be genetic and non-genetic (protein aggregates) at the same time? Genetically distinct S. cerevisiae strains

  43. Aggregation = more read-through

  44. Aggregation = more read-through UTR mutations usually occur and have no effect

  45. Aggregation = more read-through UTR mutations usually occur and have no effect, so organism doesn’t die and allele is maintained.

  46. Aggregation = more read-through UTR mutations usually occur and have no effect, so organism doesn’t die and allele is maintained. Now in PSI+, they manifest!

  47. Aggregation = more read-through Sequence differences in read-through region cause phenotypic differences between PSI+ strains.

  48. Cryptic variation: DNA sequence differences between individuals that are usually not expressed

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