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 G G TF ORF Locally acting regulatory variant G kinase TF TF TF ORF Locally acting polymorphisms 25 of varying mRNAs are caused by locally acting polymorphism QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Polymorphism responsible for mRNA difference is at the locus of the gene itself Nonlocal polymorphisms QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Association in multiple populations QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Association of human transcripts linkage families assoc unrelated QuickTime and a TIFF Uncompressed decompressor are needed to see this picture A new brand of genetic variation Translation Fig 8 25 Translation Fig 8 25 PSI yeast read through STOPs PSI yeast read through STOPs PSI yeast read through STOPs 40 150 bp Weird genetics of read through Haploid PSI Haploid psi Diploid PSI Weird genetics of read through Haploid PSI Haploid psi Diploid PSI sporulate Haploid PSI Haploid PSI Haploid PSI Haploid PSI Cytoplasmic aggregates of Sup35 Cytoplasmic aggregates of Sup35 How would this explain the results Hard to make aggregate easy to join QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Protein inheritance Protein inheritance Original from PSI nucleates in all progeny PSI begets more PSI Not due to dominant genetics in the usual way Nucleating prions in mad cow disease Is PSI the yeast analog of mad cow or Alzheimer s If bad would be lost QuickTime and a TIFF Uncompressed decompressor are needed to see this picture If bad would be lost Pichia methanolica vs S cerevisiae QuickTime and a TIFF Uncompressed decompressor are needed to see this picture a ompressor picture PSI phenotypes a ompressor picture Genetically distinct S cerevisiae strains PSI phenotypes Genetically distinct S cerevisiae strains PSI phenotypes a ompressor picture QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Genetically distinct S cerevisiae strains PSI phenotypes QuickTime and a TIFF Uncompressed decompressor are needed to see this picture a ompressor picture 50 C Genetically distinct S cerevisiae strains PSI phenotypes QuickTime and a TIFF Uncompressed decompressor are needed to see this picture a ompressor picture 50 C PSI phenotypes Why would aggregates result in so many novel abilities and traits PSI phenotypes Why would aggregates result in so many novel abilities and traits Apparently does not happen in Alzheimer s The clincher QuickTime and a TIFF Uncompressed decompressor are needed to see this picture The clincher partial LOF QuickTime and a TIFF Uncompressed decompressor are needed to see this picture The clincher partial LOF QuickTime and a TIFF Uncompressed decompressor are needed to see this picture What do you conclude A Sup35 does not cause resistance to paraquat B Prions do not cause resistance to paraquat C Aggregation is not necessary to cause resistance to paraquat D Aggregation is not sufficient to cause resistance to paraquat The clincher partial LOF QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Aggregates per se don t cause resistance The clincher partial LOF QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Aggregates per se don t cause resistance Losing function of sup35 does Aggregation more read through Aggregation more read through New extra long forms of proteins cause new traits PSI allows epigenetic change in protein sequence Genetically distinct S cerevisiae strains Genetic effects a ompressor picture Phenotypes varied between genetically diverse PSI strains Genetically distinct S cerevisiae strains Genetic effects a ompressor picture Phenotypes varied between genetically diverse PSI strains How can the cause be genetic and non genetic protein aggregates at the same time Aggregation more read through Aggregation more read through UTR mutations usually occur and have no effect Aggregation more read through UTR mutations usually occur and have no effect so organism doesn t die and allele is maintained 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 Aggregation more read through Sequence differences in readthrough region cause phenotypic differences between PSI strains Cryptic variation DNA sequence differences between individuals that are usually not expressed
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