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Does shared expression profile = shared function?. Text offers four genes of unrelated function but similar expression patterns (same correlation coefficient) The four genes were all on the same chromosome – 7
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Does shared expression profile = shared function? • Text offers four genes of unrelated function but similar expression patterns (same correlation coefficient) • The four genes were all on the same chromosome – 7 • The correlation coefficients were an artifact produced by higher amount of chromosome 7 DNA in these yeast cells
Aneuploidy • Abnormal amount of chromosomal DNA • Erg4 and erg18 have two copies of chromosome 7 • Further studies found ~8% of all yeast mutant strains exhibited aneuploidy leading to slower growth rates • Ie. rnr1 and rps24a
Mechanism of suppression • Both rnr1 and rps24A have isozymes encoded on chromosome 9, coincidence? • Chromosome bias? Put redundant copies of genes on chromosomes whose levels can be modulated – a genetic safety valve? • Re-analysis of the DeRisi paper reveals aneuploidy in the Tup1 deletion strain.
Alternative uses of microarrays • Verifying and defining exons • Sequencing by hybridization • Diagnostics
DLBCL – diffuse large B-cell lymphoma • Only 40% of those diagnosed respond to chemotherapy • Dealing with more than one type of disease? • Microarrays and clustering analysis revealed signature genes indicative of certain cells or cell states – activated B cells vs. germinal B cells • Normal cells labeled red; lymphoma green
Two or more types of DLBCL • Germinal cell (GC) – like and activated B-cell like • GC-like had the higher survival rate • Unfortunately, this methodology has yet to yield signifcant results concerning other cancers such as breast cancer • GeneXplorer http://genetics.stanford.edu/~rees/ • Discovery questions 20-23
Assessing genomic changes in cancer cells • Use PCR fragments representing different portions of the genome • Panel A – fragments derived from genome used to make microarray • Panel B – fragments derived from independent human genome • Panel C – fragments derived from one normal one cancer • For each, probe is DNA (not RNA) derived
Measuring genomic variability • Posed as problem in vaccine efficacy • Laboratory conditions have selected for genomic deletions over time • How long did I leave that culture on the shaker???
Looking at drug effects • Signal transduction pathway