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Hms_9327 - Harvard-MIT Division of Health Sciences and Technology HST.512 Genomic Medicine Prof Isaac Samuel Kohane Genomic Medicine Lecture 1

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Genomic Medicine Lecture 1 Block 1 Isaac S. Kohane Harvard-MIT Division of Health Sciences and Technology HST.512: Genomic Medicine Prof. Isaac Samuel Kohane
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Overview ± The future is now ± Genomic vs genetic ± Heredity ± Resequencing of the diagnostic process ± Accelerating consumer activation
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Overview ± The future is now ± Genomic vs genetic ± Heredity ± Resequencing of the diagnostic process ± Accelerating consumer activation
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Nathan Baker UCSD The Long Path from Genotype to Function DNA Transcription Trans- lation Structural Biology Sequencing Transcriptional Proteomics and Profiling genotyping
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Magnitude of the Task
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Magnitude of the Task
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Madonna Complex ± Some say Madonna Mus > Madonna Person ic ± 4.7 GB vs ± (3 x 10 9 ) x 2 (bits/base) / 8 (bits/byte) = 0.75GB ± Is Madonna, her DNA sequence? ± No, and her current state is captured by. . Alternative splicing (x 3/gene) Post-translational modification (x 100 -1000) Location of gene product ( x 10 12 ) ± She s a little more complicated than her music (are you surprised?)
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RNA/DNA expression detection chips Tissue or Tissue under influence wi l RNA Tagged th f uor cDNA copy cDNA spotted on glass slide or Please refer to following papers: oligonucleotides built on slide Schena M, et al. Proc Natl Acad Sci USA; 93: 10614 (1996). Entire issue. Nature Genetics, 21: supplement (Jan 1999). Microarray of genes aka gene chips
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The Promise: The New Diagnostics Please see Nature. 2000 Feb 3;403(6769):503-11. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Alizadeh AA, et al.
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Retreading the cancer chemotherapeutic protocol ± Cancer and Leukemia Group B (CALGB) ± CALGB has grown into a national network of 29 university medical centers, over 185 community hospitals and more than almost 3000 physicians who collaborate in clinical research studies aimed at reducing the morbidity and mortality from cancer ± Dozens of new protocols (breast cancer, prostate cancer, renal cancer) that use genome-wide Which genes best predict survival? Which adjuvant improves surgical outcome the best? Can we find expression measure proxies for Stage, Grade and Cell Type
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New Taxonomy of Human Disease ± Clinicians may have moved on from calling ‘fever a disease, but they still rely on phenotypic criteria to define most diseases, ± Yet these may obscure the underlying mechanisms and often mask significant heterogeneity. ± Thomas Lewis pointed out in 1944, diagnosis of most human disease provides only “insecure and temporary conceptions” ± Of the main common diseases, only the infectious diseases have a truly mechanism-based nomenclature.
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Please see Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10613-8. A common polymorphism associated with antibiotic-induced cardiac arrhythmia.
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This note was uploaded on 03/27/2008 for the course HST 512 taught by Professor Ramoni during the Spring '06 term at MIT.

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Hms_9327 - Harvard-MIT Division of Health Sciences and Technology HST.512 Genomic Medicine Prof Isaac Samuel Kohane Genomic Medicine Lecture 1

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