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Advances in Genomics Since the Publication of the Human Genome. Greg Feero, M.D., Ph.D. Faculty, Maine-Dartmouth Family Practice Residency Program, Fairfield, ME Contributing editor, Journal of the American Medical Association. Disclosures.
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Advances in Genomics Since the Publication of the Human Genome Greg Feero, M.D., Ph.D. Faculty, Maine-Dartmouth Family Practice Residency Program, Fairfield, ME Contributing editor, Journal of the American Medical Association
Disclosures • No financial or intellectual conflicts of interest. • I am a primary care doctor. • For better or worse, my opinions are my own!!
Outline • Still waiting for the revolution? • Discovery apace. • An unsatisfying answer? • The final word – education!
Impact of genomics Degree of specialization
February 2011 NHGRI Published New Vision for Genomics
Genomic Accomplishments: Base Pairs to Bedside Understanding the Structure of Genomes Understanding the Biology of Genomes Understanding the Biology of Disease Advancing the Science of Medicine Improving the Effectiveness of Healthcare 1990-2003 Human Genome Project 2004-2010 2011-2020 Beyond 2020
Sequence from chromosome 7 GAAATAATTAATGTTTTCCTTCCTTCTCCTATTTTGTCCTTTACTTCAATTTATTTATTTATTATTAATATTATTATTTTTTGAGACGGAGTTTCACTCTTGTTGCCAACCTGGAGTGCAGTGGCGTGATCTCAGCTCACTGCACACTCCGCTTTCTGGTTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTACAGTCACACACCACCACGCCCGGCTAATTTTTGTATTTTTAGTAGAGTTGGGGTTTCACCATGTTGGCCAGACTGGTCTCGAACTCCTGACCTTGTGATCCGCCAGCCTCTGCCTCCCAAAGAGCTGGGATTACAGGCGTGAGCCACCGCGCTCGGCCCTTTGCATCAATTTCTACAGCTTGTTTTCTTTGCCTGGACTTTACAAGTCTTACCTTGTTCTGCCTTCAGATATTTGTGTGGTCTCATTCTGGTGTGCCAGTAGCTAAAAATCCATGATTTGCTCTCATCCCACTCCTGTTGTTCATCTCCTCTTATCTGGGGTCACATATCTCTTCGTGATTGCATTCTGATCCCCAGTACTTAGCATGTGCGTAACAACTCTGCCTCTGCTTTCCCAGGCTGTTGATGGGGTGCTGTTCATGCCTCAGAAAAATGCATTGTAAGTTAAATTATTAAAGATTTTAAATATAGGAAAAAAGTAAGCAAACATAAGGAACAAAAAGGAAAGAACATGTATTCTAATCCATTATTTATTATACAATTAAGAAATTTGGAAACTTTAGATTACACTGCTTTTAGAGATGGAGATGTAGTAAGTCTTTTACTCTTTACAAAATACATGTGTTAGCAATTTTGGGAAGAATAGTAACTCACCCGAACAGTGTAATGTGAATATGTCACTTACTAGAGGAAAGAAGGCACTTGAAAAACATCTCTAAACCGTATAAAAACAATTACATCATAATGATGAAAACCCAAGGAATTTTTTTAGAAAACATTACCAGGGCTAATAACAAAGTAGAGCCACATGTCATTTATCTTCCCTTTGTGTCTGTGTGAGAATTCTAGAGTTATATTTGTACATAGCATGGAAAAATGAGAGGCTAGTTTATCAACTAGTTCATTTTTAAAAGTCTAACACATCCTAGGTATAGGTGAACTGTCCTCCTGCCAATGTATTGCACATTTGTGCCCAGATCCAGCATAGGGTATGTTTGCCATTTACAAACGTTTATGTCTTAAGAGAGGAAATATGAAGAGCAAAACAGTGCATGCTGGAGAGAGAAAGCTGATACAAATATAAATGAAACAATAATTGGAAAAATTGAGAAACTACTCATTTTCTAAATTACTCATGTATTTTCCTAGAATTTAAGTCTTTTAATTTTTGATAAATCCCAATGTGAGACAAGATAAGTATTAGTGATGGTATGAGTAATTAATATCTGTTATATAATATTCATTTTCATAGTGGAAGAAATAAAATAAAGGTTGTGATGATTGTTGATTATTTTTTCTAGAGGGGTTGTCAGGGAAAGAAATTGCTTTTTTTCATTCTCTCTTTCCACTAAGAAAGTTCAACTATTAATTTAGGCACATACAATAATTACTCCATTCTAAAATGCCAAAAAGGTAATTTAAGAGACTTAAAACTGAAAAGTTTAAGATAGTCACACTGAACTATATTAAAAAATCCACAGGGTGGTTGGAACTAGGCCTTATATTAAAGAGGCTAAAAATTGCAATAAGACCACAGGCTTTAAATATGGCTTTAAACTGTGAAAGGTGAAACTAGAATGAATAAAATCCTATAAATTTAAATCAAAAGAAAGAAACAAACTGAAATTAAAGTTAATATACAAGAATATGGTGGCCTGGATCTAGTGAACATATAGTAAAGATAAAACAGAATATTTCTGAAAAATCCTGGAAAATCTTTTGGGCTAACCTGAAAACAGTATATTTGAAACTATTTTTAAA About 2000 bases
At one slide per second, this lecture will be done in about 35 days!
“The race was to sequence the human genome, all 3 billion genetic letters of it… a race not to the finish but to the starting line. Moreover, … the new race marked by that starting line was a marathon.”
Genomic Accomplishments: Base Pairs to Bedside Understanding the Structure of Genomes Understanding the Biology of Genomes Understanding the Biology of Disease Advancing the Science of Medicine Improving the Effectiveness of Healthcare 1990-2003 Human Genome Project 2004-2010 2011-2020 Beyond 2020
Progress in Mendelian disease gene discovery 1990 2011 Known Unknown, suspected Mendelian Sources: Lander, E. Nature , Feb. 2011 www.genetests.org, Feb 2011
Cystic fibrosis Adult onset diabetes AIDS
SNP A SNP B Diabetes Diabetes Unaffected Unaffected
Continued Progress in Genotyping Technology Affymetrix 500K Illumina 550K Illumina 650Y Illumina 317K Cost per person (USD) July 2005 Oct 2006 Courtesy S. Gabriel, Broad/MIT
NHGRI Catalog of Published Genome-Wide Association Studies (GWAS) > 5619 SNPs!!
Equation of a Variant’s Predictive Potential = X Association Strength Predictive Potential Effect size
Classical genetic study“mutation” = X Association Strength Predictive Potential Effect size Association => Causality
Genome Wide Association Study“SNP” = X Association Strength Predictive Potential Effect size
Genome Wide Association Study“SNPs” = X ? Association Strength Predictive Potential Effect size
Quantum Leaps in Technology: .….Genome sequencing at $1000 or less for a mammalian genome….. Nature, April 2003
Advances in Genome Biology and Technology Conference February 2012
Sequencing ?? ? = X Association Strength Predictive Potential Effect size
Frequency vs. Effect ? Classical mutation Effect size SNP-like variation Frequency in population
Quality Health Care Genomics Personalized Medicine
Solutions – primary care style… • 33% of diabetics are undiagnosed --- blood glucose. (Almanac, 2008) • 24%of hypertensives undiagnosed --- blood pressure measurements. (Almanac, 2008) • 37% of high cholesterol undiagnosed --- fasting lipid panel. (Almanac, 2008) • Universal health care, better screening programs, smoking cessation, exercise programs, improved nutrition etc…
WSJ, Nov. 2, 2013 $1,600,000!!!!!!
Are the expenses of targeted treatments sustainable?For:Patients?Insurers?State budgets?National economies?
EBM PM