advances in genomics since the publication of the human genome
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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. - PowerPoint PPT PresentationTRANSCRIPT
Advances in Genomics Since the Publication of
the Human GenomeGreg Feero, M.D., Ph.D.
Faculty, Maine-Dartmouth FamilyPractice 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!
Science 4 Feb 2011
Degree of specialization
Impa
ct o
f gen
omic
s
February 2011NHGRI Published New Vision for Genomics
Understandingthe Structure of
Genomes
Understandingthe Biology of
Genomes
Understandingthe Biology of
Disease
Advancingthe Science of
Medicine
Improving theEffectivenessof Healthcare
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Genomic Accomplishments: Base Pairs to Bedside
Sequence from chromosome 7
GAAATAATTAATGTTTTCCTTCCTTCTCCTATTTTGTCCTTTACTTCAATTTATTTATTTATTATTAATATTATTATTTTTTGAGACGGAGTTTCACTCTTGTTGCCAACCTGGAGTGCAGTGGCGTGATCTCAGCTCACTGCACACTCCGCTTTCTGGTTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTACAGTCACACACCACCACGCCCGGCTAATTTTTGTATTTTTAGTAGAGTTGGGGTTTCACCATGTTGGCCAGACTGGTCTCGAACTCCTGACCTTGTGATCCGCCAGCCTCTGCCTCCCAAAGAGCTGGGATTACAGGCGTGAGCCACCGCGCTCGGCCCTTTGCATCAATTTCTACAGCTTGTTTTCTTTGCCTGGACTTTACAAGTCTTACCTTGTTCTGCCTTCAGATATTTGTGTGGTCTCATTCTGGTGTGCCAGTAGCTAAAAATCCATGATTTGCTCTCATCCCACTCCTGTTGTTCATCTCCTCTTATCTGGGGTCACATATCTCTTCGTGATTGCATTCTGATCCCCAGTACTTAGCATGTGCGTAACAACTCTGCCTCTGCTTTCCCAGGCTGTTGATGGGGTGCTGTTCATGCCTCAGAAAAATGCATTGTAAGTTAAATTATTAAAGATTTTAAATATAGGAAAAAAGTAAGCAAACATAAGGAACAAAAAGGAAAGAACATGTATTCTAATCCATTATTTATTATACAATTAAGAAATTTGGAAACTTTAGATTACACTGCTTTTAGAGATGGAGATGTAGTAAGTCTTTTACTCTTTACAAAATACATGTGTTAGCAATTTTGGGAAGAATAGTAACTCACCCGAACAGTGTAATGTGAATATGTCACTTACTAGAGGAAAGAAGGCACTTGAAAAACATCTCTAAACCGTATAAAAACAATTACATCATAATGATGAAAACCCAAGGAATTTTTTTAGAAAACATTACCAGGGCTAATAACAAAGTAGAGCCACATGTCATTTATCTTCCCTTTGTGTCTGTGTGAGAATTCTAGAGTTATATTTGTACATAGCATGGAAAAATGAGAGGCTAGTTTATCAACTAGTTCATTTTTAAAAGTCTAACACATCCTAGGTATAGGTGAACTGTCCTCCTGCCAATGTATTGCACATTTGTGCCCAGATCCAGCATAGGGTATGTTTGCCATTTACAAACGTTTATGTCTTAAGAGAGGAAATATGAAGAGCAAAACAGTGCATGCTGGAGAGAGAAAGCTGATACAAATATAAATGAAACAATAATTGGAAAAATTGAGAAACTACTCATTTTCTAAATTACTCATGTATTTTCCTAGAATTTAAGTCTTTTAATTTTTGATAAATCCCAATGTGAGACAAGATAAGTATTAGTGATGGTATGAGTAATTAATATCTGTTATATAATATTCATTTTCATAGTGGAAGAAATAAAATAAAGGTTGTGATGATTGTTGATTATTTTTTCTAGAGGGGTTGTCAGGGAAAGAAATTGCTTTTTTTCATTCTCTCTTTCCACTAAGAAAGTTCAACTATTAATTTAGGCACATACAATAATTACTCCATTCTAAAATGCCAAAAAGGTAATTTAAGAGACTTAAAACTGAAAAGTTTAAGATAGTCACACTGAACTATATTAAAAAATCCACAGGGTGGTTGGAACTAGGCCTTATATTAAAGAGGCTAAAAATTGCAATAAGACCACAGGCTTTAAATATGGCTTTAAACTGTGAAAGGTGAAACTAGAATGAATAAAATCCTATAAATTTAAATCAAAAGAAAGAAACAAACTGAAATTAAAGTTAATATACAAGAATATGGTGGCCTGGATCTAGTGAACATATAGTAAAGATAAAACAGAATATTTCTGAAAAATCCTGGAAAATCTTTTGGGCTAACCTGAAAACAGTATATTTGAAACTATTTTTAAA
About 2000 bases
Only about 3,000,000 more slides to go.
At one slide per second, this lecture will be done in about 35 days!
The human genome is pretty darn big.
“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.”
Circa 2000
Circa 2012
Understandingthe Structure of
Genomes
Understandingthe Biology of
Genomes
Understandingthe Biology of
Disease
Advancingthe Science of
Medicine
Improving theEffectivenessof Healthcare
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Genomic Accomplishments: Base Pairs to Bedside
Progress in Mendelian disease gene discovery
KnownUnknown, suspected Mendelian
1990 2011
Sources: Lander, E. Nature , Feb. 2011www.genetests.org, Feb 2011
Cystic fibrosis Adult onset diabetes AIDS
Diabetes Diabetes
Unaffected Unaffected
SNP A SNP B
0
300
600
900
1200
1500
1800
Jul-05 Oct-05 Jan-06 Apr-06 Jul-06 Oct-06
Affymetrix 500K
Illumina 317K
Illumina 550K Illumina
650Y
Continued Progress in Genotyping Technology
Courtesy S. Gabriel, Broad/MITJuly 2005 Oct 2006
Cost
per
per
son
(USD
)
NHGRI Catalog of Published Genome-Wide Association Studies (GWAS)
> 5619 SNPs!!
Equation of a Variant’s Predictive Potential
Effect size
X =AssociationStrength
PredictivePotential
Classical genetic study“mutation”
Effect size
X =AssociationStrength
PredictivePotential
Association => Causality
Genome Wide Association Study“SNP”
Effect size
X =AssociationStrength
PredictivePotential
Genome Wide Association Study“SNPs”
Effect size
?X =AssociationStrength
PredictivePotential
Nature, April 2003
Quantum Leaps in Technology:
.….Genome sequencing at $1000 or less for a
mammalian genome…..
Advances in Genome Biology and Technology Conference
February 2012
genome.gov/sequencingcosts
Sequencing
???
Effect size
X =AssociationStrength
PredictivePotential
Frequency vs. Effect
Frequency in population
Effe
ct s
ize Classical
mutation
SNP-like variation
?
Published online April 2, 2012
Nature 9/23/12
30 JUNE 2011
16 June 2011
You are not alone in there….
Genomics
Personalized Medicine
Quality Health Care
JAMA, March 14,2012
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?
Understandingthe Structure of
Genomes
Understandingthe Biology of
Genomes
Understandingthe Biology of
Disease
Advancingthe Science of
Medicine
Improving theEffectivenessof Healthcare
1990-2003Human Genome Project
2004-2010
2011-2020
Beyond 2020
Genomic Accomplishments: Base Pairs to Bedside
2011Medical Education Issue9/7/2011
Genomics theme issues:JAMAArchives of:DermatologyFacial Plastic SurgeryGeneral PsychiatryInternal MedicineNeurologyOphthalmologyOtolaryngology—Head & Neck SurgeryPediatrics & Adolescent MedicineSurgery
Coming April 2013!
2012 – The rising tide of genomics….2000 – The genomic tsunami
Conclusions• The revolution is here, and happening all about
you.
• The front lines are in specialty care, but not for long.
• Considerably more basic, clinical, and translational research will be need to answer the “cost curve” question.
Some slides courtesy of:
Eric Green, NHGRI
Jean Jenkins, NHGRI
Teri Manolio, NHGRI
THANKS!