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By Michele Dragoescu E25, 2010

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Overview <ul><li>Genetic sequencing technique </li></ul><ul><li>Direct to Consumer (DTC) Genetic Testing </li></ul><ul><ul><li>Purposes and benefits </li></ul></ul><ul><ul><li>Financial impact </li></ul></ul><ul><ul><li>Current examples </li></ul></ul><ul><ul><li>Privacy concerns </li></ul></ul><ul><ul><li>Tips for the future </li></ul></ul>

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What’s a genome, anyway? <ul><li>Review from class </li></ul>

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Sequencing Technology <ul><li>Quick review of Solexa technique from class </li></ul><ul><li>Break down double stranded genomic DNA into fragments </li></ul><ul><li>Add single 3’ A overhangs, then ligate adapters that have 3’ T overhangs </li></ul><ul><li>Get 4 possible results </li></ul>

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Continue E25 review <ul><li>Amplify fragments with two different adapters using PCR. Heat them, make single stranded </li></ul><ul><li>Attach 5’ end to a solid surface that contains attached primers complementary to the adapters </li></ul><ul><li>Perform bridge amplification by solid phase PCR </li></ul><ul><li>Solid surface coated with primers </li></ul>

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Still Review <ul><li>Use helicase to separate the strands. Now have single stranded clusters </li></ul><ul><li>Cleave all of one type of the two adapter types </li></ul><ul><li>Left with image: </li></ul><ul><li>Add fluorescently labeled terminating dNTP, DNA polymerase, and sequencing primer complementary to the adapter. </li></ul>

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Final Steps to Sequencing <ul><li>DNA polymerase adds only one nucleotide because of the terminating group </li></ul><ul><li>A laser excites the fluorescent terminating group </li></ul><ul><li>The color indicates which base is present </li></ul><ul><li>Terminator removed, next base is read </li></ul><ul><li>Sequence many fragments with repeated sections, piece them together for full sequence </li></ul>

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More Seq. Technologies <ul><li>454 Life Sciences </li></ul><ul><li>Illumina, Inc. </li></ul><ul><li>Pacific Biosciences http://www.dnatube.com/video/3003/SMRT-DNA-Sequencing or PB homepage for demo video </li></ul><ul><li>Helicos BioSciences Corporation </li></ul><ul><li>Applied Biosystems’ SoLiD system </li></ul>

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Human Genome Project <ul><li>Completed in 2003 and coordinated by the U.S. Dept. of Energy and the NIH </li></ul><ul><li>Identified the 20,000-25,000 genes in human DNA </li></ul><ul><li>Determined the sequences of the 3 billion chemical base pairs </li></ul><ul><li>Then, cost about $1 billion. Goal: $1,000 </li></ul><ul><li>Stanford prof (Steve Quake) who sequenced his entire genome, says he could use Helicos for $12,000 now and the $1,000 goal can be met within three years </li></ul>

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Genotyping <ul><li>Not the same as full sequencing </li></ul><ul><li>Genotyping - determining which genetic variants an individual possesses. At 23andMe, they look at Single Nucleotide Polymorphisms (SNPs) </li></ul><ul><li>Sequencing - determining the exact sequence of a certain length of DNA. A given stretch may include some SNPs, in addition to regions that are constant </li></ul>

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Direct to Consumer (DTC) Genetics <ul><li>At home genetic testing! Predict phenotype based on genotype </li></ul><ul><li>It’s controversial – because no doctor advice involved </li></ul><ul><li>Often test for (1) genetic novelties (fun things like wet or dry earwax), (2) ancestry, and (3) health risks </li></ul>

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Expanding Market <ul><li>23andMe </li></ul><ul><li>Navigenics </li></ul><ul><li>Pathway Genomics </li></ul><ul><li>The March 2010 version of this chart is 14 pages long! </li></ul>

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What is Pharmacogenomics? <ul><li>Predicting efficiency and safety of a drug on an individual based on their genes and SNPs (regions of variability among humans) </li></ul><ul><li>PharmacoKinetics – how the body absorbs and metabolizes drugs </li></ul><ul><li>PharmacoDynamics - how the drug acts on the body: target region and mechanism of action </li></ul><ul><li>Even having the same SNP can lead to different phenotypes, depending on how many copies you have </li></ul>

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Pharmacogenomic Database

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Warfarin <ul><li>Used to thin blood, prevent clots/strokes/heart attacks </li></ul><ul><li>Very difficult to dose--can’t predict based on size of patient </li></ul><ul><ul><li>Overdose & underdose both dangerous </li></ul></ul><ul><li>SNPs on two genes explain much of variability in dose needed (CYP2C9 and VKORC1) </li></ul><ul><li>Research set the dose using demographics + genetics </li></ul><ul><li>Stanford Prof. Russ Altman’s (creator of PharmGKB) dosing algorithm now on FDA labels for warfarin </li></ul>

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<ul><li>Health spending $4.3 trillion or 19.5% of GDP by 2017 </li></ul><ul><li>The global market for personalized medicine is expected to grow to $452 billion in 2015 (Pricewaterhouse Coopers) </li></ul><ul><li>The core diagnostic and targeted therapeutic segment of the market is presently estimated at $24 billion </li></ul><ul><ul><li>expected to grow by 10 percent annually, reaching $42 billion by 2015 </li></ul></ul>Personalized medicine - a good investment

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Current Events <ul><li>Walgreens is awaiting FDA approval to sell genetic testing kits </li></ul><ul><li>The kit would be $20, with a vial and envelope to ship off to Pathway Genomics </li></ul><ul><li>The report would cost $79 to $179, depending on the type of test </li></ul><ul><li>Signals trend of ease of access of genetic testing </li></ul><ul><li>No doctor intervention is required, and scientists worry that consumers will misinterpret the tests, which don’t give definite diagnoses </li></ul>

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Genetic Testing In the News <ul><li>UC Berkeley is asking the Class of 2014 to voluntarily submit sample for genetic testing for susceptibility to too much alcohol, dairy, and not enough vegetables </li></ul><ul><li>Freshmen get two bar code labels, one to put on the sample and one to keep. </li></ul><ul><li>After genotyping, results will be posted online using only the bar code identification to protect privacy </li></ul>

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Privacy Concerns <ul><li>Too many SNPs revealed lead to the ability to figure out the identity of the individual in question </li></ul>

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Privacy Concerns <ul><li>Increasing number of genetic databases exist to support research, and they have long stretches of DNA. </li></ul><ul><li>Of 1,000,000 locations in genome where people may differ, only 60-100 need to be measured to give a unique fingerprint of a person </li></ul><ul><li>If this information is associated with phenotype data, it can be a risk to the study subjects </li></ul>

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Past Issues of Re-Identifiability <ul><li>Sperm donor in UK </li></ul><ul><ul><li>A teenager used some genetic information, general region of country to look up the identity of his father (a sperm donor) </li></ul></ul><ul><ul><li>Is the father now responsible for playing a role in his son’s life? </li></ul></ul><ul><li>Governor of Massachusetts used public records (public health, voter, DMV) to prove she could trace identities </li></ul><ul><li>Patients with rare diseases are easily identified (public health records, Medicaid billing, voter, DMV) </li></ul>

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The Future <ul><li>The world is eagerly awaiting the future of pharmacogenomics and personalized medicine </li></ul><ul><li>Industry experts are making their predictions </li></ul><ul><li>And also offering some words of advice </li></ul>

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Key Findings <ul><li>Executive summary of Price Waterhouse Cooper </li></ul><ul><li>The blockbuster model currently pursued by the pharmaceutical industry won’t disappear any time soon </li></ul><ul><ul><li>Blockbuster means huge costs, but huge rewards </li></ul></ul><ul><li>Unexpectedly, stratifying prospective patients through pharmacogenomics can increase a product’s market </li></ul><ul><ul><li>Even though you’re making a smaller market, you’re can reduce advertising and dominate the niche </li></ul></ul>

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More findings on pharmacogenomics future <ul><li>Regulatory and reimbursement structures related to pharmacogenomics are in place </li></ul><ul><ul><li>Both the FDA and 3 rd party payers are drafting policies </li></ul></ul><ul><li>Pharm. will give life science companies greater options for leveraging their skills, expertise, and discoveries </li></ul><ul><li>Pharm. will likely be driven by a successful, compelling product </li></ul><ul><ul><li>The first high-profile pharmacogenomics product will probably be related to cancer </li></ul></ul>

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Suggestions for Future <ul><li>Nature paper compares two DTC genetics-testing companies </li></ul><ul><ul><li>Craig Venter one of the authors </li></ul></ul><ul><li>For seven diseases, 50% or less of the predictions of two companies agreed across five individuals </li></ul><ul><li>Paper advises: Companies should communicate high risks better and test for drug response markers </li></ul><ul><li>Community should study markers in all ethnicities and look at behavior after tests </li></ul>

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Bibliography <ul><li>&quot;- Genetics & Public Policy Center || News & Events || News Releases || Updated Chart of Direct-to-consumer Genetic Testing Companies Available.&quot; - Genetics & Public Policy Center - . The Genetics and Public Policy Center Johns Hopkins University Berman Institute of Bioethics, 9 Mar. 2010. Web. 24 May 2010. <http://www.dnapolicy.org/news.release.php?action=detail&pressrelease_id=137>. </li></ul><ul><li>Colliver, Victoria. &quot;Ethics of UC Berkeley's Gene Testing Questioned - SFGate.&quot; Featured Articles From The SFGate . Web. 24 May 2010. <http://articles.sfgate.com/2010-05-21/bay-area/20907654_1_genetic-testing-test-results-testing-kits>. </li></ul><ul><li>Justin. &quot;Healthcare Costs under the Microscope of Personalized Medicine « TheOTCInvestor.com.&quot; TheOTCInvestor.com . Web. 24 May 2010. <http://theotcinvestor.com/health-care-costs-under-the-microscope-of-personalized-medicine-715/>. </li></ul><ul><li>Ng, Pauline C., Craig J. Venter, Sarah S. Murray, and Samuel Levy. &quot;Access : An Agenda for Personalized Medicine : Nature.&quot; Nature Publishing Group : Science Journals, Jobs, and Information . J. Craig Venter Institute, Oct. 2009. Web. 24 May 2010. <http://www.nature.com/nature/journal/v461/n7265/pdf/461724a.pdf>. </li></ul><ul><li>Perton, Marc. &quot;FDA Investigating Walgreens Genetic-Testing Kits.&quot; The Consumerist . Web. 24 May 2010. <http://consumerist.com/2010/05/fda-investigating-walgreens-genetic-testing-kits.html>. </li></ul><ul><li>Wade, Nicholas. &quot;The New York Times Log In.&quot; The New York Times - Breaking News, World News & Multimedia . Web. 24 May 2010. <http://www.nytimes.com/2009/08/11/science/11gene.html?_r=3&hp>. </li></ul><ul><li>&quot;What Is the Difference between Genotyping and Sequencing? | PPH.&quot; The Mission of Palomar Pomerado Health Is to Heal, Comfort, and Promote Health in the Communities We Serve. Web. 24 May 2010. <http://www.pph.org/PPHContentPage.aspx?nd=44>. </li></ul><ul><li>Russ Altman’s talks on pharmacogenomics </li></ul><ul><li>Pharmgkb.org </li></ul>