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Page 1: 2010StanfordE25 Michele Dragoescu E25 Project

By Michele Dragoescu E25, 2010

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OverviewGenetic sequencing techniqueDirect to Consumer (DTC) Genetic Testing

Purposes and benefitsFinancial impactCurrent examplesPrivacy concernsTips for the future

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What’s a genome, anyway?Review from class

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Sequencing TechnologyQuick review of Solexa technique from class

Break down double stranded genomic DNA into fragments

Add single 3’ A overhangs, then ligate adapters that have 3’ T overhangs

Get 4 possible results

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Continue E25 reviewAmplify fragments with two different

adapters using PCR. Heat them, make single stranded

Attach 5’ end to a solid surface that contains attached primers complementary to the adapters

Perform bridge amplification by solid phase PCR

Solid surface coated with primers

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Still ReviewUse helicase to separate the strands. Now have

single stranded clustersCleave all of one type of the two adapter typesLeft with image:

Add fluorescently labeled terminating dNTP, DNA polymerase, and sequencing primer complementary to the adapter.

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Final Steps to SequencingDNA polymerase adds only one

nucleotide because of the terminating group

A laser excites the fluorescent terminating group

The color indicates which base is presentTerminator removed, next base is read

Sequence many fragments with repeated sections, piece them together for full sequence

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More Seq. Technologies454 Life SciencesIllumina, Inc. Pacific Biosciences or PB homepage for demo video

Helicos BioSciences CorporationApplied Biosystems’ SoLiD system

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Human Genome ProjectCompleted in 2003 and coordinated by the U.S.

Dept. of Energy and the NIHIdentified the 20,000-25,000 genes in human

DNADetermined the sequences of the 3 billion

chemical base pairsThen, cost about $1 billion. Goal: $1,000Stanford 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

Page 10: 2010StanfordE25 Michele Dragoescu E25 Project

GenotypingNot the same as full sequencingGenotyping - determining which genetic

variants an individual possesses. At 23andMe, they look at Single Nucleotide Polymorphisms (SNPs)

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

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Direct to Consumer (DTC) GeneticsAt home genetic testing! Predict phenotype

based on genotype It’s controversial – because no doctor advice

involvedOften test for (1) genetic novelties (fun things

like wet or dry earwax), (2) ancestry, and (3) health risks

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Expanding Market23andMeNavigenicsPathway

GenomicsThe March

2010 version of this chart is 14 pages long!

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What is Pharmacogenomics?Predicting efficiency and safety of a drug on an

individual based on their genes and SNPs (regions of variability among humans)

PharmacoKinetics – how the body absorbs and metabolizes drugs

PharmacoDynamics - how the drug acts on the body: target region and mechanism of action

Even having the same SNP can lead to different phenotypes, depending on how many copies you have

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Pharmacogenomic Database

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WarfarinUsed to thin blood, prevent clots/strokes/heart

attacksVery difficult to dose--can’t predict based on size

of patientOverdose & underdose both dangerous

SNPs on two genes explain much of variability in dose needed (CYP2C9 and VKORC1)

Research set the dose using demographics + genetics

Stanford Prof. Russ Altman’s (creator of PharmGKB) dosing algorithm now on FDA labels for warfarin

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Health spending $4.3 trillion or 19.5% of GDP by 2017

The global market for personalized medicine is expected to grow to $452 billion in 2015 (Pricewaterhouse Coopers)

The core diagnostic and targeted therapeutic segment of the market is presently estimated at $24 billion expected to grow by 10 percent annually,

reaching $42 billion by 2015

Personalized medicine - a good investment

Page 17: 2010StanfordE25 Michele Dragoescu E25 Project

Current EventsWalgreens is awaiting FDA approval to sell

genetic testing kitsThe kit would be $20, with a vial and envelope to

ship off to Pathway GenomicsThe report would cost $79 to $179, depending

on the type of test Signals trend of ease of access of genetic

testingNo doctor intervention is required, and

scientists worry that consumers will misinterpret the tests, which don’t give definite diagnoses

Page 18: 2010StanfordE25 Michele Dragoescu E25 Project

Genetic Testing In the NewsUC 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

Freshmen get two bar code labels, one to put on the sample and one to keep.

After genotyping, results will be posted online using only the bar code identification to protect privacy

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Privacy ConcernsToo many SNPs revealed lead to the ability to

figure out the identity of the individual in question

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Privacy ConcernsIncreasing number of genetic databases exist

to support research, and they have long stretches of DNA.

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

If this information is associated with phenotype data, it can be a risk to thestudy subjects

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Past Issues of Re-IdentifiabilitySperm donor in UK

A teenager used some genetic information, general region of country to look up the identity of his father (a sperm donor)

Is the father now responsible for playing a role in his son’s life?

Governor of Massachusetts used public records (public health, voter, DMV) to prove she could trace identities

Patients with rare diseases are easily identified (public health records, Medicaid billing, voter, DMV)

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The FutureThe world is eagerly awaiting the future of

pharmacogenomics and personalized medicine

Industry experts are making their predictionsAnd also offering some words of advice

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Key FindingsExecutive summary of Price Waterhouse Cooper

The blockbuster model currently pursued by the pharmaceutical industry won’t disappear any time soonBlockbuster means huge costs, but huge rewards

Unexpectedly, stratifying prospective patients through pharmacogenomics can increase a product’s marketEven though you’re making a smaller market,

you’re can reduce advertising and dominate the niche

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More findings on pharmacogenomics futureRegulatory and reimbursement structures

related to pharmacogenomics are in placeBoth the FDA and 3rd party payers are drafting

policiesPharm. will give life science companies greater

options for leveraging their skills, expertise, and discoveries

Pharm. will likely be driven by a successful, compelling productThe first high-profile pharmacogenomics product

will probably be related to cancer

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Suggestions for FutureNature paper compares two DTC genetics-

testing companiesCraig Venter one of the authors

For seven diseases, 50% or less of the predictions of two companies agreed across five individuals

Paper advises: Companies should communicate high risks better and test for drug response markers

Community should study markers in allethnicities and look at behavior after tests

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Bibliography "- Genetics & Public Policy Center || News & Events || News Releases || Updated Chart of Direct-to-

consumer Genetic Testing Companies Available." - Genetics & Public Policy Center -. The Genetics and Public Policy Center Johns Hopkins University Berman Institute of Bioethics, 9 Mar. 2010. Web. 24 May 2010. <>.

Colliver, Victoria. "Ethics of UC Berkeley's Gene Testing Questioned - SFGate." Featured Articles From The SFGate. Web. 24 May 2010. <>.

Justin. "Healthcare Costs under the Microscope of Personalized Medicine «" Web. 24 May 2010. <>.

Ng, Pauline C., Craig J. Venter, Sarah S. Murray, and Samuel Levy. "Access : An Agenda for Personalized Medicine : Nature." Nature Publishing Group : Science Journals, Jobs, and Information. J. Craig Venter Institute, Oct. 2009. Web. 24 May 2010. <>.

Perton, Marc. "FDA Investigating Walgreens Genetic-Testing Kits." The Consumerist. Web. 24 May 2010. <>.

Wade, Nicholas. "The New York Times Log In." The New York Times - Breaking News, World News & Multimedia. Web. 24 May 2010. <>.

"What Is the Difference between Genotyping and Sequencing? | PPH." The Mission of Palomar Pomerado Health Is to Heal, Comfort, and Promote Health in the Communities We Serve. Web. 24 May 2010. <>.

Russ Altman’s talks on pharmacogenomics

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