The Perils & Promises of Genomic Medicine Carrie Iwema,
PhD, MLS, AHIP 13 th January 2015 NN/LM MAR Boost Box
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Predictive Am I at risk for a genetic disease? Diagnostic Does
my disease have a genetic basis? Carrier Might I pass on a genetic
mutation to a potential child? Prenatal What can I learn about the
genetic profile of my fetus? Genetic Testing Rationale
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How an individuals genetic inheritance affects the bodys
response to drugs Pharmacogenomics
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HER2 oncogene Over-expressed in 25-30% patients Cancer cell
replication increased Treat w/Herceptin, a monoclonal antibody
inhibiting HER2 BENEFITS Herceptin targets ONLY cancerous cells,
thus eliminating need to administer large drug doses Identification
of ONLY patients w/gene over-expression, thus preventing
unnecessary treatments Examplebreast cancer
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Predictive Use patients genome to determine probability of
developing certain diseases Preventive Based on individual risk
profile, start therapies in advance to reduce likelihood of illness
Personalized Create drug therapies to suit each genome
Participatory Patients will maintain own health by learning about
their predispositions Human Genome, US Medicine, & the 4 Psthe
4 Ps
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Timeline: Human Genome Sequence 1995 2014? 2000 2003 2007 2010
Human Genome Draft Sequence Complete Human Reference Genome
Individual Human Diploid Genome Jim Watsons Genome $2.7 B 13 yrs
$24 K 15 days $1 M 1 mth $1K 15 mins 1 st sequenced genome of a
free living organism: Haemophilus Influenzae 2007
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Impossible to see, the future is.
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Sequencing cost over time
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Sequencing & analysis of an individuals genome Looks for
mutations & differences in your genome compared to others Whole
Genome Sequencing (WGS) vs Genotyping vs Exome sequencing Genotype
versus Phenotype What is Personal Genomics?
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From the cell to nucleotides
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SNP: single nucleotide polymorphism
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Gene Chips
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Next Gen Sequencing (NGS)
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1.Order kit 2.Spit into a tube 3.Send tube back 4.Company puts
your DNA sample on a chip 5.science occurs 6.Report mailed back to
you; may only be raw data 7.Genotype NOT full sequence (typically)
8.Consultations, analysis, worry, confusion DTC: Direct-To-Consumer
Genetic Testing
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Walgreens, Pathway Genomics, & FDA (May 2010) Government
Accountability Office (GAO) 22 July 2010 DTC genetic testing
companies provide results that are misleading and of little or no
practical use. Companies: 23andMe, Navigenics, Pathway Genomics +
others Degree of Regulation vs Public Right to Personal Info
Congress & DTC
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Federal Regulation
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Access & Trust
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GINA: Genetic Information Non-discrimination Act The first
civil rights legislation of the 21st century -Senator Ted Kennedy
Signed 28 May 2008 (After 13 years of debate.)
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GINA GINA : Prohibits genetic discrimination in health
insurance & employment Title 1: Prohibits discrimination in
group and individual health insurance plans. Forbids genetic
information being used to deny coverage, adjust premiums, or
require someone to take a genetic test. Title 2: Prohibits
employers from using genetic information to make hiring, firing or
promotion decisions. Severely limits employers rights to request,
require, or purchase an employees genetic information.
California
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Genome Statute & Legislation DB
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2009 BRCA1 and BRCA2 Back & forth in court (Supreme Court
4/15/13) Isolated genes CANNOT be patented, but cDNA CAN (9-0)
(6/13/13) Myriad sued Ambry Genetics & Gene by Gene 2014: GxG
settled; Ambry denied Australia upheld Myriads claim! Are Genes
Patentable?
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Source: Mark Hakkarinen and Bob Cook-Deegan, DNA Patent
Database, 12 February 2014 Creative Commons "free use with
attribution" license, with the attribution to Genomics Policy
Resource.
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11 th Oct 2012 Data access & sharing policies Privacy
protections Security Compliance w/regulatory schemes (HIPAA)
Informed consent process & issues Facilitate research progress
Public benefit
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Incidental Findings? 22 March 2013 Labs performing genome/exome
clinical sequencing to also report on 56 specific genes No age
restrictions, no choice to not know (since revised to include opt
out) Clinicians provide pre- & post-test counseling Modified as
needed due to technical advances
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Genetic Counselors
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SNPedia: wiki investigating human genetics SNPedia Promethease:
uses SNPedia to analyze & Promethease help explain your DNA Do
it yourself?
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Crowdsourcing Health Info
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Noninvasive Fetal Sequencing I am your father.
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Mom the worrier You Crazy Uncle Ben Skeptical brother- in-law
Early adopter sister Dad already signed up to get sequenced Grandpa
says no way! Uncle Q-G worried about losing his insurance because
of his sons DNA sequence Cousin Chewie wants to donate his sequence
to science and make it totally public Great-Grandpa is gone, but a
sample of his DNA still exists Impact on FamilyFamily Your niece
& nephew Your potential kid?
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Perils of genetic testing What are the privacy concerns for
individual and families? How much should we fear discrimination at
work and with insurance? How far ahead is the technology of its
clinical usefulness? Will fair weight given to environmental &
social factors? How can we ensure access for all who want to be
sequenced? What surprises and secrets might be revealed? How
realistic are promises of anonymity?
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1997
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Promises of genetic testing Ideas for more tests and
interventions if I learn Im at risk Finding the right drugs, in the
right doses, for my conditions Motivation to change my habits Might
reveal details of my family tree and genealogy Planning for my long
term medical and financial needs I am an early adopter and
information altruist I want to use my genome as a social networking
tool To inform my reproductive decisions
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Online Resources Internet resources in medical genetics.
Waggoner DJ. Curr Protoc Hum Genet. 2014 Jan 21;80:Unit 9.12.. doi:
10.1002/0471142905.hg0912s80. PMID: 24510683 Genetic Testing
Databases GeneTests; GTR; GeneReviews; Clinic Directory; Testing
Labs Microarray & Next Gen Sequencing UCSC Genome; DECIPHER;
ISCA; DGV; HGMD; dbSNP; OMIM Newborn Screening National Newborn
Screening & Global Resource Center; Babys First Test Genetic
Disease Resources, Advocacy, & Support Groups Genetic Alliance;
GHR; Unique; The Genetics Education Center; NORD; NIREHG Genetics
Professional Societies ACMG; ASHG; NSGC; ISNG; AMP; ABMG; ABGC;
APHMG
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Carrie Iwema, PhD, MLS, AHIP Information Specialist in
Molecular Biology Health Sciences Library System University of
Pittsburgh [email protected]