Personal Genomics Personalized Medicine YOU Carrie Iwema Ph

Personal Genomics, Personalized Medicine, & YOU Carrie Iwema, Ph. D, MLS, AHIP 30 th April 2014 TLA’ 14

1997

Outline 1. Context 2. Personal Genomics 3. Personalized Medicine 4. You (Consumer Impact)

Context

Broad Timeline of Genetics (video) from Genetics & Society: A Course for Educators by Rob De. Salle, Ph. D & David Randle, Ph. D

DNA Tutorials

NGS cost over time…

Timeline: Human Genome Sequence $24 K 15 days $2. 7 B 13 yrs Human Genome Draft Sequence Individual Human Diploid Genome 2000 2007 1995 1 st sequenced genome of a free living organism: Haemophilus Influenzae 2010 2003 2007 Complete Human Reference Genome Jim Watson’s Genome $1 M 1 mth 2014 $1 K 15 mins

Human Genome Project

GWAS: Genome Wide Association Studies

http: //genome. ucsc. edu/ENCODE/ http: //www. nature. com/encode/ http: //www. genome. gov/10005107

Genome. TV Lecture Series

Personal Genomics

Personal Genome Project

What is a Personal Genome Sequence? • An analysis of all your genes • Looks for mutations & differences in your genome • Like taking all current and future genetic tests simultaneously • A Human Genome Project performed on YOU personal genetics education project (link)

Why get genetic testing? Ideas for more tests and interventions if I learn I’m at risk To find the right drugs, in the right doses, for my conditions Planning for my long term medical and financial needs I want to use my genome as a social networking tool I am an early adopter and information altruist Might reveal details of my family tree and genealogy To inform my reproductive decisions personal genetics education project (link) Motivation to change my habits

Genetic Testing Rationale – Predictive testing • Am I at risk for a genetic disease? – Diagnostic testing • Does my disease have a genetic basis? – Carrier testing • Might I pass on a genetic mutation to a potential child? – Prenatal testing • What can I learn about the genetic profile of my fetus? personal genetics education project (link)

DTC: Direct-To-Consumer Genetic Testing How do they work? • Order kit • Spit into a tube • Send tube back • Company puts your DNA sample on a chip • “science” occurs • Report mailed back to you; may only be raw data • Genotype NOT full sequence (typically) • Consultations, analysis, worry, confusion…

SNP: single nucleotide polymorphism

DTC: Major Companies • 23 and. Me: genetics just go personal. – Personal genome API – FDA clearance $99 • Navigenics: clinically guided genetic analysis – Bought out by Life Technologies • Pathway Genomics: The Value of Knowing – Must be ordered through a U. S. physician registered w/PG • de. CODEme: de. CODE your health – Discontinued sales

https: //www. 23 andme. com/

“Nutrigenomics” etc…

Congress & DTC – 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: 23 and. Me, Navigenics, Pathway Genomics + others Degree of Regulation vs Public Right to Personal Info

Suggested Regulation 1. Ensure appropriate info & consent procedures 2. Formal laboratory accreditation 3. Evidence of a valid disease association gene- 4. Appropriately qualified staff to interpret the test result 5. Consumer protection legislation to prevent false or misleading claims Regulating direct-to-consumer genetic tests: What is all the fuss about? Wright CF, Hall A, Zimmern RL. Genet Med. 2010 Oct 1. [Epub ahead of print] PMID: 20921893

Genetic testing on campus? Summer 2010 o o UC Berkeley • • Undergrads Free In-house testing 3 gene variants Stanford U • • Medical/grad $99 Navigenics or 23 and. Me Full genotype sequencing

I’m doing it! So you’ve got your sequence…now what? • Talk to the company’s genetic counselors • Talk to your physician/genetic counselor • Do it yourself…? – SNPedia: wiki investigating human genetics – Promethease: uses SNPedia to analyze & help explain your DNA

Promethease Report

Crowdsourcing Health Conditions 23 and. Me & Cure. Together

Crowdsourcing Example

Personalized Medicine

Human Genome, US Medicine, & the 4 P’s • Predictive – Use patient’s 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

Pharmacogenomics How an individual’s genetic inheritance affects the body’s response to drugs

Example—breast cancer • • HER 2 oncogene Over-expressed in 25 -30% patients Results in increase in replication of cancer cells Treat w/Herceptin, a monoclonal antibody that inhibits HER 2 BENEFITS – Herceptin targets ONLY cancerous cells, thus eliminating need to administer large drug doses – Identification of ONLY patients w/gene overexpression, thus preventing unnecessary treatments

Impact of genetic variation on drug response

Challenges How much should we fear discrimination at work and with insurance? What are the privacy concerns for individual and families? How realistic are promises of anonymity? How can we ensure access for all who want to be sequenced? Will fair weight given to environmental & social factors? What surprises and secrets might be revealed? How far ahead is the technology of its clinical usefulness? personal genetics education project (link)

Access & Trust Your doctor Your spouse Researchers studying genetics Law enforcement Your health insurer Your employer personal genetics education project (link)

Incidental Findings? • • 22 March 2013 Labs performing genome/exome clinical sequencing to also report on 57 specific genes No age restrictions, no choice to not know Clinicians provide pre- & post-test counseling Modified as needed due to technical advances

FEARS!!!

Genetic Discrimination

GINA: Genetic Information Non-discrimination Act “ The first civil rights legislation of the 21 st century” -Senator Ted Kennedy Signed 28 May 2008 (After 13 years of debate. ) personal genetics education project (link)

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 employee’s genetic information. California… personal genetics education project (link)

Genome Statute & Legislation DB

Are Genes Patentable? Myriad Genetics case – – – 2009 -current BRCA 1 and BRCA 2 Back & forth in court (Supreme Court 4/15/13) Genes CANNOT be patented (9 -0) (6/13/13) Myriad now suing Ambry Genetics & Gene by Gene Sci. Show: Patenting Person Parts

13 0 37 0 27 0 30 0 29 0 22 0 26 0 42 0 72 0 86 0 105 0 96 0 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 Year Source: Mara Snyder and Bob Cook-Deegan, DNA Patent Database, 2 January 2012 Creative Commons "free use with attribution" license, with the attribution to Genomics Policy Resource. 2011 2010 3 238 3 175 3 587 3 474 4 389 4 293 4 463 7708 7848 7897 8680 10225 10016 9941 9894 9590 10000 2009 2008 2007 2006 2005 2 722 3 055 3 536 3 872 3 828 4105 3788 13603 Published Applications (n/a from 1970 -2000) 2004 1124 2556 14000 2003 0 0 1588 8000 2002 2001 2000 1999 0 0 955 819 783 597 491 375 373 4000 1998 1997 0 0 0 0 280 219 2000 1996 1995 1994 1993 1992 1991 1990 1989 0 0 Issued Patents 1988 1987 134 13 0 1973 0 10 0 1972 1986 11 0 0 1971 Number of items loaded into the DNA Patent Database by year as of 2012 12000 6000

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

WEBINAR SERIES

Learning from One’s Genome

YOU!

Genetic Testing Scenarios http: //www. pbs. org/wgbh/nova/body/genetic-testing-dilemmasintro. html

personal genetics education project (link) Impact on Family Early adopter sister You Skeptical brother Dad already signed up to get sequenced Mom the worrier Grandpa says no way! Crazy Uncle Bill Aunt Erma worried about losing her insurance because of her son’s DNA sequence Your kids Grandma is gone, but a sample of her DNA still exists… Cousin Betty wants to donate her sequence to science and make it totally public Your potential kid?

Henrietta Lacks controversy

NPR series: $1, 000 genome 18 Sept 2012 http: //tinyurl. com/bde 79 hm

Noninvasive Fetal Sequencing

Pre-implantation Genetic Diagnosis • Method to test for certain genetic traits in an embryo • Embryo is created via in vitro fertilization • Genetic testing occurs when embryo is 2 -4 days old, typically at the 8 -cell stage • A single cell is removed and tested • Results of testing are used to decide which embryos to implant in prospective mother’s uterus personal genetics education project (link)

Common uses of PGD personal genetics education project (link)

Public attitudes towards PGD personal genetics education project (link)

Genetic Counselors

Family History Resources

Counseling & Testing Resources

http: //www. ncbi. nlm. nih. gov/gtr/

Resources for the General Public

Resources

Video Summary

Thanks for your attention. Carrie Iwema, Ph. D, MLS, AHIP Information Specialist in Molecular Biology Health Sciences Library System University of Pittsburgh iwema@pitt. edu