Personal Genomics

Carrie Iwema, PhD, MLS, AHIP

19th March 2014Molecular Biology Information

Service

1997

Outline

1.Context

2.Personal Genomics

3.Personalized Medicine

4.Consumer Impact

Context

Broad Timeline of Genetics(video)from

Genetics & Society: A Course for Educators

by

Rob DeSalle, PhD & David Randle, PhD

NGS cost over time…

Timeline: Human Genome Sequence

1995

2014

2000

2003

2007

2007

2010

Human Genome Draft

Sequence

Complete Human Reference Genome

Individual Human

Diploid Genome

Jim Watson’s Genome

$2.7 B13 yrs

$24 K15

days

$1 M1

mth

$1K15

mins

1st sequenced

genome of a free living organism:

Haemophilus

Influenzae

Human Genome Project

GWAS: Genome Wide Association Studies

http://genome.ucsc.edu/ENCODE/

http://www.nature.com/encode/

http://www.genome.gov/10005107

GenomeTV

Lecture Series

http://www.youtube.com/watch?v=TwXXgEz9o4w

Personal Genomics

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

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

personal genetics education project (link)

– 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?

Genetic Testing Rationale

personal genetics education project (link)

http://www.youtube.com/watch?v=mVZI7NBgcWM

Personal Genome Project

• 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…

DTC: Direct-To-Consumer Genetic Testing

How do they work?

SNP: single nucleotide polymorphism

• 23andMe: genetics just go personal.

– Personal genome API– FDA clearance

• 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

• deCODEme: deCODE your health– Discontinued sales

DTC: Major Companies

$99

– 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

1. Ensure appropriate info & consent

procedures

2. Formal laboratory accreditation

3. Evidence of a valid gene-disease association

4. Appropriately qualified staff to interpret the test result

5. Consumer protection legislation to prevent false or misleading claimsRegulating 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

Suggested Regulation

• 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

I’m doing it!

So you’ve got your sequence…now what?

Promethease Report

Personalized Medicine

• 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

Human Genome, US Medicine, & the 4 P’s

How an individual’s

genetic inheritance

affects the body’s

response to drugs

Pharmacogenomics

• HER2 oncogene • Over-expressed in 25-30% patients• Results in increase in replication of cancer

cells• Treat w/Herceptin, a monoclonal antibody that

inhibits 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

Example—breast cancer

Impact of genetic variation on drug response

ChallengesWhat 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?

personal genetics education project (link)

Access & Trustpersonal genetics education project

(link)

Your doctor

Your spouse

Your employer

Your health insurer

Law enforcement

Researchers studying genetics

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

personal genetics education project (link)

“ The first civil rights legislation

of the 21st century”

-Senator Ted Kennedy

Signed 28 May 2008

(After 13 years of debate.)

GINA: Prohibits genetic discrimination in health insurance & employment

personal genetics education project (link)

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…

Genome Statute & Legislation DB

Myriad Genetics case – 2009-current– BRCA1 and BRCA2– 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

Are Genes Patentable?

SciShow: Patenting Person Parts

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.

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9941

Number of items loaded into the DNA Patent Database by year as of 2012

Issued Patents Published Applications (n/a from 1970-2000)

Year

11th Oct 2012• Data access & sharing policies• Privacy protections• Security• Compliance w/regulatory schemes

(HIPAA)• Informed consent process & issues• Facilitate research progress• Public benefit

Consumer Impact

Learning from One’s Genome

Mom the worrier

You

Crazy Uncle Bill

Skeptical brother

Early adopter sister

Dad already signed up to get sequenced

Grandpa says no way!

Aunt Erma worried about losing her insurance because of her son’s DNA sequence

Cousin Betty wants to donate her sequence to science and make it totally public

Grandma is gone, but a sample of her DNA still exists…

Impact on Familypersonal genetics education project (

link)

Your kids

Your potential kid?

Henrietta Lacks

controversy

Noninvasive Fetal Sequencing

• 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

Pre-implantation Genetic Diagnosis

personal genetics education project (link)

Genetic Counselors

http://www.genesinlife.org/

Family History Resources

Counseling & Testing Resources

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

Resources

Genetic Testing Scenarioshttp://www.pbs.org/wgbh/nova/body/genetic-testing-dilemmas-intro.html

Thanks for your

attention.

Carrie Iwema, PhD, MLS, AHIPInformation Specialist in Molecular

BiologyHealth Sciences Library System

University of Pittsburghiwema@pitt.edu