Personal Genomics, Personalized Medicine, & You

Personal Genomics, Personalized Medicine, & You
5/4/2013 The Perils & Promises of Genomic Medicine Carrie Iwema, PhD, MLS, AHIP 13th January 2015 NN/LM MAR Boost Box MLA 2013 CE---Iwema---U.Pittsburgh

NEW HOPE Personal Genomics, Personalized Medicine, & You 5/4/2013 Although Star Wars took place a long time ago in a galaxy far, far away…. it provides a useful framework for us to think about the future of personalized medicine thanks to advances in genomics. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Genetic Testing Rationale 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? MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Pharmacogenomics How an individual’s genetic inheritance affects the body’s response to drugs More powerful medicines Better, safer drugs appropriately matched to patients More accurate drug dosages Advanced screening for disease Better vaccines Decrease in overall health care costs Improvements in drug discovery & approval process MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Example—breast cancer 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 There are dramatic implications with genetic technologies on the health professions, their education and on patient care. Genetic services are not always adequately linked into medical specialties and there is a shortage of resources to bring new genetic-based techniques into mainstream health service provision. As more becomes known about how faulty genes cause disease, a new generation of therapeutics based on an individual’s genetic makeup and drug design is and will be revolutionary. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 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 Leroy Hood: Institute for Systems Biology Inventions include automated DNA sequencer and tool for synthesizing DNA 1987 Lasker Award for Basic Medical Research Key player in Human Genome Project MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Timeline: Human Genome Sequence $24 K 15 days $2.7 B 13 yrs Human Genome Draft Sequence Individual Human Diploid Genome 2000 2007 2007 2010 1995 2003 2007 2014? Illumina--$800 for reagents, $135 equipment depreciation, $65 overhead; 3 days But…interpretation. Really closer to $15K at minimum Jim Watson’s Genome 1st sequenced genome of a free living organism: Haemophilus Influenzae Complete Human Reference Genome $1 M 1 mth $1K 15 mins MLA 2013 CE---Iwema---U.Pittsburgh

Impossible to see, the future is.

5/4/2013 Sequencing cost over time… Moore’s Law: a computing term which originated around 1970; the simplified version of this law states that processor speeds, or overall processing power for computers will double every two years. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 What is Personal Genomics? Sequencing & analysis of an individual’s genome Looks for mutations & differences in your genome compared to others Whole Genome Sequencing (WGS) vs Genotyping vs Exome sequencing Genotype versus Phenotype "Genotype" is an organism's full hereditary information. "Phenotype" is an organism's actual observed properties, such as morphology, development, or behavior. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 From the cell to nucleotides MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 This graphic shows the chromosomes arranged in a circular orientation, shown as wedges, marked with a length scale. Data placed outside of the chromosome ring represents degree of small- and large- scale variation in the genome at a given position found between different populations. Data placed on top of the chromosome ring highlights positions of genes implicated in disease, such as cancer, diabetes, and glaucoma. Data placed inside the ring links disease-related genes found in the same biochemical pathway (grey) and the degree of similarity for a subset of the genome (colored). MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 SNP: single nucleotide polymorphism DNA sequence variations that occur when a single nucleotide (A, C, T, G) in the genome sequence is altered Variations in DNA sequence have an impact on how humans respond to disease Must occur in at least 1% of the population SNP maps help identify genes associated with complex ailments MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Gene Chips Expression profiling Parallel processing Each spot on a microarray contains multiple identical strands of DNA. The DNA sequence on each spot is unique. Each spot represents one gene. Thousands of spots are arrayed in orderly rows and columns on a solid surface (usually glass). MLA 2013 CE---Iwema---U.Pittsburgh

Next Gen Sequencing (NGS)

5/4/2013 DTC: Direct-To-Consumer Genetic Testing 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… Point out difference between DTC and clinical genetics testing MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 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: 23andMe, Navigenics, Pathway Genomics + others Degree of Regulation vs Public Right to Personal Info DTC companies in USA 23andMe (adoption, deep ancestry, ethnicity, exome sequencing, genealogy, health) Counsyl (preconception screening) DNA DTC (research, exome sequencing, whole genome sequencing) DNATraits (health) Genelex (paternity, pharmacogenetics) Interleukin Genetics (health) InVitae (health) Knome (health) Pathway Genomics (health) Stanford Sports Genetics (sports) Ubiome (microbiome sequencing) MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Federal Regulation How to evaluate a genetic test: Is the test accurate and reliable? (Analytical validity) Is the test result medically meaningful? (Clinical validity) Does the test improve healthcare? (Clinical utility) MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Access & Trust MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 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.) MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 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. Jan 1, 2011 California Governor Jerry Brown signed into law civil rights protections to prevent discrimination against people based on their genetic information. Authored by State Sen. Alex Padilla, the California law the use of genetic information to discriminate against a person in housing, employment, education, health insurance, life insurance, mortgage lending and elections. California… MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Genome Statute & Legislation DB Search by year, state, topic NY: since 2007, 33 bills and 6 statutes 21 bills failed; 7 bills referred to other committees; 2 enacting clauses stricken; 3 amended & recommitted PA: since 2007, 11 bills and 1 statute 7 bills failed; 1 inactive; 1 approved; 1 referred to Insurance committee; 1 referred to Senate Banking & Insurance cmte; 1 statute MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Are Genes Patentable? 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 Myriad’s claim! Also in Australia! 20% genes in human genome patented; big deal in 1980s, 1990s (4K out of 23K) 40,000 patents over 30 yrs Myriad holds patents on the genes along with the University of Utah Research Foundation. As a result, Myriad is the only company that can market a test for the mutations. Will patenting DNA sequences limit their accessibility and development into useful products? 11/30/2012 Supreme Court granted a writ of certiorari, meaning agreed to hear appeal on question: “are human genes patentable?” Thus, 4 judges have something to say… Final decision on one ruling: the bulk of Myriad’s challenged diagnostic method patents are invalid Ruling: “Myriad did not create anything,” Thomas wrote. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” He added that “groundbreaking, innovative, or even brilliant discovery does not by itself” overcome the fact that “laws of nature, natural phenomena, and abstract ideas” are beyond the domain of patent protection.” “ I.e. isolated genomic DNA NOT patentable, but cDNA is MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Allerca of San diego offers “no sneeze kitties” a hypoallergenic cat or “lifestyle pets” at a cost of $7000. They are bred so that the glands don’t produce protein responsible for most human cat allergies. Another breed of cat is $28,000, and a dog is $16,000 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. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 11th Oct 2012 Data access & sharing policies Privacy protections Security Compliance w/regulatory schemes (HIPAA) Informed consent process & issues Facilitate research progress Public benefit Advisory panel of the nation’s leaders in medicine, science, ethics, religion, law, and engineering. The Commission advises the President on bioethical issues arising from advances in biomedicine and related areas of science and technology. The Commission seeks to identify and promote policies and practices that ensure scientific research, health care delivery, and technological innovation are conducted in a socially and ethically responsible manner. Privacy and Progress in Whole Genome Sequencing MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 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 Only guidelines! Presidential Bioethics: Anticipate & Communicate, Dec 2013: The ACMG acknowledge “there are insufficient data on clinical utility to fully support these recommendations… and… insufficient evidence about benefits, risks and costs of disclosing incidental findings to make evidence-based recommendations”. Yet, they clearly felt the need to draw a line in the sand and create a starting point. This is a bold and fearless move. Recently, the ACMG released recommendations for return of incidental findings following genome or exome sequencing, garnering a great deal of attention in the science media and some in the popular media as well – most of it stressing two points: the fact that the guidelines call for certain results to be returned regardless of patient preferences, and that they call for the same results to be returned regardless of patient age. These are big departures from current practice, and they have drawn a lot of fire for going too far (or for not going far enough). MLA 2013 CE---Iwema---U.Pittsburgh

Genetic Counselors 5/4/2013 Analysis is key!!!
Genetics counselors are professionals who have completed a masters program and then have to pass a certification exam administered by the American Board of Genetic Counseling. Evaluating family history and medical records Order genetic tests Evaluate the results of investigation Help people understand and reach decisions about what to do next Most couples planning a pregnancy or who are expecting, don’t need genetic counseling. The best time to seek genetic counseling is before pregnancy, when counseling can help assess risk factors.

5/4/2013 Do it yourself…? SNPedia: wiki investigating human genetics Promethease: uses SNPedia to analyze & help explain your DNA openSNP.org --allows DTC customers to publish their test results, find others w/similar genvar, etc. MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Impact of direct-to-consumer genomic testing at long term follow-up. Bloss CS, Wineinger NE, Darst BF, Schork NJ, Topol EJ. J Med Genet Jun;50(6): doi: /jmedgenet Epub 2013 Apr 4. PMID: Dr. Cinnamon Bloss, best name ever, from Scripps Inst. 2,240 participants 1,325 completed long term follow up See nature article: From Oct 19: Also: And:

5/4/2013 Crowdsourcing Health Info Go to link MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Hyperlink to tool

Noninvasive Fetal Sequencing
Personal Genomics, Personalized Medicine, & You 5/4/2013 Noninvasive Fetal Sequencing Noninvasive sequencing of human fetuses holds clinical utility. Since the approaches pioneered by Kitzman and Fan don’t rely on amniocentesis or chorionic villous sampling (CVS) for obtaining fetal DNA, they do not pose a risk to the developing fetus. Both amniocentesis and CVS are invasive procedures that carry a small risk of miscarriage. But it’s likely going to take some time before fetal sequencing is actually offered to the general public. The costs need to drop significantly — it’s currently around $20,000-$50,000 per fetal genome. More work is also needed to refine the approach and improve the accuracy. I am your father. MLA 2013 CE---Iwema---U.Pittsburgh

Impact on Family You Skeptical brother-in-law Early adopter sister
5/4/2013 Impact on Family Skeptical brother-in-law You Early adopter sister Mom the worrier Dad already signed up to get sequenced Grandpa says no way! Crazy Uncle Ben Cousin Chewie wants to donate his sequence to science and make it totally public Sample letter to family addressing concerns: Uncle Q-G worried about losing his insurance because of his son’s DNA sequence Your niece & nephew Great-Grandpa is gone, but a sample of his DNA still exists… Your potential kid?

5/4/2013 Perils of genetic testing 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? Analysis analysis analysis! Variation issues What surprises and secrets might be revealed? How far ahead is the technology of its clinical usefulness? MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 1997 Gattaca is film with Ethan Hawke and Uma Thurman. The plot: Gattaca Corp. is an aerospace firm in the future. During this time society analyzes your DNA and determines where you belong in life. Ethan Hawke's character was born with a congenital heart condition which would cast him out of getting a chance to travel in space. So in turn he assumes the identity of an athlete who has genes that would allow him to achieve his dream of space travel. He is one of the last "natural" babies born into a sterile, genetically-enhanced world, where life expectancy and disease likelihood are ascertained at birth. Myopic and due to die at 30, he has no chance of a career in a society that now discriminates against your genes, instead of your gender, race or religion. Use dry erase board Why taking this CE (introductions) Class Participation: views on PG & PM MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Promises of genetic testing Finding the right drugs, in the right doses, for my conditions Ideas for more tests and interventions if I learn I’m at risk Planning for my long term medical and financial needs I want to use my genome as a social networking tool Might reveal details of my family tree and genealogy I am an early adopter and information altruist Motivation to change my habits To inform my reproductive decisions MLA 2013 CE---Iwema---U.Pittsburgh

5/4/2013 Online Resources Internet resources in medical genetics. Waggoner DJ. Curr Protoc Hum Genet Jan 21;80:Unit doi: / hg0912s80. PMID: 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; Baby’s 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 SO! Many more resources than this, contact me for additional info. --elsi, blogs, PGP… MLA 2013 CE---Iwema---U.Pittsburgh

Carrie Iwema, PhD, MLS, AHIP
Information Specialist in Molecular Biology Health Sciences Library System University of Pittsburgh

Personal Genomics, Personalized Medicine, & You

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