Bringing Genomics Home Your DNA: A Blueprint for Better Health Dr. Brad Popovich Chief Scientific Officer Genome British Columbia March 24, 2015 / Vancouver, BC

Welcome and overview Dr. Brad Popovich (Genome BC) Overview of Genome BC and our areas of focus over the next 5 years Dr. Joe Connors (BC Cancer Agency) Example of how genomics is transforming the diagnosis and management of cancer in BC Dr. Clara van Karnebeek (BC Children’s Hospital) Example of how genomic technology is impacting the diagnosis and management of patients with rare diseases Dr. Mel Krajden (BC Centre for Disease Control) Overview of Hepatitis C diagnosis, management, and now cure in BC Our objective today is to educate and inspire you about the growing role of genomics in healthcare in BC

A catalyst for the life sciences cluster on Canada's West Coast Our mission is to generate social and economic benefits through genomics Cumulative portfolio of over $660M in 211 genomics research projects and science and technology Focusing on sectors of economic importance to BC and Canada: Human health Aquaculture & Fisheries Forestry Mining, Energy & Environment Agriculture Genome British Columbia

Why genomics? What is the impact on medicine?

Genomics: Provides an understanding of a disease from the inside out If you understand a disease at the DNA level, you understand the root cause of the disease Contrast this to looking at symptoms Genetic / genomic information is beneficial for disease Prevention Diagnosis Treatment Family planning List of examples is rapidly growing

100 Years 40 Years 30 Years First to ubiquitous

DNA’s Journey 2014 Data Source: National Human Genome Research Institute

Next Generation Medicine

Genomic medicine continuum

Breadth of opportunities and need to focus Health continuum Health & wellness Prevention & risk assessment Diagnosis Treatment & monitoring Disease / Condition Chronic diseases Infectious diseases Inherited conditions Health & wellness Benefits Improved health outcomes Improved healthcare system efficiency Economic growth Scientific discoveries Focus areas for clinical application Strategy for health research Near term feasibility Long term feasibility

Genome BC’s strategy for investment in health Invest in genomic health research across diseases based on merit and potential impact Enable application of genomics at the level of populations Cancer, rare diseases, infectious diseases, pharmacogenomics* *Pharmacogenomics is the study of how genomic variation influences drug response (can be based on the genome of host / human, tumour, or infectious agent). Major cross-disease focus is on avoiding adverse events and optimizing dose across many diseases. Progression towards benefits Discovery and applied research Translational research Pilot then population level application Health-related need Potential genomic tool / technology Validated genomic tool / technology Health benefits for BC Investment phase Genome BC focus areas MIND THE GAP

Prime opportunities for genomics in health (5 years) CancerRare Diseases / Rare Mutations Infectious DiseasesPharmacogenomics 1.Diseases with relatively simple genetics 2.Diseases where genomic information can influence healthcare 3.Technically and clinically feasible

Dr. Brad Popovich (Genome BC) Overview of Genome BC and our areas of focus over the next 5 years Dr. Joe Connors (BC Cancer Agency) Example of how genomics is transforming the diagnosis and management of cancer Dr. Clara van Karnebeek (BC Children’s Hospital) Example of how genomic technology is impacting the diagnosis and management of patients with rare diseases Dr. Mel Krajden (BC Centre for Disease Control) Overview of Hepatitis C diagnosis, management, and now cure in BC Our objective today is to educate and inspire you about the growing role of genomics in healthcare in BC

CLOSING COMMENTS

BC’s Journey

Aligning stakeholders 17

For More Information: Website: THANK YOU!

Potential questions Mel Krajden Where are some of the other big opportunities you see for genomics to help with infectious diseases in the near future? Clara Van Karnebeek What are some of the other exciting areas of application for genomics in disease diagnosis? What advice do you have for people wondering how they or their loved one can get access? Joe Connors Describe your long term vision for the role of genomics in cancer care What advice do you have for people wondering how they or their loved one can get access? Public What are your big concerns?

Digital Health Source: (Provided by Paul Sonner)

Personalized Medicine : a New Paradigm “One-size-fits-all” paradigm: Same frequency of testing for large population (e.g. mammograms) Symptom-driven diagnosis Therapy based on clinical symptoms Monitoring based on clinical symptoms Personalized medicine paradigm: Test for markers that ↑ risk (e.g. genetic variants in cancer) Focused prevention efforts in people with ↑ risk Focused monitoring in people with ↑ risk Molecular monitoring for disease subtypes Targeted therapy based on disease subtype, risk of adverse response Molecular monitoring for response to therapy Source: Personalized Medicine Coalition 21

RARE DISEASES ARE COMMON 5-10% of the population may have a genetic condition, many undiagnosed 1 in 500-1,000 has a cardiomyopathy, Cardiomyopathy.org 1 in 2,000 has Long QT Syndrome, Circulation 120:1761, % of the population is carrying multiple rare genetic conditions Every individual carries multiple (50-100?) mutations that completely disrupt protein function MacArthur et al. Science: Feb 17, : % of the population carries genetic variation that effects their response to certain drugs A significant effect on efficacy and adverse events JAMA 286:2270, 2001 Every “common” disease is either caused or effected by genetic differences Most of which is not yet known Nature Genetics 33:177, 2003

Sequencing is being used in many ways Human GeneticsCancer Consumer Reproductive Health Forensics Biopharm Infectious Disease Agriculture Research 40% 30% 10% 5% 10% 30% 20% 30% 5% % penetration

Genomes are Here

Human Genome Shared among all humans 99.9% genome is identical across all people Most human variation is shared Yet we are unique

2.9 billion positions called 3.42 million variants 1.5 million variants in genes 21,000 coding 10,082 NS 83 Stop What’s in My Genome? 3.1 Billion base positions