Genomics 101: An Introduction HAS 4320

Genomics 101: An Introduction What factors influence our behavior?

Genomics 101: An Introduction Human Genome Program, U.S. Department of Energy, Genomics and Its Impact on Medicine and Society: A 2001 Primer, 2001

Genomics 101: An Introduction What is genomics? n Genomics is “the study of functions and interactions of all the genes in the genome, including their interactions with environmental factors.” (Source: Collins, Francis, and Alan Guttmacher. “Genomic Medicine—A Primer,” NEJM, Vol. 347: )

Genomics 101: An Introduction What is genomics? (cont.) n A genome is “all the DNA contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria… all our genes together.” (Source: National Human Genome Research Institute)

Genomics 101: An Introduction What is genomics? (cont.) n From a public health perspective, genomics is the study of the gene-environment-host interaction that leads to disease — or disease prevention — in populations.

Genomics 101: An Introduction The Human Genome Project n A public-private collaborative, supported by the National Institutes of Health and the U.S. Department of Energy, that is mapping all human genes. n The final draft of the genome was published in April 2003.

Genomics 101: An Introduction The Human Genome Project n Goals… u Generate a high-quality reference DNA sequence for the human genome’s 3 billion base pairs u Identify all human genes

Genomics 101: An Introduction Human Genome Project n Milestones: u 1990: Project initiated as joint effort of U.S. Department of Energy and the National Institutes of Health u June 2000: Completion of a working draft of the entire human genome u February 2001: Analyses of the working draft are published u April 2003: HGP sequencing is completed and Project is declared finished two years ahead of schedule

Genomics 101: An Introduction The Human Genome Project n Data is shared…

Genomics 101: An Introduction The Human Genome Project n Some of what takes place…

Explore how DNA impacts HEALTH Identify and understand the differences in DNA sequence (A, T, C, G) among human populations Scientific Discovery Path

Understand what all the GENES do Discover the functions of human genes by experimentation and by finding genes with similar functions in the mouse, yeast, fruit fly, and other sequenced organisms Scientific Discovery Path

Learn what the rest of the human genome does Identify important elements in the non-gene regions of DNA that are present in many different organisms, including humans Scientific Discovery Path

Understand how the genome enables life Explore life at the ultimate level of the whole organism instead of single genes or proteins. The DOE Genomes to Life program provides a foundation for this understanding by using the information found in the genomes of microbes, life’s simplest organisms, to study how proteins—the products of genes—carry out all activities of living cells. Scientific Discovery Path

Genomics 101: An Introduction The Human Genome Project n The human genome is nearly the same (99.9%) in all people. n Only about 2% of the human genome contains genes, which are the instructions for making proteins.

Genomics 101: An Introduction Traditional Public Health Genetics n Rare diseases n Single gene disorders n Public health activities u Newborn screening u Reproductive health u Genetic services

Genomics 101: An Introduction Contemporary Public Health Genetics n Common diseases n Multiple genes n Gene/environment interactions n Public health activities/implications u Chronic diseases u Infectious diseases u Environmental health u Epidemiology

Genomics 101: An Introduction Genetic Mutations n All of us may have at least one genetic mutation. u Some are inherited. u Others occur randomly or as a result of environmental factors, such as diet, drugs, and infections.

Genomics 101: An Introduction Genetic Mutations (cont.) n Most diseases have multifactorial causation (genetic and environmental). n Genetic variations put individuals at increased risk for developing certain diseases, but they do not make it certain that those diseases will occur.

Genomics 101: An Introduction Genetic Mutations (cont.) n Genetic mutations have been identified that play a role in: u Chronic diseases l Cancer l Cardiovascular disease u Occupational diseases l Bladder cancer u Infectious diseases l HIV/AIDS

Genomics 101: An Introduction Genes and 10 U.S. Killers: 2000 Preliminary Data n Heart disease n Malignant neoplasms n Cerebrovascular diseases n Chronic lower respiratory diseases n Accidents (unintentional injuries) n Diabetes mellitus n Influenza and pneumonia n Alzheimer’s disease n Nephritis, nephrotic syndrome, and nephrosis (kidney disease) n Septicemia (Source: Centers for Disease Control and Prevention)

Genomics 101: An Introduction What’s new in genomics? n Genetic testing u To detect mutations l For disease diagnosis and prognosis l For the prediction of disease risk in individuals or families

Genomics 101: An Introduction What’s new in genomics? (cont.) n Several hundred genetic tests are in use. u Rare genetic disorders (muscular dystrophies, cystic fibrosis, Huntington’s disease) u Complex conditions (breast, ovarian, and colon cancers)

Genomics 101: An Introduction What’s new in genomics? (cont.) n Pharmacogenomics u The development of drugs tailored to specific subpopulations based on genes u Pharmacogenomics has the potential to: l Decrease side effects of drugs l Increase drug effectiveness l Make drug development faster and less costly

M edicine Develop more accurate and rapid diagnostics Design customized treatments Diverse Applications

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Molecular Medicine u improve diagnosis of disease u detect genetic predispositions to disease u create drugs based on molecular information u use gene therapy and control systems as drugs u design “custom drugs” (pharmacogenomics) based on individual genetic profiles

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Microbial Genomics u rapidly detect and treat pathogens (disease-causing microbes) in clinical practice u develop new energy sources (biofuels) u monitor environments to detect pollutants u protect citizenry from biological and chemical warfare u clean up toxic waste safely and efficiently

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Risk Assessment u evaluate the health risks faced by individuals who may be exposed to radiation (including low levels in industrial areas) and to cancer-causing chemicals and toxins

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Bioarchaeology, Anthropology, Evolution, and Human Migration u study evolution through germline mutations in lineages u study migration of different population groups based on maternal inheritance u study mutations on the Y chromosome to trace lineage and migration of males u compare breakpoints in the evolution of mutations with ages of populations and historical events

Genomics 101: An Introduction Anticipate Benefits of Genome Research n DNA Identification (Forensics) u identify potential suspects whose DNA may match evidence left at crime scenes u exonerate persons wrongly accused of crimes u identify crime and catastrophe victims u establish paternity and other family relationships u identify endangered and protected species as an aid to wildlife officials (could be used for prosecuting poachers)

Genomics 101: An Introduction Anticipate Benefits of Genome Research n DNA Identification (Forensics) u detect bacteria and other organisms that may pollute air, water, soil, and food u match organ donors with recipients in transplant programs u determine pedigree for seed or livestock breeds u authenticate consumables such as caviar and wine

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Agriculture, Livestock Breeding, and Bioprocessing u grow disease-, insect-, and drought-resistant crops u breed healthier, more productive, disease-resistant farm animals u grow more nutritious produce

Genomics 101: An Introduction Anticipate Benefits of Genome Research n Agriculture, Livestock Breeding, and Bioprocessing u develop biopesticides u incorporate edible vaccines incorporated into food products u develop new environmental cleanup uses for plants like tobacco

M icrobes for energy and the environment Clean up toxic wastes Capture excess carbon to help reduce global climate change Generate clean energy sources (e.g., hydrogen) Microbes thrive in every environment on earth, but the vast majority DO NOT cause disease. Understanding them at a basic level will enable use of their diverse and sophisticated abilities. Diverse Applications

Genomics 101: An Introduction What’s new in genomics? (cont.) n Recent research in genomics includes: u Learning more about the genetic underpinnings of chronic diseases u Developing mouse models of human genes u Developing genetic fingerprinting for childhood cancer u Conducting stem cell research u Identifying tumor suppressor genes

Genomics 101: An Introduction What’s new in genomics? (cont.) n Policy developments related to genomics include: u Activities related to anti-discrimination and ethics u Expanded newborn screening u New funding for research on rare diseases

Genomics 101: An Introduction ELSI: Ethical, Legal, and Social Issues Privacy and confidentiality of genetic information. Fairness in the use of genetic information by insurers, employers, courts, schools, adoption agencies, and the military, among others. Psychological impact, stigmatization, and discrimination due to an individual’s genetic differences. Reproductive issues including adequate and informed consent and use of genetic information in reproductive decision making. Clinical issues including the education of doctors and other health-service providers, people identified with genetic conditions, and the general public about capabilities, limitations, and social risks; and implementation of standards and quality ‑ control measures. U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Genomics 101: An Introduction ELSI Issues (cont.) Uncertainties associated with gene tests for susceptibilities and complex conditions (e.g., heart disease, diabetes, and Alzheimer’s disease). Fairness in access to advanced genomic technologies. Conceptual and philosophical implications regarding human responsibility, free will vs genetic determinism, and concepts of health and disease. Health and environmental issues concerning genetically modified (GM) foods and microbes. Commercialization of products including property rights (patents, copyrights, and trade secrets) and accessibility of data and materials. U.S. Department of Energy Genome Programs, Genomics and Its Impact on Science and Society, 2003

Genomics 101: An Introduction Resources u ASTHO Genetics Program u u Centers for Disease Control and Prevention Office of Genomics and Disease Prevention u u Health Research and Services Administration Genetic Services Branch u u National Human Genome Research Institute u

Drugs

Industry profile…World market U.S. = 34.5% U.S. = 34.5% Europe = 29% Europe = 29% Japan = 15.9% Japan = 15.9%

Funds In Out-of-pocket = 32% Out-of-pocket = 32% Private insurance = 46% Private insurance = 46% Medicare = 2% Medicare = 2% Medicaid = 17% Medicaid = 17% Other public programs = 3% Other public programs = 3%

Use of Funds

Drug discovery and development Pre-clinical phase Pre-clinical phase Phase 1 trials Phase 1 trials Phase 2 trials Phase 2 trials Phase 3 trials Phase 3 trials Phase 4 trials Phase 4 trials

Generics Hatch-Waxman Hatch-Waxman

Drug Expenditures 1960 = $3 billion 1960 = $3 billion 1990 = $38 billion 1990 = $38 billion 2008 = projected $243 billion 2008 = projected $243 billion

Pricing Factors Factors Price strategies Price strategies Private markets Private markets

Medicaid supplements

Do Americans pay too much?