Genomics 101: An Introduction HAS 4320 Genomics 101: An Introduction What factors influence our...
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Transcript of Genomics 101: An Introduction HAS 4320 Genomics 101: An Introduction What factors influence our...
Genomics 101: An IntroductionHuman 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?
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. 347:1512-1520.)
Genomics 101: An Introduction
What is genomics? (cont.)
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.)
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
A public-private collaborative, supported by the National Institutes of Health and the U.S. Department of Energy, that is mapping all humangenes.
The final draft of the genome was published in April 2003.
Genomics 101: An Introduction
The Human Genome Project
Goals… Generate a high-quality reference DNA sequence for
the human genome’s 3 billion base pairs
Identify all human genes
Genomics 101: An Introduction
Human Genome Project
Milestones: 1990: Project initiated as joint effort of U.S. Department
of Energy and the National Institutes of Health
June 2000: Completion of a working draft of the entire human genome
February 2001: Analyses of the working draft are published
April 2003: HGP sequencing is completed and Project is declared finished two years ahead of schedule
Genomics 101: An Introduction
The Human Genome Project
Data is shared…
http://www.ncbi.nlm.nih.gov/
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
The human genome is nearly the same (99.9%) in all people.
Only about 2% of the human genome contains genes, which are the instructions for making proteins.
Genomics 101: An Introduction
Traditional Public HealthGenetics
Rare diseases Single gene disorders Public health activities
Newborn screening Reproductive health Genetic services
Genomics 101: An Introduction
Contemporary Public Health Genetics
Common diseases Multiple genes Gene/environment interactions Public health activities/implications
Chronic diseases Infectious diseases Environmental health Epidemiology
Genomics 101: An Introduction
Genetic Mutations
All of us may have at least one genetic mutation. Some are inherited.
Others occur randomly or as a result of environmental factors, such as diet, drugs, and infections.
Genomics 101: An Introduction
Genetic Mutations (cont.)
Most diseases have multifactorial causation (genetic and environmental).
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.)
Genetic mutations have been identified that play a role in: Chronic diseases
Cancer Cardiovascular disease
Occupational diseases Bladder cancer
Infectious diseases HIV/AIDS
Genomics 101: An Introduction
Genes and 10 U.S. Killers:2000 Preliminary Data
Heart disease Malignant neoplasms Cerebrovascular
diseases Chronic lower
respiratory diseases Accidents
(unintentional injuries)
Diabetes mellitus
Influenza and pneumonia Alzheimer’s disease Nephritis, nephrotic
syndrome, and nephrosis (kidney disease)
Septicemia
(Source: Centers for DiseaseControl and Prevention)
Genomics 101: An Introduction
What’s new in genomics?
Genetic testing To detect mutations
For disease diagnosis and prognosis For the prediction of disease risk in
individuals or families
Genomics 101: An Introduction
What’s new in genomics? (cont.)
Several hundred genetic tests are in use. Rare genetic disorders (muscular
dystrophies, cystic fibrosis, Huntington’s disease)
Complex conditions (breast, ovarian,and colon cancers)
Genomics 101: An Introduction
What’s new in genomics? (cont.)
Pharmacogenomics The development of drugs tailored to specific
subpopulations based on genes
Pharmacogenomics has the potential to: Decrease side effects of drugs Increase drug effectiveness Make drug development faster and less costly
Medicine
• Develop more accurate and rapid diagnostics• Design customized treatments
Diverse Applications
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
Molecular Medicine improve diagnosis of disease
detect genetic predispositions to disease
create drugs based on molecular information
use gene therapy and control systems as drugs
design “custom drugs” (pharmacogenomics) based on individual genetic profiles
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
Microbial Genomics rapidly detect and treat pathogens (disease-causing
microbes) in clinical practice
develop new energy sources (biofuels)
monitor environments to detect pollutants
protect citizenry from biological and chemical warfare
clean up toxic waste safely and efficiently
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
Risk Assessment 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
Bioarchaeology, Anthropology, Evolution, and Human Migration study evolution through germline mutations in lineages
study migration of different population groups based on maternal inheritance
study mutations on the Y chromosome to trace lineage and migration of males
compare breakpoints in the evolution of mutations with ages of populations and historical events
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
DNA Identification (Forensics) identify potential suspects whose DNA may match
evidence left at crime scenes
exonerate persons wrongly accused of crimes
identify crime and catastrophe victims
establish paternity and other family relationships
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
DNA Identification (Forensics) detect bacteria and other organisms that may pollute
air, water, soil, and food
match organ donors with recipients in transplant programs
determine pedigree for seed or livestock breeds
authenticate consumables such as caviar and wine
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
Agriculture, Livestock Breeding, and Bioprocessing grow disease-, insect-, and drought-resistant crops
breed healthier, more productive, disease-resistant farm animals
grow more nutritious produce
Genomics 101: An Introduction
Anticipate Benefits of Genome Research
Agriculture, Livestock Breeding, and Bioprocessing develop biopesticides
incorporate edible vaccines incorporated into food products
develop new environmental cleanup uses for plants like tobacco
Microbes 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.)
Recent research in genomics includes: Learning more about the genetic
underpinnings of chronic diseases
Developing mouse models of human genes
Developing genetic fingerprinting for childhood cancer
Conducting stem cell research
Identifying tumor suppressor genes
Genomics 101: An Introduction
What’s new in genomics? (cont.)
Policy developments related togenomics include: Activities related to anti-discrimination and ethics
Expanded newborn screening
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
ASTHO Genetics Program www.astho.org/?template=1genetics.html
Centers for Disease Control and Prevention Office of Genomics and Disease Prevention
www.cdc.gov/genomics
Health Research and Services AdministrationGenetic Services Branch
http://mchb.hrsa.gov/
National Human Genome Research Institute www.genome.gov
Industry profile…World Industry profile…World marketmarket
U.S. = 34.5%U.S. = 34.5% Europe = 29%Europe = 29% Japan = 15.9%Japan = 15.9%
Funds InFunds 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%
Drug discovery and Drug discovery and developmentdevelopment
Pre-clinical phasePre-clinical phase Phase 1 trialsPhase 1 trials Phase 2 trialsPhase 2 trials Phase 3 trialsPhase 3 trials Phase 4 trialsPhase 4 trials
Drug ExpendituresDrug Expenditures
1960 = $3 billion1960 = $3 billion 1990 = $38 billion1990 = $38 billion 2008 = projected $243 billion2008 = projected $243 billion