genomics 101: an introduction has 4320 genomics 101: an introduction what factors influence our...

Genomics 101: An Introduction

HAS 4320


What factors influence our behavior?

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


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.)


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)


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.


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.



Goals… Generate a high-quality reference DNA sequence for

the human genome’s 3 billion base pairs

Identify all human genes


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



Data is shared…

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






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


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


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.




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.


Traditional Public HealthGenetics

Rare diseases Single gene disorders Public health activities

Newborn screening Reproductive health Genetic services


Contemporary Public Health Genetics

Common diseases Multiple genes Gene/environment interactions Public health activities/implications

Chronic diseases Infectious diseases Environmental health Epidemiology


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.


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.


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


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)


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


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)



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


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



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



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



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



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)



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



Agriculture, Livestock Breeding, and Bioprocessing grow disease-, insect-, and drought-resistant crops

breed healthier, more productive, disease-resistant farm animals

grow more nutritious produce



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



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



Policy developments related togenomics include: Activities related to anti-discrimination and ethics

Expanded newborn screening

New funding for research on rare diseases


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


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


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

http://www.astho.org/?template=1genetics.html



http://www.cdc.gov/genomics




http://mchb.hrsa.gov/

DrugsDrugs

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%

Use of FundsUse of Funds

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

GenericsGenerics

Hatch-WaxmanHatch-Waxman

Drug ExpendituresDrug Expenditures

1960 = $3 billion1960 = $3 billion 1990 = $38 billion1990 = $38 billion 2008 = projected $243 billion2008 = projected $243 billion

PricingPricing

FactorsFactors Price strategiesPrice strategies Private marketsPrivate markets

Medicaid supplementsMedicaid supplements

Do Americans pay too Do Americans pay too much?much?

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