Human Genome Project

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Human Genome Project

• Janice S. Dorman, PhD
• University of Pittsburgh
• School of Nursing

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(No Transcript)
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Nature 422835-846, 2003

• A vision for the future of genomics research A
  blueprint for the genomic era
• Francis S. Collins, Eric D. Green, Alan E.
  Guttmacher, Mark S Guyer on behalf of the US
  National Human Genome Research Institute

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Future of Genomics
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Resources - Comprehensive and Publicly Available

• Genome maps and sequences
• Human and model organisms
• Tools for mining these data
• Population studies
• Genetic variation and disease
• Healthy cohorts
• Libraries of small molecules and robotic methods
  to screen them to facilitate drug discovery

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Technology Development

• Cheaper sequencing and genotyping technologies
• In vivo monitoring of gene expression
• Proteomics
• Modulation of gene expression
• Correlate genetic variation to human health and
  disease

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Computational Biology

• New approaches to problem solving
• Identification of different features in DNA
  sequence
• Elucidation of protein structure and
  protein-protein interactions
• Determination of genotype to phenotype
• Better computer software / database technologies
• Methods to study environmental effects on genes
• Database technology to integrate and visualize
  pathways, protein structure, etc.

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Training

• Computational skills
• Critical because biomedical research is becoming
  increasingly data intensive
• Interdisciplinary skills
• Expanded interactions between researchers in
• The sciences (biology, computer science, physics,
  mathematics, statistics, chemistry, engineering)
• The basic and the clinical sciences (health
  professionals)
• Different perspectives
• Minority or disadvantaged populations must be
  represented as researchers and participants in
  genomics research

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ELSI

• Focused research to develop policies and
  practices
• Translational research to provide knowledge for
  clinicians, policy makers and the public
• Development of
• Searchable databases of genomic legislation
• ELSI aspects of clinical genetic tests
• Methods to evaluate genomic tests / technologies
  and ensure effective oversight

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Education

• Health professionals
• Need to be knowledgeable about genomics to apply
  the outcomes of genomics research effectively
• Public
• Need to be knowledgeable to make informed
  decisions participation in genomics research /
  genomics health care
• Media are crucial sources of information about
  genomics and societal implications
• Education should start in public schools

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Future of Genomics
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Genomics to Biology

• Imagine a world where we know (and have immediate
  access to information about)
• The function of every genome sequence
• Humans
• Other organisms
• What determines gene expression patterns in all
  cell types and how to control this
• Gene-gene and gene-environment interactions
• Extent of human genome variation
• Disease
• Human vs. non-humans
• Basis for evolution

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Future of Genomics
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Genomics to Health

• Imagine a world where we know (and have immediate
  access to information about)
• An individuals
• Susceptibility to disease (and ability to
  identify it early and accurately through
  molecular diagnosis)
• Drug response based on genetic profile
• Personalized prescription for disease
  prevention
• Diagnosis and detection of pre-clinical disease
  at the molecular level
• Application of knowledge to make informed
  decisions about genetic testing
• Use of genomic information to reduce health care
  costs and increase longevity
• Relationship between genomics and health
  disparities

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Future of Genomics
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Genomics to Society

• 4 Grand Challenges
• Develop policy options for the uses of genomics
  in medical and non-medical settings
• Understand the relationships between genomics,
  race and ethnicity, and the consequences of
  uncovering these relationships
• Understand the consequences of uncovering the
  genomic contribution to human traits and behavior
• Assess how to define the ethical boundaries for
  uses of genomics

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Genomics to Society

• Grand Challenge 1 Develop policy options for
  the uses of genomics in medical and non-medical
  settings
• Potential for discrimination based on personal
  genetic information
• Health insurance and employment
• Some US states have passed anti-discrimination
  legislation
• Proposal for effective federal legislation

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Genomics to Society

• Grand Challenge 1 Develop policy options for
  the use of genomics in medical and non-medical
  settings
• FDA has been requested to provide oversight to
  review new predictive genetic tests prior to
  marketing
• Concerns about proper conduct of genetic research
  involving human subjects

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Genomics to Society

• Grand Challenge 2 Understand the relationship
  between genomics, race, ethnicity, and the
  consequences of uncovering these relationships
• Race is largely a non-biological concept
• Confounded by misunderstanding and a long history
  of prejudice
• More variation within vs. between groups
• Some alleles are more frequent in certain
  populations
• Need research on how individuals and cultures
  conceive of race, ethnicity, group identity and
  self-identity
• How does the scientific community understand and
  use these concepts to design research and present
  results?

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Genomics to Society

• Grand Challenge 3 Understand the consequences
  of uncovering the genomic contributions to human
  traits and behaviors
• Stigmatization because alleles are associated
  with some negative physiological or behavioral
  traits
• These may vary by population
• Need scientifically valid information about
  genetic and environmental factors and human
  traits / behaviors
• Need research on the implications (for
  individuals and society) of uncovering any
  genomic contributions there may be to these
  traits and behaviors

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Genomics to Society

• Grand Challenge 4 Assess how to define the
  ethical boundaries for uses of genomics
• Society needs to define the appropriate /
  inappropriate uses of genomics
• Reproductive genetic testing, genetic
  enhancement, germline gene transfer, etc.
• How do different individuals, cultures, religious
  traditions view the ethical boundaries for the
  uses of genomics?

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Genomics and Global Health

• Need to introduce preventive genetics methods in
  developing countries
• Will help bridge the gap in health care between
  developing / developed countries
• Will inform the global community about progress
  in genomic medicine in these areas
• Advisory Committee on Health Research. Genomics
  and World Health. WHO, Geneva, 2002.

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WHO Report, 2002

• Were there already genomic advances that could
  now be applied in developing countries ?
• Should international community wait for further
  progress in genomics research in developed
  countries?

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Conclusions of WHO Report

• Widespread support for the introduction of DNA
  technology into developing countries now
• Monogenetic disorders
• Thalassemia, sickle cell anemia
• Communicable diseases
• Human genetic variation relates to susceptibility
  to malaria
• Will offer appropriate point of entry for DNA
  technology into primary care
• Ideal infrastructure to introduce genetic testing
  for further development

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Example - Thalassaemia

• Amenable to control and better management through
  genetic testing
• Research
• Underlying mutations are different in each ethnic
  group
• Technology
• Reliable molecular methods for carrier detection
  / prenatal diagnosis
• Disease prevention
• Reduction in incidence due to genetic testing

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Thalassaemia

• 2-18 of population in Mediterranean, Middle East
  and Asia are carriers
• Treatment
• Blood transfusion, which is costly
• Iron overload requires treatment with chelating
  agent
• Extends life, escalating health care costs
• Prevention by carrier detection (population
  screening), genetic counseling and early prenatal
  diagnosis
• Cost of prevention is 1-12 cost of patient care

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WHO Recommendations for Developing Countries

• Appoint individual in Ministry of Health to
  coordinate national medical genetics program
• Create multidisciplinary team to
• Review national expertise in genetics
• Review local epidemiology of genetically
  determined disorders
• Define ethical framework for genetic services
• Review curricula of health professional
  institutions
• Develop plan to introduce appropriate genetic
  services

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WHO Recommendations for Developing Countries

• Share expertise and develop concepts and
  approaches through networking
• Collect data and publish outcomes of programs