Transcript goals of the human genome project

Human Genome
Project
Janice S. Dorman, PhD
University of Pittsburgh
School of Nursing
Nature 422:835-846, 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
Future of Genomics
Resources - Comprehensive
and Publicly Available

Genome maps and sequences

Tools for mining these data

Population studies

Libraries of small molecules and robotic
methods to screen them to facilitate
drug discovery
– Human and model organisms
– Genetic variation and disease
– Healthy cohorts
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
Computational Biology

New approaches to problem solving
– Identification of different features in DNA
sequence
– Elucidation of protein structure and proteinprotein 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.

Training

Computational skills

Interdisciplinary skills
– Critical because biomedical research is
becoming increasingly data intensive
– 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
ELSI

Focused research to develop policies and
practices

Translational research to provide
knowledge for clinicians, policy makers
and the public

Development of

Methods to evaluate genomic tests /
technologies and ensure effective
oversight
– Searchable databases of genomic legislation
– ELSI aspects of clinical genetic tests
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

Future of Genomics
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
Future of Genomics
Genomics to Health

Imagine a world where we know (and have
immediate access to information about)
– An individual’s
• 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
Future of Genomics
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
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 antidiscrimination legislation
• Proposal for effective federal legislation
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
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?
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
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?
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.
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?
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
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
Thalassaemia

2-18% of population in Mediterranean,
Middle East and Asia are carriers

Treatment

Prevention by carrier detection
(population screening), genetic counseling
and early prenatal diagnosis
– Blood transfusion, which is costly
– Iron overload requires treatment with
chelating agent
– Extends life, escalating health care costs
– Cost of prevention is 1-12% cost of patient
care
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
WHO Recommendations for
Developing Countries

Share expertise and develop
concepts and approaches through
networking

Collect data and publish outcomes
of programs