Human Genome Project

1. Human Genome Project Janice S. Dorman, PhD University of Pittsburgh School of Nursing

3. 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

4. Futureof Genomics

5. 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

6. 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

7. 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.

8. 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

9. 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

10. 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

11. Futureof Genomics

12. 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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14. 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

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16. 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

17. 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

18. 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

19. 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?

20. 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

21. 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?

22. 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.

23. 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?

24. 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

25. 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

26. 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

27. 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

28. WHO Recommendations for Developing Countries • Share expertise and develop concepts and approaches through networking • Collect data and publish outcomes of programs