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

Nature 422: , 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 –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

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 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.

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

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

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 anti- discrimination 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 –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

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