Genomics Applications in Public Health Across All Populations, Environment, and Work Settings

1

• Genomics Applications in Public Health Across All
  Populations, Environment, and Work Settings
• Genomic Epidemiology/International Health
• American public Health Association Conference
• Philadelphia, Pennsylvania
• December 10, 2005
• William Ebomoyi, Ph.D.
• Professor International Health Consultant
  (APHA)
• Community Health
• College of Natural and Health Sciences
• University of Northern Colorado
• Greeley, Colorado
• William.ebomoyi_at_unco.edu

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What is genomics?

• View point of the Institute of Medicine (21st
  Century)
• In Genomics and the Publics Health the study
  of the entire human genome1.
• potential benefits of genomics
• improving the health of the public (not only the
  actions of single genes, but also the
  interactions of multiple genes with each other
  and with the environments1)
• differentiating genomics from genetics (functions
  and effects of single genes). Harwells
  definition of genomics is the study of the whole
  genome
• development and application of more effective
  mapping, sequencing and bio-informatics
  computational tools
• Genomicists molecular techniques for linkage
  analysis, physical mapping, and the sequencing of
  genomes to generate detailed data which are
  subjected to analysis using high-speed computer
  facility
• A typical genome is the entire collection of
  chromosomes which are present in the nucleus of
  each cell of an individual organism2.

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Statement of Purpose Institute Overview

• Milestones accomplished in sequencing the human
  genome with genomics technology
• public health careers will become the pre-eminent
  discipline in neonatal screening for genetic, and
  in chronic and degenerative diseases
• monumental role in environmental health
• enabling scientists to identify microbial agents
  which can sequester carbon dioxide gas
  (predominant greenhouse gas)
• enhance the physical, emotional and cognitive
  development of children

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Sequencing of the Human Genome

• 1990s International Scientific Community
  Sequenced the Human Genome
• 2003 Completed draft
• Deciphering profound understanding of the
  structure of genes and their functions
• Creativity understanding of gene structure and
  the complex network of cells
• Benefits of advances revolutionized the
  epidemiological knowledge about the etiology of a
  broad spectrum of diseases their progression and
  preventive medicine
• Understanding amplified the biochemical
  constituents of biological cells, tissues and
  fluids which are relevant in explaining disease
  pathways
• Improvement in technology for biochemical
  analysis facilitated knowledge about the
  incipient signs of diseases, diagnosis, treatment
  and preventive services.
• Recently developed technologies chromatography
  and electrophoresis, gene amplifications and
  polymerase chain reaction tests and micro arrays
  sequencing

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US Department of Energy NIH

• International collaborators identification of
  30,000 genes in human
• Sequencing of the human DNA revealed 3 billion
  chemical base pairs
• Astonishing data
• 1) The human genome contains 3 billion chemical
  nucleotide bases (adenine (A), cytosine (C),
  thymine(T) and guanine(G))
• 2) an average gene contains 3000 bases and 3)
  almost (99.0) of the nucleotide bases are
  identical in all humans4

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Relevance of Human Genome Project to Public Health

• CDCs definition of public health genomics the
  study and application of knowledge about the
  element of the human genome and their functions,
  including interactions with the environment, in
  relation to health and disease in population5
• Used to diagnose understanding of single
  multi-factorial genetic disorders
• Chromatography
• Radiometry
• enzyme and immunoassay
• 1985-1986 United States National Academy of
  Science and the Nation Research Councils
  proposal map first sequence later6.
• Scientific breakthrough of locating specific
  chromosomes identification of genes for
  inherited disorders

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Relevance of Human Genome Project to Public Health

• Possibility to develop cures for several single
  and multi-factorial genetic diseases
• Potential breakthroughs
• gene-replacement therapy to correct those genes
  associated with sickle hemoglobinopathies
• Human gene transfer could assist people with
  genetic disorders that result from inherited
  errors in a single gene
• comprehensive list of some single gene defects
  are listed in
• detect mutations for a handful of more complex
  diseases such as breast, ovarian and colon
  cancers
• Rapid progress will
• Improve diagnosis of disease
• Detect genetic predispositions to disease
• Create drug based on molecular information
• Use gene therapy and control systems as drugs and
• Design custom drugs (pharmacogenomics) ased on
  individual genetic profiles7

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Genomics in Neonatal Screening

• Early identification of disease for which timely
  intervention can lead to reduction and possible
  elimination of morbidity of diseases
• Neonatal Screening is now performed for 4 million
  infants each year in United States
• Successful Cost effective

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Human Genome Project (HGP)

• 3 tools
• Diagnose
• Treat
• Prevent various diseases

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Sickle Cell Disease

• Recessive hereditary disorder
• This disease involves the possession of two
  abnormal allelemorphic genes related to
  hemoglobin formation, at least one of which is
  the sickle cell gene, the genotype constituting
  sickle cell disease b being SS, Sc, S Thal, SE,
  SF high gene and SD8
• Sickle cell disease is caused by a change in just
  one nucleotide of our six billion cells.
• The clinical abnormality caused by sickle cell
  anemia includes manifestations of sever pain, leg
  ulcers, swelling of the joints, pains in the
  abdomen, arms, fatigue, and sometimes death9,10.
• sickle cell disease vs. sickle cell trait (SCI)
• quantity of erythrocytes of sickle cell trait and
  sickle cell disease
• involvement of greater reduction in the partial
  pressure of oxygen (required for a significant
  quantity of trait to sickle than sickle cell
  disease)
• sickle cell trait one normal hemoglobin gene
  (A) inherited from one parent and one abnormal
  gene (S) from the other parent
• sickle cell disease two abnormal genes are
  inherited, one from each parent

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Sickle Cell Disorder Reasons for Screening

• Reasons for Screening
• No known cure.
• Consensus Conference report12, hemoglobinopathies
  represent one of the significant public health
  problems in the United States
• Sickle cell disease most common genetic
  dysfunction in some populations
• one of every 400 African-American newborns
  affected
• In other countries the technology for screening
  infants for hemoglobinopathis in the newborn may
  not be efficient
• United States widespread adoption of screening
  was not instituted, some reasons are
• inertia about who to test
• lack of overt improvement in outcome with early
  diagnosis
• technical difficulties arising from the increased
  level of fetal hemoglobin in the neonate
• unresolved issues about obligation to those
  diagnosed as carriers of the sickling genes12

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Reasons for Neonatal Screening Sickle Cell

• Prevention of unnecessary mortality among infants
• prompt referral of diagnosed children to tertiary
  health care centers
• Life-threatening complications associated with
  sickle cell disease
• acute splenic sequestration crisis
• bacterial infection (Streptococcus pneumonia)
  most severe in children under 3 years of age
• Identify infants with SCD is necessary to enable
  health care providers to institute effective
  measures of prophylaxis and intervention.
• High pressure liquid chromatography (HPLC) very
  sensitive rapid
• Differentiates between hemoglobinpathies13
• solubility testing procedures are not
  satisfactory for screenign purposes.14
• cellulose acetate accompanied by citrate agar
  electrophoresis remains the method

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Medical Management of Sickle Cell Disease

• No effective treatment of sickle cell disease
• Individuals suffering from SCD are encouraged to
  avoid low oxygen tension which occurs during
  flight in an unpressurized aircraft
• Patients are kept well hydrated if an episode of
  crisis occures14
• blood transfusion becomes advisable in some cases
• SCD tolerate hemoglobin levels of 5 to 6 g/100 ml
  blood adequately

14
Indicators of Sickle Cell Disease

• Initial clinical tests
• paked cell volume (PCV)
• reticulocyte cou nt on blood film
• white cell and differential counts
• Urinalysis
• hemoglobin electrophoresis
• x-ray of the chest to determine the size of the
  heart and X-ray fo the asffected bone if observed
  uring crisis.
• Common signs of SCD
• inactive crises
• anemic crisis
• susceptibility to bacteria infections
  (streptococcus pneumonia1,15).

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Public Health Workforce

• Unprecedented tasks of meeting the needs of the
  society
• visual impairment
• hearing and cognitive deficits
• School Health Curriculum infused with genomics
  science information
• health services appraisal, preventive
  screening, remedial activities
• health instruction planned instruction,
  integrated learning incidental instruction
• healthful school living physical environment
• Genomic applications in school health curriculum
  transcend the three components of school health
  program. But by far most crucial are the various
  screening programs to prepare the
  elementary-school child for meaningful cognitive
  ventures.

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Public Health Workforce
Source Creswell WH, School Health Practice, St.
Louis, Mosby Press 1993 P.40
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Genomics in Chronic Degenerative Diseases

• Genomics in Chronic and Degenerative Diseases
• Cardiovascular diseases leading cause of death
  worldwide
• 1st time in 65 years is not leading in U.S.

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Genomics in Chronic Degenerative Diseases

• Public health interventions which yielded
  positive epidemiological outcomes have been
• Abstaining from tobaccco
• Health promotion initiative prohibiting smoking
  in public places across the nation
• Education of the public about diet modification
• Encouragement of physical activities
• Avoidance of excessive alcohol
• Of the ten leading causes of death in United
  States, nine of them are associated with genetic
  etiologies. Although there is no evidence that
  accidents have genetic link, the major causes of
  death in United States continue to be heart
  disease, cancer, cardiovascular disease, chronic
  lower respiratory disease, diabetes,
  pneumonia/influenza, kidney disease and
  septicemia.
• Genetic susceptibility, the environment, immune
  status and behavioral patterns play major role in
  the onset of many of the leading causes of death
  in United States.

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Genomics in Environmental Health

• Environment - physical and biological
  characteristics of an area
• microbial organisms
• bioremediation
• environmentally induced diseases
• natures most abundant, simplest organisms
  ubiquitous able to thrive under extreme
  conditions (heat, cold, pressure, radiation)
• It is therefore axiomatic that the ability of
  this planet to sustain life is mainly dependent
  on microbes, which to a large extent are not
  pathogenic.21

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Genomics in Environmental Health (cont).

• United States Department of Energy
• microbes are the foundation of the biosphere
  (lithosphere, atmosphere, and hydrosphere)
• Microbes control
• earths natural biogeochemical cycling
• affect the nutrient level and productivity of the
  soil, quality of water
• stability of global climate
• They can be used to
• transform various waste products
• organic matter
• cycling nutrients
• converting sunlight energy
• storing carbon dioxide from the atmosphere22.

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Genomics in Environmental Health (cont).

• Microbial genomics
• application of bacterial and other microbial
  agents
• environmental health problems
• Toxic waste sites contain a myriad of
  contaminates
• possible to develop designer bacteria to
  degrade those compounds in these
  wasteland/landfills
• Rapid detection and treatment of environmentally
  induced microbial diseases
• Development of new energy sources (biofuels)
• Monitoring of air, land, and water environment to
  isolate pollutants
• Protection of citizenry from biological and
  chemical warfare and clean up of toxic waste
  safely and efficiently23.

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Integration of Genomic Science into Statewide
Public Health Programs

• Statewide offices of public health
• Essential components of such units
• administrative leadership care
• environmental health
• maternal and child health
• clinical laboratory services
• health promotion units
• demographic units where vital statistical records
  on births, marriages and death records are stored
• The Institute of Medicine (IOM) in the Future of
  Public Health outlined the process of integration
  of genomics into public health through policy
  development, assessment of programs and assurance
  of services.

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Integration of Genomic Science into Statewide
Public Health Programs

• The integration of genomics must include
• regular systematic collection
• Assembly
• Analysis of health status information
• dissemination of health status information
• Genomic data are used judiciously
• Genetic tests are used to meet the national goal
  of promoting healthy living
• System management
• Capacity building
• An eclectic initiative involving data elicitation
  from all program staff can create meaningful
  insights about how best to integrate genomics
  into public health services.

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Prospects for Genomic Science Applications

• Genetic variation can be characterized and
  charted for many ethnic groups
• Microbial genomes can be explored for
• protein machines that perform critical life
  functions
• Bioinformatics could be integrated, understood
  and the copious data derived used to model
  complex biological systems.

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Ethical, Legal, Social Implications

• James Watson25, the first director of NIH genomic
  center
• first biologist to advocate the relevance of the
  ethical, legal and social issues about advances
  in genomic technology
• NIH, United States and the Department of Energy,
  Genome programs
• adhere to stringent and sanctimonious principles
• Seek genetic information from potential clients

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Ethical, Legal, Social Implications

• Collectively, their resolutions enforced
• Maintaining privacy and confidentiality of
  genetic information.
• Adoption of fairness in the use of genetic
  information by insurance companies, employers,
  court, schools, the military, adoption agencies
  and health associations among others.
• Avoidance of social stigmatization status and
  discrimination against an individual due to a
  persons genetic differences.
• Ensuring that researchers seek adequate and
  informed consent while working with patients with
  specific genetic defects.

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Ethical, Legal, Social Implications

• Resolutions (cont.)
• Education of physicians, other clinicians, health
  service providers about clients identities with
  genetic conditions and the general public about
  the capabilities, limitations and social risks
  associated with certain disorders and the
  implementation of standards and quality control
  measure at all laboratories and counseling
  centers.
• Use of experiences geneticists and other
  clinicians to explain the uncertainties
  associated with gene tests for susceptibility,
  particularly for multi-factorial complex diseases
  such as heart disease, diabetes and Alzheimers
  disease.
• Ensuring that there is fairness in access to
  advanced genomic technology and other pertinent
  philosophical and conceptual leanings of clients.

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Acknowledgements

• The author would like to express his gratitude to
  the late professor William H. Creswell, Jr.
  formerly the University of Illinois at
  Urbana-Champaign and Dr. Flora F. Cherry, my
  preceptor at the Tulane Medical School in New
  Orleans and the late professor Emmanuel Shapiro,
  a medical geneticist who made his lab available
  to me while undergoing NIH post-doctoral training
  at the Tulane Medical Center. Without the
  assistance from The National Institutes of Health
  and Ms. Anita Johnson of United States Department
  of Energy, this report would not have been
  completed. The author thanks Dr. Freddie Asinor
  and Ms. Karon Moody and Dona Wright for
  coordinating the Continuing Education Institute
  for the American Public Health Association.

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References

• Institute of Medicine (IOM) Implications of
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  National Academy Press, 2005.
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• CDC A guide to public Health http//www.genomics
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• Marchi, E. China at 50 A test for functional
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• United States Department of Energy, Office of
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• Pauling L. et al. Sickle cell anemia A
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• McCarthy M. USA Reocmmends universal sickle cell
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• Consensus conference, ibid
• Creswell WH and Newman IM School health practice
  St. Louis MI Times Mirror/Mosby college
  publishing 1989.
• Ibid,7, 10, 35-40, 35-42, 114-129, 115-130
• United States Department of Energy (DOE)
  Genomics GTL Exploring microbial genomics for
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• Institute of Medicine (IOM) Future of public
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  2005