Transcript Document

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
[email protected]
What is genomics?
View point of the Institute of Medicine (21st Century)
In Genomics and the Public’s Health: “the study of the entire human
genome”1.
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). Harwell’s 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.
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
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
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
Relevance of Human Genome Project to Public Health
CDC’s 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 Council’s proposal “map first & sequence
later”6.
Scientific breakthrough of locating specific chromosomes &
identification of genes for inherited disorders
Relevance of Human Genome Project to Public Health
Possibility to develop cures for several single and multifactorial 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
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
Human Genome Project (HGP)
3 tools:
• Diagnose
• Treat
• Prevent various diseases
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 SD”8
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
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
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
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
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 Xray fo the asffected bone if observed uring crisis.
Common signs of SCD
inactive crises
anemic crisis
susceptibility to bacteria infections (streptococcus
pneumonia1,15).
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.
Public Health Workforce
School health program
Health Services
1.
Appraisal Aspects
Health examination, dental
examination, teacher health
assessment, vision testing,
hearing testing, height and
weight measurement,
cleanliness inspection,
guidance and supervision,
teacher health
2.
1.
Remedial Aspects
Follow-up services,
correction of remediable
defects, practitioner services,
school functions
Planned Instruction
Healthful living
1.
Practices, attitudes,
knowledge
2.
3.
Integrated learning
2.
Personal experiences, pupilteacher relationships,
classroom experiences,
school experiences…
4.
Mentally healthy
environment
Pupil status, pupil-teacher
relationships, provision for
individual differences,
curriculum adaptation,
atmosphere of mutual
respect
Incidental instruction
Personal experiences,
classroom experiences,
school activity, community
events…
Physical environment
Site, plant plan, heating,
ventilation, lighting, water,
lunch room facilities, sewage
disposal
Correlated instruction
Arts, social studies, sciences
Preventive aspects
Communicable disease
control, safety, emergency
care, first aid…
3.
Health Instruction
3.
Practices
Schedules, time allotments,
activity and rest, fire
protection safety, inspection,
housekeeping…
Source: Creswell WH, School Health Practice, St. Louis, Mosby Press 1993; P.40
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.
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.
Genomics in Environmental Health
Environment - physical and biological
characteristics of an area
microbial organisms
bioremediation
environmentally induced diseases
nature’s 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
Genomics in Environmental Health (cont).
United States Department of Energy
microbes are the foundation of the biosphere
(lithosphere, atmosphere, and hydrosphere)
Microbes control:
earth’s 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.
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.
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.
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.
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.
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
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
person’s genetic differences.
Ensuring that researchers seek adequate and
informed consent while working with patients with
specific genetic defects.
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 multifactorial complex diseases such as heart disease,
diabetes and Alzheimer’s disease.
Ensuring that there is fairness in access to
advanced genomic technology and other pertinent
philosophical and conceptual leanings of clients.
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 postdoctoral 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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