Transcript Genomics
Genomics
Erik Haley
Chronic Diseases
4/1/13
Genomics
Public Health Genomics focuses on the application of
genomic research to health benefits.
Genomics plays a role in 9 of the 10 leading causes of death
in the US- most in cancer or heart disease
One of the main risks for heart disease is familial
hypercholesterolemia – a family condition that results in high
levels of bad cholesterol
Genetics of Humans
Humans have approximately 29,000 genes but this only
amounts to about 2% of the genome
The remaining DNA is either non-coding introns,
transposable elements, regulatory sequences or a variety of
other elements
Of the known proteins in the human body, only half have a
well known function
Epigenetics
Epigenetics involves looking at environmental or
developmental factors that influence gene expression
Methods of modifying DNA expression include histone
modification, methylation, non-coding RNA interference –
all of which help reprogram the genome during
embryogenesis
This reprogramming is essential for cell differentiation –
understanding how it occurs can allow deprogramming
Family History
People who have a family member with a chronic health
condition have an increased risk of developing the disease
A good record of family history would contain three
generations of family members, ages and causes of death and
age of diagnosis for any chronic diseases
Family Health Portrait Website:
https://familyhistory.hhs.gov/fhh-web/home.action
Family History Data
Genetic Testing
Currently, there are over 2000 genetic tests available at
clinical settings. Most diagnose rare genetic disorders such as
duchenne muscular dystrophy.
Research is trying to develop tests that will measure an
individual’s risk factors for chronic diseases or response to
medicine
Genetic Testing- Drawbacks
Most genetic testing available now has limited use due to the
genetic components for many chronic diseases being
unknown.
Effective testing mostly for uncommon ailments
Many genetic tests are misused due to premature marketing
Evaluation of Genomic Applications in Practice & Prevention
Some genetic tests for hereditary cancers not effectively
implemented into practice
Genetic Testing
One of the main fears of genetic testing is the possibility of
genetic discrimination
In 2008, the Genetic Information Nondisclosure Act was put
into practice to prevent discrimination in both employment
and insurance on the basis of genetics
The Affordable Care Act also prohibits variation of insurance
premiums based on disease or genetics
Perinatal Genomics
Pre-conception genetic screening is currently available that
can identify inheritable conditions before a child is conceived
as well as pre-implantation genetic screening
Pre-implanatation screening can lead to parents selecting
which embryo to implant via in vitro fertilization
Newborn screening involves a genetic screen for several
conditions upon birth – amount varies by state
Autoimmune Diseases
Most autoimmune diseases, including Diabetes Type 1 and
Rheumatoid Arthritis, have a genetic component
Over 200 genetic loci have been linked to autoimmune
disorders- no causal information has been currently
identified
Most genetic factors carry moderate risk but are involved
with other environmental factors- cannot use genomics alone
Gene Therapy
Gene therapy involves replacing a harmful mutant gene with
an accurate copy using a viral vector
Currently, no gene therapy programs have FDA approval, yet
over 2000 clinical trials were performed within the last 5
years
Additional use for gene therapy is to treat cancer by having
an oncolytic virus insert a sequence that leads to cell death
Gene Therapy
Gene Therapy Techniques
One method of gene therapy is to insert proper alleles to
replace mutant forms – nonsense mutants (early stop codon)
can also be repaired by inserting a random amino acid into
the mutation site
Alternative methods include using miRNA to silence certain
genes by preventing transcription or changing splice sites of
the pre-messenger RNA
Gene Therapy- Drawbacks
One of the drawbacks of using viral vectors is non-specific
insertion into a cell – one 2002 case had 25% insert before a
proto-oncogene leading to leukemia
Many cancer cells contain an over-expression of surface
proteins found on normal cells – normal cells can uptake
oncolytic viruses leading to tissue death
Regeneration
Genetic analysis of newts and zebrafish determined that they
are able to re-grow limbs by using highly proliferative
muscle, cartilage, neural cells
In humans, Rb protein and ARF prevent muscle cells from
continuing mitosis- RNAi was shown to relieve this blockade
Risks for such a procedure involve an higher risk for cancer
in cells with mitotic controls inhibited
Gene Mapping
The 1000 Genomes Project published a map of the variation
in the human genome to show differences in disease risk and
physical attributes
The project results showed that common mutations were
global while rarer ones are often limited to ethnic
groups/nations
Limited use – no phenotype data and population size
Health Equity
One of the hopes of genomics is that it will help reduce the
inequality of health care between racial and ethnic groups
However, genomic data has shown that there is little
difference between groups compared to within groups; many
variants have low risk factors
Genomic information may be helpful by providing better
information about who should receive specific treatments
and the size of the expected benefit
State Participation
Currently, only four states have health departments that have
integrated genomic knowledge into chronic disease
prevention problems (MI, MN, OR, UT)
Many more states have programs to analyze newborn infants
and education/awareness programs
Human Genome Epidemiology Network
OPGH established the HuGE network to help translate
genetic research findings into opportunities for preventative
medicine
HuGE is currently a network containing scientific research
data as well as synthesis of new research projects and
translation of results to humans
http://hugenavigator.net/HuGENavigator/home.do
Value
The current benefit from genetic testing remains small – genetics
only plays a small role in many chronic diseases and few therapies
exist to treat disease
Whole genome sequencing fails to predict risk of most common
diseases
Ideally, genomics can reveal areas for possible interventions to take
place – ie. B and T cell inhibitors for patients who show
autoimmune disorders
Unfortunately, most genetic information about chronic diseases is
very limited
Cost
Pharmaceutical companies have used genomic strategies for
drug development but this has normally not led to late- stage
development
Cost of therapeutic development has tripled since 1990 while
the number of FDA approved drugs per year remains
constant – many drug failures after investment
Drug companies often work with academia or government to
increase effectiveness of produced drugs
Future Plans
One of the largest gaps in genetic research is why individuals
respond differently to drugs and treatment
CDC’s Office of Public Health Genetics has the following
goals for 2013:
Integrate evidence based genomic applications into public
health
2. Evaluate genomic tests to identify opportunities to improve
health/transform healthcare
3. Develop and provide communications about public health
genomics to various audiences
1.
Sources
CDC Genomics:
http://www.cdc.gov/genomics/about/AAG/index.htm
Targeting DNA:
http://www.commed.vcu.edu/Chronic_Disease/genetics/
2013/clinicalintervention.pdf
Epigenetics:
http://www.commed.vcu.edu/Chronic_Disease/genetics/
whatisepigenetics.pdf
Genome Sequencing Failures:
http://www.commed.vcu.edu/Chronic_Disease/genetics/
2013/practicalgenetics.pdf