Download 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