3. DiaGenomi Team
DiaGenomi Ltd.
Klemen Spaninger, PhD, M. Pharm
CEO
spaninger@diagenomi.eu
Rok Kosir, PhD, B.A. Biology
CTO
kosir@diagenomi.eu
Cooperation with:
Prof. dr. Maritha J. Kotze, PhD
Department of Pathology , Faculty of
Health Sciences, University of Stellenbosch
Ronald van Klaveren, MBA, B.A.
Biology
Head UK
klaveren@diagenomi.co.uk
James Harris, MBA
Head US
harris@diagenomi.com
Prof. dr. Vita Dolžan, MD, PhD
Head of the Pharmacogenetics Laboratory
at the Institute of Biochemistry, Faculty of
Medicine, University of Ljubljana
6. The different types of genetic tests
Diagnostic genetic tests
Diagnostic genetic tests are intended to diagnose a genetic disorder in a person who
already has symptoms. The results of this test may help to make choices about how to
treat or manage health problems.
Carrier tests
Carrier tests are used to identify people who ‘carry’ a mutated allele of gene which is
associated with a specific disease (e.g. cystic fibrosis). Carriers may show no signs of the
disease. However, there is a risk that their children will be affected.
Pharmacogenomic tests
Pharmacogenomic tests are performed to test individuals sensitivity to a specific
therapy. For example, some individual might need higher dosage while others may
display an adverse reaction to certain medications.
Predictive genetic tests
Predictive genetic tests are performed on individuals who show no symptoms as yet. They
are geared to detecting genetic changes which suggest a risk of developing a disorder
later in life.
Genetic testing
Source: Council of Europe & European Society of Human Genetics
8. Are based on Genome-Wide Association Studies (GWAS)
Compare common genetic variants (SNPs) across the genome in large
numbers of affected cases and controls to determine whether association
with a disease exists.
Genetic testing
Published GWAS Reports,
2005 – 6/2012
TotalNumberof
Publications
Calendar Quarter
0
200
400
600
800
1000
1200
1400
2005 2006 2007 2008 2009 2010 2011 2012
Direct to consumer genetic tests
9. Are based on Genome-Wide Association Studies (GWAS)
Compare common genetic variants (SNPs) across the genome in large
numbers of affected cases and controls to determine whether association
with a disease exists.
Genetic testing
Direct to consumer genetic tests
10. - number of these tests lack data on their accuracy and reliability
- interpretation of results difficult and inconsistent
- Estimation of disease likelyhood is dependent upon mutations
chosen and studies included in the calculation
- lack appropriate individual and family genetic counseling
- misinterpretation of results, including false positive or false
reassurance, with limited or no benefits
Genetic testing
What is the problem with DTC?
11. Genetic testing
How DTC companies do the test?
DTC 1 DTC 2 DTC 3
SNP‘s from
study 1
Data from
study 1
SNP‘s from
study 2
Data from
study 2
SNP‘s from
study 3
Data from
study 3
Result:
Likelyhood for
breast cancer:
16%
Different calculation
procedures
Different calculation
procedures
Different calculation
procedures
Result:
Likelyhood for
breast cancer:
32%
Result:
Likelyhood for
breast cancer:
8%
17. What is CardioRISQ?
CVDs are the number one cause of death globally: more people die
annually from CVDs than from any other cause. Key to healty hart is the
prevention.
Stratification into low medium and high risk group for CVD without
genetic information is deficient.
CardioRISQ is a first cardiac risk assesment test combining your genetic
make-up with your lifestyle.
With CardioRISQ you get clear, personalized data on your risk to develop
CVD (based on your genetic predispositions and lifestyle) together with
the guidelines how to avoid it. Rembember, key to healthy heart is the
prevention!
CardioRISQ
18. 1st cardiac risk assessment test
combining your cardiac genetic
make-up with your lifestyle.
CardioRISQ
19. If you look only at genetic mutation two seemingly identical pictures can be seen (pictures above).
However when you combine your specific genetic mutations with your medical information a clear
and distinct difference can be seen (pictures below).
CardioRISQ
20. Structure of the test – 3 steps
1. Genetic testing - mutations
(from the saliva sample)
2. Filled in questionnaire
(nurse can fill in the
questtionaire together with the
patient)
3. Both information (genetics +
questionnaire) are gathered in
the medical report that has to
be interpreted by doctor to the
patient.
CardioRISQ
SALIVA SAMPLE
COLLECTIING KIT
CardioRISQ
QUESTIONNAIRE
ONLINE
ONLINE MEDICAL
REPORT FOR THE
DOCTOR
21. Saliva collection
Step 1: MyRISQ SALIVA SAMPLE
COLLECTION – for genetic analyses
Collect high quality DNA samples for molecular diagnostics.
Genetic testing starts with the collection of DNA samples. Use Oragene•Dx® for proven
collection, stabilization and transportation of DNA from saliva.
Oragene•Dx is an FDA cleared device.
• Painless, non-invasive collection
• Median A260/280 of 1.7‡
• Easy collection and transportation
• Oragene•Dx/saliva samples are stable for long-term room temperature storage
• Standardized tube format is compatible with automated processing equipment
• Oragene•Dx solution is bacteriostatic
• Intended for use with molecular diagnostic applications†
• Integrated barcode on tube for workflow efficiency
22. Saliva collection
Saliva sampe collection procedure:
IMPORTANT ! !
Do NOT eat, drink, smoke or chew gum for
30 minutes before giving your saliva sample.
Do NOT remove the plastic film from the
funnel lid.
Do NOT spit above the top line on the tube
24. Mutations determined by CardioRISQ
The selection of genes and mutations included in the CardioRISQ test is based
on the phenotypic expression (clinical manifestation), prevalence in the general
population and availability of appropriate intervention or treatment options that
may be required. (Kotze et al 2003, Kotze and Thiart 2003)
All together CardioRISQ determines 8 mutation in 5 genes which are involved in:
• cholesterol and fat metabolism - ApoE
• folate and homocysteine metabolism - MTHFR,
• blood clotting and thrombophilia - FII, FV and
• iron overload and oxidative stress - HFE
Mutation are determined using:
- Quantitative real-time PCR (qPCR)
- Sequencing
CardioRISQ
25. Relevant genetic variants that are being tested in CardioRISQ:
• affect the function or level (expression) of the gene products,
• affect biological processes involved in CVD or related disorders, and
• have apparent metabolic/clinical implications, either alone or in
combination with other genetic or environmental risk factors.
CardioRISQ
Mutations determined by CardioRISQ
Gene Mutation RS Numbers
ApoE
ApoE
MTHFR
MTHFR
FV
FII
HFE
HFE
C > T
T > C
C > T
A > C
G > A
G > A
G > A
G > C
rs429358
rs7412
rs1801133
rs1801131
rs6025
rs1799963
rs1800562
rs1799945
26. Step 2: Online Questionnaire
Nurse fills in the questtionaire together with the patient.
Online process will be presented later on.
CardioRISQ
27. Questionnaire data
Personal and family medical
conditions
Metabolic indicators and
blood biochemistry
Environmental risk factors
and nutrition
•Angina
•Alzheimer's disease
•Cancer (specify type)
•Chronic periodontitis
•Chronic inflammation
•Coronary heart disease
•Deep vein thrombosis
•Diabetes Type II
•Familial
hypercholesterolaemia
•High blood cholesterol
•High blood iron
•High blood pressure
•Hypothyroidism
•Metabolic syndrome
•Non-alcoholic fatty liver
disease
•Body mass index
•Waist circumference
•Hip circumference
•Systolic blood pressure
•Diastolic blood pressure
•Total cholesterol
•LDL-cholesterol
•HDL-cholesterol
•Triglycerides
•Lipoprotein (a)
•Homocysteine
•Ultrasensitive C-reactive
protein
•Glucose,
•Insulin
•Serum ferritin
•Transferrin saturation
•Lifestyle assessment:
•Physical activity
•Smoking status
•Alcohol consumption
•Dietary intake –
•Saturated fats
•Trans fats
•Fruit
•Vegetables
•Fibre
•Folate
•Hormone replacement
therapy
•Oral contraceptive use
•Drug side effects
•Food allergies
•Food intolerances
CardioRISQ
28. Step 3: Medical Report Online
Data obtained from the clinical evaluation and genetic testing are pooled to
generate a comprehensive test report that integrates clinical, metabolic,
genetic and lifestyle risk factors into a treatment plan for the individual. The
impact of this holistic approach on patient management depends:
• on the number and type of genetic alterations detected in the DNA of the
individual and
• how gene expression is affected by these genetic alteration(s) in relation
to environmental risk factors relevant to the patient.
CardioRISQ
29. MyRISQ security
• All data transfer between the myrisq web-server and your web client is
encrypted using the HTTPS protocol - Secure Socket Layer (SSL)
• Your saliva sample sent to us and the DNA extracted from the sample will be
stored by DiaGenomi only for the time necessary to perform the analysis and
will be discarded (destroyed) upon successful measurements.
• All your data stored in the myrisq database is stored under a random 13 digit
number, that you receive in the MyRISQ kit. The number is know only to you
and your doctor.
• DiaGenomi will under no circumstances provide any 3'rd party, including
insurance companies, health management organizations, hospitals, and
government agencies, access to any of your personal data or data derived
from your samples, unless you grant us an explicit authorization in your privacy
setting.
MyRISQ security
30. To whom we recommend CardioRISQ?
Patients who have direct family members with cardiac disease,
Patients who have a high cholesterol level,
Patients with type II diabetes
Patients with hypertension
Patients who have interest in finding your risk for a cardiac event,
Those who want to check their lifestyle and its impact on their "heart health
Patients whose treatment of CVD was not so far successful – CardioRISQ as
an additional information to the doctor to adapt the therapy.
CardioRISQ
31. References
• Kathiresan S, Melander O, Anevski D, et al. Polymorphisms associated with
cholesterol and risk of cardiovascular events. N Engl J Med 2008; 358: 1240-1249.
• Kotze MJ, Davis HJ, Bissbort S, et al. Intrafamilial variability in the clinical expression
of familial hypercholesterolemia: importance of risk factor determination for
genetic counselling. Clin Genet 1993a; 43: 295-299.
• Kotze MJ, de Villiers WJS, Steyn K, et al. Phenotypic variation among familial
hypercholesterolemics heterozygous for either one of two Afrikaner founder LDL
receptor mutations. Arterioscler Thromb 1993b; 13: 1460-1468.
• Kotze MJ, Kriegshäuser G, Thiart R, et al. Simultaneous detection of multiple familial
hypercholesterolaemia mutations facilitates an improved diagnostic service in
South African patients at high risk of cardiovascular disease. Mol Diagn 2003; 7:
169-74.
• Kotze MJ, Thiart R. Genetics of dyslipidaemia. CME Journal 2003; 21: 399-402.
CardioRISQ
33. What is Multiple Sclerosis
MultipleSclerosisRISQ
MS is a chronic neurodegenerative and demyelinating disease of the central
nervous system.
NEURODEGENERATION - progressive loss of structure or function of neurons,
including death of neurons
DEMYELINATING DISEASE - any disease of the nervous system in which the myelin
sheath of neurons is damaged
brain
Spinal
cord
34. Main treatment of MS
MultipleSclerosisRISQ
A lot of controversy and contradictions about what MS is:
Autoimmune disorder or
Primary loss of oligodendrocytes followed by inflammation.
Multiple Sclerosis is not yet curable, but there are ways for patients to
improve their disease status.
MS is mostly treated with disease modifying drugs
such as interferon-ß.
Problem:
Fewer then half of patients have no benefit
In Non-responders it may worsen outcome
Unpleasant side effects
Limited effect on disability progression
35. Multiple Sclerosis and PSGT
MultipleSclerosisRISQ
Myelin is synthesized and repaired on an ongoing basis by
oligodendrocytes.
MS patients have higher turnover of glia and myelin increased
nutritional demands.
MS patients often develop deficiencies (iron, folat-vitamin B12, vitamin
D, unsaturated fatty acids).
Availability of these components is a prerequisite for optional myelin
synthesis and repair.
36. MultipleSclerosisRISQ?
MultipleSclerosisRISQ
DNA and pathology tests are combined to analyze a combination of
genetic variants in individuals previously diagnosed with MS.
We CAN NOT change genes! (yet)
We can modifie environmental risk factors!
Results
Blood
biochemistry
Family history
Lifestyle
factors
Genetic
analysis
MS is a complex interaction
between various factors:
Genetics
Infectious
Environmental
37. To whom we recommend
MultipleSclerosisRISQ?
MultipleSclerosisRISQ
MultipleSclerosisRISQ test is only suitable for patients with already
diagnosed multiple sclerosis.
It is not a test to determine the likely hood of developing multiple
sclerosis.
MultipleSclerosisRISQ provides information about how to improve
quality of life by enhancing myelin repair and maintenance,
when viewed in the context of lifestyle factors that can be
changed by the individual.
38. Structure of the test – 3 steps
1. Genetic testing - mutations
(from the saliva sample)
2. Filled in questionnaire
(nurse can fill in the questtionaire
together with the patient)
3. Both information (genetics +
questionnaire) are gathered in
the medical report that has to be
interpreted by doctor to the
patient.
MultipleSclerosisRISQ
SALIVA SAMPLE
COLLECTIING KIT
MultipleSclerosisRISQ
QUESTIONNAIRE
ONLINE
ONLINE MEDICAL
REPORT FOR THE
DOCTOR
40. Pharmacogenetics?
As the majority of drugs today are prescribed in a "one size fits all"
manner, they do not work for everybody.
DrugResponseRISQ
41. What is DrugResponseRISQ?
Panel of pharmacogenomic tests aimed to provide doctors with useful
information that will support personalized treatment decisions for their
patients.
For patient
who are already receiving a particular drug treatment and show either adverse
effects or no treatment effect
who are planning to start with a treatment, especially if it is associated with a
high risk for non-efficacy or adverse events
Based on analysis we provide you with an informative report about
treatment decisions that are in accordance with international guidelines.
DrugResponseRISQ
42. For which drugs is DrugResponseRISQ
suitable?
Warfarin: widely used coumarin oral anticoagulant drug
Clopidogrel: acute coronary syndrome and/or following
percutaneous coronary intervention
Statins: low-density lipoprotein cholesterol-lowering drugs
Tamoxifen: selective estrogen receptor modulator (SERM)
used for the adjuvant treatment and prevention of
estrogen receptor (ER) positive breast cancer
Atomoxetine: non-stimulant drug approved for the
treatment of attention-deficit hyperactivity disorder
(ADHD)
Antidepressants
DrugResponseRISQ
44. Medical Report
Data obtained from the clinical evaluation and genetic testing are pooled to
generate a comprehensive test report that integrates clinical and genetic
factors into a treatment plan for the individual. The impact of this holistic
approach on patient management depends:
• on the number and type of genetic alterations detected in the DNA of the
individual and
DrugResponseRISQ
47. MyRISQ security
• All data transfer between the myrisq web-server and your web client is
encrypted using the HTTPS protocol - Secure Socket Layer (SSL)
• Your saliva sample sent to us and the DNA extracted from the sample will be
stored by DiaGenomi only for the time necessary to perform the analysis and
will be discarded (destroyed) upon successful measurements.
• All your data stored in the myrisq database is stored under a random 13 digit
number, that you receive in the MyRISQ kit. The number is know only to you
and your doctor.
• DiaGenomi will under no circumstances provide any 3'rd party, including
insurance companies, health management organizations, hospitals, and
government agencies, access to any of your personal data or data derived
from your samples, unless you grant us an explicit authorization in your privacy
setting.
MyRISQ security
NCD are a major problem today and will be even more in the future
Can genetics help us to find a solution where the personalised risk management could benefit from eraly detection of modifiable genetic contriution. You can not change the genetics, but you can change the environment theexpression of the genes can be influenced.
AIMtako kot piše.
