predictive genetic tests: what do we know?...what do we know? peter ray, phd the hospital for sick...
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Predictive Genetic Tests:What Do We Know?
Peter Ray, PhDThe Hospital for Sick Childrenp
April 16, 2010
The Era of Genomic MedicineWhat you are Who you areWhat you are. Who you are.
Your genome is the ultimate form of information(past-present-future),
“NGS is erasing the barriers of entry and theNGS is erasing the barriers of entry and the boundaries to creativity in genomics”
The Human Genome Project
Has created:Has created:
• Major advances in technology for analyzing DNAanalyzing DNA
• An explosion in knowledge of genetics and genetic diseasegenetics and genetic disease
Molecular Genetic Testing
2500
3000
Disease Genes Identified
Molecular Tests Offered in
2000
2500 Molecular Tests Offered in North America
Molecular Tests Offered In Ontario
1500
Ontario
500
1000
0
500
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
www.ncbi. nlm.nih.govwww.genetests.org
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
9 of the 10 Leading Causes of Mortality9 of the 10 Leading Causes of Mortality Have Genetic Components
Heart disease (31.0% of deaths in ‘98) Cancer (23.2%) St k (6 8%)Stroke (6.8%)COPD (4.8%)Injury (4.2%)Injury (4.2%)Pneumonia/Influenza (3.9%)Diabetes (2.8%)
d ( )Suicide (1.3%)Kidney disease (1.1%)Chronic liver disease (1 1%)Chronic liver disease (1.1%)
The Value of PresymptomaticDiagnosisDiagnosis
“In about 20 percent of patients, sudden death is the first sign of
heart disease.”
Roger Blumenthal, M.D, Johns Hopkins
Complex DisordersComplex Disorders
Environmental
Multiple gene effects
Environmental factors
effects
Complex Disease Polygenic Inheritance
Gene B
yg
Gene ADisease
Gene D
Gene C
Gene D
Small number of common variants with small effect
Complex Disease pHeterogenetic Inheritance
Gene BGene A
Disease
Gene CGene D
Large n mber of rare ariants ith large effectLarge number of rare variants with large effect
Heterogenetic Disorders
Number of Genes
B t C 2Breast Cancer 2Colorectal Cancer (HNPCC) 5Ahrrythmogenic Right Ventricular Cardiomyopathy 5Congenital Muscular Dystrophy 5g y p yNeuronal Ceroid Lipofusinosis (Batten Disease) 8Focal Segmental Glomerulosclerosis 4Hereditary Spastic Paraplegia (recessive) 9Fanconi Anemia 12Fanconi Anemia 12
Complex Disease Polygenic Inheritance
Gene B
yg
Gene ADisease
Gene D
Gene C
Gene D
Small number of common variants with small effect
Genetic Risk Association
Direct to Consumer Genetic TestingDirect to Consumer Genetic Testing
Direct to Consumer Genetic TestingDirect to Consumer Genetic Testing
Heart attackObesitObesity
Risk Factors for Heart Disease
SmokingSmokingHigh Blood PressureHigh CholesterolObesity
Lack of ExerciseUnhealthy DietStressT A litType A personality
Personalizing Risk FactorsObesity increases risk of heart disease
A ti t t lik th l b tA genetic test, like any other laboratory test is a tool that when used by a trained health care provider can improve diagnosis and patient management.
Without informed consultation testingWithout informed consultation testing could be over-interpreted or misinterpreted resulting in increased patient risk
Complex Genetic Testing
Clinical Utility
• Incomplete knowledge base to interpret the clinical significance of the results
• Applying population statistics to individual prediction• Inadequate understanding of genetics by public and
physicians• Genetic data is generally beyond the experience of theGenetic data is generally beyond the experience of the
public• assumed to be “scientific” and thus accurate
Complex Disease Polygenic Inheritance
Gene B
yg
Gene ADisease
Gene D
Gene C
Gene D
Small number of common variants with small effect
www.uwcvb.org
Identifying the Genetic Cause of Disease
The Personal Genome Project (www.personalgenomes.org)• Sequence 100,000 genomes• Collect extensive medical and physical information• Identify genetic variants predisposing to disease
C t $1B fi d b l• Cost $1B - financed by google
DNA Sequencing Technologyq g gyCost
Per GenomeData Points
1993 $3,000,000,000 40,000
2003 $3,000,000 100,000
2009 $30,000 100,000,000,000
? $1,000
$1000 genome$10,000 Interpretation
Issues in Implementation ofIssues in Implementation of Genomic Diagnostics
G ti K l d
Laboratory Issues:Genetic Knowledge
• Phenotype /genotype correlationsV l li i l d t b• Very large clinical databases
• Longitudinal studies• Many thousands of patientsy p
• Genetic Interactions
Issues in Implementation ofIssues in Implementation of Genomic Diagnostics
N “ li i l” bi i f ti l ith
Clinical Issues:• New “clinical” bioinformatics algorithms• New counseling algorithms
• Selective information transfer• Selective information transfer• “Need to know” counseling
• Utilization of primary health care providersp y p• Need to regularly reanalyze genome in light
of new knowledge
Future DiagnosticsFuture DiagnosticsGenomic Profiling
Sequence each individual's genome and detect all CVNs at birth to determine:
• carrier status of all genetic disorders• predisposition to all common disease• all drug sensitivities• all drug sensitivities• optimal treatments/therapies
• behavioural traits• personality
IQ• IQ
Toronto Star Aug 15, 2007
Th k YThank-You