Overview of Genetic Testing in Korea: Current Status and Problematic Issues
Han-Wook Yoo, M.D., Ph.D.,
Medical Genetics Clinic & Laboratory, Department of Pediatrics, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Korea
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Outlines of Presentation
Genetic testing: definition, classification
Prerequisite for clinical DNA testing
Current status of genetic testing in Korea
DNA testing in single gene disorders
DNA profiling
Susceptibility DNA testing in Polygenic disorders
Pharmacogenomic DNA testing
Current issues of genetic testing in Korea
Regulatory process of genetic testing in Korea
Conclusion
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Classification & Definition of Genetic Testing
Maternal serum screening
Cancer, DM, Alzheimer disease, Hypertension, Drug response
Disease prediction(susceptibility &resistance)
Inborn error of metabolism
Chromosomenumerical &structural disorder
Micro-deletion & duplication syndrome
Monogenic Mendelian disease, Mitochondrial disease
Disease diagnosis (prenatal, presymptomatic, carrier testing)
Paternity testing, Forensic investigation
DNA profiling
Biochemicalgenetic test
ing
Cytogenetic testing
Molecular cyto-genetictesting
DNA testingTesting
Purpose
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Classification & Definition of Genetic Testing
Clinical test: diagnostic testing, predictive testing, carrier testing, prenatal testing, preimplantation testing, newborn screening
Investigational test
Research test
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Prerequisite for clinically applicable DNA testing
Preferably single gene disorderKnown gene structure & functionAppropriate marker linked to morbid geneLimited locus heterogeneity and genetic heterogeneityAvailability of genetic epidemiological dataReplacing or complementary for preexisting diagnostic testLess cost-higher benefitSensitivity, specificity, positive & negative predictive valuesPre- & Post- test genetic counselingMaintenance of privacy and confidentiality
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DNA testing for single gene disorders in Korea
Number of laboratories 5 Commercial laboratories >10 Institutional laboratories
Number of testing diseases 3 to more than 50 monogenic diseases
Methods Medical DNA sequencing, DHPLC, PCR-RFLP, methyl
ation specific PCR, ASO hybridization, PCR-Southern, genomic Southern, MLPA, real time PCR, linkage analysis....
Reimbursement by national insurance (As of Jan-2008) Reimbursed in 17 tests (13 monogenic diseases,
3 familial cancer syndrome, 1 predictive testing) Regulated by price of ceiling in 62 tests (4
2 monogenic diseases, 12 oncogenes or tumor suppressor genes, 8 pharmacogenetic testings)
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Single Gene (Monogenic) Disorder
Victor A. Mckusilk: Mendelian Inheritance in Man
Online version of Mendelian Inheritance in Man(OMIM) > 10,000 diseases or trait >2,500 human disease relate
d >2,000 loci mapped - mutatio
n (7% of total 29,000 genes) > 1500 genetic tests are avail
able.
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DNA testing for single gene disorders in Korea
Inherited metabolic disorders: urea cycle defects, Gaucherdisease, GSD Ia, Fabry disease, Wilson disase
Skeletal dysplasia: achondroplasia, osteogenesis imperfecta, craniosynostosis
Neuromuscular disorders: DMD/BMD, spinal muscular atrophy
Triplet repeat expansion disorders: spinocerebellar ataxia,fragile-X syndrome, myotonic dystrophy, Kennedy disease,Huntington’s disease, DRPLA
Neurogenetic disorders: adrenoleukodystrophy, CADASIL,dystonia
Hematologic disorders: hemophilia, factor V Leiden
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DNA testing for single gene disorders
Familial cancer syndromes: BRCA1, BRCA2, APC, Rb
Endocrine genetic disorder: MEN, congenital adrenal hyperplasia
Monogenic renal disorder: familial hyperuricemic nephropathy, nephrogenic DI
Monogenic eye disorder: corneal dystrophy
Dysmorphic syndromes: Prader-Willi/Angelman syndrome,Rett syndrome, Holt-Oram syndrome, Marfan sydnrome
Mitochondrial disorders: MFLAS, MERRF, LHON, Kearn-Sayers syndrome, Leigh disease
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DNA testing for DNA profiling in Korea
Forensic Medicine: National Institute of ScientificInvestigation, Department of Forensic Medicine in Medical Schools (>2)
Paternity testing: More than 10 commercial laboratories
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SNP-based DNA testing for susceptibility genesin polygenic disorders in Korea
Thrombophilia panel : Factor V Leiden in Caucacians, prothrombin(factor II), MTHFR (methylenetetrahydrofolate reductase)
Coronary heart disease panel: lipoprotein (Lp(a), apoE), coagulation factor, MTHFR
Hypertension : ACEInsulin dependent diabetes mellitus : HLACancer disease (non-familial) : tumor suppressor genes, on
cogenes (n-myc gene, breakpoint cluster region (bcr) (BCR-ABL), breast cancer, colon cancer
Hemochromatosis : population screening for CaucaciansAlzheimer disease : familial vs sporadic (APOE genotyping)Neural tube defect : MTHFR gene
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Pharmacogenetic variants that have been significantly associated with drug re
sponse in at least two studies (Nat Rev Genet 2003;4:937-947)
Pharmacogenomic DNA testing in Korea
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Warfarin genotyping: CYP2C9 & VKORC1
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Current Issues of Genetic Testing in Korea (I)
DTC (direct to consumer) or “Over the Counter” DNA testing More than 15 laboratories Advertised and sold over the Internet Limited oversight of the analytic & clinical validity of ge
netic tests No pre & post test genetic counseling
Implementation of legislation Oversight of genetic testing laboratories Approval of diagnostic kits & methods Biomedical ethical-legal-social issues
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6. 유전자건강정보센터 (www.9191114.com/gene) – 검사종목
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Regulatory process of genetic testing (I)
Initiated by Korean Society of Medical Genetics by reviewing mostcommonly sold DTC tests on web sites Clinical validity evaluation by literature review and meta-analy
sis Publication of reports
Implemented by the Ministry of Health & Welfare Funding a grant for research Organizing advisory committee of genetic testing composed of
expert physicians, geneticist, scientists, expert of bioethics, lawyer, representative from NGO
Holding a conference for public hearing Enhancing legislation by National Advisory Committee of “Bioe
thics & Security”
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Regulatory process of genetic testing (II)
Since 2007-Jan, 14 DNA-based genetic tests are banned as a clinical test and 6 tests are limitedly allowed in specific clinical situation Prohibited DNA tests for clinical diagnostic purpose
Hyperlipidemia related gene: LPL Hypertension related gene: Angiotensinogen Osteoporosis related genes: VDR, ER Diabete mellitus related genes: IRS-2. Mt16189 Obesity related genes: UCP-1, Leptin, PPAR-gamma, ADRB3(B3AR) Alcoholism related gene: ALDH2 Depression related gene: 5-HTT Longevity related gene: Mt5178A Intelligence related genes: IGF2R, CALLAsthma related genes: IL-4, beta2-AREndurance related gene: ACELung cancer related gene: CYP1A1Violence related gene: SLC6A4Curiosity related gene: DRD2. DRD4
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Regulatory process of genetic testing (III)
limitedly allowed in specific clinical situation Ankylosing spondylitis related gene: HLA-B27 Leukemia related genes: BCR/ABL Short stature related gene: SHOX Cancer related gene: P53 Breast cancer genes: BRCA1, BRCA2 Alzheimer related gene: Apolipoprotein E
Any genetic tests for trait identification are prohibited. The banned genetic test will be reviewed and updated on a regular basis. Protection of genetic information privacy and informed consent should be
ensured. The DTC tests are strictly prohibited except DNA profiling for paternity test
ing. Pre & post-test genetic counseling and request for diagnostic DNA testing
should be offered exclusively by medical doctor. DNA-diagnostic kit is regulated by KFDA and law related medical practice. The introduction of positive system is currently being considered.
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Current Issues of Genetic Testing in Korea (II)
Establishment of “Korea Institute of Genetic Testing Evaluation” in2005 Evaluation of clinical validity of genetic testing Quality assurance of genetic testing
Enhancement of public & medical professionals’ awareness of pros& cons of genetic testing by education
Accreditation of genetic testing laboratories and personnel by Korean Society of Medical Genetics
Issues of insurance reimbursement Issues of certification & training program of medical geneticist as
a medical specialty Issues of oversight and regulation of DTC DNA testings
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Genetic Testing in Korea
“Medicalization”
“Subspecialization”
“Professionalization”
“Molecularization”
“Commercialization”
“Cosumerization”
SNP-based susceptibility genetic testing in polygenicdisorders
Unproven clinical & analytical validities
Unresolved ethical, legal, and social issues
Conclusion