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Characteristics Of Genetic Data Joann Boughman, Ph.D. [email protected] Characteristics of Genetic Data Genetic Data is: Personal Permanent Predictive Prejudicial Pedigree-sensitive Context and Implications MEDICAL ETHICAL, LEGAL & SOCIAL (ELSI) Definition of ‘Genetic Test’ Genetic test – An analysis of chromosomes, genes, and/or gene products to determine whether a genetic variation related to a specific disease or condition is present Types of Genetic Tests Diagnostic testing Newborn screening Carrier testing Prenatal testing Predictive testing Diagnostic Testing Diagnostic testing is used to confirm or rule out a known or suspected genetic disorder in a symptomatic individual. May help: as an adjunctive test “ “ “ in making a prognosis in treatment choice in planning/intervention strategies determine risk to relatives Healthcare Practitioners Already Use Genetic Tests in General Medical Care 41yo male with chest pain in ER father & paternal uncle had MI’s at 40 and 44 information alters admission decision and f/u 3yo female with delayed speech, slow reaction abnormal audiogram, Connexin 26 mutation GENETIC INFORMATION IS POWERFUL Newborn Screening Mandatory testing to detect cases at birth (i.e., as soon as possible) Diagnosis: – – – – – – – – PKU MSUD galactosemia congenital hypothroidism sickle cell disease homocystinuria biotinidase congenital adrenal hyperplasia Next – – – – Steps: Intervention Follow-up, treatment and prevention Carrier Screening Recessive, monogenic disorders cystic fibrosis hemophilia Selected (at-risk) population Tay-Sachs disease Sickle cell disease Carrier Test Results Definition of “negative” or “noncarrier” complicated by multiple allelic mutations Definition of “positive” only fully understood by patient when put in context of risk to offspring Prenatal Testing Reasons for Testing: To assess health of fetus, often when pregnancy is at increased risk of a genetic condition depending on the mother’s: - maternal age - family history - ethnicity - suggestive multiple marker screen - fetal ultrasound Predictive Testing Offered to asymptomatic individuals with increased risk of a genetic disorder (i.e. with a family history of the disorder) – Presymptomatic: eventual development of the disorder is certain if mutation is present – Predispositional: eventual development of symptoms is likely but not certain in presence of mutation Predictive Testing Predictions are tricky………… especially ones about the future. Yogi Berra Predictive Genetic Tests (PGT) How do they differ from other medical tests? Give information about the “future” in addition to the present condition Will results of test affect other relatives? (Is info pedigree sensitive?) - some choose not to test - recognized risks to offspring Results are complex and probabilistic - definitions of negative and positive results and their impact on the patient and family Some Common Diseases with a Known Genetic Component DM I/II Cancer(s) CVD Glaucoma Alzheimer Schizophrenia Bipolar disease Head trauma outcome HNPCC Clinical Features Accounts for 5-10% of “sporadic” colon cancer cases Early but variable age at CRC diagnosis (~45) Tumor site in proximal colon predominate Associated extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors Familial Risk for Colorectal Cancer 100 70% 80 Approximate lifetime CRC risk (%) 60 40 20 0 2% 6% None One 1° 8% 10% 17% One 1° One 1° Two 1° and two age 2° <45 HNPCC mutation Affected family members Aarnio M et al. Int J Cancer 64:430, 1995 Houlston RS et al. Br Med J 301:366, 1990 St John DJ et al. Ann Intern Med 118:785, 1993 ASCO Pedigree S.H. colon cancer colon and uterine cancer ovarian cancer died @ 22 colon @ 50, uterine @ 52 colon @40 uterine @ 44 Ovarian @ 44 died at 22 Cancer Risks in HNPCC 100 % with 80 cancer 60 Colorectal 78% Endometrial 43% 40 Stomach 19% Biliary tract 18% Urinary tract 10% Ovarian 9% 20 0 0 20 40 60 80 Age (years) Aarnio M et al. Int J Cancer 64:430, 1995 ASCO Surveillance Reduces Risk of Colorectal Cancer in HNPCC 30 No surveillance Surveillance % of subjects 20 with CRC 11.9% 10 4.5% 0 0 3 6 Years of follow-up Jarvinen HJ et al. Gastro 108:1405, 1995 9 ASCO Other Predictive Scenarios Breast Cancer – BRCA1 – BRCA2 Diabetes – Type I versus Type II Alzheimer – ApoE Disease Problems with Predictive Testing Analytical sensitivity Clinical validity and utility Complexity of interpreting results Challenge of assuring patient understanding – Need informed consent? – Transmission of results – Translation of results Potential Harms of Genetic Testing Knowledge can cause (undue) anxiety - especially if considered deterministic Family relationships may be disrupted - when results are shared - when results are not shared Possible misuses of genetic information - insurance discrimination - employment discrimination - social stigmatization Balance of Value vs. Potential Harms Healthcare practice must change as new treatments are introduced Adjust if preventions are available AND used Depends on the individual and the context - Ability to utilize information - Family situation - Reproductive options This balance will improve with increased public understanding of genetics Genetic Information is: Personal Permanent Predictive Prejudicial Pedigree-sensitive POWERFUL