Categorization of Genetic Tests Clinical validity accuracy of the - PDF document

Categorization of Genetic Tests • Clinical validity –accuracy of the test to predict an outcome – Often uncertain for new genetic tests-limited and potentially biased populations –e.g. BRCA1, BRCA2 • Availability of Effective Treatment • Burke et al. Am J Med Gen. 2001;106:233-240 Categorization of Genetic Tests to Identify Ethical Legal and Social Implications Effective Effective Treatment-Yes Treatment -No High Clinical Validity PKU, MEN2, FAP HD (high penetrance) Low Clinical Validity HFE gene, LRRK2 ApoE (low penetrance) (hemochromatosis) 1

Utility of Predictive Testing BMJ 2001;322:1052-1056 Parkinson Disease Postural change Rest tremor Bradykinesia Rigidity 2

Genetics of Parkinson’s Disease Locus Gene Chromosome Inherit. Age onset α synuclein Park 1/4 4q.21.3 AD 45 Park 2 Parkin 6q25.2-q27 AR <40 Park 3 Unknown 2p13 AD 59 Park 5 UCHL1 4p14 AD 50 Park 6 PINK 1 1p35-p36 AR 40 Park 7 DJ1 1p36 AR 33 Park 8 LRRK2 12p11.2-q13 AD 51 Park 9 Unknown 1 p36 AR Park 10 Unknown 1p32 Comp. 66 LRRK2 and PD Subjects Total LRRK2 % OR Controls 314 3 0.6 PD 504 28 5.6 9.2 (2.2, 38.8) AJControls 98 2 2 AJ PD 181 18 9.9 3.5 (1.6, 7.7) AJ w/o FH 155 12 7.7 AJ w FH 23 6 26.1 4.2 (1.4, 12.7) NJ controls 216 0 0 NJ PD 323 10 3.1 2.7 (1.1, 6.8) NJ w/o FH 263 7 2.7 NJ w FH 38 1 2.6 1.0 (0.1, 8.3) 3