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Is cascade testing a sensible method of screening a population for autosomal recessive disorders?
J K Morris1, M R Law, N J Wald
1Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom. j.k.morris@qmul.ac.uk
American Journal of Medical Genetics. Part A
|June 25, 2004
Summary
Cascade testing is not an effective population screening method for autosomal recessive disorders. Computer simulations show it identifies few cases, making it impractical for widespread use.
Area of Science:
- Medical Genetics
- Population Screening
- Genetic Epidemiology
Background:
- Autosomal recessive disorders require carrier screening for early detection.
- Cascade testing, a family-based approach, has been proposed for population screening.
- The efficiency of cascade testing for common genetic disorders is not well-established.
Purpose of the Study:
- To evaluate the performance of cascade testing as a population screening strategy for autosomal recessive disorders.
- To estimate the proportion of the population that would need to be tested and the detection rate for specific disorders.
- To assess the impact of varying parameters like carrier frequency, family size, and relationship to carriers on screening effectiveness.
Main Methods:
- Computer simulations were employed to model cascade testing scenarios.
- Simulations varied carrier frequency, family size, and the extent of testing (siblings, first/second cousins).
- Performance was assessed by the proportion of the population located and tested versus the number of new cases detected.
Main Results:
- For cystic fibrosis (4% carrier frequency), testing siblings and first cousins of carriers required testing 1.9% of the population but detected only 15% of new cases.
- For congenital adrenal hyperplasia (1% carrier frequency), testing siblings and first cousins required testing 0.1% of the population but detected only 3.1% of new cases.
- Increasing detection rates required testing a larger population proportion, with diminishing returns.
Conclusions:
- Cascade testing demonstrates poor performance as a population screening tool for autosomal recessive disorders.
- The method is inefficient, detecting a small fraction of cases relative to the number of individuals tested.
- Current cascade testing strategies are not recommended for implementation in public health screening programs for these conditions.