The recent identification of the gene involved in cystic fibrosis (CF) and the finding that the most common mutation is present in only about 70% of CF chromosomes has led to much debate within the genetics community regarding the potential efficacy, psychological impact, cost effectiveness, and ethics of widespread carrier screening by DNA analysis. As the most common lethal recessive disorder in Caucasians, the sheer numbers involved in such a program would be unprecedented, and the inability to detect 15- 20% of mutations using even a battery of the most common markers raises serous questions about ultimate effectiveness and appropriate counseling mechanisms to convey such complex information. Experience derived from screening programs for other recessive disorders indicates that understanding of and stigmatization by the carrier state may vary significantly among different target populations, depending upon ethnic group, level of education, religion, and socioeconomic status, and may be modified by appropriate counseling. There is general agreement that pilot studies are urgently needed to explore these factors as they apply to CF before large-scale population screening can be introduced. We propose to initiate such a pilot study in Southern California, exploring the technical feasibility and cost-effectiveness of a polymerase chain reaction-based mutation detection method using easily collected dried blood spots. We will screen for the five most common CF mutations (deltaF508, G551D, R553X, G542X, N1303K) in approximately 12,000 women of reproductive age and in the mates of those who test positive. Our West Coast target population is unique in that it is among the most ethnically diverse in the U.S. and because it includes large numbers of Hispanic Americans and Asian Americans, two groups which have not been studied extensively for either their Cf allele frequencies or their response to screening and counseling. Pre- and post-test questionnaires will be used to determine level of understanding of CF, predictors of consent to testing, and emotional responses to implications of the DNA findings in the various ethnic and socioeconomic subgroups. Strategies of pre- and post-test counseling will be compared for their effectiveness. In cooperation with other funded groups, our findings should help to complete a realistic national picture of what we can expect from large-scale population screening, and can serve as a paradigm for the introduction of other DNA-based genetic tests for common diseases in the coming years.
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