A proposed model for the inheritance of cystic fibrosis. pp. 291-307.

To geneticists, cystic fibrosis, perhaps the most frequently encountered genetic disease among 
Caucasians of European origin, presents an enigmatic dilemma on various levels. 
Those problem areas which complicate our understanding of this disease include 
methods of diagnosis, ascertainment, and analysis and interpretation of data. In 
spite of an apparently clear-cut mode of inheritance (autosomal recessive), several 
conceptual difficulties exist in the acceptance of this formal transmission pattern. 
The most pressing problem of all, perhaps, is the population genetics 
of CF. The fact that a lethal gene may be maintained 
at such elevated frequencies and restricted to given population groups represents 
a seemingly genetic paradox. Our aim is to review some of 
the problems encountered in a genetic study of CF and to 
propose a theoretical model which may help in their elucidation. Topics 
discussed include problems of diagnosis, ascertainment, and data analysis; family studies 
and inferences as to the mode of inheritance; population studies; and 
a proposed model for the inheritance of CF. The main tenet 
of this model states that CF is determined by dominant alleles 
at two autosomal loci, with interaction between them. 