The research plan is to provide centralized access to a resource of well-defined cystic fibrosis (CF) families from whom biological specimens can be obtained for use in genetic studies. A unique Amish-Mennonite Kindred (over 10,000 people) has been identified. 36 CF-affected individuals (19 living), in 22 sibships containing 62 non-affected siblings, have been ascertained. Family units reside in 9 States and in Canada. Family members have been contacted and are participating in CF genetic research. 96 (13 with CF) have provided blood specimens from which lymphoblastoid cell line cultures have been established. The clinical phenotypic spectrum of CF is broad, suggesting that more than one gentic mechanism may be responsible for what is regarded generically as CF. It is very likely that a single CF locus is common to all affected sibships within the resource kindred. This information will be helpful in the interpretation of laboratory data.
The specific aims are: (1) to characterize the clinical phenotypes and statuses of 36 ascertained CF kindred members, (2) to continue the search for other CF affected kindred members, (3) to perform sweat tests on all donors of biological specimens, and (4) to continue collection of patient blood samples and to maintain a repository of transformed lymphoblastoid cell lines (and/or fibroblast cell cultures) for collaborative investigations. The methodology includes the maintenance and expansion of networks of communication which exist between members of the kindred, their genealogists, their physicians and the program director. Collaborating laboratory scientists are studying these cells and DNA prepared from them in order to find a restriction fragment length polymorphism (RFLP) closely linked to the CF gene locus and/or a primary gene product. When found, a test for detection of the CF heterozygote and for prenatal diagnosis of the CF homozygote will be developed. More direct approaches to understanding the basic abnormality and the pathogenesis of CF will become possible, and rational specific therapies can be developed. This cascade of events will be expedited by the opportunity to study this unique resource kindred and the biological specimens obtained from them. Family members will be surveyed with regard to their presesnt attitudes about CF gene testing and their future interests in using a CF gene test for reproductive decision-making.
