DNA analysis of cystic fibrosis genotypes in relatives with equivocal sweat test results

Restriction fragment length polymorphism linkage analysis of cystic fibrosis (CF) is used primarily for pre-pregnancy family studies, prenatal diagnosis, and carrier testing among close relatives of an affected individual. We undertook to clarify the status of six individuals with borderline or elevated sweat chloride concentrations and a relative with CF by testing for haplotype sharing. Their families and physicians expressed concern about management of these generally asymptomatic individuals. We typed DNA from family members with pJ3.11, pXV2C, pKM19, pmetH, pmetD, and p7C22. Each family was fully informative, enabling us to track the CF region of chromosome 7. Our analysis identified five individuals from four families as CF heterozygotes. A sixth individual, whose maternal first cousin died from CF, has the same haplotype as six of his seven healthy siblings, and thus we predict that he is unaffected. These family studies are a novel application of an emerging genetic technology. DNA linkage analysis is useful for elucidation of the CF genotype in families where the clinical features are equivocal and management is an issue.