Cystic fibrosis: linked DNA markers in prenatal diagnosis and carrier detection
Voss, R.; Hertz, B.; Chemke, J.; Katznelson, D.; Yahav, Y.
Harefuah 114(7): 317-320
1988
ISSN/ISBN: 0017-7768 PMID: 3371783 Document Number: 309080
Cystic fibrosis is the most frequent genetic disease among Caucasians. The gene of the disease has not been identified, but it has been mapped to chromosome 7. The use of genetic polymorphisms closely linked to the gene of cystic fibrosis permits DNA analysis in families with at least one affected individual. Prenatal diagnosis and identification of heterozygous carriers is possible in fully or half "informative" families, in which the polymorphisms of genes in the neighborhood of the CF gene can be used as indicators of all or half of the 4 parental #7 chromosomes. Thus all 3 genotypes in the CF locus can be deduced in some families. We studied 27 Israeli families using at least 3 polymorphisms closely linked to the cystic fibrosis gene and performed prenatal diagnosis in 8 families with a 25% risk of having another affected child. 89% of the families were informative. Of 61 children, 29 were phenotypically normal. Of these, 17 were heterozygous carriers, 5 were normal homozygotes and in 7 it was not possible to determine whether or not they were carriers. The proportion of heterozygotes found among all the healthy children (59%) is that expected among sibs of affected children (2/3). Prenatal diagnosis in 8 families showed good correlation betwen DNA analysis and amniotic fluid microvillar enzymes. This study demonstrates the importance of recombinant DNA techniques in prenatal diagnosis and in the detection of heterozygotes in families with cystic fibrosis, despite our ignorance of the basic defect itself.