Linkage studies between polymorphic markers on chromosome 4 and cystic fibrosis.

It has been suggested that a protein factor causing ciliary dyskinesis is a marker for the basic defect causing cystic fibrosis (CF), and that the structural gene for this protein may be (amongst others) on human chromosome 4. We have isolated two DNA sequences mapping to chromosome 4 which show restriction fragment length polymorphisms (RFLPs), and have followed their segregation in families in which cystic fibrosis occurs. Eleven families with a total of 30 children with CF and ten unaffected sibs were studied. We have also followed the inheritance of RFLPs revealed by two probes mapping to chromosome 4 and obtained from another laboratory, polymorphisms revealed by cloned coding sequences for albumin and fibrinogen, and the inheritance of the MNS blood group. Although the level of albumin is altered in children with CF, the gene does not segregate with CF, and therefore albumin can be excluded as the site of the basic defect. Tight linkage with CF was not found with any of the seven markers investigated, and therefore, assuming that the markers (excepting MNS and fibrinogen) are unlinked to one another, approximately half of the total genetic length of chromosome 4 may be excluded.