Linkage analysis in eight CF families shows no evidence of cosegregation between CF and the gene for factor X, strongly suggesting that the locus for the defect causing cystic fibrosis is not at 13q34.
There are significant allelic associations between CF, MET, D7S8 and D7S16; these allelic associations affect the risk of random individuals to be carriers of CF.
However, examination of the ratio of cystic fibrosis antigen to lactoferrin in serum samples from cystic fibrosis heterozygotes suggests that there is some specific association between this antigen and the cystic fibrosis gene.
To investigate a possible role for a defective VIP-gene in cystic fibrosis, we have used a panel of rodent-human hybrid cells, retaining defined complements of human chromosomes to localize the VIP-gene to the human chromosome region 6p21----6qter.
A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF.
The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.
The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.
Together with the previously identified markers, MET, D7S8, D7S13 and D7S16, these new markers should provide a fine genetic and physical map for the chromosomal region surrounding CF.
These data and in situ chromosomal hybridization analysis would indicate that MET and, therefore, the cystic fibrosis locus are located at bands q31-q32 on human chromosome 7.
Preliminary large-scale restriction mapping of the fragment showed that the NotI polymorphic site is 200-370 kb distant from the MET locus; thus it defines a new polymorphic locus in the CF region.
Using pulsed-field gel electrophoresis we have determined the physical order of these markers to be cen-7C22-Lcn2-met-C2/5-XV-2c-CS.7-J3.11-tel and have localized the CF mutation to an interval of less than 1500 kb.
We also show that other DNA restriction fragment length polymorphism markers tightly linked with the inheritance of cystic fibrosis are deleted on der(7).
Our previous linkage analysis suggested that the DNA segment D7S122 is located between MET and D7S8, the two genetic markers that are thought to flank the cystic fibrosis locus (CF).
Data for XV2c and MET markers in 16 American black patients and their families revealed a different haplotype distribution and LD pattern with the CF locus.
In a 1:4 risk family, the usefulness of probes at the D7S23 locus for prenatal diagnosis of cystic fibrosis is discussed by comparison with probes at the MET, D7S8, and D7S18 loci that did not allow accuracy in this family.