We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1).
Our results show that to avoid misinterpretation it is important to investigate the occurrence of an alpha-gene deletion when polymorphisms situated in the alpha-globin locus are used for linkage studies on ADPKD.
In these families, linkage analysis was carried out with a cloned DNA sequence from the alpha-globin locus known to be closely linked to the disease gene in adult onset ADPKD.
Hitherto, mutations that lead to autosomal dominant adult-type polycystic kidney disease have been found to be linked to the alpha-globin genes on the short arm of chromosome 16.
The results show that APKD is closely linked to the PGP locus on the short arm of chromosome 16 (16p13----p12), which is consistent with the previously reported linkage both to PGP and to the alpha globin locus.
Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster.
Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05).