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Nucleic Acids Research, 1990, Vol. 18, No. 23 7071-7075
© 1990

Articles

Cosmid walking and chromosome jumping in the region of PKD1 reveal a locus duplication and three CpG islands

Gerald A.J. Gillespie1, Gregory G. Germino1, Stefan Somio1, Debra Weinstat-Saslow1, Martijn H. Breuning2 and Stephen T. Reeders1,3

1Yale University School of Medicine New Haven, CT, USA 2University of Leiden Leiden, The Netherlands 3Howard Hughes Medical Institute, Yale University New Haven, CT, USA

Received July 16, 1990. Revised October 15, 1990. Accepted October 15, 1990.

The locus responsible for the most common form of autosomal dominant polycystic kidney disease (PKD1) is located on chromosome l6p13.3. Genetic mapping studies indicate that PKD1 is flanked on the proximal side by the DNA marker 26.6 (D16S125). Here we show that 26.6 has undergone a locus duplication and that the two loci are less than 150kb apart. One of the two loci contains a polymorphic Taql site that has been used In genetic studies and represents the proximal boundary for the PKD1 locus. We demonstrate that the polymorphic locus is the more proximal of the two 26.6-hybridizing loci. Therefore, four cosmids isolated from the distal 26.6-hybridizing locus contain candidate sequences for the PKD1 gene. These cosmids were found to contain two CpG islands that are likely markers for transcribed regions. A third CpG island was detected and cloned by directional chromosome jumping.


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T C Burn, T D Connors, T J Van Raay, W R Dackowski, J M Millholland, K W Klinger, and G M Landes
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