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Nucleic Acids Research, 1988, Vol. 16, No. 24 11769-11780
© 1988

MOLECULAR BIOLOGY

Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4

William L. Whaley, Frank Michiels1, Marcy E. MacDonald, Donna Romano, Michael Zimmer1, Barbara Smith2, Julie Leavitt, Maja Bucan1, Jonathan L. Haines, T. Conrad Gilliam, Gunther Zehetner1, Cassandra Smith3, Charles R. Cantor3, Anna-Maria Frischauf1, John J. Wasmuth2, Hans Lehrach1 and James F. Gusella

Neurogenetics Laboratory, Massachusetts General Hospital and Department of Genetics, Harvard Medical School Boston, MA 02114, USA

Received August 30, 1988. Revised November 16, 1988. Accepted November 16, 1988.

The dominant gene defect in Huntington's disease (HD) is linked to the DNA marker D4S10, near the telomere of the chromosome 4 short arm. Two other markers, D4S43 and D4S95, are closer, but still proximal to the HD gene in 4p16.32. We have characterized a new locus, D4S114, identified by cloning the end of a NotI fragment resolved by pulsed-field gel electrophoresis. D4S114 was localized distal to D4S43 and D4S95 by both physical and genetic mapping techniques. The ‘end’-clone overlaps a previously isolated NotI ‘linking’ clone, and is within 150 kb of a second ‘linking’ clone defining D4S113. Restriction fragment length polymorphisms for D4S113 and D4S114, one of which is identical to a SacI polymorphism detected by the anonymous probe pB5731B-C (D4S98), were typed for key crossovers in HD and reference pedigrees. The data support the locus order D4S10-(D4S43, D4S98, D4S95)-D4S98/S114/S113-HD-telemere. The D4S98/S114/S113 cluster therefore represents the nearest cloned sequences to HD, and provides a valuable new point for launching directional cloning strategies to isolate and characterize this disease gene.

1Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK

2Department of Biological Chemistry, University of California, Irvine, CA 92717

3Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA


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