Fine Localization of the Torsion Dystonia Gene (DYT1) on Human Chromosome 9q34: YAC Map and Linkage Disequilibrium
- Laurie J. Ozelius1,
- Jeffrey Hewett1,
- Patricia Kramer4,
- Susan B. Bressman2,
- Christo Shalish1,
- Deborah de Leon2,
- Marc Rutter1,
- Neil Risch3,
- Mitchell F. Brin7,
- Elena D. Markova5,
- Svetlana A. Limborska6,
- Irina A. Ivanova-Smolenskaya5,
- Mary Kay McCormick1,
- Stanley Fahn2,
- Alan J. Buckler1,
- James F. Gusella1, and
- Xandra O. Breakefield1,8
- 1Molecular Neurogenetics Unit, Massachusetts General Hospital and Departments of Neurology and Genetics, Harvard Medical School, Boston, Massachusetts 02114; 2Dystonia Clinical Research Center, Department of Neurology, Columbia Presbyterian Medical Center, New York, New York 10032; 3Department of Genetics, Stanford University, Stanford, California 94305; 4Department of Neurology, Oregon Health Sciences University, Portland, Oregon 97201; 5Institute of Neurology, Moscow, 123367 Russia; 6Institute of Molecular Genetics, Moscow, 123367 Russia; 7Department of Neurology, Movement Disorders Center, Mt. Sinai Hospital, New York, New York 10029
Abstract
The DYT1 gene, which maps to chromosome 9q34, appears to be responsible for most cases of early-onset torsion dystonia in both Ashkenazic Jewish (AJ) and non-Jewish families. This disease is inherited in an autosomal dominant mode with reduced penetrance (30%–40%). The abnormal involuntary movements associated with this disease are believed to be caused by unbalanced neural transmission in the basal ganglia. Previous linkage disequilibrium studies in the AJ population placed the DYT1 gene in a 2-cM region between the loci D9S62a and ASS. A YAC contig has now been created spanning 600 kb of this region including D9S62a. The location of the DYT1 gene has been refined within this contig using several new polymorphic loci to expand the linkage disequilibrium analysis of the AJ founder mutation. The most likely location of theDYT1 gene is within a 150 kb region between the lociD9S2161 and D9S63.
Footnotes
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↵8 Corresponding author.
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E-MAIL breakefield{at}helix.mgh.harvard.edu; FAX (617) 726-5736.
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- Received December 24, 1996.
- Accepted March 12, 1997.
- Cold Spring Harbor Laboratory Press
