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Article
Nature Genetics  9, 152 - 159 (1995)
doi:10.1038/ng0295-152

Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population

Neil Risch1, 9, Deborah de Leon3, Laurie Ozelius4, 7, Patricia Kramer6, Laura Almasy2, Burton Singer8, Stanley Fahn3, Xandra Breakefield4, 5 & Susan Bressman3

  1Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA

  2Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA

  3Dystonia Clinical Research Center, Neurological Institute, Columbia Presbyterian Medical Center, New York, New York 10032, USA

  4Molecular Neurogenetics Unit, Neuroscience Center (Neurology), Massachusetts General Hospital East, Charlestown, Massachusetts, USA 02129

  5Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA 02115

  6Department of Neurology, Oregon Health Sciences University, Portland, Oregon, USA 97201

  7Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA 02115

  8Office of Population Research, Princeton University, Princeton, NJ 08544

  9Current address: Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305

 Correspondence should be addressed to N.R.

We have examined data on six closely linked microsatellite loci on chromosome 9q34 from 59 Ashkenazi Jewish families with idiopathic torsion dystonia (ITD). Our data show that the vast majority (>90%) of early−onset ITD cases in the Ashkenazi population are due to a single founder mutation, which we estimate first appeared approximately 350 years ago. We also show that carriers preferentially originate from the northern part of the historic Jewish Pale of settlement (Lithuania and Byelorussia). The recent origin of this dominant mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest that the Ashkenazi population descends from a limited group of founders, and emphasize the importance of genetic drift in determining disease allele frequencies in this population.

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