GENETIC-ANALYSIS OF IDIOPATHIC TORSION DYSTONIA IN ASHKENAZI JEWS ANDTHEIR RECENT DESCENT FROM A SMALL FOUNDER POPULATION

We have examined data on six closely linked microsatellite loci on chr omosome 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 founde r mutation, which we estimate first appeared approximately 350 years a go. We also show that carriers preferentially originate from the north ern part of the historic Jewish Pale of settlement (Lithuania and Byel orussia). The recent origin of this dominant mutation and its current high frequency (between 1/6,000 and 1/2,000) suggest that the Ashkenaz i population descends from a limited group of founders, and emphasize the importance of genetic drift in determining disease allele frequenc ies in this population.