Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
Purchase on Springer Link
Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Goodman, R.M., Disorders among the Jewish People. (Johns Hopkins University Press, Baltimore, 1978).
Motulsky, A.G. Possible selective effects of urbanization on Ashkenazi Jews. In Genetic Diseases among Ashkenazi Jews, eds Goodman, R. A. & Motulsky, A. G. 301–314 (Raven Press, New York, 1979).
Chakravarti, A. & Charaborty, R. Elevated frequency of Tay-Sachs disease among Ashkenazi Jews unlikely by genetic drift alone. Am. J. hum. Genet. 30, 256–261 (1978).
Yokoyama, S. Role of genetic drift in the high frequency of Tay-Sachs disease among Ashkenazi Jews. Ann. hum. Genet. 43, 133–136 (1979).
Rotter, J.I. & Diamond, J.M. What maintains the frequencies of human genetic diseases? Nature 329, 289–290 (1987).
Jorde, L. Genetic diseases in the Ashkenazi population: Evolutionary considerations. In Genetic Diversity Among Jews: Diseases and Markers at the DNA Level, eds Bonne-Tamir, B. & Adam, A., 305–318 (Oxford University Press, New York, 1992).
Diamond, J.M. Jewish lysosomes. Nature 368, 291–292 (1994).
Fraikor, A.L. Tay-Sachs disease: genetic drift among the Ashkenazim Jews. Soc Bio 24, 117–134 (1977).
Wagener, D., Cavali-Sforza L.L. & Barakat, R . Ethnic variation of genetic disease: roles of drift for recessive lethal genes. An. J. hum. Genet. 30, 262–270 (1978).
Chase, G.A. & McKusick, V.A. Controversy in human genetics: founder effect in Tay-Sachs disease. Am. J. hum. Genet. 24, 339–340 (1972).
Fahn, S. Generalized dystonia: concept and treatment. Clin. Neuropharmacol. 9, 537–548 (1986).
Zeman, W. & Dyken, P. Dystonia musculorum deformans: clinical, genetic and pathoanatomical studies. Psychiatr. Neurol. Neurochir. 70, 77–121 (1967).
Korczyn, D. et al. Torsion dystonia in lsrael. Ann. Neurol. 8, 387–391 (1980).
Bressman, S.B. et al. Idiopathic dystonia among Ashkenazi Jews: evidence for autosomal dominant inheritance. Ann. Neurol. 26, 612–620 (1989).
Eldridge, R. The torsion dystonias: literature review: genetic and clinical studies. Neurology 20, 1–78 (1970).
Eldridge, R. & Gottlieb, R. The primary hereditary dystonias: genetic classification of 768 families and revised estimate of gene frequency, autosomal recessive form, and selected bibliography. Adv. Neurol. 14, 457–474 (1976).
Zilber, N. et al. Inheritance of idiopathic torsion dystonia among Jews. J. Med. Genet. 218, 13–20 (1984).
Risch, N. et al. Segregation analysis of Idiopathic torsion dystonia in Ashkenazi Jews suggests autosomal dominant inheritance. Am. J. Hum. Genet. 46, 533–538 (1990).
Ozelius, L. et al. Human gene for torsion dystonia located on chromosome 9q32-34. Neuron 2, 1427–1434 (1989).
Kramer, P.L. et al. Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32-34. Ann. Neurol. 27, 114–120 (1990).
Ozelius, L. et al. Strong allelic association between the torsion dystonia gene (DYT1) and loci on chromosome 9q34 in Ashkenazi Jews. Am. J. Hum. Genet. 50, 619–628 (1992).
Kwaitkowski D. et al. Construction of a GT polymorphism map of human 9q. Genomics 12, 229–240 (1992).
Bressman, S.B. et al. Idiopathic torsion dystonia in Ashkenazi Jews: clinical characterization of a founder mutation. Ann. Neurol. 36, 771–777 (1994).
Serre, J.L. et al. Studies of RFLP closely linked to the cystic fibrosis locus throughout Europe lead to new considerations in population genetics. Hum. Genet 84, 449–454 (1990).
Cox, T.K. et al. Mapping of the cystic fibrosis gene using putative ancestral recombinants. Am. J. Hum. Genet. 45, A136 (1989).
Hastbacka, J. et al. Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nature Genet. 2, 204–211 (1992).
Schwalbe, W. Eine eigentumliche tonische Krampffoum mit hysterischen Symptonen. Medicin und chirurgie [Dissertation]. (Unlversitats-Buchdrukerei von Gustav Schade, Berline, 1908).
American Jewish Yearbook (The Jewish Publication Society of America, Philadelphia, 1992).
Fletcher, N.A., Harding, A.E. & Marsden, C.D. A genetic study of idiopathic torsion dystonia in the United Kingdom. Brain 113, 379–395 (1990).
U.S. Bureau of the Census. Statistical Abstract of theUnited States: 1993 (113th edition). (Washington, D. C., 1993).
Weinryb, B.D. The Jews of Poland. A social and Economic History of the Jewish Community of Poland from 1100 to 1800. (The Jewish Publication Society of America, Philadelphia, 1972).
Blumenfeld, A. et al. Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nature Genet. 4, 160–164 (1993).
Ellis, A. et al. Linkage disequillbrium between the FES, D15S727, and BLM Loci in Ashkenazi Jews with Bloom Syndrome. Am. J. hum. Genet. 55, 453–460 (1994).
Haines, J.L. et al. A genetic linkage map of chromosome 17. Genomics 8, 1–6 (1990).
Anderson, M. & Gusella, J. Use of cyclosporin A establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro 29, 856–858 (1984).
Breakefield, X. et al. Linkage analysis in a family with domlnantly-inherited torsion dystonia: exclusion of the pro-opiomelanocortln and glutamlc acid decarboxyiase genes and other chromosomal regions using DNA polymorphisms. J. Neurogenetics. 3, 159–175 (1986).
Henske, E. et al. A high-resolution linkage map of human 9q34. J. Genomics 17, 587–591 (1993).
Ott, J. A computer program for linkage analysis of general human pedigrees. Am. J. Hum. Genet. 28, 528–529 (1976).
Bengtsson, B.O. & Thomson, G. Measuring the strength of associations between HLA antigens and diseases. Tissue Antigens 18, 356–363 (1981).
Thomson, G. A review of theoretical aspects of HLA and disease associations. Theor. Pop. Biol. 20, 168–208 (1981).
Ott, J. Analysis of Human Genetic Linkage. (The Johns Hopkins University Press, Baltimore. 1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Risch, N., Leon, D., Ozelius, L. et al. Genetic analysis of idiopathic torsion dystonia in Ashkenazi Jews and their recent descent from a small founder population. Nat Genet 9, 152–159 (1995). https://doi.org/10.1038/ng0295-152
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0295-152
This article is cited by
-
Baseline characteristics in the Israel refraction, environment, and devices (iREAD) study
Scientific Reports (2023)
-
The importance of genetic testing for dystonia patients and translational research
Journal of Neural Transmission (2021)
-
Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene
European Journal of Human Genetics (2021)
-
Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal
npj Genomic Medicine (2020)
-
Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population
Scientific Reports (2019)