Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Jan;56(1):193–201.

The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2.

G Stevanin 1, G Cancel 1, A Dürr 1, H Chneiweiss 1, O Dubourg 1, J Weissenbach 1, H M Cann 1, Y Agid 1, A Brice 1
PMCID: PMC1801316  PMID: 7825578

Abstract

SCA3, the gene for spinal cerebellar ataxia 3, was recently mapped to a 15-cM interval between D14S67 and D14S81 on chromosome 14q, by linkage analysis in two families of French ancestry. The SCA3 candidate region has now been refined by linkage analysis with four new microsatellite markers (D14S256, D14S291, D14S280, and AFM343vf1) in the same two families, in which 19 additional individuals were genotyped, and in a third French family. Combined two-point linkage analyses show that the new markers, D14S280 and AFM343vf1, are tightly linked to the SCA3 locus, with maximal lod scores, at recombination fraction, (theta) = .00, of 7.05 and 13.70, respectively. Combined multipoint and recombinant haplotype analyses localize the SCA3 locus to a 3-cM interval flanked by D14S291 and D14S81. The same allele for D14S280 segregates with the disease locus in the three kindreds. This allele is frequent in the French population, however, and linkage disequilibrium is not clearly established. The SCA3 locus remains within the 29-cM region on 14q24.3-q32.2 containing the gene for the Machado-Joseph disease, which is clinically related to the phenotype determined by SCA3, but it cannot yet be concluded that both diseases result from alterations of the same gene.

Full text

PDF
193

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belal S., Cancel G., Stevanin G., Hentati F., Khati C., Ben Hamida C., Auburger G., Agid Y., Ben Hamida M., Brice A. Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus. Neurology. 1994 Aug;44(8):1423–1426. doi: 10.1212/wnl.44.8.1423. [DOI] [PubMed] [Google Scholar]
  2. Cancel G., Dürr A., Stevanin G., Chneiweiss H., Duyckaerts C., Serdaru M., de Toffol B., Agid Y., Brice A. Is DRPLA also linked to 14q? Nat Genet. 1994 Jan;6(1):8–8. doi: 10.1038/ng0194-8. [DOI] [PubMed] [Google Scholar]
  3. Chung M. Y., Ranum L. P., Duvick L. A., Servadio A., Zoghbi H. Y., Orr H. T. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet. 1993 Nov;5(3):254–258. doi: 10.1038/ng1193-254. [DOI] [PubMed] [Google Scholar]
  4. Dürr A., Chneiweiss H., Khati C., Stevanin G., Cancel G., Feingold J., Agid Y., Brice A. Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity. Brain. 1993 Dec;116(Pt 6):1497–1508. doi: 10.1093/brain/116.6.1497. [DOI] [PubMed] [Google Scholar]
  5. Gispert S., Twells R., Orozco G., Brice A., Weber J., Heredero L., Scheufler K., Riley B., Allotey R., Nothers C. Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1. Nat Genet. 1993 Jul;4(3):295–299. doi: 10.1038/ng0793-295. [DOI] [PubMed] [Google Scholar]
  6. Giunti P., Sweeney M. G., Spadaro M., Jodice C., Novelletto A., Malaspina P., Frontali M., Harding A. E. The trinucleotide repeat expansion on chromosome 6p (SCA1) in autosomal dominant cerebellar ataxias. Brain. 1994 Aug;117(Pt 4):645–649. doi: 10.1093/brain/117.4.645. [DOI] [PubMed] [Google Scholar]
  7. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  8. Iizuka R., Hirayama K., Maehara K. A. Dentato-rubro-pallido-luysian atrophy: a clinico-pathological study. J Neurol Neurosurg Psychiatry. 1984 Dec;47(12):1288–1298. doi: 10.1136/jnnp.47.12.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Khati C., Stevanin G., Durr A., Chneiweiss H., Belal S., Seck A., Cann H., Brice A., Agid Y. Genetic heterogeneity of autosomal dominant cerebellar ataxia type 1: clinical and genetic analysis of 10 French families. Neurology. 1993 Jun;43(6):1131–1137. doi: 10.1212/wnl.43.6.1131. [DOI] [PubMed] [Google Scholar]
  10. Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K., Takahashi H., Kondo R., Ishikawa A., Hayashi T. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 1994 Jan;6(1):9–13. doi: 10.1038/ng0194-9. [DOI] [PubMed] [Google Scholar]
  11. Matilla T., Volpini V., Genís D., Rosell J., Corral J., Dávalos A., Molins A., Estivill X. Presymptomatic analysis of spinocerebellar ataxia type 1 (SCA1) via the expansion of the SCA1 CAG-repeat in a large pedigree displaying anticipation and parental male bias. Hum Mol Genet. 1993 Dec;2(12):2123–2128. doi: 10.1093/hmg/2.12.2123. [DOI] [PubMed] [Google Scholar]
  12. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nagafuchi S., Yanagisawa H., Sato K., Shirayama T., Ohsaki E., Bundo M., Takeda T., Tadokoro K., Kondo I., Murayama N. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet. 1994 Jan;6(1):14–18. doi: 10.1038/ng0194-14. [DOI] [PubMed] [Google Scholar]
  14. Neitzel H. A routine method for the establishment of permanent growing lymphoblastoid cell lines. Hum Genet. 1986 Aug;73(4):320–326. doi: 10.1007/BF00279094. [DOI] [PubMed] [Google Scholar]
  15. Orr H. T., Chung M. Y., Banfi S., Kwiatkowski T. J., Jr, Servadio A., Beaudet A. L., McCall A. E., Duvick L. A., Ranum L. P., Zoghbi H. Y. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993 Jul;4(3):221–226. doi: 10.1038/ng0793-221. [DOI] [PubMed] [Google Scholar]
  16. Pulst S. M., Nechiporuk A., Starkman S. Anticipation in spinocerebellar ataxia type 2. Nat Genet. 1993 Sep;5(1):8–10. doi: 10.1038/ng0993-8c. [DOI] [PubMed] [Google Scholar]
  17. Ranum L. P., Duvick L. A., Rich S. S., Schut L. J., Litt M., Orr H. T. Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds, within an 8-cM subregion of chromosome 6p. Am J Hum Genet. 1991 Jul;49(1):31–41. [PMC free article] [PubMed] [Google Scholar]
  18. Stevanin G., Le Guern E., Ravisé N., Chneiweiss H., Dürr A., Cancel G., Vignal A., Boch A. L., Ruberg M., Penet C. A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome 14q24.3-qter: evidence for the existence of a fourth locus. Am J Hum Genet. 1994 Jan;54(1):11–20. [PMC free article] [PubMed] [Google Scholar]
  19. Takiyama Y., Nishizawa M., Tanaka H., Kawashima S., Sakamoto H., Karube Y., Shimazaki H., Soutome M., Endo K., Ohta S. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet. 1993 Jul;4(3):300–304. doi: 10.1038/ng0793-300. [DOI] [PubMed] [Google Scholar]
  20. Volz A., Fonatsch C., Ziegler A. Regional mapping of the gene for autosomal dominant spinocerebellar ataxia (SCA1) by localizing the closely linked D6S89 locus to 6p24.2----p23.05. Cytogenet Cell Genet. 1992;60(1):37–39. doi: 10.1159/000133291. [DOI] [PubMed] [Google Scholar]
  21. Warner T. T., Williams L., Harding A. E. DRPLA in Europe. Nat Genet. 1994 Mar;6(3):225–225. doi: 10.1038/ng0394-225a. [DOI] [PubMed] [Google Scholar]
  22. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
  23. Yakura H., Wakisaka A., Fujimoto S., Itakura K. Letter: Hereditary ataxia and HL-A. N Engl J Med. 1974 Jul 18;291(3):154–155. doi: 10.1056/NEJM197407182910314. [DOI] [PubMed] [Google Scholar]
  24. Zoghbi H. Y., Jodice C., Sandkuijl L. A., Kwiatkowski T. J., Jr, McCall A. E., Huntoon S. A., Lulli P., Spadaro M., Litt M., Cann H. M. The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds. Am J Hum Genet. 1991 Jul;49(1):23–30. [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES