Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10 (original) (raw)

Nature Genetics volume 26, pages 191–194 (2000)Cite this article

Abstract

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13–qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, _P_=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.

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

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Matsuura, T. et al. Mapping of the gene for a novel spinocerebellar ataxia with pure cerebellar signs and epilepsy. Ann. Neurol. 45, 407–411 (1999).
    Article CAS Google Scholar
  2. Zu, L., Figueroa, K.P., Grewal, R. & Pulst, S.M. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am. J. Hum. Genet. 64, 594–599 (1999).
    Article CAS Google Scholar
  3. Orr, H.T. et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genet. 4, 221–226 (1993).
    Article CAS Google Scholar
  4. Pulst, S.M. et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nature Genet. 14, 269–276 (1996).
    Article CAS Google Scholar
  5. Sanpei, K. et al. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nature Genet. 14, 277–284 (1996).
    Article CAS Google Scholar
  6. Imbert, G. et al. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nature Genet. 14, 285–291 (1996).
    Article CAS Google Scholar
  7. Kawaguchi, Y. et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genet. 8, 221–228 (1994).
    Article CAS Google Scholar
  8. David, G. et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nature Genet. 17, 65–70 (1997).
    Article CAS Google Scholar
  9. Zhuchenko, O. et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α 1A-voltage-dependent calcium channel. Nature Genet. 15, 62–69 (1997).
    Article CAS Google Scholar
  10. Holmes, S.E. et al. Expansion of a novel CAG trinucleotide repeat in the 5′ region of P2R2B is associated with SCA12. Nature Genet. 23, 391–392 (1999).
    Article CAS Google Scholar
  11. Koob, M.D. et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nature Genet. 21, 379–384 (1999).
    Article CAS Google Scholar
  12. Matsuura, T., Watase, K., Nagamitsu, S., Zoghbi, H.Y. & Ashizawa, T. Fine mapping of the spinocerebellar ataxia type 10 region and search for a polyglutamine expansion. Ann. Neurol. 46, 480 (1999).
    Google Scholar
  13. Dunham, I. et al. The DNA sequence of human chromosome 22. Nature 402, 489–495 (1999).
    Article CAS Google Scholar
  14. Schalling, M., Hudson, T.J., Buetow, K.H. & Housman, D.E. Direct detection of novel expanded trinucleotide repeats in the human genome. Nature Genet. 4, 135–139 (1993).
    Article CAS Google Scholar
  15. Trottier, Y. et al. Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature 378, 403–406 (1995).
    Article CAS Google Scholar
  16. Bidichandani, S.I., Ashizawa, T. & Patel, P.I. The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am. J. Hum. Genet. 62, 111–121 (1998).
    Article CAS Google Scholar
  17. Wells, R.D. & Warren, S.T. Genetic Instability and Hereditary Neurological Diseases (Academic, San Diego, 1998).
    Google Scholar
  18. Koob, M.D. et al. Rapid cloning of expanded trinucleotide repeat sequences from genomic DNA. Nature Genet. 18, 72–75 (1998).
    Article CAS Google Scholar
  19. Ikeuchi, T. et al. A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q. Genomics 49, 321–326 (1998).
    Article CAS Google Scholar
  20. Breschel, T.S. et al. A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on chromosome 18q21.1. Hum. Mol. Genet. 6, 1855–1863 (1997).
    Article CAS Google Scholar

Download references

Acknowledgements

We thank the patients for cooperation; L.P.W. Ranum for confirming RED analysis results; and The Sanger Centre for BAC, PAC and cosmid clones located in the chromosome 22 region of interest. This work was supported by grants from the Oxnard Foundation/National Ataxia Foundation (T.A.), National Ataxia Foundation (S.M.P.), Howard Hughes Medical Institute (H.Y.Z.), the National Institute of Health/NICHD HD29256 (D.L.N.), MRRC HD24064, NINDS NS27699 and GCRCM01RR00188 (H.Y.Z.), NS29709 (J.L.N.), NS33123 and NS37883 (S.M.P.), and K12-AG0052-01 (R.P.G.). The fellowship of T.M. was partly supported by the Cell Science Research Foundation, the Yamanouchi Foundation for Research on Metabolic Disorders and the Nakayama Foundation for Human Science, Japan. D.L.B. was supported by an American Epilepsy Society Fellowship.

Author information

Author notes

  1. Takanori Yamagata and Daniel L. Burgess: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
    Tohru Matsuura, Daniel L. Burgess, Mehrdad Khajavi, Caleb F. Davis, Jeffrey L. Noebels & Tetsuo Ashizawa
  2. Division of Neurosciences, Baylor College of Medicine, Houston, Texas, USA
    Daniel L. Burgess, Caleb F. Davis & Jeffrey L. Noebels
  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
    Takanori Yamagata, Kei Watase, Alanna E. McCall, Jeffrey L. Noebels, David L. Nelson & Huda Y. Zoghbi
  4. Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    Huda Y. Zoghbi
  5. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA
    Huda Y. Zoghbi
  6. Neurology Service, Veterans Affairs Medical Center, Houston, Texas, USA
    Tohru Matsuura, Mehrdad Khajavi & Tetsuo Ashizawa
  7. Instituto Nacional de Neurologia y Neurocirugia, Mexico, D.F., Mexico
    Astrid Rasmussen & Elisa Alonso
  8. New Jersey Neuroscience Institute, JFK Medical Center, Edison, New Jersey, USA
    Raji P. Grewal
  9. Division of Neurology, Rose Moss Laboratory for Parkinson and Neurodegenerative Diseases, Burns and Allen Research Institute, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA
    Lan Zu & Stefan M. Pulst
  10. Private practice, Houston, Texas, USA
    Madhureeta Achari

Authors

  1. Tohru Matsuura
  2. Takanori Yamagata
  3. Daniel L. Burgess
  4. Astrid Rasmussen
  5. Raji P. Grewal
  6. Kei Watase
  7. Mehrdad Khajavi
  8. Alanna E. McCall
  9. Caleb F. Davis
  10. Lan Zu
  11. Madhureeta Achari
  12. Stefan M. Pulst
  13. Elisa Alonso
  14. Jeffrey L. Noebels
  15. David L. Nelson
  16. Huda Y. Zoghbi
  17. Tetsuo Ashizawa

Corresponding author

Correspondence toTetsuo Ashizawa.

Rights and permissions

About this article

Cite this article

Matsuura, T., Yamagata, T., Burgess, D. et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.Nat Genet 26, 191–194 (2000). https://doi.org/10.1038/79911

Download citation

This article is cited by