Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Spinocerebellar ataxia type 1

H Y Zoghbi1

  • 1Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.

Clinical Neuroscience (New York, N.Y.)
|January 1, 1995
PubMed
Summary

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expanded CAG repeats in the ataxin-1 gene. This genetic mutation leads to neuronal loss and progressive symptoms, suggesting a gain of function mechanism.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The clinical and genetic spectrum of spinocerebellar ataxia 14.

Neurology·2005
Same author

Mutations in exon 1 of MECP2 are a rare cause of Rett syndrome.

Journal of medical genetics·2005
Same author

Spinocerebellar ataxia type 10 is rare in populations other than Mexicans.

Neurology·2002
Same author

Reduction of Purkinje cell pathology in SCA1 transgenic mice by p53 deletion.

Neurobiology of disease·2001
Same author

Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome.

Brain & development·2001
Same author

Requirement of Math1 for secretory cell lineage commitment in the mouse intestine.

Science (New York, N.Y.)·2001

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder.
  • Characterized by ataxia, dysarthria, ophthalmoparesis, amyotrophy, and neuropathy.
  • Symptoms typically manifest in the third or fourth decade, with anticipation in juvenile cases.

Purpose of the Study:

  • Identify the genetic basis of SCA1.
  • Characterize the mutation responsible for SCA1.
  • Propose a pathogenetic model for SCA1.

Main Methods:

  • Positional cloning approach to identify the SCA1 gene.
  • Analysis of CAG trinucleotide repeat expansions in the ataxin-1 gene.
  • Comparison of repeat configurations in normal and SCA1 alleles.

Main Results:

  • The SCA1 gene was mapped to chromosome 6p.
  • The mutation involves an expanded CAG trinucleotide repeat encoding a polyglutamine tract in ataxin-1.
  • Normal alleles have 6-39 repeats (interrupted by CAT units), while SCA1 alleles have 40-81 repeats (perfect CAG configuration).
  • Both normal and expanded alleles are transcribed, indicating transcription efficiency is not impaired.

Conclusions:

  • The expanded polyglutamine tract in ataxin-1 is the disease-causing mutation in SCA1.
  • Neurodegeneration in SCA1 may result from a gain of function mechanism.
  • Aberrant interactions involving the expanded polyglutamine tract could mediate neurotoxicity.

Related Experiment Videos