An expanded CAG repeat sequence in spinocerebellar ataxia type 7.
Authors:
- K LindbladKLK Lindblad
- M L SavontausMSM L Savontaus
- G StevaninGSG Stevanin
- M HolmbergMHM Holmberg
- K DigreKDK Digre
- C ZanderCZC Zander
- H EhrssonHEH Ehrsson
- G DavidGDG David
- A BenomarABA Benomar
- E NikoskelainenENE Nikoskelainen
- Y TrottierYTY Trottier
- G HolmgrenGHG Holmgren
Open Access
- 1 October 1996
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 6 (10) , 965-971
Abstract
Expanded CAG repeat sequences have been identified in the coding region of genes mutated in several neurodegenerative disorders, including spinocerebellar ataxia type 1 and Machado-Joseph disease. In all disorders described to date the CAG expansion codes for an elongated polyglutamine chain. An increased polyglutamine chain size leads to a more severe disease, thus correlating with the genetic anticipation seen in repeat expansion disorders. Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant spinocerebellar ataxia with anticipation and a progressive degeneration of the cerebellar cortex. Using repeat expansion detection (RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, we have analyzed 8 SCA7 families for the presence of CAG repeat expansions. RED products of 150-240 bp were found in all affected individuals and found to cosegregate with the disease (P < 0.000001, n = 66), indicating strongly that a CAG expansion is the cause of SCA7. On the basis of a previously established correlation between RED product sizes and actual repeat sizes in Machado-Joseph disease, we were able to estimate the average expansion size in SCA7 to be 64 CAG copies.Keywords
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