Related Experiment Video
Updated: Dec 8, 2025

Measuring RAN Peptide Toxicity in C. elegans
Published on: April 30, 2020
ATXN1 repeat expansions confer risk for amyotrophic lateral sclerosis and contribute to TDP-43 mislocalization
Gijs H P Tazelaar1, Steven Boeynaems2,3,4, Mathias De Decker2,3
1Department of Neurology, Brain Center Rudolf Magnus, University Medical Center, Utrecht, University of Utrecht, 3508 GA, Utrecht, The Netherlands.
Abstract:
Increasingly, repeat expansions are being identified as part of the complex genetic architecture of amyotrophic lateral sclerosis. To date, several repeat expansions have been genetically associated with the disease: intronic repeat expansions in C9orf72, polyglutamine expansions in ATXN2 and polyalanine expansions in NIPA1. Together with previously published data, the identification of an amyotrophic lateral sclerosis patient with a family history of spinocerebellar ataxia type 1, caused by polyglutamine expansions in ATXN1, suggested a similar disease association for the repeat expansion in ATXN1. We, therefore, performed a large-scale international study in 11 700 individuals, in which we showed a significant association between intermediate ATXN1 repeat expansions and amyotrophic lateral sclerosis (P = 3.33 × 10-7). Subsequent functional experiments have shown that ATXN1 reduces the nucleocytoplasmic ratio of TDP-43 and enhances amyotrophic lateral sclerosis phenotypes in Drosophila, further emphasizing the role of polyglutamine repeat expansions in the pathophysiology of amyotrophic lateral sclerosis.
Related Concept Videos
Non-LTR Retrotransposons
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
RNA Splicing
Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...

