title: Evaluating noncoding nucleotide repeat expansions in amyotrophic lateral sclerosis.
abstract: Intermediate-length polyglutamine expansions in ataxin 2 are a risk factor for amyotrophic lateral sclerosis (ALS). The polyglutamine tract is encoded by a trinucleotide repeat in a coding region of the ataxin 2 gene (ATXN2). Noncoding nucleotide repeat expansions in several genes are also associated with neurodegenerative and neuromuscular diseases. For example, hexanucleotide repeat expansions located in a noncoding region of C9ORF72 are the most common cause of ALS. We sought to assess a potential larger role of noncoding nucleotide repeat expansions in ALS. We analyzed the nucleotide repeat lengths of 6 genes (ATXN8, ATXN10, PPP2R2B, NOP56, DMPK, and JPH3) that have previously been associated with neurologic or neuromuscular disorders, in several hundred sporadic patients with ALS and healthy control subjects. We report no association between ALS and repeat length in any of these genes, suggesting that variation in the noncoding repetitive regions in these genes does not contribute to ALS.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Standford, CA, USA; Stanford Neuroscience Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Figley
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Standford, CA, USA; Presentation High School, San Jose, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Standford, CA, USA. Electronic address: agitler@stanford.edu.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gitler
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000067736:Ataxin-10; D000067528:Ataxins; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D065636:Myotonin-Protein Kinase; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D054648:Protein Phosphatase 2 / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C503889:ATXN10 protein, human; C539186:ATXN8 protein, human; D000067736:Ataxin-10; D000067528:Ataxins; C585517:DMPK protein, human; C486600:NOP56 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D022661:RNA, Untranslated; C097188:polyglutamine; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; C505936:PPP2R2B protein, human; D054648:Protein Phosphatase 2
keywords: ALS; Ataxin; Noncoding; Nucleotide repeat expansion; polyQ