Journal article
Ataxin-2 repeat-length variation and neurodegeneration
Human molecular genetics, v 20(16), pp 3207-3212
15 Aug 2011
PMID: 21610160
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Expanded glutamine repeats of the ataxin-2 (ATXN2) protein cause spinocerebellar ataxia type 2 (SCA2), a rare neurodegenerative disorder. More recent studies have suggested that expanded ATXN2 repeats are a genetic risk factor for amyotrophic lateral sclerosis (ALS) via an RNA-dependent interaction with TDP-43. Given the phenotypic diversity observed in SCA2 patients, we set out to determine the polymorphic nature of the ATXN2 repeat length across a spectrum of neurodegenerative disorders. In this study, we genotyped the ATXN2 repeat in 3919 neurodegenerative disease patients and 4877 healthy controls and performed logistic regression analysis to determine the association of repeat length with the risk of disease. We confirmed the presence of a significantly higher number of expanded ATXN2 repeat carriers in ALS patients compared with healthy controls (OR = 5.57; P = 0.001; repeat length > 30 units). Furthermore, we observed significant association of expanded ATXN2 repeats with the development of progressive supranuclear palsy (OR 5 5.83; P = 0.004; repeat length > 30 units). Although expanded repeat carriers were also identified in frontotemporal lobar degeneration, Alzheimer's and Parkinson's disease patients, these were not significantly more frequent than in controls. Of note, our study identified a number of healthy control individuals who harbor expanded repeat alleles (31-33 units), which suggests caution should be taken when attributing specific disease phenotypes to these repeat lengths. In conclusion, our findings confirm the role of ATXN2 as an important risk factor for ALS and support the hypothesis that expanded ATXN2 repeats may predispose to other neurodegenerative diseases, including progressive supranuclear palsy.
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Details
- Title
- Ataxin-2 repeat-length variation and neurodegeneration
- Creators
- Owen A. Ross - Department of NeuroscienceNicola J. Rutherford - Department of NeuroscienceMatt Baker - Department of NeuroscienceAlexandra I. Soto-Ortolaza - Department of NeuroscienceMinerva M. Carrasquillo - Department of NeuroscienceMariely DeJesus-Hernandez - Department of NeuroscienceJennifer Adamson - Department of NeuroscienceMa Li - Department of NeuroscienceKathryn Volkening - Mayo ClinicElizabeth Finger - Western UniversityWilliam W. Seeley - University of California, San FranciscoKimmo J. Hatanpaa - The University of Texas Southwestern Medical CenterCatherine Lomen-Hoerth - University of California, San FranciscoAndrew Kertesz - Western UniversityEileen H. Bigio - Northwestern UniversityCarol Lippa - Drexel UniversityBryan K. Woodruff - Mayo Clinic, Scottsdale AZ.David S. Knopman - Mayo Clinic Rochester, MNCharles L. White - The University of Texas Southwestern Medical CenterJay A. Van Gerpen - Mayo ClinicJames F. Meschia - Mayo ClinicIan R. Mackenzie - University of British ColumbiaKevin Boylan - Mayo ClinicBradley F. Boeve - Mayo Clinic Rochester, MNBruce L. Miller - University of California, San FranciscoMichael J. Strong - Western UniversityRyan J. Uitti - Mayo ClinicSteven G. Younkin - Department of NeuroscienceNeill R. Graff-Radford - Mayo ClinicRonald C. Petersen - Mayo Clinic Rochester, MNZbigniew K. Wszolek - Mayo ClinicDennis W. Dickson - Department of NeuroscienceRosa Rademakers - Department of Neuroscience
- Publication Details
- Human molecular genetics, v 20(16), pp 3207-3212
- Publisher
- Oxford Univ Press
- Number of pages
- 6
- Grant note
- P50; NS072187 / NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) P30AG013854 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) ALS association P50NS072187 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) MCF 90052018; MCF 90052030 / Mayo Clinic Florida Winspear Family Center for Research on the Neuropathology of Alzheimer Disease 74580 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) R01 NS42733 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Pacific Alzheimer's Disease Research Foundation Peebler PSP Research Foundation family of Carl and Susan Bolch R01 NS065782 P50 AG16574; U01 AG06576; R01 NS065782; R01 AG26251; R01 AG18023; AG1657303; AG25711; AG17216; AG03 949; AG13854; P30 AG19610-01; R01 NS057567; 1RC2NS070276; 5P30AG012300 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA McCune Foundation
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000293027100009
- Scopus ID
- 2-s2.0-79960811611
- Other Identifier
- 991019312386004721
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- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity