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Genome-wide associa...
Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis
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Awano, Tomoyuki (author)
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Johnson, Gary S. (author)
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Wade, Claire M. (author)
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Katz, Martin L. (author)
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Johnson, Gayle C. (author)
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Taylor, Jeremy F. (author)
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Perloski, Michele (author)
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Biagi, Tara (author)
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- Baranowska, Izabella (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics
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Long, Sam (author)
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March, Philip A. (author)
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Olby, Natasha J. (author)
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Shelton, G. Diane (author)
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Khan, Shahnawaz (author)
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O'Brien, Dennis P. (author)
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- Lindblad-Toh, Kerstin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Coates, Joan R. (author)
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(creator_code:org_t)
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- 2009-02-24
- 2009
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:8, s. 2794-2799
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http://www.pnas.org/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Awano, Tomoyuki
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Johnson, Gary S.
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Wade, Claire M.
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Katz, Martin L.
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Johnson, Gayle C ...
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Taylor, Jeremy F ...
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show more...
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Perloski, Michel ...
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Biagi, Tara
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Baranowska, Izab ...
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Long, Sam
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March, Philip A.
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Olby, Natasha J.
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Shelton, G. Dian ...
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Khan, Shahnawaz
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O'Brien, Dennis ...
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Lindblad-Toh, Ke ...
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Coates, Joan R.
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
- Articles in the publication
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Proceedings of t ...
- By the university
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Uppsala University
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Swedish University of Agricultural Sciences