Letko, Anna; Brülisauer, Franz; Häfliger, Irene M; Corr, Eilidh; Scholes, Sandra; Drögemüller, Cord (2023). Loss-of-function variant in the ovine TMCO6 gene in north country Cheviot sheep with motor neuron disease. Genomics, 115(5), p. 110689. Elsevier 10.1016/j.ygeno.2023.110689
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In North Country Cheviot lambs with early-onset progressive ataxia and motor neuron degeneration, whole-genome sequencing identified a homozygous loss-of-function variant in the ovine transmembrane and coiled-coil domains (TMCO6) gene. The familial recessive form of motor neuron disease in sheep is due to a pathogenic 4 bp deletion leading to a 50% protein truncation that is assumed to result in the absence of a functional TMCO6. This uncharacterised protein is proposed to interact with ubiquilin 1which is associated with Alzheimer's disease, whereas sporadic forms of amyotrophic lateral sclerosis are caused by variants in Ubiquilin 2. Our findings provide a first spontaneous animal model for TMCO6, which could have implications in the studies of other comparative neurodegenerative diseases. In addition, these results will allow the design of a genetic test to prevent the occurrence of this fatal disease in the affected sheep population.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) |
UniBE Contributor: |
Letko, Anna, Häfliger, Irene Monika, Drögemüller, Cord |
Subjects: |
500 Science > 590 Animals (Zoology) 600 Technology > 630 Agriculture |
ISSN: |
0888-7543 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
25 Jul 2023 09:33 |
Last Modified: |
30 Sep 2023 00:14 |
Publisher DOI: |
10.1016/j.ygeno.2023.110689 |
PubMed ID: |
37488055 |
Uncontrolled Keywords: |
Membrane trafficking Neurogenetic disorder Ovis aries Precision medicine Protein degradation Whole-genome sequencing |
BORIS DOI: |
10.48350/185050 |
URI: |
https://boris.unibe.ch/id/eprint/185050 |