Loss-of-function variant in the ovine TMCO6 gene in North Country Cheviot sheep with motor neuron disease.

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 1 which is associated with Alzheimer's disease, whereas sporadic forms of amyotrophic lateral sclerosis are caused by variants in UBQLN2. 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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Anna Letko, Franz Brülisauer, Irene M Häfliger, Eilidh Corr, Sandra Scholes, Cord Drögemüller. Loss-of-function variant in the ovine TMCO6 gene in North Country Cheviot sheep with motor neuron disease. Genomics. 2023 Sep;115(5):110689

PMID: 37488055

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