Frameshift variant in PRICKLE1 identified as cause of skeletal dysplasia in Cheviot sheep

Researchers have posted a preprint to bioRxiv reporting that a frameshift mutation in PRICKLE1 — a gene encoding a component of the planar cell polarity pathway — underlies an achondroplasia-like skeletal dysplasia that has been documented in South Country Cheviot sheep in Scotland. The syndrome, which causes disproportionate dwarfism, has been recognised in the breed for some time, but its genetic basis had not previously been resolved.

Using a combination of phenotypic characterisation and genomic approaches, the authors identified the PRICKLE1 frameshift variant as the causal mutation. PRICKLE1 encodes a scaffold protein involved in non-canonical Wnt and planar cell polarity signalling, pathways known to regulate skeletal morphogenesis. The finding adds PRICKLE1 to the set of genes implicated in skeletal dysplasia across vertebrate species.

For the livestock-genetics community, the result offers a molecular target for genotyping-based management to reduce the prevalence of the syndrome in affected flocks, moving beyond selective breeding based on phenotype alone. More broadly, the Cheviot sheep model may be useful for studying the developmental mechanisms through which planar cell polarity disruption produces skeletal abnormalities. The work remains a preprint and has not yet been peer-reviewed.