A frameshift mutation in PRICKLE1 causes skeletal dysplasia in Cheviot sheep
- 1The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Roslin, Midlothian, Scotland, EH25 9RG, UK.
Abstract
Skeletal dysplasias can occur in animals, including humans, and are attributed to both environmental and genetic causes. As our understanding of the distinguishing phenotypes of different skeletal dysplasias improves, alongside elucidation of the mechanisms and genetic networks that contribute to skeletal development, identifying and controlling genetic mutations in livestock populations has become increasingly possible, including approaches beyond selective breeding alone. Within Scotland an 'achondroplasia' syndrome that was first described in the South Country Cheviot breed of sheep (OMIA 000004-9940), has continued to occur periodically within the same geographical locations, despite culling of affected lambs over many decades. Affected lambs exhibit rounded heads, short legs, a loss of hooves, abnormal stance and short twisted tails. As the condition has been observed in flocks and as progeny from specific ram and ewe matings, and cases have been co-twinned to normal siblings, this suggests a syndrome caused by a recessive genetic condition rather than environmental factors. Through homozygosity mapping and whole genome sequence analyses, we identified a 10 bp deletion in the open reading frame of the PRICKLE1 gene that encodes prickle planar cell polarity protein 1 and is essential for normal vertebrate embryonic development. We identified additional phenotypes present in affected lambs, including a loss of phalanges, neural tube defects, vertebral and articular chondrocyte defects, hair orientation differences and polycystic kidneys, consistent with a loss of PRICKLE1 function based on comparisons to mouse mutant lines. These findings enabled the development of a simple DNA test for the identified PRICKLE1 mutation that was made commercially available to facilitate the elimination of this genetic disease from sheep flocks.
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BibTeX
@misc{matika2026frameshift,
title = {{A frameshift mutation in PRICKLE1 causes skeletal dysplasia in Cheviot sheep}},
author = {O. Matika and M. G. Davey and J. del Pozo and H. A. Finlayson and C. Farquharson and D. J. Headon and J. W. Kijas and L. McTeir and C. Bathos-Samblas and E. Watson and V. Riggio and J. J. Schoenebeck and T. Schwarz and K. A. Staines and R. Pong-Wong and Z. H. Lu and S. C. Bishop and J. A. Woolliams and A. L. Archibald},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757262},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757262v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A frameshift mutation in PRICKLE1 causes skeletal dysplasia in Cheviot sheep
AU - O. Matika
AU - M. G. Davey
AU - J. del Pozo
AU - H. A. Finlayson
AU - C. Farquharson
AU - D. J. Headon
AU - J. W. Kijas
AU - L. McTeir
AU - C. Bathos-Samblas
AU - E. Watson
AU - V. Riggio
AU - J. J. Schoenebeck
AU - T. Schwarz
AU - K. A. Staines
AU - R. Pong-Wong
AU - Z. H. Lu
AU - S. C. Bishop
AU - J. A. Woolliams
AU - A. L. Archibald
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757262
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757262v1
AB - Skeletal dysplasias can occur in animals, including humans, and are attributed to both environmental and genetic causes. As our understanding of the distinguishing phenotypes of different skeletal dysplasias improves, alongside elucidation of the mechanisms and genetic networks that contribute to skeletal development, identifying and controlling genetic mutations in livestock populations has become increasingly possible, including approaches beyond selective breeding alone. Within Scotland an 'achondroplasia' syndrome that was first described in the South Country Cheviot breed of sheep (OMIA 000004-9940), has continued to occur periodically within the same geographical locations, despite culling of affected lambs over many decades. Affected lambs exhibit rounded heads, short legs, a loss of hooves, abnormal stance and short twisted tails. As the condition has been observed in flocks and as progeny from specific ram and ewe matings, and cases have been co-twinned to normal siblings, this suggests a syndrome caused by a recessive genetic condition rather than environmental factors. Through homozygosity mapping and whole genome sequence analyses, we identified a 10 bp deletion in the open reading frame of the PRICKLE1 gene that encodes prickle planar cell polarity protein 1 and is essential for normal vertebrate embryonic development. We identified additional phenotypes present in affected lambs, including a loss of phalanges, neural tube defects, vertebral and articular chondrocyte defects, hair orientation differences and polycystic kidneys, consistent with a loss of PRICKLE1 function based on comparisons to mouse mutant lines. These findings enabled the development of a simple DNA test for the identified PRICKLE1 mutation that was made commercially available to facilitate the elimination of this genetic disease from sheep flocks.
ER -