OMIA 001474-9615 : Rupture of the cranial cruciate ligament in Canis lupus familiaris

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Species-specific name: anterior cruciate ligament rupture

Species-specific symbol: RCCL

Inheritance: Wilke et al. (2006) showed that this disorder is heritable, but the form of inheritance remains to be determined.

GWAS conducted by Baker et al. (2017) and Hayward et al. (2019) established the multifactorial nature of this disorder, with numerous QTL reported. The latter study reported a QTL of relatively large effect "on CFA20: 42,827,199 . . . in the gene LIM Domain-Containing 1 (LIMD1), which is involved in regulating stress osteoclastogenesis, and osteoblast function and differentiation"


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2021 Jiang, L., Li, Z., Hayward, J.J., Hayashi, K., Krotscheck, U., Todhunter, R.J., Tang, Y., Huang, M. :
Genomic prediction of two complex orthopedic traits across multiple pure and mixed breed dogs. Front Genet 12:666740, 2021. Pubmed reference: 34630503. DOI: 10.3389/fgene.2021.666740.
2020 Anderson, K.L., Zulch, H., O'Neill, D.G., Meeson, R.L., Collins, L.M. :
Risk factors for canine osteoarthritis and its predisposing arthropathies: A systematic review. Front Vet Sci 7:220, 2020. Pubmed reference: 32411739. DOI: 10.3389/fvets.2020.00220.
Baker, L.A., Momen, M., Chan, K., Bollig, N., Lopes, F.B., Rosa, G.J.M., Todhunter, R.J., Binversie, E.E., Sample, S.J., Muir, P. :
Bayesian and machine learning models for genomic prediction of anterior cruciate ligament rupture in the canine model. G3 (Bethesda) 10:2619-2628, 2020. Pubmed reference: 32499222. DOI: 10.1534/g3.120.401244.
Cook, S.R., Conzemius, M.G., McCue, M.E., Ekenstedt, K.J. :
SNP-based heritability and genetic architecture of cranial cruciate ligament rupture in Labrador Retrievers. Anim Genet :, 2020. Pubmed reference: 32696518. DOI: 10.1111/age.12978.
2019 Hayward, J.J., White, M.E., Boyle, M., Shannon, L.M., Casal, M.L., Castelhano, M.G., Center, S.A., Meyers-Wallen, V.N., Simpson, K.W., Sutter, N.B., Todhunter, R.J., Boyko, A.R. :
Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies. PLoS Genet 15:e1008003, 2019. Pubmed reference: 31525180. DOI: 10.1371/journal.pgen.1008003.
Healey, E., Murphy, R.J., Hayward, J.J., Castelhano, M., Boyko, A.R., Hayashi, K., Krotscheck, U., Todhunter, R.J. :
Genetic mapping of distal femoral, stifle, and tibial radiographic morphology in dogs with cranial cruciate ligament disease. PLoS One 14:e0223094, 2019. Pubmed reference: 31622367. DOI: 10.1371/journal.pone.0223094.
2018 Baker, L.A., Rosa, G.J.M., Hao, Z., Piazza, A., Hoffman, C., Binversie, E.E., Sample, S.J., Muir, P. :
Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model. BMC Genet 19:39, 2018. Pubmed reference: 29940858. DOI: 10.1186/s12863-018-0626-7.
2017 Baker, L.A., Kirkpatrick, B., Rosa, G.J., Gianola, D., Valente, B., Sumner, J.P., Baltzer, W., Hao, Z., Binversie, E.E., Volstad, N., Piazza, A., Sample, S.J., Muir, P. :
Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture. PLoS One 12:e0173810, 2017. Pubmed reference: 28379989. DOI: 10.1371/journal.pone.0173810.
Belanger, J.M., Bellumori, T.P., Bannasch, D.L., Famula, T.R., Oberbauer, A.M. :
Correlation of neuter status and expression of heritable disorders. Canine Genet Epidemiol 4:6, 2017. Pubmed reference: 28560045. DOI: 10.1186/s40575-017-0044-6.
Huang, M., Hayward, J.J., Corey, E., Garrison, S.J., Wagner, G.R., Krotscheck, U., Hayashi, K., Schweitzer, P.A., Lust, G., Boyko, A.R., Todhunter, R.J. :
A novel iterative mixed model to remap three complex orthopedic traits in dogs. PLoS One 12:e0176932, 2017. Pubmed reference: 28614352. DOI: 10.1371/journal.pone.0176932.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021. DOI: 10.2460/javma.242.11.1549.
2009 Clements, DN., Short, AD., Barnes, A., Kennedy, LJ., Ferguson, JF., Butterworth, SJ., Fitzpatrick, N., Pead, M., Bennett, D., Innes, JF., Carter, SD., Ollier, WE. :
A candidate gene study of canine joint diseases. J Hered 101:54-60, 2009. Pubmed reference: 19965910. DOI: 10.1093/jhered/esp088.
Wilke, VL., Zhang, S., Evans, RB., Conzemius, MG., Rothschild, MF. :
Identification of chromosomal regions associated with cranial cruciate ligament rupture in a population of Newfoundlands. Am J Vet Res 70:1013-7, 2009. Pubmed reference: 19645583. DOI: 10.2460/ajvr.70.8.1013.
2008 Witsberger, TH., Villamil, JA., Schultz, LG., Hahn, AW., Cook, JL. :
Prevalence of and risk factors for hip dysplasia and cranial cruciate ligament deficiency in dogs. J Am Vet Med Assoc 232:1818-24, 2008. Pubmed reference: 18598150. DOI: 10.2460/javma.232.12.1818.
2006 Wilke, VL., Conzemius, MG., Kinghorn, BP., Macrossan, PE., Cai, W., Rothschild, MF. :
Inheritance of rupture of the cranial cruciate ligament in Newfoundlands. J Am Vet Med Assoc 228:61-4, 2006. Pubmed reference: 16426167. DOI: 10.2460/javma.228.1.61.

Edit History

  • Created by Frank Nicholas on 27 Oct 2009
  • Changed by Frank Nicholas on 18 Sep 2019
  • Changed by Imke Tammen2 on 20 Apr 2021
  • Changed by Imke Tammen2 on 27 Aug 2021
  • Changed by Imke Tammen2 on 28 Aug 2021