OMIA:002186-9615 : Screw tail in Canis lupus familiaris (dog)

Categories: Limbs / fins / digit / tail phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 602151 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Species-specific name: Robinow-like syndrome; curly tail

Inheritance: Mansour et al. (2018): "Segregation of the caudal vertebral column malformations and genotype at DVL2 was consistent with a fully penetrant recessive mode of inheritance in Boston Terriers, Shih Tzus, Pit Bulls and mixed breeds ... . Segregation of the thoracic vertebral malformations was consistent with a recessive mode of inheritance with variable penetrance between breeds. In order to evaluate the molecular contribution to brachycephalic skull shape, the DVL2 mutant breeds were genotyped for the previously identified brachycephaly associated Line insertion affecting SMOC 2 splicing. Bulldogs and French Bulldogs were homozygous for the variant and the Boston Terriers had an allele frequency of 90.3% ... . Similar allele frequency for the BMP3 missense mutation was also reported for these three breeds indicating that they are homozygous or have a high allele frequency for three mutations that affect head shape [Schoenebeck et al., 2012].

Mapping: Jones et al. (2008) conducted an across-breed GWAS on 2,801 dogs from 147 breeds, each genotyped for 674 equally spaced SNPs, plus an additional 862 SNPs located in regions of interest. The results highlighted regions on CFA1, 9, 25 and 38. By conducting a mammoth proof-of-principle GWAS on "11 [breeds] with curly tails and 7 [breeds] with straight tails", with each dog being genotyped with Illumina CanineHD array (yielding 157,393 SNPs for analysis) developed for this study, Vaysse et al. (2011) highlighted a region between 96.26 and 96.96Mb on chromosome CFA1, which is flanked by the genes RCL1 and JAK2.

Molecular basis: Mansour et al. (2018) " identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) ... as the most strongly associated [with screw tail] variant in the canine genome ... . DVL2 cDNA was sequenced from the skeletal muscle of a dog with a normal tail and a screw tail Bulldog ... to confirm the presence of the mutation in the mRNA in the Bulldog sample (DVL2c.2044delC). ... This deletion is predicted to lead to a frameshift mutation, causing a premature stop codon that truncates the translated protein by 23 amino acids (p.Pro684LeufsX26)."

Clinical features: Mansour et al. (2018): "One group of three breeds (Bulldog, French Bulldog and Boston Terrier) is characterized by a wide head, short muzzle, widely spaced eyes, small size and abnormalities of the vertebral bones of the back and tail. These breeds are referred to as the screw tail breeds since the characteristic that is unique and easy to see in these breeds is their shortened and kinked tails." Niskanen et al. (2021): "The DVL2 variant segregates in a recessive manner with caudal vertebral malformations and has incomplete and variable penetrance for thoracic vertebral malformations (Mansour et al. 2018). ... With CT examinations in American Staffordshire Terriers, we confirmed that the DVL2 allele is associated with caudal vertebral malformations and a brachycephalic phenotype. We also hypothesize that the variant may be linked to additional health conditions, including brachycephalic obstructive airway syndrome and congenital heart defects."

Prevalence: Mansour et al. (2018): "This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers." These same authors also reported that "To confirm the association of the DVL2c.2044delC mutation with the screw tail phenotype, 667 dogs, from 49 breeds, were genotyped for the DVL2 mutation . . . . 177 dogs were from the screw tail breeds including 33 Bulldogs, 79 French Bulldogs and 65 Boston Terriers. All were homozygous for the mutant allele except 6 of the Boston Terriers (4 heterozygous, 2 wildtype). In addition, we identified dogs from several other breeds, including Pit bulls, Staffordshire Bull Terrier, Shih Tzu and mixed breeds, that are heterozygous or homozygous for the DLV2 mutation. The Pug breed has sometimes been classified with the screw tail breeds due to its curled tail; however, the tail is full length and does not have caudal vertebral malformations . . . . 29 Pugs tested were wild-type for the DVL2 mutation. Likewise, the Pug dogs do not share the high MAF with the screw tail breeds around the DVL2 mutation . . . . Three hundred and eighty five dogs from 43 other breeds were also tested and were all wild-type."

Breeds: American Bulldog (Dog) (VBO_0200034), American Pit Bull Terrier (Dog) (VBO_0200054), American Staffordshire Terrier (Dog) (VBO_0200055), Boston Terrier (Dog) (VBO_0200204), Dogue de Bordeaux (Dog) (VBO_0200450), English Bulldog (Dog) (VBO_0200485), French Bulldog (Dog) (VBO_0201455), Shih Tzu (Dog) (VBO_0201223), Staffordshire Bull Terrier (Dog) (VBO_0201296).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
DVL2 dishevelled segment polarity protein 2 Canis lupus familiaris 5 NC_051809.1 (32307523..32299943) DVL2 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1056 Boston Terrier (Dog) Bulldog (Dog) French Bulldog (Dog) Screw tail DVL2 deletion, small (<=20) Naturally occurring variant CanFam3.1 5 g.32195051del c.2051del p.(P684Lfs*26) XM_005619960.3; XP_005620017.1; published as g.32195043_32195044del; c.2044delC and changed to HGVS nomenclature in this table 2018 30521570

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:002186-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

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.

2024 Estevam, M.V., Toniollo, G.H., Apparicio, M. :
The most common congenital malformations in dogs: Literature review and practical guide. Res Vet Sci 171:S0034-5288(24)00096-1:105230, 2024. Pubmed reference: 38492280. DOI: 10.1016/j.rvsc.2024.105230.
Pilkington, E.J., De Decker, S., Skovola, E., Cloquell Miro, A., Gutierrez Quintana, R., Faller, K.M.E., Aguilera Padros, A., Goncalves, R. :
Prevalence, clinical presentation, and etiology of myelopathies in 224 juvenile dogs. J Vet Intern Med , 2024. Pubmed reference: 38483074. DOI: 10.1111/jvim.17045.
2021 Niskanen, J.E., Reunanen, V., Salonen, M., Bannasch, D., Lappalainen, A.K., Lohi, H., Hytönen, M.K. :
Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies. Hum Genet 140:1535-1545, 2021. Pubmed reference: 33599851. DOI: 10.1007/s00439-021-02261-8.
2019 Bertram, S., Ter Haar, G., De Decker, S. :
Congenital malformations of the lumbosacral vertebral column are common in neurologically normal French Bulldogs, English Bulldogs, and Pugs, with breed-specific differences. Vet Radiol Ultrasound 60:400-408, 2019. Pubmed reference: 31050057. DOI: 10.1111/vru.12753.
2018 Mansour, T.A., Lucot, K., Konopelski, S.E., Dickinson, P.J., Sturges, B.K., Vernau, K.L., Choi, S., Stern, J.A., Thomasy, S.M., Döring, S., Verstraete, F.J.M., Johnson, E.G., York, D., Rebhun, R.B., Ho, H.H., Brown, C.T., Bannasch, D.L. :
Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds. PLoS Genet 14:e1007850, 2018. Pubmed reference: 30521570. DOI: 10.1371/journal.pgen.1007850.
2014 Guevar, J., Penderis, J., Faller, K., Yeamans, C., Stalin, C., Gutierrez-Quintana, R. :
Computer-assisted radiographic calculation of spinal curvature in brachycephalic "screw-tailed" dog breeds with congenital thoracic vertebral malformations: reliability and clinical evaluation. PLoS One 9:e106957, 2014. Pubmed reference: 25198374. DOI: 10.1371/journal.pone.0106957.
Gutierrez-Quintana, R., Guevar, J., Stalin, C., Faller, K., Yeamans, C., Penderis, J. :
A proposed radiographic classification scheme for congenital thoracic vertebral malformations in brachycephalic "screw-tailed" dog breeds. Vet Radiol Ultrasound 55:585-91, 2014. Pubmed reference: 24833506. DOI: 10.1111/vru.12172.
2012 Schoenebeck, J.J., Hutchinson, S.A., Byers, A., Beale, H.C., Carrington, B., Faden, D.L., Rimbault, M., Decker, B., Kidd, J.M., Sood, R., Boyko, A.R., Fondon, J.W., Wayne, R.K., Bustamante, C.D., Ciruna, B., Ostrander, E.A. :
Variation of BMP3 contributes to dog breed skull diversity. PLoS Genet 8:e1002849, 2012. Pubmed reference: 22876193. DOI: 10.1371/journal.pgen.1002849.
2011 Vaysse, A., Ratnakumar, A., Derrien, T., Axelsson, E., Rosengren Pielberg, G., Sigurdsson, S., Fall, T., Seppälä, E.H., Hansen, M.S., Lawley, C.T., Karlsson, E.K. :
Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping. PLoS Genet 7:e1002316, 2011. Pubmed reference: 22022279. DOI: 10.1371/journal.pgen.1002316.
2008 Jones, P., Chase, K., Martin, A., Davern, P., Ostrander, EA., Lark, KG. :
Single-nucleotide-polymorphism-based association mapping of dog stereotypes. Genetics 179:1033-44, 2008. Pubmed reference: 18505865. DOI: 10.1534/genetics.108.087866.

Edit History


  • Created by Frank Nicholas on 29 Mar 2019
  • Changed by Frank Nicholas on 29 Mar 2019
  • Changed by Imke Tammen2 on 08 Apr 2021
  • Changed by Imke Tammen2 on 10 Jul 2021
  • Changed by Imke Tammen2 on 25 Jan 2022
  • Changed by Imke Tammen2 on 24 May 2022
  • Changed by Imke Tammen2 on 02 Jun 2022