OMIA 000810-9615 : Polydactyly in Canis lupus familiaris
Category: Limbs / digit / tail phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2008
Cross-species summary: Often called preaxial polydactyly (PPD)
Species-specific name: Dew claws, canine preaxial polydactyly
Species-specific symbol: PPD
Mapping: Park et al. (2004) mapped dew claws (an extra first digit on the hind limb) in the Korean breed Sapsaree to canine chromosome 16. The maximum two-point lod score of 20.76 was obtained for microsatellite markers REN85M08/REN85N14. Finemapping via haplotype analysis refined the location of the dewclaw locus to an interval delimited by markers UCMCF12 and CXX876.
Park et al. (2008): "The candidate locus was further limited to a linkage disequilibrium (LD) block of <213 kb composing the single gene, LMBR1, by LD mapping with single nucleotide polymorphisms (SNPs) for affected individuals from both Korean and Western breeds." In several species, polydactyly results from mutations in the ZPA regulatory sequence (ZRS), an enhancer of the developmental gene Sonic Hedgehog (SHH). ZRS is located in intron 5 of the LMBR1 gene.
Molecular basis: Park et al. (2008) identified within the two identified distinct affected haplotypes for Asian and Western breeds two different single-base changes in the upstream sequence (pZRS) of the ZRS. A G to A variant named DC-1 was found in the 1-kb region upstream of the 5′-end of the ZRS in 150 affected Sapsaree (144 affected dogs were heterozygous G/A and 6 affected dogs homozygous A/A) and six affected Korean Tosas, whereas 65 unaffected Sapsaree dogs were homozygous G/G. DC-1 was invariable (G/G) in 42 dogs of several Western breeds which included dogs with and without dew claws.
Another G/A variant (named DC-2), located 246 bp downstream of DC-1, was identified as the likely causal variant for PPD in 26 affected dogs of Western breeds (including, Beagle, Cocker Spaniel, Malinois, Rottweiler, Shetland Sheepdog, Standard Poodle, Standard Schnauzer, Shih Tzu, and Yorkshire Terrier). 14 affected dogs were heterozygous G/A and 12 affected dogs homozygous A/A, whereas 23 unaffected individuals from the same breeds were homozygous G/G.
Park et al. (2008) “investigated the role of the ZRS in transcriptional regulation by generating a luciferase reporter construct. … the core ZRS region displaying almost 100% identity in mammalian sequences exhibited the highest enhancer activity …. When we introduced DC-1 or DC-2 mutations in the wild-type ZRS region, >50% reduction in enhancer activity was evident ….”
Kropatsch et al. (2015) identified that Norwegian Lundehund, a breed that is characterised by the presence of extra toes in the fore and hind limbs, were homozygous A/A for the DC-2 variant identified by Park et al. (2008). This provided further support that this variant is causing canine PPD.
However, other suspected genetic causes for polydactyly have been reported in dogs. Fondon and Garner (2004) investigated repeat expansion or contraction alleles in selected genes and analysed their association with morphometric traits. They noted that a 51bp deletion in the Alx4 gene occurred in homozygosity in four Great Pyrenees, a breed in which bilateral rear first digit polydactyly is common. Alx4 is known to cause polydactyly in mice. The deletion was not present in dogs from other breeds investigated in this study and was also absent in a single Great Pyrenees without polydactyly. The authors state that hind limb polydactyly in Great Pyreneesis is not a simple Mendelian trait but concluded that polydactyly in this breed is likely caused in part by the 17-aa deletion.
Clinical features: Park et al. (2008): “Canine preaxial polydactyly (PPD) in the hind limb is a developmental trait that restores the first digit lost during canine evolution. … As described previously (Park et al. 2004), the restored phenotype is slightly overmanifested, generating one or more preaxial digits. As a matter of fact, the external morphology of hind-limb-specific canine PPD is slightly different from other polydactylies in that only the claw is observed as having an extra digit with fibrous tissue connecting the region between the tarsal and the first metatarsal bones, which either is reduced in size or is incomplete with a lesser deposit of bony material (Miller 1979; Park et al. 2004).”
Breeds: Beagle, Cocker Spaniel, Great Pyrenees, Korean Tosa, Malinois, Rottweiler, Saint Bernard, Sapsaree, Shetland Sheepdog, Shih-Tzu, Standard Poodle, Standard Schnauzer, Yorkshire Terrier.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SHH||sonic hedgehog||Canis lupus familiaris||16||NC_051820.1 (20392367..20382879)||SHH||Homologene, Ensembl, NCBI gene|
|ALX4||ALX homeobox 4||Canis lupus familiaris||18||NC_051822.1 (45583479..45629082)||ALX4||Homologene, Ensembl, NCBI gene|
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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1444||Beagle Cocker Spaniel Lundehund Malinois Rottweiler Shetland Sheepdog Shih-Tzu Standard Poodle Standard Schnauzer Yorkshire Terrier||Dew claws||SHH||DC-2||regulatory||Naturally occurring variant||CanFam3.1||16||g.19380592C>T||2008||18689889||Thank you to Heidi Anderson for suggesting to add this variant [8/4/2022]|
|1445||Korean Tosa Sapsaree||Dew claws||SHH||DC-1||regulatory||Naturally occurring variant||CanFam3.1||16||g.19380829C>T||2008||18689889||Thank you to Heidi Anderson for suggesting to add this variant [8/4/2022]|
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.
|2015||Kropatsch, R., Melis, C., Stronen, A.V., Jensen, H., Epplen, J.T. :|
|Molecular Genetics of Sex Identification, Breed Ancestry and Polydactyly in the Norwegian Lundehund Breed. J Hered 106:403-6, 2015. Pubmed reference: 25994807. DOI: 10.1093/jhered/esv031.|
|2008||Park, K., Kang, J., Subedi, K.P., Ha, J.H., Park, C. :|
|Canine polydactyl mutations with heterogeneous origin in the conserved intronic sequence of LMBR1. Genetics 179:2163-72, 2008. Pubmed reference: 18689889. DOI: 10.1534/genetics.108.087114.|
|2004||Fondon, J.W., Garner, H.R. :|
|Molecular origins of rapid and continuous morphological evolution. Proc Natl Acad Sci U S A 101:18058-63, 2004. Pubmed reference: 15596718. DOI: 10.1073/pnas.0408118101.|
|Park, K., Kang, J., Park, S., Ha, J., Park, C. :|
|Linkage of the locus for canine dewclaw to chromosome 16. Genomics 83:216-24, 2004. Pubmed reference: 14706450. DOI: 10.1016/s0888-7543(03)00234-9.|
|1985||Alberch, P. :|
|Developmental constraints: why St. Bernards often have an extra digit and poodles never do American Naturalist 126:430-433, 1985.|
|1979||Miller, M. E. :|
|Miller's Anatomy of the Dog Saunders, Philadelphia. Ed. 2. :, 1979.|
|1954||Grundman, I. :|
|The inheritance of polydactyly in the domestic dog :, 1954.|
|1941||Falaschini, A. :|
|On the mode of inheritance of dew claws in the domestic dog Nuova Veterinaria 19:126, 1941.|
- Created by Frank Nicholas on 06 Sep 2005
- Changed by Imke Tammen2 on 22 Jan 2022
- Changed by Imke Tammen2 on 08 Apr 2022