OMIA 000323-9615 : Ectodermal dysplasia in Canis lupus familiaris

In other species: chicken

Possibly relevant human trait(s) and/or gene(s) (MIM number): 305100

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Semi-Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Cross-species summary: Hairless

Species-specific name: Canine ectodermal dysplasia

Species-specific symbol: CED

Species-specific description: Canine ectodermal dysplasia is characterized by hairlessness and missing or abnormally shaped teeth. Early breeding studies demonstrated embryonal lethality of homozygous mutant animals and an autosomal semidominant mode of inheritance (Robinson, 1985). In detail, homozygous mutant embryos die very early during pregnancy and are resorbed, heterozygous dogs exhibit the ectodermal dysplasia phenotype, which is characteristic of several hairless dog breeds. Later studies showed the trait is caused by a 7 bp duplication in exon 1 of FOXI3. This is a desired trait in several breeds, including the Peruvian Inca, Mexican Hairless, and Chinese Crested Dog.

Edited by Dr. Margret Casal

Mapping: By conducting a GWAS on "20 hairless and 19 coated Chinese Crested dogs", each of which had been genotyped with the Affymetrix v2 SNP chip (yielding 12,353 informative SNPs) Drögemüller et al. (2008) highlighted a single SNP on chromosome CFA17. Fine-mapping reduced the candidate region to "a 102-kb interval between positions 41,045,331 and 41,147,100 on CFA 17", containing only two predicted genes.

Molecular basis: By sequencing the more likely of the two positional candidate genes (see Mapping section), Drögemüller et al. (2008) showed that this disorder is due to a 7-bp tandem duplication in exon 1 of FOXI3, a member of the family of forkhead box transcription factor genes. This gene was previously unknown to contribute to the development of ectodermal structures.

Clinical features: Affected dogs have varying degrees of hairlessness but most commonly, almost the entire body is affected. Depending on the breed, there will be tufts of hair on the distal limbs and the top of the head. Some dogs have very abnormal teeth, many of which are missing. Others appear to have only mild abnormalities. Toenails may be long and brittle. Neonatal deaths are more common in hairless pups than in their normal littermates. Wiener et al. (2013) provided extensive details of the clinical and histological differences between the "three subphenotypes (true hairless, semi-coated and powderpuffs) of Chinese crested dogs" and also "clearly demonstrated distinct differences between the canine ectodermal dysplasia in Chinese crested dogs and dogs with X-linked ectodermal dysplasia".

Pathology: Histological examination of hairless skin and foot pads shows an absence of hair follicles, adnexal structures, and eccrine glands.

Prevalence: The condition is prevalent in specific breeds. It is considered a desired trait.

Control: As this is a desired trait, no control is needed. However in some breeds, such as the Chinese crested, breeding hairless individuals to each other may result in smaller litter sizes as the presence of a double dose of the mutation in homozygote puppies leads to prenatal mortality.

Genetic testing: Mutation testing is available.

Breeds: Chinese Crested Dog, Mexican Hairless Dog (Xoloitzcuintli), Peruvian Hairless Dog (Inca Hairless).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FOXI3 forkhead box I3 Canis lupus familiaris 17 NC_006599.3 (38032479..38036424) FOXI3 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Chinese Crested Dog Mexican Hairless Dog (Xoloitzcuintli) Peruvian Hairless Dog (Inca Hairless) Ectodermal dysplasia FOXI3 insertion, small (<=20) a 7-bp tandem duplication in exon 1 of FOXI3 2008 18787161

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.
2017 Kupczik, K., Cagan, A., Brauer, S., Fischer, M.S. :
The dental phenotype of hairless dogs with FOXI3 haploinsufficiency. Sci Rep 7:5459, 2017. Pubmed reference: 28710361. DOI: 10.1038/s41598-017-05764-5.
Parker, H.G., Harris, A., Dreger, D.L., Davis, B.W., Ostrander, E.A. :
The bald and the beautiful: hairlessness in domestic dog breeds. Philos Trans R Soc Lond B Biol Sci 372:, 2017. Pubmed reference: 27994129. DOI: 10.1098/rstb.2015.0488.
2013 Shirokova, V., Jussila, M., Hytönen, M.K., Perälä, N., Drögemüller, C., Leeb, T., Lohi, H., Sainio, K., Thesleff, I., Mikkola, M.L. :
Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes. Dev Dyn 242:593-603, 2013. Pubmed reference: 23441037. DOI: 10.1002/dvdy.23952.
Wiener, D.J., Gurtner, C., Panakova, L., Mausberg, T.B., Müller, E.J., Drögemüller, C., Leeb, T., Welle, M.M. :
Clinical and histological characterization of hair coat and glandular tissue of Chinese crested dogs. Vet Dermatol 24:274-e62, 2013. Pubmed reference: 23413772. DOI: 10.1111/vde.12008.
2008 Drögemüller, C., Karlsson, E.K., Hytönen, M.K., Perloski, M., Dolf, G., Sainio, K., Lohi, H., Lindblad-Toh, K., Leeb, T. :
A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321:1462, 2008. Pubmed reference: 18787161. DOI: 10.1126/science.1162525.
2005 O'Brien, DP., Johnson, GS., Schnabel, RD., Khan, S., Coates, JR., Johnson, GC., Taylor, JF. :
Genetic mapping of canine multiple system degeneration and ectodermal dysplasia loci. J Hered 96:727-34, 2005. Pubmed reference: 15958791. DOI: 10.1093/jhered/esi086.
Sander, P., Drögemüller, C., Cadieu, E., André, C., Leeb, T. :
Analysis of the canine EDAR gene and exclusion as a candidate for the hairless phenotype in the Chinese Crested dog. Anim Genet 36:168-71, 2005. Pubmed reference: 15771734. DOI: 10.1111/j.1365-2052.2005.01242.x.
1993 Kimura, T., Ohshima, S., Doi, K. :
The Inheritance and Breeding Results of Hairless Descendants of Mexican Hairless Dogs Laboratory Animals 27:55-58, 1993. Pubmed reference: 8437436.
1985 Robinson, R. :
Chinese crested dog Journal of Heredity 76:217-218, 1985. Pubmed reference: 3998444.

Edit History


  • Created by Frank Nicholas on 01 Sep 2009
  • Changed by Frank Nicholas on 12 Aug 2011
  • Changed by Martha MaloneyHuss on 02 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 25 Apr 2013
  • Changed by Frank Nicholas on 21 May 2013
  • Changed by Frank Nicholas on 05 Aug 2013
  • Changed by Tosso Leeb on 06 Jan 2016