OMIA 001821-9615 : Coat colour, albinism, oculocutaneous type IV in Canis lupus familiaris

In other species: western gorilla , Japanese medaka , cattle

Possibly relevant human trait(s) and/or gene(s) (MIM number): 606574

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Species-specific name: White Doberman Pinscher

Species-specific symbol: WDP

History: As reported by Winkler et al. (2014), "In 1976, a female Doberman pinscher with novel “white” coat-coloration was born and registered with the American Kennel Club. The uniqueness of the light coat-color prompted breeders to utilize line breeding to maintain the phenotype, resulting in an extensive pedigree in which all living white Doberman pinschers (WDPs) are traceable to this initial white female."

Inheritance: As reported by Winkler et al. (2014), "A research study conducted by the DPCA [Doberman Pincher Club of America] concluded an autosomal recessive mode of inheritance (http://dpca.org/BreedEd/index.php/articles/44-history/381-albinism-science)".

Mapping: Based on the very strong phenotypic resemblance between the white phenotype of Doberman Pinschers and oculocutaneous albinism (OCA) in humans, Winkler et al. (2014) obtained flanking markers from the canine genome assembly for the canine orthologues of four of the genes involved in OCD in humans, namely tyrosinase (TYR) for OCA1, P-gene for OCA2, tyrosinase-related protein 1 (TYRP1) for OCA3, and solute carrier family, member 2 (SLC45A2) for OCA4. An exclusion analysis involving 20 white and 20 standard Doberman Pinchers eliminated all but the last candidate gene.

Molecular basis: Sequencing of the candidate gene in one white and one standard Doberman Pincher "revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4[ratio]77,062,968–77,067,051)" (g.27141_31223del (CanFam2)) as a highly likely causative mutation (Winkler et al., 2014). As also reported by Winkler et al. (2014), "This mutation is predicted to cause the last 50 amino acids of exon 7 to be replaced by 191 new amino acids before an in-frame stop codon is found, as predicted from the canine reference genome (CanFam2.0) . . . . This deletion also removes the poly-A addition signal (AATAAA), and the next predicted polyadenylation signal for the mutant chromosome is 6,106 bp downstream from the new stop codon."

Wijesena and Schmutz (2015): c.1478G>A; p.G493D in exon 7 in a female albino Lhasa Apso and in "an albino Pekingese, 2 albino Pomeranians, and an albino mixed breed dog that was small and long haired"

Caduff et al. (2017) reported a likely causal variant in Bullmastiffs: "a single base deletion in exon 6 of the SLC45A2 gene (NM_001037947.1:c.1287delC) . . . This deletion is predicted to result in an early premature stop codon. It was confirmed by Sanger sequencing and perfectly co-segregated with the phenotype in the available family members. We genotyped 174 unrelated dogs from diverse breeds, all of which were homozygous wildtype."

Breeds: Bull Mastiff, Doberman Pincher, Lhasa Apso, Pekingese, Pomeranian.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC45A2 solute carrier family 45, member 2 Canis lupus familiaris 4 NC_006586.3 (73838684..73868222) SLC45A2 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.

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
Doberman Pinscher Coat colour, albinism, oculocutaneous type IV SLC45A2 deletion, gross (>20) "a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4[ratio]77,062,968-77,067,051)" (g.27141_31223del; CanFam2.0) 2014 24647637
Lhasa Apso Mixed breed Pekingese Pomeranian Coat colour, albinism, oculocutaneous type IV SLC45A2 missense c.1478G>A p.G493D 2015 25790827
Bull Mastiff Coat colour, albinism, oculocutaneous type IV SLC45A2 deletion, small (<=20) CanFam3.1 4 g.73864860delC c.1287delC p.Met430CysfsTer4 2017 28737247

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 Caduff, M., Bauer, A., Jagannathan, V., Leeb, T. :
A single base deletion in the SLC45A2 gene in a Bullmastiff with oculocutaneous albinism. Anim Genet 48:619-621, 2017. Pubmed reference: 28737247. DOI: 10.1111/age.12582.
2015 Wijesena, H.R., Schmutz, S.M. :
A Missense Mutation in SLC45A2 Is Associated with Albinism in Several Small Long Haired Dog Breeds. J Hered 106:285-8, 2015. Pubmed reference: 25790827. DOI: 10.1093/jhered/esv008.
2014 Winkler, P.A., Gornik, K.R., Ramsey, D.T., Dubielzig, R.R., Venta, P.J., Petersen-Jones, S.M., Bartoe, J.T. :
A Partial Gene Deletion of SLC45A2 Causes Oculocutaneous Albinism in Doberman Pinscher Dogs. PLoS One 9:e92127, 2014. Pubmed reference: 24647637. DOI: 10.1371/journal.pone.0092127.

Edit History


  • Created by Frank Nicholas on 28 Mar 2014
  • Changed by Frank Nicholas on 28 Mar 2014
  • Changed by Frank Nicholas on 23 Mar 2015
  • Changed by Frank Nicholas on 29 Aug 2017