OMIA 002130-9615 : Coat colour, oculocutaneous albinism, OCA2-related in Canis lupus familiaris

In other species: Mexican tetra , corn snake

Possibly relevant human trait(s) and/or gene(s) (MIM number): 203200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Cross-species summary: Tyrosinase-positive oculocutaneous albinism (OCA, type II) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes.

Mapping: Caduff et al. (2017) performed linkage analysis and autozygosity mapping in a family of German Spitzes consisting of both non-affected parents, three affected puppies and three non-affected puppies. Only one ~15 Mb genome segment, Chr3:28,747,944 - 43,731,542 (CanFam 3.1) showed both linkage and homozygosity with shared alleles across the cases.

Molecular basis: The OCA2 gene is located in the critical interval on chromosome 3. Whole genome sequencing of one of the affected dogs revealed a splice site variant in the OCA2 gene that co-segregated with the phenotype in the German Spitz family. The variant did not occur in 181 normally pigmented dogs from various breeds. As OCA2 loss of function variants have been shown to cause oculocutaneous albinism in many other species, the OCA2 variant represents a compelling candidate causative variant. The variant is not easy to describe as the study by Caduff et al. (2017) also unveiled an assembly error concerning the OCA2 gene in the CanFam 3.1 genome reference assembly. The variant affects the conserved GT dinucleotide at the 5'-splice site of an early intron. It can be described as Chr3:31,715,704A>C (CanFam3.1) or OCA2:LT844587.1:c.-45+2T>G.

Clinical features: The three affected German Spitz puppies reported in Caduff et al. (2017) showed a light brown (hazel) coat colour and blue eyes. Pigmentation of the coat and eyes became slightly darker with age. The owner reported that the affected puppies used to squint in bright sunlight (photophobia) and had difficulties to perceive hand signals in bright sunlight. Photophobia and mild to moderate visual deficits are also common in human patients with oculocutaneous albinism type II.

Breed: German Spitz.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
OCA2 oculocutaneous albinism II Canis lupus familiaris 3 NC_006585.3 (32361825..32713631) OCA2 Homologene, Ensembl, NCBI gene

Variants

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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
German Spitz Coat colour, oculocutaneous albinism, OCA2-related OCA2 splicing CanFam3.1 3 g.31715704A>C "LOC100855460 (XM_005618224.1:c.377+2T>G LT844587.1:c.-45+2T>G) . . . Comparative sequence analyses revealed that LOC100855460 actually represents the 5'-end of the canine OCA2 gene. The CanFam 3.1 reference genome assembly is incorrect and separates the first two exons from the remaining exons of the OCA2 gene. We amplified a canine OCA2 cDNA fragment by RT-PCR and determined the correct full-length mRNA sequence (LT844587.1)." 2017 28973042

Reference


2017 Caduff, M., Bauer, A., Jagannathan, V., Leeb, T. :
OCA2 splice site variant in German Spitz dogs with oculocutaneous albinism. PLoS One 12:e0185944, 2017. Pubmed reference: 28973042. DOI: 10.1371/journal.pone.0185944.

Edit History


  • Created by Tosso Leeb on 10 Oct 2017
  • Changed by Tosso Leeb on 10 Oct 2017
  • Changed by Frank Nicholas on 11 Oct 2017