Categories: Pigmentation phene

Mendelian trait/disorder: unknown

Disease-related: no

Year key variant first reported: 2022

Species-specific description: Batcher et al. (2022): "The Poodle breed has a wide range of officially recognized coat colors, including the pheomelanin-based white, cream, apricot and red coat colors, which are not fully explained by the previously identified genetic variants involved in pigment intensity."

Mapping: Batcher et al. (2022): "a genome-wide association study for pheomelanin intensity was performed in Poodles which identified an association on canine chromosome 18."

Molecular basis: Batcher et al. (2022): "Whole genome sequencing data revealed an SNN retrocopy insertion (SNNL1) in apricot and red Poodles within the associated region on chromosome 18. ... Sanger sequencing confirmed the insertion as a full length SNN retrocopy ..., referred to here as SNNL1. SNNL1 is inserted within the intron of COG5 and 2.8kbp upstream of and in the same orientation as GPR22. The SNNL1 retrocopy sequence contains two SNV in the 3’ UTR (chr6:31,139,403 C>A and chr6:31,140,045 G>A), but is otherwise identical to the parent gene sequence. SNNL1 has a 3’ poly (A) tail approximately 27bp in length, and a 17bp target site duplication (TGTGAAATACTGAAGTT) was also observed flanking the insertion, putting the exact insertion location at chr18:13,134,248‐13,134,264. ... While equal numbers of melanocytes were observed in all Poodle skin hair bulbs, higher melanin content was observed in the darker Poodles. Several genes involved in melanogenesis were also identified as highly overexpressed in red Poodle skin. The most differentially expressed gene however was GPR22, which was highly expressed in red Poodle skin while unexpressed in white Poodle skin ... . GPR22 is an orphan G-protein coupled receptor normally expressed exclusively in the brain and heart. The SNNL1 retrocopy inserted 2.8kb upstream of GPR22 and is likely disrupting regulation of the gene, resulting in atypical expression in the skin. Thus, we identify the SNNL1 insertion as a candidate variant for the CFA18 pheomelanin intensity locus in red Poodles. ... SNNL1 copy number was highly predictive of red coat color in the breed ... . All (N=125) white Poodles had 0 copies of SNNL1, and all red Poodles (N=48) had at least one copy of SNNL1, with 38/48 of them having 2 copies. Most (19/25) apricot Poodles had 1 copy of SNNL1."

Breed: Poodle (Dog) (VBO_0201048).
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: