Categories: Pigmentation phene

Links to MONDO diseases: No links.

Mendelian trait/disorder: unknown

Considered a defect: no

Cross-species summary: pheomelanin dilution, pigment intensity

Species-specific description: Slavney et al. (2021): "In order to gain further insight into the extent of multigenicity and epistatic interactions underlying coat pheomelanin intensity in dogs, we leveraged a large dataset obtained via a direct-to-consumer canine genetic testing service. This consisted of genome-wide single nucleotide polymorphism (SNP) genotype data and owner-provided photos for 3,057 pheomelanic mixed breed and purebred dogs from 63 breeds and varieties spanning the full range of canine coat pheomelanin intensity. We first performed a genome-wide association study (GWAS) on 2,149 of these dogs to search for additional genetic variants that underlie intensity variation. GWAS identified five loci significantly associated with intensity, of which two (CFA15 29.8 Mb and CFA20 55.8 Mb) replicate previous findings [OMIA 002197-9615, OMIA 002228-9615] and three (CFA2 74.7 Mb, CFA18 12.9 Mb, CFA21 10.9 Mb) have not previously been reported. In order to assess the combined predictive power of these loci across dog breeds, we used our GWAS data set to fit a linear model, which explained over 70% of variation in coat pheomelanin intensity in an independent validation dataset of 908 dogs."

Molecular basis: Slavney et al. (2021): "The top CFA2 variant, BICF2P1302896, falls within the second exon of the long intergenic non-coding RNA (lincRNA) ENSCAFG00000042716 ... . The top CFA18 variant, chr18_12910382, is a missense mutation p.I487M in a conserved residue of the twelfth exon of the solute carrier family 26 member 4 gene (SLC26A4). ... The top CFA21 variant, BICF2G630655755, falls within the second intron of the tyrosinase gene (TYR). ... The top CFA15 variant, BICF2G630433130, is located approximately 8 kilobases (kb) downstream of a 6 kb copy number variant (CNV) near the KIT ligand gene (KITLG) that was previously associated with variation in coat pheomelanin intensity in Nova Scotia Duck Tolling Retrievers and Poodles [OMIA 002228-9615]. ... The top CFA20 variant is the same variant reported in another coat pheomelanin intensity GWAS using over 90 different breeds, which was used to fine map the peak to a nearby missense mutation in the major facilitator superfamily domain containing 12 gene (MFSD12) at CFA20: 55,856,000 bp [OMIA 002197-9615]."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing