Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 131243 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Disease-related: no

Key variant known: yes

Year key variant first reported: 2016

Inheritance: The causative genetic variant is a copy number variant (CNV). Currently 3 alleles with 1, 2, or 3 copies of a 1 Mb genomic segment are known. The proportion of non-pigmented white skin increases with increasing total copy numbers. The standard Boer goat with the traditional coat colour involving a non-pigmented white body and a pigmented red head and neck has a 2/2 genotype with 2 copies on each allele. Animals with the genotypes 3/2 or 3/3 have less pigmented skin on the head whereas animals with the genotype 1/2 often have large pigmented spots on the body. Goats with the wildtype genotype 1/1 are fully pigmented.

Mapping: Menzi et al. (2016) "mapped the locus causing this white spotting phenotype to chromosome 17 by genome wide association".

Molecular basis: "Whole genome sequencing [by Menzi et al., 2016] identified a 1 Mb copy number variant (CNV) harboring 5 genes including EDNRA. The analysis of 358 Boer goats revealed 3 alleles with one, two, and three copies of this CNV. The copy number is correlated with the degree of white spotting in goats." The duplicated EDNRA copies contain a missense variant (p.Tyr129His) [ARS1 17:60223612T>C] predicted to increase the affinity of the encoded mutant receptor for endothelin 3. Menzi et al. proposed a hypothesis whereby ectopic overexpression of a mutant EDNRA scavenges EDN3 required for EDNRB signaling and normal melanocyte development and thus likely leads to an absence of melanocytes in the non-pigmented body areas of Boer goats.

Breed: Boer (Goat) (VBO_0000736).
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: