In other species: cattle , horse , dog , domestic cat , sheep , pig , golden hamster , North American deer mouse , American mink , rabbit , Mongolian gerbil , American black bear

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612271 (trait) , 203290 (trait) , 115501 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2015

Species-specific name: Brown, (Coppernecked Goat)

History: The Valais Blacknecked goat in southern Switzerland is characterised by black forequarters and white hindquarters that are separated by a sharp vertical boundary. A rare coat colour variant of this breed showing brown instead of black forequarters is called Coppernecked goat. Even though this phenotypic variant has probably existed for more than 120 years, there are fewer than 150 animals today. One reason is that the copper-coloured animals do not fit into the scheme of the official breed standards and are not included in the herd book of the Swiss Goat Breeders Association. However, the Swiss foundation for the cultural history and genetic diversity of animals and plants, ProSpecieRara, is dedicated to preserving the Coppernecked goats (www.prospecierara.ch).

Inheritance: Becker et al. (2015) reported a likely candidate causative variant, TYRP1:p.Gly496Asp. According to Becker et al. (2015) the 496-Asp allele is dominant to the wildtype 496-Gly allele. Pedigree records of 522 informative matings strongly suggested a dominant mode of inheritance (Becker et al. 2015). This is very unexpected as most brown coat color phenotypes in many mammalian species are caused by recessive loss-of-function alleles at the TYRP1 locus. Dietrich et al. (2015) proved the dominant inheritance by mating a Coppernecked buck homozygous for the 496-Asp allele to black Nera Verzasca goats. The authors obtained 3 offspring from two matings and all three offspring showed the brown coat colour. Dietrich et al. (2015) noticed that the brown Toggenburg goats also carry the 496-Asp allele. Thus the brown coat colour in Coppernecked goats and Toggenburg goats is due to the same genetic variant and there has most likely been some genetic exchange between these two breeds.

Mapping: Becker at al. (2015) genotyped 22 cases 23 controls on the illumina SNP50 Beadchip. The authors performed a genome-wide association study (GWAS) with 46,724 informative SNP markers and mapped the locus for brown coat colour in Coppernecked goats to chromosome 8.

Molecular basis: Becker et al. (2015) investigated the positional and functional candidate gene TYRP1 in 8 Coppernecked and 8 Blacknecked goats and identified 49 variants including four non-synonymous variants. Two of the non-synonymous variants were present in homozygous state in black goats and considered functionally neutral. The variant c.1487G>A predicted to affect the transmembrane domain of the TYRP1 protein (p.Gly496Asp) was found exclusively in Coppernecked goats. The vast majority of Coppernecked goats (77 out of 81 investigated animals) carried the 496-Asp allele in either heterozygous or homozygous state, whereas this allele was not found in 74 Blacknecked goats or in goats from other breeds. Becker et al. (2015) concluded that the 496-Asp allele is most likely responsible for a dominantly inherited brown phenotype. Solely based on the association data Becker et al. (2015) further observed that the rare variant c.1433T>C [ARS1 8:31503219A>G] predicted to result in p.Ile478Thr possibly represents another functional variant. It thus cannot be excluded that this variant leads to a recessive brown allele. However, so far, no homozygous goat for this variant has been found, which would allow to prove or disprove this hypothesis. Becker et al. (2015) had 4 brown goats in their study, which could initially not be explained by any of the identified TYRP1 variants. However, incorrect phenotype assignments and a sample mix-up are the most likely explanations for these discrepant results (Becker et al. 2015, Corrigendum).

Breeds: Toggenburg (Goat) (VBO_0000846), Valais Blackneck (Goat) (VBO_0000849).

Associated gene: