OMIA 000214-9925 : Coat colour, white spotting in Capra hircus

In other species: domestic cat , dog , cattle , horse , water buffalo , domestic guinea pig

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 193510 , 103500

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Semi-Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2016

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism"), not by failure in the biochemical reactions required for pigment synthesis.

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) 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.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
EDNRA endothelin receptor type A Capra hircus 17 NC_030824.1 (60218131..60292066) EDNRA 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
Coat colour, white spotting EDNRA repeat variation "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" 2016 27329507

Reference


2016 Menzi, F., Keller, I., Reber, I., Beck, J., Brenig, B., Schütz, E., Leeb, T., Drögemüller, C. :
Genomic amplification of the caprine EDNRA locus might lead to a dose dependent loss of pigmentation. Sci Rep 6:28438, 2016. Pubmed reference: 27329507. DOI: 10.1038/srep28438.

Edit History


  • Created by Frank Nicholas on 05 Aug 2016
  • Changed by Frank Nicholas on 05 Aug 2016
  • Changed by Tosso Leeb on 12 Aug 2016