title: Genomic amplification of the caprine EDNRA locus might lead to a dose dependent loss of pigmentation.
abstract: The South African Boer goat displays a characteristic white spotting phenotype, in which the pigment is limited to the head. Exploiting the existing phenotype variation within the breed, we mapped the locus causing this white spotting phenotype to chromosome 17 by genome wide association. Subsequent whole genome sequencing 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. We propose a hypothesis that ectopic overexpression of a mutant EDNRA scavenges EDN3 required for EDNRB signaling and normal melanocyte development and thus likely lead to an absence of melanocytes in the non-pigmented body areas of Boer goats. Our findings demonstrate the value of domestic animals as reservoir of unique mutants and for identifying a precisely defined functional CNV.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Menzi
authors.affiliation: Department of Clinical Research and Swiss Institute of Bioinformatics, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Keller
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Reber
authors.affiliation: Chronix Biomedical, Goetheallee 8, 37073 Göttingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Beck
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Göttingen, Burckhardtweg 2, 37077 Göttingen, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Brenig
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Göttingen, Burckhardtweg 2, 37077 Göttingen, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schütz
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.|Dermfocus, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.|Dermfocus, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D056915:DNA Copy Number Variations; D019334:Endothelin-3 / Q000235:genetics; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study / Q000379:methods*; D006041:Goats / Q000235:genetics*; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D040641:Quantitative Trait Loci; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics
chemical_list: D019334:Endothelin-3; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B