In other species: horse , pig , taurine cattle , goat , sheep , alpaca

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 184745 (gene) , 611664 (trait)

Mendelian trait/disorder: yes

Disease-related: no

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: see also: OMIA 002264-9615 : Coat colour, ticked in Canis lupus familiaris

Mapping: Brancalion et al. (2021) "applied genome-wide association to compare English Cocker Spaniels [ECS] of roan phenotype (N = 34) with parti-color (non-roan) English Cocker Spaniels (N = 9) .... An interval of genome‐wide significant association with roan coat color spans CFA38:10 268 280–11 341,635 (canfam3.1). ... Association over the denser marker set revealed the strongest association at CFA38:11 069 051G>A (Praw = 8.0 × 10−8) for roan vs. parti‐color in ECSs. ... Among ESSs [English Springer Spaniel], two markers demonstrated indicative association with ticked vs. clear: CFA38:11 122 467G>T (Praw = 1.7 × 10−5) and CFA38 11 124 294A>C (Praw = 1.7 × 10−5). ... In Spaniels, the haplotypes work as an allelic series including alleles (t, recessive clear; T, dominant ticked/parti‐color; and TR, incomplete dominant roan) to control the appearance of pigmented spots or flecks in otherwise white areas of the canine coat." Kawakami et al. (2021) identified the same "genomic region on chromosome 38 that is strongly associated with a mottled coat pattern (roaning) by genome-wide association study" in Wirehaired Pointing Griffons and Australian Cattle Dogs.

Molecular basis: Brancalion et al. (2021): "The roan (TR) haplotype is diverged from the reference/clear haplotype at four putative functional sites. Two are missense variants CFA38:g.11 085 443G>A and CFA38:g.11 111 286C>T ... . By analysis of regional coverage in representative individuals, we identified a duplicated DNA segment (11 398 bp) lying within the 67th intron of USH2A and spanning CFA38:11 131 841–11 143 239 (canfam3.1), which is unique to the TR [roan] haplotype ... . Subsequent testing for the presence of the PCR product capturing the junction between the duplicated segments identified the product in roan ECSs [English Cocker Spaniel], all Dalmatians (typically described as evenly spotted), German Short‐haired Pointer (typically roan) and Australian Cattle Dogs (typically roan). ... DBVC coverage data (Fig. S1) show the presence of a VNTR mutation at CFA38:11 112 907–11 113 501. This variant lies close to an intron–exon boundary (ENSCAFG00000010731.4 exon 62/71) and it may affect the phenotypic expression of the USH2A gene." Kawakami et al. (2021) identified the same duplication in Wirehaired Pointing Griffons and Australian Cattle Dogs: a "putative causal variant in this region, an 11-kb tandem duplication (11,131,835–11,143,237) characterized by sequence read coverage and discordant reads of whole-genome sequence data, microarray probe intensity data, and a duplication-specific PCR assay. The tandem duplication is in an intronic region of usherin gene (USH2A), which was perfectly associated with roaning but absent in non-roaned dogs. ... Surprisingly, all Dalmatians (N = 262) carried the duplication embedded in identical or similar haplotypes with roaned dogs, indicating this region as a shared target of selection during the breed’s formation. We propose that the Dalmatian’s unique spots were a derived coat pattern by establishing a novel epistatic interaction between roaning “R-locus” on chromosome 38 and an uncharacterized modifier locus."

Breeds: Australian Cattle Dog (Dog) (VBO_0200088), English Cocker Spaniel (Dog) (VBO_0200486), German Shorthaired Pointer (Dog) (VBO_0200583), Wirehaired Pointing Griffon (Dog) (VBO_0201427).
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: