Roan, ticked and clear coat patterns in the canine are associated with three haplotypes near usherin on CFA38

Abstract

Summary White coat patterning is a feature of many dog breeds and is known to be coded primarily by the gene micropthalmia‐associated transcription factor (MITF). This patterning in the coat can be modified by other factors to produce the attractive phenotypes termed ‘ticked’ and ‘roan’ that describe the presence of flecks of color that vary in distribution and intensity within otherwise ‘clear’ white markings. The appearance of the pigment in the white patterning caused by ticking and roaning intensifies in the weeks after birth. We applied genome‐wide association to compare English Cocker Spaniels of roan phenotype (N = 34) with parti‐color (non‐roan) English Cocker Spaniels (N = 9) and identified an associated locus on CFA 38, CFA38:11 057 040 (Praw = 8.9 × 10−10, Pgenome = 2.7 × 10−5). A local case–control association in English Springer Spaniels comparing 11 ticked and six clear dogs identified indicative association with a different haplotype, CFA38:11 122 467G>T (Praw = 1.7 × 10−5) and CFA38:11 124 294A>C (Praw = 1.7 × 10−5). We characterize three haplotypes in Spaniels according to their putative functional variant profiles at CFA38:11 111 286C>T (missense), CFA38:11 131 841–11 143 239DUP.insTTAA (using strongly linked marker CFA38:11 143 243C>T) and CFA38:11 156 425T>C (splice site). 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. In Spaniels the associated haplotypes are t (CCT), T (TCC) and TR (TTT) for SNP markers on CFA38 at 11 111 286C>T, 11 143 243C>T and 11 156 425T>C respectively. It is likely that other alleles exist in this series and together the haplotypes result in a complex range of patterning that is only visible when dogs have white patterning resulting from the epistatic gene Micropthalmia‐associated transcription factor (the S‐locus).

Canine coat pigmentation genetics: a review

“…Whereas these haplotypes effectively differentiate clear from ticked dogs, no markers were identified that correlated with ticking density. Brancalion et al (2021) recognise that other haplotypes for the ticked phenotype also exist across the USH2A region. The functional mechanisms by which USH2A variants influence canine coat colour phenotypes have not yet been described.…”

“…White markings are common across a range of canine coat colour phenotypes and can be highly variable, ranging from small flecks of white fur to fully or almost fully depigmented coats (Brancalion et al 2021). Blue eyes, occurring owing to a lack of melanin in the irides, are also commonly associated with such phenotypes (Caduff et al 2017).…”

“…12b). The colour of the pigmented hairs is controlled by several loci independent of ticking and roan variants (Brancalion et al 2021). In some breeds exhibiting ticking and roan, the phenotypes are described by different names, such as blue (roan Australian cattle dog) and Belton (ticked English Setter).…”

“…A recent study, however, has demonstrated that the canine Usherin (USH2A) gene determines both ticking and roan coat colour patterns through a complex mode of inheritance. Located in the basement membrane of the extracellular matrix, the USH2A protein is composed of several fibronectin motifs and a pentaxin domain containing epidermal growth factors (Weizmann Institute of Science 2020e; Brancalion et al 2021).…”

“…In this allelic series, roan is incompletely dominant over ticked and both are dominant over clear. Originally mapped in spaniels, the ticked (T) and/or roan (T R ) alleles have also been identified in several other breeds including Australian Cattle dogs, Dalmatians, German Wire-haired Pointers, German Short-haired Pointers, Standard Poodles and Basset Hounds (Brancalion et al 2021).…”