Identification of a Mutation that Is Associated with the Saddle Tan and Black-and-Tan Phenotypes in Basset Hounds and Pembroke Welsh Corgis

Abstract

The causative mutation for the black-and-tan (a (t) ) phenotype in dogs was previously shown to be a SINE insertion in the 5' region of Agouti Signaling Protein (ASIP). Dogs with the black-and-tan phenotype, as well as dogs with the saddle tan phenotype, genotype as a (t) /_ at this locus. We have identified a 16-bp duplication (g.1875_1890dupCCCCAGGTCAGAGTTT) in an intron of hnRNP associated with lethal yellow (RALY), which segregates with the black-and-tan phenotype in a group of 99 saddle tan and black-and-tan Basset Hounds and Pembroke Welsh Corgis. In these breeds, all dogs with the saddle tan phenotype had RALY genotypes of +/+ or +/dup, whereas dogs with the black-and-tan phenotype were homozygous for the duplication. The presence of an a (y) /_ fawn or e/e red genotype is epistatic to the +/_ saddle tan genotype. Genotypes from 10 wolves and 1 coyote indicated that the saddle tan (+) allele is the ancestral allele, suggesting that black-and-tan is a modification of saddle tan. An additional 95 dogs from breeds that never have the saddle tan phenotype have all three of the possible RALY genotypes. We suggest that a multi-gene interaction involving ASIP, RALY, MC1R, DEFB103, and a yet-unidentified modifier gene is required for expression of saddle tan.

True Colors: commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential

“…The remaining 32 breeds have breed standards that would permit for the occurrence of a saddle phenotype, but the pattern is rarely observed due to low frequency of the required tan point genotype. These instances reiterate the findings of the initial canine RALY research, suggesting at least one additional modifier gene that is required for the production of the saddle tan phenotype (32).…”

“…There is, of course, the possibility that either the a y or a t variants previously described are not causal variants, but rather very accurate markers. However, both variants have been successfully used to predict coat color genotypes in multiple studies without raising concern (7,32,50,51). Further pursuit of the phenotypic impact of the a yt allele, along with determining its inheritance pattern, is ongoing.…”

Insights into Morphology and Disease from the Dog Genome Project

“…By most accounts, the use of GWAS to locate heritable traits has been wildly successful in dogs, identifying loci for eye diseases, skin disorders, cancer, deafness, neurological disorders, heart disease, and a host of other disorders (Ahonen et al 2013, Grall et al 2012, Karyadi et al 2013, Olsson et al 2011, Tengvall et al 2013, Yokoyama et al 2012), as well as morphological traits (Boyko et al 2010, Vaysse et al 2011), including body size, skull shape, leg length, and fur type and color (Cadieu et al 2009, Clark et al 2006, Dreger et al 2013, Drögemüller et al 2008, Karlsson et al 2007, Parker et al 2009, Rimbault et al 2013, Schoenebeck et al 2012). Loci of large effect, a fraction of which are described below, were rapidly identified in population-based approaches that compared SNP allele frequencies with a myriad of phenotypic traits.…”

An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts

“…Multiple SNP arrays were designed based on the canine draft genome assembly and these were effectively used to map by genome-wide association (GWAS) some of the phenotypically plastic traits under selection, including coat color [7], [8] and morphology [9]–[11]. Whilst those studies offered insight into basic biology (pigmentation, bone formation), parallel investigations into specific heritable diseases suffered by humans and their canine companions revealed novel pathways (NFAT in SLE-like disease [12], HAS2 biosynthesis in autoinflammatory disease [13]) and candidate genes for disease biology such as LGI2 in remitting focal epilepsy [14], and SLC4A3 in progressive retinal atrophy [15].…”