Coat variation in the domestic dog is governed by variants in three genes

Abstract

Coat color and type are essential characteristics of domestic dog breeds. Although the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5, and keratin-71, respectively), that together account for most coat phenotypes in purebred dogs in the United States. Thus, an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.

Fig. 1

GWAS and fine-mapping identify RSPO2 as the associated gene for moustache and eyebrow growth pattern (furnishings). (A) Three types of coat segregate in dachshunds: (from left to right) smooth-coated, long-haired, and wire-haired with furnishings. (B) Results of the GWAS in the dachshund using wire-haired dogs as cases and smooth-coated and long-haired dogs as controls. The best P value (3.35 × 10⁻²⁷), highlighted by the arrow, is located on CFA13 at position 11,095,120. (C) Results of the GWAS for furnishings in the CanMap data set. The arrow highlights the best association (P = 10⁻²⁴¹) at CFA13 position 11,659,792. Both P values were obtained with single-marker χ² analyses. (D) Homozygous regions identified in cases from GWAS and fine-mapping. The red rectangle represents the associated haplotype in the dachshund; the blue rectangle spans the homozygous region from 19 breeds fixed for furnishings based on the multibreed data set; the green rectangle indicates the region of homozygosity in 18 breeds fixed for the furnishings after fine-mapping. A 167-bp deletion, indicated by the small red rectangle, is located within all three haplotypes in the 3′UTR of the RSPO2 gene. The positions of genes in the region are represented by open boxes at the bottom of the figure, labeled to the left, with arrows indicating reading-frame direction (www.genome.ucsc.edu).

Fig. 2

Regions of homozygosity identify genes for pelage length and curl. (A) Homozygous region found on CFA32 defining the length locus. The red bar indicates the 520-kb associated haplotype from 29 long-haired dachshunds; the blue bar spans the 125-kb homozygous region found in 319 dogs from 31 long-haired breeds; the green bar represents the 67-kb reduced homozygous region found after fine-mapping in 293 dogs from 39 long-haired breeds. The best-associated SNP, represented by the small red rectangle, is within these three homozygous regions in exon 1 of the FGF5 gene. (B) PWDs display two coat varieties: curly (two left panels) and wavy (two right panels). (C) Haplotype analysis at the curl locus on CFA27. The green bar represents the 32-kb homozygous haplotype found after fine-mapping in 65 dogs from five curly haired breeds. The best-associated SNP, represented by the small red rectangle, was found within the homozygous haplotype in exon 2 of the KRT71 gene. The positions of genes in both regions (A and C) are represented by open boxes at the bottom of each figure, labeled to the left, with arrows indicating reading-frame direction (www.genome.ucsc.edu). Curly PWD photos courtesy of M. Bloom (Copyright AKC).

Fig. 3

Combinations of alleles at three genes create seven different coat phenotypes. Plus (+) and minus signs (−) indicate the presence or absence of variant (nonancestral) genotype. A characteristic breed is represented for each of the seven combinations observed in our data set: (A) short hair; (B) wire hair; (C) “curly-wire” hair; (D) long hair; (E) long, soft hair with furnishings; (F) long, curly hair; and (G) long, curly hair with furnishings. [Photos courtesy of M. Bloom (Copyright AKC)].