Insights into morphology and disease from the dog genome project

Abstract

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.

Keywords: body size; breed standard; disease; genomics; morphology; skull.

Figure 1

More than 180 breeds exist in the United States, 215 are recognized by the Kennel Club in the United Kingdom, and approximately 490 are noted worldwide. The closest living ancestor to the dog is the gray wolf. Shown here are (a) a gray wolf and (b–i ) some interesting breed examples, including the (b) Pembroke Welsh Corgi, (c) Boxer, (d ) French Bulldog, (e) Papillon, ( f ) Miniature Dachshund, ( g) Borzoi, (h) Greyhound, and (i ) Mastiff. Photo credit: Mary Bloom courtesy of American Kennel Club (panels a, b, d–i ) and courtesy of Wikipedia (panel c).

Figure 2

The dog’s morphological diversity belies its genetic diversity. (a) Linkage disequilibrium (LD) by breed. Each line represents the average R² of markers within a single breed or between groups of ten breeds (dashed lines). For simplification, only breeds highlighted in Figure 1 are assigned colored lines. Considered individually, the LD of each breed of dog is more extensive than that of wolves. Considered collectively, the LD of breed dogs approaches that of gray wolves. (b) Intrabreed haplotype diversity is greatly reduced relative to the gray wolf. Panels a and b were adapted with permission from Boyko et al. (2010).

Figure 3

Derived alleles that are putatively causal (or tightly linked to causal variants) are carried at higher frequencies among small and toy breeds. Standard breed weights are listed on the y-axis as pounds and kilograms. One exception to this trend is the Rottweiler. Despite weighing ~100–105 lb, Rottweilers appear to carry the derived IGF1 variant, suggesting either that the causal mutation occurred on an ancestral haplotype carried by this breed or that an epistatic genetic interaction occurs to mute the derived IGF1 variant’s effects on size. Figure adapted from Rimbault et al. (2013).

Figure 4

Canine brachycephaly and its connection to the cranial base. Boxplots of skull PC1 breed averages illustrate the continuum of shape that exists between brachycephalic and dolichocephalic breeds. Figure adapted from Schoenebeck et al. (2012) to include additional dog breeds.

Figure 5

Computed tomography scans of a six-month-old Golden Retriever and Cavalier King Charles Spaniel (a CBa breed). Asterisks indicate the position of the synchondroses. In this example, the spheno-occipital synchondrosis of the Cavalier King Charles Spaniel is ossified (arrow). Accompanying schematics illustrate the changes that occur at the cranial base between bones ( yellow) and the cartilaginous synchondroses (blue). Abbreviations: CER, cerebellum; ISS, intersphenoid synchondrosis; SES, spheno-ethmoidal synchondrosis; SOS, spheno-occipital synchondrosis. Scanned images provided courtesy of Dr. Martin Schmidt.