Nearly half of size reduction in dogs explained by six genes
Rimbault M and Beale HC et al. (2013) Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Research 23:1985-1995. doi: 10.1101/gr.157339.113
Somewhere between 15,000 and 100,000 years ago, people started domesticating wolves through intense artificial selection for whatever traits they fancied. A majority of modern breeds were developed in last 300 years, today resulting in 175 AKC recognized breeds that are codified by very distinct standards. Such intense selection pressure means that within breeds, there’s going to be very little genetic diversity in those distinct traits [[not all purebreds are inbred, but they did start out that way, which is why you see more health issues in purebred dogs]].Â
The genetic loci determining size in particular have very strong signatures of selection. The CanMap project used 60,968 SNPs [[single nucleotide polymorphisms, or single DNA base pair changes]] to highlight a number of phenotype-associated loci, which the authors then fine-mapped to four autosomal loci and then further mapped to 6 specific gene loci polymorphisms. Another gene, IGF1, was implicated as a size factor in other studies, so it was also examined. This brought the total number of markers up to 7. [[Markers referring to specific DNA sequences that you know the location of and therefore can actually find.]]
Experiment:
1. Drew blood from AKC show dogs from 93 recognized breeds across the full range of canine body size. Average AKC “standard breed weight” (SBW) was used as a surrogate for body size.  All dogs were unrelated to one another at the grandparent level so there was no similarity due to recent inbreeding. At least 2 males and 2 females of each breed were tested.
2. Genotyped the dogs at the 7 markers [[looked at the dogs’ gene sequences at these 7 specific points]].
3. Determined the ancestral allele [[what the genome looked like before humans started making puggles]] for each marker by looking at 26 grey wolves, 2 red wolves, 2 coyotes.Â
They found that genotypes at each marker corresponded to differences in size, with dogs possessing more derived markers trending towards a smaller and smaller standard breed weight. For each variant, SBWs of dogs homozygous for the derived allele were significantly less than SBWs of dogs homozygous for the ancestral genes. SBWs of D/D dogs were also significantly less than SBWs of heterozygotes (A/D) at four of the seven markers.Â
These genes generally could not explain any of the size variation for the large dogs. Nearly all of the rottweilers were actually derived for one of the markers, IGF1, which was highly unusual. But, if a dog with a high SBW did have any derived markers, it was usually in the same place - IGF1. Large dogs clearly must have other size factors at play.
Genotypes at these seven loci (conservatively) account for between 46 and 52.5% of the SBW variance. This is crazy. Half of the size variation in small purebreds can be traced back to (essentially) 7 transcription errors that somehow only changed the size of the dog without too many other problems. Other mutations in these same genes have been implicated in growth disorders in mice and humans.Â
Just as a comparison, we’ve identified 180 loci significantly associated with height in humans, and these are highly heritable genes, but these loci all together only account for around 10% of the variation in human heights. Granted, these were all show dogs so environmental factors (diet changes, poor upbringings, etc) were likely out of the picture, but the amount of control humans have exerted over the dog genome in just 300 years is astounding. People must have really wanted those puggles.Â















