Thursday, August 27, 2009

What happened to the eighth dog hair style?

For the second time this summer Science has another step forward in understanding the genetics of dog breeds. Previously it was the identification of a post-wolf event which led to short-legged dogs (which includes my faithful assistant); this time it is that a large (600+ dogs) genetic study has shown that vast majority of dog coat types can be explained by just three genes (you'll need a Science subscription to access these).

Figure 3 of the paper makes the point quite graphically. The three genes found in the study are FGF5, RSPO2 and KRT71. FGF5 is a secreted growth factor previously implicated in hair development, RSPO2 is a regulator of the Wnt pathway known to be important in hair follicles and KRT71 is a keratin which causes a curly phenotype when mutated in mice. So even though these were found by a genome-wide genetic study, they are all excellent candidate genes. Below is my version of Figure 3 (which has illustrations of the dog breeds). Furnishings are extra hair around the eyebrows. Wolf means the ancestral genotype and novel a genotype that post-dates domestication.

ShortBasset houndwolfwolfwolf
Wire Australian terrierwolfnovelwolf
Wire and CurlyAiredale Terrierwolfnovelnovel
Long Golden Retrievernovelwolfwolf
Long with FurnishingsBearded Collienovelnovelwolf
Curly Irish Water Spanielnovelwolfnovel
Curly with FurnishingsBichon Frise novelnovelnovel

Now, this covers a lot of furry ground. The paper claims it describes coat configuration in 95% of the 108 breeds examined. There are some strange coats probably not covered by this work (for example, the Komondor and Puli, which grow dreadlocks -- I haven't seen one personally yet). They do note that a few very long haired breeds (Afghan hound) lack the FGF5 mutation found here, suggesting that some breeds use a different genetic strategy.

The variants themselves are a mix (mutts?). RSPO2 as a mutation in the 3' non-coding region which the paper shows increases expression by about 3 fold. The FGF5 mutation changes a conserved amino acid from Cys to Phe; that Cys may well be involved in a covalent Cys-Cys bond in the structure (common in secreted proteins). The KRT71 mutation is also a coding region mutation.

But the more obvious question to me is they describe 3 essentially binary genetic determinants of coat style -- but describe only 7 combinations not the 8 which could be expected. The missing genotype in the table is wolf-like at FGF5 and RSPO2 but with the novel (post-domestication) genotype at KRT71. Presumably this would yield a short, curly phenotype -- perhaps too short for curling to observed and the trait pair to be selected by breeders.

Cadieu, E., Neff, M., Quignon, P., Walsh, K., Chase, K., Parker, H., VonHoldt, B., Rhue, A., Boyko, A., Byers, A., Wong, A., Mosher, D., Elkahloun, A., Spady, T., Andre, C., Lark, K., Cargill, M., Bustamante, C., Wayne, R., & Ostrander, E. (2009). Coat Variation in the Domestic Dog Is Governed by Variants in Three Genes Science DOI: 10.1126/science.1177808

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