Just four gene locations account for horse size

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Thumbelina - the world's smallest horse, at 44.5cm tall - meets Radar, who is 200.6cm tall (19.3hh).
Thumbelina – the world’s smallest horse, at 44.5cm tall – meets Radar, who is 200.6cm tall (19.3hh).

Variations in genes at just four locations are responsible for 83 per cent of the major size variation in horses, American researchers have shown.

By contrast, nearly 1 per cent of all human genes are implicated in contributing to size variation.

“We show here that, in stark contrast, the control of the majority of horse size is genetically fairly simple,” the researchers wrote in the open-access journal, PLoS ONE.

“Genes controlling size in the horse are drawn largely from the broad set already identified in this role in humans.

“By combining our results with previous findings in cattle and dogs we have identified a very short list of genes that were selected repeatedly in domestication to act as major drivers of rapid and extreme size diversification.”

The study, led by Cornell University researchers, noted that horse body size varied greatly due to intense selection within each breed.

American Miniatures were less than one meter tall at the withers, while Shires and Percherons can exceed two meters, they noted.

Their research showed that genetic variation at just four locations explained the great majority of variation in horses.

“Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci [locations] with alleles [a variant of the DNA sequence] of large effect.”

They found that three of the four gene locations were found to contain genes previously found to control human height.

“Extreme size diversification is a hallmark of domestication,” they said. “Our results in the horse, complemented by the prior work in cattle and dogs, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.”

By contrast, previous research has identified nearly 200 gene locations influenzing size in the human genome.

“Control of human size is mediated by a huge number of genes of very small effect. In fact, it has been estimated that 697 genes, if identified, would explain just 15.7 per cent of variance in human height.

“In contrast, a single gene, IGF1, explains about 10 to 15 per cent of dog-size variation, and the majority of dog breed-average mass can be explained by as few as six loci.”

Domestic mammals therefore offered a powerful system in which to investigate genes controlling size, they said.

The research team’s work was based on DNA collected from 48 horses of 16 different large and small breeds, using three horses per breed, plus 48 thoroughbreds of variable size.

They inspected pedigrees to avoid including close relatives.

They hypothesized that two genes identified in their study, HMGA2 or LCORL, or both, may also drive size variation in other domestic mammals.

“By highlighting here a small but important subset of the size genes found in humans, the horse also offers guidance for exploring size genetics in humans and other mammals.”

The researchers were Shokouh Makvandi-Nejad, Gabriel Hoffman, Jeremy Allen, Erin Chu, Esther Gu, Alyssa Chandler, Ariel  Loredo, Rebecca  Bellone, Jason  Mezey, Samantha  Brooks, and Nathan Sutter.

 

Citation: Makvandi-Nejad S, Hoffman GE, Allen JJ, Chu E, Gu E, et al. (2012) Four Loci Explain 83% of Size Variation in the Horse. PLoS ONE 7(7): e39929. doi:10.1371/journal.pone.0039929

Association with size at the locus.
Association with size at the locus.

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