Equine Height Variants (LCORL & HMGA2)
Gene or region: LCORL / NCAPG
Reference allele: T
Mutant allele: C
Affected Breeds: Many
Research Confidence: Moderate confidence, findings reproduced in multiple studies
What it does:
The domestic horse displays a wide range of size variation, from the tiny Miniature Horses to the towering draft breeds. While height is a complex trait involving a variety of genetic and environmental factors, the breeding systems of domestic animals has led to a small number of genes being responsible for large amounts of variation in several species. One study in the horse has shown four loci can explain up to 83.5% of body size variation. This SNP in particular explained 68.5% of the measured variation in height, with the T allele being associated with small body size, and the C allele with large size (T/C animals displaying an intermediate size).
T/T - Typical/Average risk; no contribution to height from this variant
T/C - Likely taller/larger than like-bred siblings or breeds (formerly LCORL/n)
C/C - Likely taller/larger than like bred siblings or breeds (average of 2.9 inches taller than "T/T" horses) (formerly LCORL/LCORL)
LCORL is a transcription factor that has been associated with body size in a variety of species. One study in the horse has suggested that the C allele removes a binding site for TFIID (which is involved with skeletal development), which is further associated with decreased expression of LCORL. This alteration of gene expression could be the molecular basis for the association with body size.
Gene or region: HMGA2
Reference allele: G
Mutant allele: A
Affected Breeds: Many (APHA, AQHA, Appaloosa, Curly, Falabella, Gypsy, Irish Cob, Miniature Horse, Mustangs, Diverse Pony breeds, Shetland, Welsh Cob Section A and Section B.)
Research Confidence: HIGH Gene variations demonstrated effect in height in diverse horse breeds and other model species.
What it does:
The domestic horse displays a wide range of size variation, from the tiny Miniature Horses to the towering draft breeds. While height is a complex trait involving a variety of genetic and environmental factors, the breeding systems of domestic animals has led to a small number of genes being responsible for large amounts of variation in several species.
G/G - Average or taller height.
G/A - Up to 9.5cm/3.74in (about 1 hand) smaller than like-bred siblings or breeds
A/A - Up to 19cm/7.48in (about 2 hands) smaller than like-bred siblings or breeds
HMGA2 is proposed as a transcription factor associated with body size in a variety of species, including humans, mice, rabbits, cows, chickens and dogs - as well as horses. One study in the Shetland Pony suggested that the A allele affects the first AT-hook DNA binding domain of the HMGA2 protein (c.83G>A; p.G28E), an in vivo DNA binding site, leading to reduced growth and smaller stature. Etalon is currently working on studies regarding the impact of this variant in other horse breeds.
Signer-Hasler H et al., “A genome-wide association study reveals loci influencing height and other conformation traits in horses.” (2012) PLoS One. 7: e37282. PMID: 22615965
Makvandi-Nejad S et al., “Four loci explain 83% of size variation in the horse.” (2012) PLoS One. 7: e39929. PMID: 22808074
Metzger J et al., “Expression levels of LCORL are associated with body size in horses.” (2013) PLoS One. 8: e56497. PMID: 23418579
Tetens J et al., “A genome-wide association study indicates LCORL/NCAPG as a candidate locus for withers height in German Warmblood horses.” (2013) Anim Genet. 44: 467-71. PMID: 23418885
Boyko AR et al., “Genomic analysis establishes correlation between growth and laryngeal neuropathy in Thoroughbreds.” (2014) BMC Genomics. 15: 259. PMID: 24707981
Frischknecht M et al. “A Non-Synonymous HMGA2 Variant Decreases Height in Shetland Ponies and Other Small Horses.” (2015) PLoS ONE 10(10): e0140749. doi:10.1371/journal.pone.0140749
Lee MO et al., “Hmga2 deficiency is associated with allometric growth retardation, infertility, and behavioral abnormalities in mice” (2021) G3 Genes|Genomes|Genetics, 2021;, jkab417, https://doi.org/10.1093/g3journal/jkab417